Comparison of BNCT and GdNCT efficacy in treatment of canine cancer

International Nuclear Information System (INIS)

Mitin, V.N.; Kulakov, V.N.; Khokhlov, V.F.; Sheino, I.N.; Arnopolskaya, A.M.; Kozlovskaya, N.G.; Zaitsev, K.N.; Portnov, A.A.

2009-01-01

In this study efficacy of antineoplastic action of gadolinium NCT and boron NCT in cases of canine melanoma and osteosarcoma was compared. Canine spontaneous tumors, such as melanoma and osteosarcoma, have clinical common features with human malignancies, so these tumors in dogs can be considered as clinical model of human melanoma and osteosarcoma. The study has been carried out on 33 dogs with oral cavity melanoma and 9 dogs with osteosarcoma. Dogs with spontaneous melanoma of oral cavity and osteosarcoma of extremities were selected by the results of clinical examination. Irradiation was carried out at the NCT facility of the IRT MEPhI reactor. Neutron irradiation without boron or gadolinium was chosen as a control method to evaluate the efficacy of NCT.

Enhancing Brief Cognitive Behavioral Therapy with Motivational Enhancement Techniques in Cocaine Users

Science.gov (United States)

McKee, Sherry A.; Carroll, Kathleen M.; Sinha, Rajita; Robinson, Jane E.; Nich, Charla; Cavallo, Dana; O’Malley, Stephanie

2008-01-01

Background We investigated the impact of enhancing brief cognitive behavioral therapy with motivational interviewing techniques for cocaine abuse or dependence, using a focused intervention paradigm. Methods Participants (n=74) who met current criteria for cocaine abuse or dependence were randomized to 3-session cognitive behavioral therapy (CBT) or 3-session enhanced CBT (MET + CBT), which included an initial session of motivational enhancement therapy (MET). Outcome measures included treatment retention, process measures (e.g., commitment to abstinence, satisfaction with treatment), and cocaine use. Results Participants who received the MET+CBT intervention attended more drug treatment sessions following the study interventions, reported significantly greater desire for abstinence and expectation of success, and they expected greater difficulty in maintaining abstinence compared to the CBT condition. There were no differences across treatment conditions on cocaine use. Conclusions These findings offer mixed support for the addition of MET as an adjunctive approach to CBT for cocaine users. In addition, the study provides evidence for the feasibility of using short-term studies to test the effects of specific treatment components or refinements on measures of therapy process and outcome. PMID:17573205

Spinal Manipulative Therapy Specific Changes In Pain Sensitivity In Individuals With Low Back Pain (NCT01168999)

Science.gov (United States)

Bialosky, Joel E; George, Steven Z; Horn, Maggie E; Price, Donald D; Staud, Roland; Robinson, Michael E

2013-01-01

Spinal Manipulative Therapy (SMT) is effective for some individuals experiencing low back pain (LBP); however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with LBP to receive SMT, placebo SMT, placebo SMT with the instructional set, “The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people”, or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over two weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following two weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (p= 0.05, partial η2= 0.07). Group dependent differences were not observed for changes in pain intensity and disability at two week. Participant satisfaction was greatest following the enhanced placebo SMT. PMID:24361109

Neutron capture therapy. Principles and applications

International Nuclear Information System (INIS)

Sauerwein, Wolfgang A.G.; Moss, Raymond; Wittig, Andrea; Nakagawa, Yoshinobu

2012-01-01

State of the art report on neutron capture therapy. Summarizes the progress made in recent decades. Multidisciplinary approach. Written by the most experienced specialists Neutron capture therapy (NCT) is based on the ability of the non-radioactive isotope boron-10 to capture thermal neutrons with very high probability and immediately to release heavy particles with a path length of one cell diameter. This in principle allows for tumor cell-selective high-LET particle radiotherapy. NCT is exciting scientifically but challenging clinically, and a key factor in success is close collaboration among very different disciplines. This book provides a comprehensive summary of the progress made in NCT in recent years. Individual sections cover all important aspects, including neutron sources, boron chemistry, drugs for NCT, dosimetry, and radiation biology. The use of NCT in a variety of malignancies and also some non-malignant diseases is extensively discussed. NCT is clearly shown to be a promising modality at the threshold of wider clinical application. All of the chapters are written by experienced specialists in language that will be readily understood by all participating disciplines.

Comparing cognitive behavioural therapy for eating disorders integrated with behavioural weight loss therapy to cognitive behavioural therapy-enhanced alone in overweight or obese people with bulimia nervosa or binge eating disorder: study protocol for a randomised controlled trial.

Science.gov (United States)

Palavras, Marly Amorim; Hay, Phillipa; Touyz, Stephen; Sainsbury, Amanda; da Luz, Felipe; Swinbourne, Jessica; Estella, Nara Mendes; Claudino, Angélica

2015-12-18

Around 40 % of individuals with eating disorders of recurrent binge eating, namely bulimia nervosa and binge eating disorder, are obese. In contrast to binge eating disorder, currently there is no evidence base for weight management or weight loss psychological therapies in the treatment of bulimia nervosa despite their efficacy in binge eating disorder. Thus, a manualised therapy called HAPIFED (Healthy APproach to weIght management and Food in Eating Disorders) has been developed. HAPIFED integrates the leading evidence-based psychological therapies, cognitive behavioural therapy-enhanced (CBT-E) and behavioural weight loss treatment (BWLT) for binge eating disorder and obesity respectively. The aim of the present study is to detail the protocol for a randomised controlled trial (RCT) of HAPIFED versus CBT-E for people with bulimia nervosa and binge eating disorder who are overweight/obese. A single-blind superiority RCT is proposed. One hundred Brazilian participants aged ≥ 18 years, with a diagnosis of bulimia nervosa or binge eating disorder, BMI > 27 to bulimia nervosa as well as with binge eating disorder. It will have the potential to improve health outcomes for the rapidly increasing number of adults with co-morbid obesity and binge eating disorder or bulimia nervosa. US National Institutes of Health clinical trial registration number NCT02464345 , date of registration 1 June 2015.

Dynamic contour tonometry (DCT) versus non-contact tonometry (NCT): a comparison study.

Science.gov (United States)

Burvenich, H; Burvenich, E; Vincent, C

2005-01-01

In a prospective study we measured the intraocular pressure (IOP) by means of a Non-Contact Tonometer (NCT) and by means of a Pascal Dynamic Contour Tonometer (DCT), and the Central Corneal Thickness (CCT) by means of a contact pachymeter in 294 emmetropic or ametropic eyes. There is a linear relation between NCT and CCT. This linear relation doesn't exist between DCT and CCT. The same measurements were done before and 6 weeks after a Lasik intervention in 58 myopic eyes. Lasik intervention influences NCT but doesn't influence DCT.

Drug delivery system and radiation therapy

International Nuclear Information System (INIS)

Shibata, Tokushi

2005-01-01

This paper describes the review of radiation therapy, neutron capture therapy (NCT) and drug delivery system for the latter. In cancer radiation therapy, there are problems of body movement like breathing, needless irradiation of normal tissues, difficulty to decide the correct irradiation position and tumor morphology. NCT has advantages to overcome these, and since boron has a big cross section for thermal neutron, NPT uses the reaction 10 B(n, α) 7 Li in the target cancer which previously incorporated the boron-containing drug. During the period 1966-1996, 246 patients were treated with this in Japan and the treatment has been continued thereafter. The tasks for NCT are developments of drug delivery system efficient to deliver the drug into the tumor and of convenient neutron source like the accelerator. (S.I.)

Resource-oriented music therapy for psychiatric patients with low therapy motivation: Protocol for a randomised controlled trial [NCT00137189

Directory of Open Access Journals (Sweden)

Aarre Trond

2005-10-01

Full Text Available Abstract Background Previous research has shown positive effects of music therapy for people with schizophrenia and other mental disorders. In clinical practice, music therapy is often offered to psychiatric patients with low therapy motivation, but little research exists about this population. The aim of this study is to examine whether resource-oriented music therapy helps psychiatric patients with low therapy motivation to improve negative symptoms and other health-related outcomes. An additional aim of the study is to examine the mechanisms of change through music therapy. Methods 144 adults with a non-organic mental disorder (ICD-10: F1 to F6 who have low therapy motivation and a willingness to work with music will be randomly assigned to an experimental or a control condition. All participants will receive standard care, and the experimental group will in addition be offered biweekly sessions of music therapy over a period of three months. Outcomes will be measured by a blind assessor before and 1, 3, and 9 months after randomisation. Discussion The findings to be expected from this study will fill an important gap in the knowledge of treatment effects for a patient group that does not easily benefit from treatment. The study's close link to clinical practice, as well as its size and comprehensiveness, will make its results well generalisable to clinical practice.

Behavioral Therapy, Incentives Enhance Addiction Treatment

Science.gov (United States)

... Research News From NIH Behavioral Therapy, Incentives Enhance Addiction Treatment Past Issues / Summer 2006 Table of Contents ... that people who are trying to end their addiction to marijuana can benefit from a treatment program ...

NCT program at the University of Missouri-Columbia

International Nuclear Information System (INIS)

Brugger, R.M.; Shih, J.A.; Wu, H.S.; Liu, H.B.; Luo, X.S.

1992-01-01

At the University of Missouri-Columbia (MU), developments continue on specific parts of NCT. These are the epithermal beam design, Gd as an alternative agent to B, dose predictions and treatment planning, and accelerator based neutron sources. At the workshop on 'Neutron Beam Design, Development and Performance' held in Boston in March 1989, beam designs for a number of epithermal neutron beams were presented. Among this set was a design for an epithermal beam from the Missouri University Research Reactor (MURR). The Monte Carlo calculations for the neutron fluxes and gamma doses of this beam showed that, if built, this beam would be a very clean and intense epithermal neutron beam for NCT. Since that meeting, improvements have been made in the design to accommodate a beam shutter and to provide more flexibility in patient positioning. Also, capital cost and operating cost projections have been made

Analysis of metastasis of melanoma-bearing hamsters in thermal neutron capture therapy

International Nuclear Information System (INIS)

Ueda, Masataka; Mishima, Yutaka; Ichihashi, Masamitsu

1985-01-01

Melanoma-bearing hamsters were divided into three groups: the MG I was treated with both 10 B 1 -para-boronophenylalanine.HCl ( 10 B 1 -BPA) and neutron capture therapy (NCT); the MG II was treated with NCT alone; and the control group (MG III). The most satisfactory effect on regression was seen in the MG I. When the opposite site to the transplanted tumor site was exposed to thermal neutrons, no enhanced effect on metastasis was seen. Tumor cells of MG I and MG II were transplanted subcutaneously 24 hr after NCT into normal hamsters (MG It and MG IIt), and their growth and metastasis abilities were examined. MG It cells possessed neither growth nor metastasis ability; while MG IIt cells showed normal growth and metastasis abilities. Lethal effects on tumor cells seemed to occur in the MG I at 24 hr after NCT, suggesting no effects of NCT on the metastasis ability of tumor cells. Metastasis was seen in 2 of 8 animals in the MG III; however, inhibitory effects on tumor cells were the same as those in the other groups MG I and MG II. When the cells were exposed to 100 rad and 300 rad of gamma rays to assess effects of gamma rays during NCT, neither tumor growth nor lung metastasis was affected. When the tumor was excised with 5 mm margin, relapse occurred in a high incidence. There was no difference in lung metastasis between NCT and gamma irradiation. (Namekawa, K.)

Neutron capture therapy

International Nuclear Information System (INIS)

Jun, B. J.

1998-11-01

The overall state of the art related with neutron capture therapy(NCT) is surveyed. Since the field related with NCT is very wide, it is not intended to survey all related subjects in depth. The primary objective of this report is to help those working for the installation of a NCT facility and a PGNAA(prompt gamma ray neutron activation analysis) system for the boron analysis understand overall NCT at Hanaro. Therefore, while the parts of reactor neutron source and PGNAA are dealt in detail, other parts are limited to the level necessary to understand related fields. For example, the subject of chemical compound which requires intensive knowledge on chemistry, is not dealt as a separated item. However, the requirement of a compound for NCT, currently available compounds, their characteristics, etc. could be understood through this report. Although the subject of cancer treated by NCT is out of the capability of the author, it is dealt focussing its characteristics related with the success of NCT. Each detailed subject is expected to be dealt more detail by specialists in future. This report would be helpful for the researchers working for the NCT to understand related fields. (author). 128 refs., 3 tabs., 12 figs

Boron neutron capture therapy combined with fractionated photon irradiation for glioblastoma: A recursive partitioning analysis of BNCT patients

International Nuclear Information System (INIS)

Nakai, K.; Yamamoto, T.; Aiyama, H.; Takada, T.; Yoshida, F.; Kageji, T.; Kumada, H.; Isobe, T.; Endo, K.; Matsuda, M.; Tsurubuchi, T.; Shibata, Y.; Takano, S.; Mizumoto, M.; Tsuboi, K.; Matsumura, A.

2011-01-01

Eight patients to received Boron Neutron Capture Therapy (BNCT) were selected from 33 newly diagnosed glioblastoma patients (NCT(+) group). Serial 42 glioblastoma patients (NCT(−) group) were treated without BNCT. The median OS of the NCT(+) group and NCT (−) group were 24.4 months and 14.9 months. In the high risk patients (RPA class V), the median OS of the NCT(+) group tended to be better than that of NCT(−) group. 50% of BNCT patients were RPA class V. - Highlights: ► We treated 8 patients with boron neutron capture therapy (NCT) for glioblastoma. ► We compare the overall survival between NCT including series and without NCT series. ► The median overall survival of the NCT including series was 24.4 months. ► In the high risk patients, the median OS of NCT including series tended to be better.

Relationship Enhancement Therapy: A Case Study for Treating Vaginismus.

Science.gov (United States)

Harman, Marsha J.; And Others

1994-01-01

A case study of Relationship Enhancement (RE) therapy with a couple, in which the woman was identified as having vaginismus, is presented including excerpts of transcripts from the therapy sessions. RE's effectiveness at improving communication skills and providing structure in which the couple could discuss the intimate issues affecting the…

Limits to human enhancement: nature, disease, therapy or betterment?

Science.gov (United States)

Hofmann, Bjørn

2017-10-10

New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia.

Science.gov (United States)

Fraietta, Joseph A; Beckwith, Kyle A; Patel, Prachi R; Ruella, Marco; Zheng, Zhaohui; Barrett, David M; Lacey, Simon F; Melenhorst, Jan Joseph; McGettigan, Shannon E; Cook, Danielle R; Zhang, Changfeng; Xu, Jun; Do, Priscilla; Hulitt, Jessica; Kudchodkar, Sagar B; Cogdill, Alexandria P; Gill, Saar; Porter, David L; Woyach, Jennifer A; Long, Meixiao; Johnson, Amy J; Maddocks, Kami; Muthusamy, Natarajan; Levine, Bruce L; June, Carl H; Byrd, John C; Maus, Marcela V

2016-03-03

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is highly promising but requires robust T-cell expansion and engraftment. A T-cell defect in chronic lymphocytic leukemia (CLL) due to disease and/or therapy impairs ex vivo expansion and response to CAR T cells. To evaluate the effect of ibrutinib treatment on the T-cell compartment in CLL as it relates to CAR T-cell generation, we examined the phenotype and function of T cells in a cohort of CLL patients during their course of treatment with ibrutinib. We found that ≥5 cycles of ibrutinib therapy improved the expansion of CD19-directed CAR T cells (CTL019), in association with decreased expression of the immunosuppressive molecule programmed cell death 1 on T cells and of CD200 on B-CLL cells. In support of these findings, we observed that 3 CLL patients who had been treated with ibrutinib for ≥1 year at the time of T-cell collection had improved ex vivo and in vivo CTL019 expansion, which correlated positively together and with clinical response. Lastly, we show that ibrutinib exposure does not impair CAR T-cell function in vitro but does improve CAR T-cell engraftment, tumor clearance, and survival in human xenograft models of resistant acute lymphocytic leukemia and CLL when administered concurrently. Our collective findings indicate that ibrutinib enhances CAR T-cell function and suggest that clinical trials with combination therapy are warranted. Our studies demonstrate that improved T-cell function may also contribute to the efficacy of ibrutinib in CLL. These trials were registered at www.clinicaltrials.gov as #NCT01747486, #NCT01105247, and #NCT01217749. © 2016 by The American Society of Hematology.

Monte Carlo and analytic simulations in nanoparticle-enhanced radiation therapy

Directory of Open Access Journals (Sweden)

Paro AD

2016-09-01

Full Text Available Autumn D Paro,1 Mainul Hossain,2 Thomas J Webster,1,3,4 Ming Su1,4 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2NanoScience Technology Center and School of Electrical Engineering and Computer Science, University of Central Florida, Orlando, Florida, USA; 3Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 4Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou Medical University, Zhejiang, People’s Republic of China Abstract: Analytical and Monte Carlo simulations have been used to predict dose enhancement factors in nanoparticle-enhanced X-ray radiation therapy. Both simulations predict an increase in dose enhancement in the presence of nanoparticles, but the two methods predict different levels of enhancement over the studied energy, nanoparticle materials, and concentration regime for several reasons. The Monte Carlo simulation calculates energy deposited by electrons and photons, while the analytical one only calculates energy deposited by source photons and photoelectrons; the Monte Carlo simulation accounts for electron–hole recombination, while the analytical one does not; and the Monte Carlo simulation randomly samples photon or electron path and accounts for particle interactions, while the analytical simulation assumes a linear trajectory. This study demonstrates that the Monte Carlo simulation will be a better choice to evaluate dose enhancement with nanoparticles in radiation therapy. Keywords: nanoparticle, dose enhancement, Monte Carlo simulation, analytical simulation, radiation therapy, tumor cell, X-ray 

The Loss and Recovery of Erotic Intimacy in Primary Relationships: Narrative Therapy and Relationship Enhancement Therapy.

Science.gov (United States)

Snyder, Maryhelen

2000-01-01

Therapists working with intimate relationships are frequently confronted with issues regarding the loss of erotic intimacy, differences in levels of sexual desire, and the existence of intimate relationships outside the primary. Proposes that an approach derived from an integration of narrative therapy and relationship enhancement therapy can be…

Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325).

Science.gov (United States)

Dehing-Oberije, Cary; Aerts, Hugo; Yu, Shipeng; De Ruysscher, Dirk; Menheere, Paul; Hilvo, Mika; van der Weide, Hiska; Rao, Bharat; Lambin, Philippe

2011-10-01

Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6. Copyright © 2011 Elsevier Inc. All rights reserved.

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

Directory of Open Access Journals (Sweden)

Gasparovic Hrvoje

2012-08-01

Full Text Available Abstract Background Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. Methods Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology as well as bleeding events will be recorded. Discussion This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639.

Dynamic contrast enhanced ultrasound for therapy monitoring

Energy Technology Data Exchange (ETDEWEB)

Hudson, John M. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Williams, Ross [Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Tremblay-Darveau, Charles; Sheeran, Paul S. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Milot, Laurent [Department of Medical Imaging, University of Toronto, Toronto, ON (Canada); Bjarnason, Georg A. [Department of Medical Oncology, University of Toronto, and Sunnybrook Odette Cancer Centre, Toronto, ON (Canada); Burns, Peter N., E-mail: burns@sri.utoronto.ca [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON (Canada)

2015-09-15

Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular. This papers reviews the principles and methodology of DCE-US, especially as applied to anti-angiogenic cancer therapies. Reproducibility is an important attribute of such a monitoring method: results are discussed. More recent technical advances in parametric and 3D DCE-US imaging are also summarised and illustrated.

General considerations for neutron capture therapy at a reactor facility

International Nuclear Information System (INIS)

Binney, S.E.

2001-01-01

In addition to neutron beam intensity and quality, there are also a number of other significant criteria related to a nuclear reactor that contribute to a successful neutron capture therapy (NCT) facility. These criteria are classified into four main categories: Nuclear design factors, facility management and operations factors, facility resources, and non-technical factors. Important factors to consider are given for each of these categories. In addition to an adequate neutron beam intensity and quality, key requirements for a successful neutron capture therapy facility include necessary finances to construct or convert a facility for NCT, a capable medical staff to perform the NCT, and the administrative support for the facility. The absence of any one of these four factors seriously jeopardizes the overall probability of success of the facility. Thus nuclear reactor facility management considering becoming involved in neutron capture therapy, should it be proven clinically successful, should take all these factors into consideration. (author)

Current status of neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-05-01

There are about 6000 new glioblastoma multiform brain tumours diagnosed each year in the United States of America alone. This cancer is usually fatal within six months of diagnosis even with current standard treatments. Research on boron neutron capture therapy (BNCT) has been considered as a method of potentially curing such cancers. There is a great interest at under-utilised research reactors institutions to identify new medical utilization, attractive to the general public. Neutron capture therapy is a true multidisciplinary topic with a large variety of individuals involved. This publication attempts to provide current information for all those thinking about being involved with NCT, based on the knowledge and experience of those who have pioneered the treatment. It covers the whole range of NCT from designing reactor conversions or new facilities, through to clinical trials and their effectiveness. However, since most work has been done with boron capture therapy for brain tumours using modified thermal research reactors, this tends to be the focus of the report. One of the factors which need to be addressed at the beginning is the timing of the further development of NCT facilities. It should be emphasised that all current work is still at the research stage. Many of those now involved believe that there is little need for many more research facilities until such time as the treatment shows more promising results. For this and other reasons discussed in the report, very serious consideration should be given by research reactor owners and operators before spending large sums of money converting their facilities for NCT.

Current status of neutron capture therapy

International Nuclear Information System (INIS)

2001-05-01

There are about 6000 new glioblastoma multiform brain tumours diagnosed each year in the United States of America alone. This cancer is usually fatal within six months of diagnosis even with current standard treatments. Research on boron neutron capture therapy (BNCT) has been considered as a method of potentially curing such cancers. There is a great interest at under-utilised research reactors institutions to identify new medical utilization, attractive to the general public. Neutron capture therapy is a true multidisciplinary topic with a large variety of individuals involved. This publication attempts to provide current information for all those thinking about being involved with NCT, based on the knowledge and experience of those who have pioneered the treatment. It covers the whole range of NCT from designing reactor conversions or new facilities, through to clinical trials and their effectiveness. However, since most work has been done with boron capture therapy for brain tumours using modified thermal research reactors, this tends to be the focus of the report. One of the factors which need to be addressed at the beginning is the timing of the further development of NCT facilities. It should be emphasised that all current work is still at the research stage. Many of those now involved believe that there is little need for many more research facilities until such time as the treatment shows more promising results. For this and other reasons discussed in the report, very serious consideration should be given by research reactor owners and operators before spending large sums of money converting their facilities for NCT

Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography.

Science.gov (United States)

Jost, Gregor; Mensing, Tristan; Golfier, Sven; Lawaczeck, Rüdiger; Pietsch, Hubertus; Hütter, Joachim; Cibik, Levent; Gerlach, Martin; Krumrey, Michael; Fratzscher, Daniel; Arkadiev, Vladimir; Wedell, Reiner; Haschke, Michael; Langhoff, Norbert; Wust, Peter; Lüdemann, Lutz

2009-06-01

Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasimonochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten Kalpha emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement

Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography

International Nuclear Information System (INIS)

Jost, Gregor; Mensing, Tristan; Golfier, Sven; Lawaczeck, Ruediger; Pietsch, Hubertus; Huetter, Joachim; Cibik, Levent; Gerlach, Martin; Krumrey, Michael; Fratzscher, Daniel; Arkadiev, Vladimir; Wedell, Reiner; Haschke, Michael; Langhoff, Norbert; Wust, Peter; Luedemann, Lutz

2009-01-01

Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasi-monochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten Kα emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement factor

Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography

Energy Technology Data Exchange (ETDEWEB)

Jost, Gregor; Mensing, Tristan; Golfier, Sven; Lawaczeck, Ruediger; Pietsch, Hubertus; Huetter, Joachim; Cibik, Levent; Gerlach, Martin; Krumrey, Michael; Fratzscher, Daniel; Arkadiev, Vladimir; Wedell, Reiner; Haschke, Michael; Langhoff, Norbert; Wust, Peter; Luedemann, Lutz [TRG Diagnostic Imaging, Bayer Schering Pharma AG, 13353 Berlin (Germany); Department of Radiotherapy, Charite Medical Centre, 13353 Berlin (Germany); TRG Diagnostic Imaging, Bayer Schering Pharma AG, 13353 Berlin (Germany); Physikalisch-Technische Bundesanstalt, 10587 Berlin (Germany); Institute of Applied Photonics e.V., 12489 Berlin (Germany); Institute for Scientific Instruments GmbH, 12489 Berlin (Germany); Department of Radiotherapy, Charite Medical Centre, 13353 Berlin (Germany)

2009-06-15

Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasi-monochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten K{alpha} emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement

RBE of the NCT beam at Petten (The Netherlands) for intestinal crypt regeneration in mice

International Nuclear Information System (INIS)

Gueulette, J.; Coster, B.M. de; Wambersie, A.; Stecher-Rasmussen, F.; Huiskamp, R.; Moss, R.; Morrissey, J.

2000-01-01

RBE of the BNCT epithermal neutron beam at Petten (The Netherlands) has been determined for intestinal crypt regeneration in mice i.e. an in vivo system. No boron was administered. This experiment is part of an IAEA programme aiming at intercomparing radiobiologically the NCT neutron beams of different facilities world-wide. Six MV photons were used as the reference radiation. For the NCT beam at Petten, irradiation times ranging between 1 and 3 hours were applied. These low dose rate irradiations (∼3 Gy/hour) were found ∼2.4 more effective than acute photon irradiations. This type of experiment - repeated at different BNCT facilities - will improve harmonisation in the radiobiological specification of NCT neutron beams and facilitate exchange of clinical information. (author)

Biodegradable magnesium nanoparticle-enhanced laser hyperthermia therapy

Directory of Open Access Journals (Sweden)

Wang Q

2012-08-01

Full Text Available Qian Wang,1 Liping Xie,1 Zhizhu He,2 Derui Di,2 Jing Liu1,21Department of Biomedical Engineering, School of Medicine, Tsinghua University, 2Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of ChinaBackground: Recently, nanoparticles have been demonstrated to have tremendous merit in terms of improving the treatment specificity and thermal ablation effect on tumors. However, the potential toxicity and long-term side effects caused by the introduced nanoparticles and by expelling them out of the body following surgery remain a significant challenge. Here, we propose for the first time to directly adopt magnesium nanoparticles as the heating enhancer in laser thermal ablation to avoid these problems by making full use of the perfect biodegradable properties of this specific material.Methods: To better understand the new nano “green” hyperthermia modality, we evaluated the effects of magnesium nanoparticles on the temperature transients inside the human body subject to laser interstitial heating. Further, we experimentally investigated the heating enhancement effects of magnesium nanoparticles on a group of biological samples: oil, egg white, egg yolk, in vitro pig tissues, and the in vivo hind leg of rabbit when subjected to laser irradiation.Results: Both the theoretical simulations and experimental measurements demonstrated that the target tissues injected with magnesium nanoparticles reached much higher temperatures than tissues without magnesium nanoparticles. This revealed the enhancing behavior of the new nanohyperthermia method.Conclusion: Given the unique features of magnesium nanoparticles – their complete biological safety and ability to enhance heating – which most other advanced metal nanoparticles do not possess, the use of magnesium nanoparticles in hyperthermia therapy offers an important “green” nanomedicine modality for treating tumors

Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

Science.gov (United States)

Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

2018-03-14

Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

Results of ENHANCED Implantable Cardioverter Defibrillator Programming to Reduce Therapies and Improve Quality of Life (from the ENHANCED-ICD Study)

DEFF Research Database (Denmark)

Mastenbroek, Mirjam H.; Pedersen, Susanne S.; van der Tweel, Ingeborg

2016-01-01

-reported outcomes. The "ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life" study (ENHANCED-ICD study) was a prospective, safety-monitoring study enrolling 60 primary and secondary prevention patients at the University Medical Center Utrecht. Patients...... programming strategy, unnecessary ICD therapy was prevented in 10% of ENHANCED-ICD patients during a median follow-up period of 1.3 years. With respect to patient-reported outcomes, levels of distress were highest and perceived health status lowest at the time of implantation, which both gradually improved...... during follow-up. In conclusion, the ENHANCED-ICD study demonstrates that programming a NID 60/80 for VT/VF detection is safe for ICD patients and does not negatively impact their quality of life....

Development of inverse-planning system for neutron capture therapy

International Nuclear Information System (INIS)

Kumada, Hiroaki; Yamamoto, Kazuyoshi; Maruo, Takeshi

2006-01-01

To lead proper irradiation condition effectively, Japan Atomic Energy Agency (JAEA) is developing an inverse-planning system for neutron capture therapy (NCT-IPS) based on the JAEA computational dosimetry system (JCDS) for BNCT. The leading methodology of an optimum condition in the NCT-IPS has been applied spatial channel theory with adjoint flux solution of Botzman transport. By analyzing the results obtained from the adjoint flux calculations according to the theory, optimum incident point of the beam against the patient can be found, and neutron spectrum of the beam which can generate ideal distribution of neutron flux around tumor region can be determined. The conceptual design of the NCT-IPS was investigated, and prototype of NCT-IPS with JCDS is being developed. (author)

TH-E-BRD-01: Innovation in (gold) Nanoparticle-Enhanced Therapy

International Nuclear Information System (INIS)

Krishnan, S; Chithrani, B; Berbeco, R

2014-01-01

Radiation therapy relies on the concept of delivering high dose to tumor volumes whilst simultaneously aiming to minimize irradiation of healthy tissue. Gold and other metallic nanoparticles (GNPs) have the potential to greatly enhance dose depositions in their close proximity. While it was originally thought that this effect would only be significant for kV photon beams, it has been shown that GNPs also enhance dose and increase cell killing and survival fraction for MV photons as well as protons. GNPs have been shown to be preferentially taken up in tumors, depending on the GNP properties either internalized in the tumor cells or clustering in the tumor vasculature. Therefore GNPs offer an intriguing additional option to target the tumor while sparing healthy tissue. While a growing amount of research shows GNP induced enhancement factors in the order of 1.5 and higher, GNPs have not yet entered into clinical routine. In this symposium we will have three presentations discussing the current status of GNP based research, the potential to include GNPs in radiation therapy and the limitations and problems to use GNPs in the clinic. Physical and biological underpinnings of radiosensitization with gold nano particles An evolving body of recent literature alludes to the potential to sensitize tumors to radiation therapy using metallic nanoparticles. In preclinical studies, the techniques that hold promise for eventual clinical deployment are nanoparticle-assisted radiation dose enhancement and hyperthermic radiosensitization. To understand the underlying nanoparticle-radiation interactions, computational techniques offer an explanation for and predict the biophysical consequences at a nano-/meso-scopic scale. Nonetheless, there are persisting gaps in knowledge relating to the molecular mechanism of action of these radiosensitization approaches — some of these issues will be addressed. Since the literature relating to the diverse disciplines involved in these efforts

TH-E-BRD-01: Innovation in (gold) Nanoparticle-Enhanced Therapy

Energy Technology Data Exchange (ETDEWEB)

Krishnan, S; Chithrani, B; Berbeco, R [Brigham and Women' s Hospital, Boston, MA (United States)

2014-06-15

Radiation therapy relies on the concept of delivering high dose to tumor volumes whilst simultaneously aiming to minimize irradiation of healthy tissue. Gold and other metallic nanoparticles (GNPs) have the potential to greatly enhance dose depositions in their close proximity. While it was originally thought that this effect would only be significant for kV photon beams, it has been shown that GNPs also enhance dose and increase cell killing and survival fraction for MV photons as well as protons. GNPs have been shown to be preferentially taken up in tumors, depending on the GNP properties either internalized in the tumor cells or clustering in the tumor vasculature. Therefore GNPs offer an intriguing additional option to target the tumor while sparing healthy tissue. While a growing amount of research shows GNP induced enhancement factors in the order of 1.5 and higher, GNPs have not yet entered into clinical routine. In this symposium we will have three presentations discussing the current status of GNP based research, the potential to include GNPs in radiation therapy and the limitations and problems to use GNPs in the clinic. Physical and biological underpinnings of radiosensitization with gold nano particles An evolving body of recent literature alludes to the potential to sensitize tumors to radiation therapy using metallic nanoparticles. In preclinical studies, the techniques that hold promise for eventual clinical deployment are nanoparticle-assisted radiation dose enhancement and hyperthermic radiosensitization. To understand the underlying nanoparticle-radiation interactions, computational techniques offer an explanation for and predict the biophysical consequences at a nano-/meso-scopic scale. Nonetheless, there are persisting gaps in knowledge relating to the molecular mechanism of action of these radiosensitization approaches — some of these issues will be addressed. Since the literature relating to the diverse disciplines involved in these efforts

The effects of enhanced access to antiretroviral therapy: a qualitative ...

African Journals Online (AJOL)

The effects of enhanced access to antiretroviral therapy: a qualitative study of community perceptions in ... Twenty FGDs comprising of 190 participants and 12 KI interviews were conducted. ... All data was tape recorded with consent from

Computational Dosimetry and Treatment Planning Considerations for Neutron Capture Therapy

International Nuclear Information System (INIS)

Nigg, David Waler

2003-01-01

Specialized treatment planning software systems are generally required for neutron capture therapy (NCT) research and clinical applications. The standard simplifying approximations that work well for treatment planning computations in the case of many other modalities are usually not appropriate for application to neutron transport. One generally must obtain an explicit three-dimensional numerical solution of the governing transport equation, with energy-dependent neutron scattering completely taken into account. Treatment planning systems that have been successfully introduced for NCT applications over the past 15 years rely on the Monte Carlo stochastic simulation method for the necessary computations, primarily because of the geometric complexity of human anatomy. However, historically, there has also been interest in the application of deterministic methods, and there have been some practical developments in this area. Most recently, interest has turned toward the creation of treatment planning software that is not limited to any specific therapy modality, with NCT as only one of several applications. A key issue with NCT treatment planning has to do with boron quantification, and whether improved information concerning the spatial biodistribution of boron can be effectively used to improve the treatment planning process. Validation and benchmarking of computations for NCT are also of current developmental interest. Various institutions have their own procedures, but standard validation models are not yet in wide use

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

Science.gov (United States)

2015-10-01

spectrum disorders , and assessing the efficacy of this approach in comparison to an active Enriched Supportive Therapy (EST) intervention . Major...This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism ...of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date

Semiempirical theory of 10B NCT

International Nuclear Information System (INIS)

Borisov, G.I.; Kondratenko, R.I.

2006-01-01

Theory is based upon the characteristic of spatial distribution of slow neutrons in irradiated object named the effective mass. Effective mass can be measured in experiments with liquid phantom, target for slow neutrons field measurements and prompt gamma-ray spectrometer. Mathematical apparatus of this theory is a number of algebraic equations with evident physical sense. These equations set connection between atomic and nuclear data characterizing dose forming reactions and their products, achieved preparations concentrations, geometrical, spectral and dose characteristics of therapeutic neutron beams. Theory allows calculation of following values as a function of preparations concentrations: partial contents of nuclear reactions and adsorbed dose; mean number of nuclear reactions in one cell, depending on its size, in the maximum of slow neutrons spatial distribution; spectral and dose characteristics of therapeutic beams, depending on their sizes; neutron flux densities, depending upon desired absorbed dose in the maximum of spatial distribution. Calculation and measurement results are given on therapeutic neutron beam for 10 B NCT, formed by thin hydrogen scatterer set in horizontal experimental channel IR-8 RRC 'Kurchatov institute' beside the reactor core. (author)

Simplified analytical solutions for free drops during NCT for radioactive material packagings

International Nuclear Information System (INIS)

Gupta, N.K.

1997-01-01

To ensure structural integrity during normal conditions of transport (NCT), Federal regulations in 10CFR71.71 require that the nuclear material package designs be evaluated for the effects of free drops. The vessel stress acceptance criteria for these drops are given in Regulatory Guide 7.6 and ASME Section III Code. During initial phases of the package design, the effects of the NCT free drops can be evaluated by simplified analytical solutions which will ensure that the safety margins specified in R. G. 7.6 are met. These safety margins can be verified during the final stages of the package design with dynamic analyses using finite element methods. This paper calculates the maximum impact open-quotes gclose quotes loading on the vessels using single degree of freedom models for different drop orientations. Only end, bottom, and corner drops are analyzed for cylindrical packages or packages with cylindrical ends

Design of a boron neutron capture enhanced fast neutron therapy assembly

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhonglu [Georgia Inst. of Technology, Atlanta, GA (United States)

2006-12-01

The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator near the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm² treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm² collimation was 21.9% per 100-ppm ¹⁰B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm² fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm² collimator. Five 1.0-cm thick 20x20 cm² tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm ¹⁰B) to measure dose due to boron neutron capture. The

Line-Enhanced Deformable Registration of Pulmonary Computed Tomography Images Before and After Radiation Therapy With Radiation-Induced Fibrosis

Science.gov (United States)

Sensakovic, William F.; Maxim, Peter; Diehn, Maximilian; Loo, Billy W.; Xing, Lei

2018-01-01

Purpose: The deformable registration of pulmonary computed tomography images before and after radiation therapy is challenging due to anatomic changes from radiation fibrosis. We hypothesize that a line-enhanced registration algorithm can reduce landmark error over the entire lung, including the irradiated regions, when compared to an intensity-based deformable registration algorithm. Materials: Two intensity-based B-spline deformable registration algorithms of pre-radiation therapy and post-radiation therapy images were compared. The first was a control intensity–based algorithm that utilized computed tomography images without modification. The second was a line enhancement algorithm that incorporated a Hessian-based line enhancement filter prior to deformable image registration. Registrations were evaluated based on the landmark error between user-identified landmark pairs and the overlap ratio. Results: Twenty-one patients with pre-radiation therapy and post-radiation therapy scans were included. The median time interval between scans was 1.2 years (range: 0.3-3.3 years). Median landmark errors for the line enhancement algorithm were significantly lower than those for the control algorithm over the entire lung (1.67 vs 1.83 mm; P 5 Gy (2.25 vs 3.31; P 5 Gy dose interval demonstrated a significant inverse relationship with post-radiation therapy fibrosis enhancement after line enhancement filtration (Pearson correlation coefficient = −0.48; P = .03). Conclusion: The line enhancement registration algorithm is a promising method for registering images before and after radiation therapy. PMID:29343206

The Motivational Enhancement Therapy and Cognitive Behavioral Therapy Supplement: 7 Sessions of Cognitive Behavioral Therapy for Adolescent Cannabis Users, Cannabis Youth Treatment (CYT) Series, Volume 2.

Science.gov (United States)

Webb, Charles; Scudder, Meleney; Kaminer, Yifrah; Kaden, Ron

This manual, a supplement to "Motivational Enhancement Therapy and Cognitive Behavioral Therapy for Adolescent Cannabis Users: 5 Sessions, Cannabis Youth Treatment (CYT) Series, Volume 1", presents a seven-session cognitive behavioral treatment (CBT7) approach designed especially for adolescent cannabis users. It addresses the implementation and…

Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy.

Science.gov (United States)

Hammerer, Fabien; Poyer, Florent; Fourmois, Laura; Chen, Su; Garcia, Guillaume; Teulade-Fichou, Marie-Paule; Maillard, Philippe; Mahuteau-Betzer, Florence

2018-01-01

The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part II: gadolinium neutron capture therapy models and therapeutic effects.

Science.gov (United States)

Wangerin, K; Culbertson, C N; Jevremovic, T

2005-08-01

The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for gadolinium neutron capture therapy (GdNCT) related modeling. The validity of COG NCT model has been established for this model, and here the calculation was extended to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating brain cancers. The computational results were compared with the widely used MCNP code. The differences between the COG and MCNP predictions were generally small and suggest that the COG code can be applied to similar research problems in NCT. Results for this study also showed that a concentration of 100 ppm gadolinium in the tumor was most beneficial when using an epithermal neutron beam.

Phantom experiment of depth-dose distributions for gadolinium neutron capture therapy

International Nuclear Information System (INIS)

Matsumoto, T.; Kato, K.; Sakuma, Y.; Tsuruno, A.; Matsubayashi, M.

1993-01-01

Depth-dose distributions in a tumor simulated phantom were measured for thermal neutron flux, capture gamma-ray and internal conversion electron dose rates for gadolinium neutron capture therapy. The results show that (i) a significant dose enhancement can be achieved in the tumor by capture gamma-rays and internal conversion electrons but the dose is mainly due to capture gamma-rays from the Gd(n, γ) reactions, therefore, is not selective at the cellular level, (ii) the dose distribution was a function of strongly interrelated parameters such as gadolinium concentrations, tumor site and neutron beam size (collimator aperture size), and (iii) the Gd-NCT by thermal neutrons appears to be a potential for treatment of superficial tumor. (author)

Prevalence of anemia amongst overweight and obese children in NCT of Delhi

Directory of Open Access Journals (Sweden)

Umesh Kapil

2014-09-01

Full Text Available Introduction: Anemia amongst children has been associated with impaired cognitive functions, developmental delays, behavioral and learning disturbances. Young children from high-income groups could be also being affected from anemia. Objective: To assess the prevalence of anemia amongst overweight and obese children in the age group of 5-18 years residing in National Capital Territory (NCT of Delhi. Material and Methods: Total of 413 children was included in the present study. The hemoglobin (Hb estimation was done by cyanmethemoglobin method. Results: In the age group of 5-11 years, the prevalence of anemia amongst overweight and obese children was found to be 38.4% and 29.2%. And in the age group of 12-18 years, the prevalence of anemia amongst overweight and obese children was found to be 33.3% and 21.7%; respectively. Conclusion: The findings of the present study revealed that there is a high prevalence of anemia amongst overweight and obese children in the age group of 5-18 years in NCT, Delhi.

Agency over Phantom Limb Enhanced by Short-Term Mirror Therapy.

Science.gov (United States)

Imaizumi, Shu; Asai, Tomohisa; Koyama, Shinichi

2017-01-01

Most amputees experience phantom limb, whereby they feel that the amputated limb is still present. In some cases, these experiences include pain that can be alleviated by "mirror therapy." Mirror therapy consists of superimposing a mirrored image of the moving intact limb onto the phantom limb. This therapy provides a closed loop between the motor command to the amputated limb and its predicted visual feedback. This loop is also involved in the sense of agency, a feeling of controlling one's own body. However, it is unclear how mirror therapy is related to the sense of agency over a phantom limb. Using mirror therapy, we investigated phantom limb pain and the senses of agency and ownership (i.e., a feeling of having one's own body) of the phantom limb. Nine upper-limb amputees, five of whom reported recent phantom limb pain, underwent a single 15-min trial of mirror therapy. Before and after the trial, the participants completed a questionnaire regarding agency, ownership, and pain related to their phantom limb. They reported that the sense of agency over the phantom limb increased following the mirror therapy trial, while the ownership slightly increased but not as much as did the agency. The reported pain did not change; that is, it was comparably mild before and after the trial. These results suggest that short-term mirror therapy can, at least transiently, selectively enhance the sense of agency over a phantom limb, but may not alleviate phantom limb pain.

Gold Nanoparticles and Their Alternatives for Radiation Therapy Enhancement

Directory of Open Access Journals (Sweden)

Daniel R. Cooper

2014-10-01

Full Text Available Radiation therapy is one of the most commonly used treatments for cancer. The dose of delivered ionizing radiation can be amplified by the presence of high-Z materials via an enhancement of the photoelectric effect; the most widely studied material is gold (atomic number 79. However, a large amount is needed to obtain a significant dose enhancement, presenting a challenge for delivery. In order to make this technique of broader applicability, the gold must be targeted, or alternative formulations developed that do not rely solely on the photoelectric effect. One possible approach is to excite scintillating nanoparticles with ionizing radiation, and then exploit energy transfer between these particles and attached dyes in a manner analogous to photodynamic therapy. Doped rare-earth halides and semiconductor quantum dots have been investigated for this purpose. However, although the spectrum of emitted light after radiation excitation is usually similar to that seen with light excitation, the yield is not. Measurement of scintillation yields is challenging, and in many cases has been done only for bulk materials, with little understanding of how the principles translate to the nanoscale. Another alternative is to use local heating using gold or iron, followed by application of ionizing radiation. Hyperthermia pre-sensitizes the tumors, leading to an improved response. Another approach is to use chemotherapeutic drugs that can radiosensitize tumors. Drugs may be attached to high-Z nanoparticles or encapsulated. This article discusses each of these techniques, giving an overview of the current state of nanoparticle-assisted radiation therapy and future directions.

SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Obeid, L; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Rhone-Alpes (France); Tessier, A [Centre Hospitalier Universitaire, La Tronche, Rhone-Alpes (France); Vautrin, M; Benkebil, M [DOSIsoft, Cachan, Ile de France (France); Sihanath, R [Centre Hospitalier Universitaire, La Tronche, Rhone- Alpes (France)

2014-06-01

Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator) were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.

Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

Directory of Open Access Journals (Sweden)

Helga Rodrigues

Full Text Available The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d =  -0.34; CI: -0.54 to -0.14, facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

Science.gov (United States)

Sandborn, William J; Su, Chinyu; Sands, Bruce E; D'Haens, Geert R; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

2017-05-04

active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.).

Implantable self-powered detector for on-line determination of neutron flux in patients during NCT treatment.

Science.gov (United States)

Miller, M E; Mariani, L E; Gonçalves-Carralves, M L Sztejnberg; Skumanic, M; Thorp, S I

2004-11-01

A novel system to determine thermal neutron flux in real time during NCT treatments was developed in the National Atomic Energy Commission of Argentina. The system is based on a special self-powered detector that can be implanted in patients owing to its small size and biocompatibility. High voltage is not required to operate this kind of detectors, which is a considerable advantage in terms of medical uses. By choosing the appropriate materials, it was possible to obtain a prototype with thermal neutron sensitivity providing for an adequate signal level in typical NCT thermal fluxes. It was also possible to minimize gamma response in order to neglect its contribution.

Implantable self-powered detector for on-line determination of neutron flux in patients during NCT treatment

Energy Technology Data Exchange (ETDEWEB)

Miller, M.E. E-mail: miller@cae.cnea.gov.ar; Mariani, L.E.; Sztejnberg Goncalves-Carralves, M.L.; Skumanic, M.; Thorp, S.I

2004-11-01

A novel system to determine thermal neutron flux in real time during NCT treatments was developed in the National Atomic Energy Commission of Argentina. The system is based on a special self-powered detector that can be implanted in patients owing to its small size and biocompatibility. High voltage is not required to operate this kind of detectors, which is a considerable advantage in terms of medical uses. By choosing the appropriate materials, it was possible to obtain a prototype with thermal neutron sensitivity providing for an adequate signal level in typical NCT thermal fluxes. It was also possible to minimize gamma response in order to neglect its contribution.

Enhancing Cold Atmospheric Plasma Treatment Efficiency for Cancer Therapy

Science.gov (United States)

Cheng, Xiaoqian

To improve efficiency and safety of anti-cancer therapies the researchers and clinicians alike are prompted to develop targeted combined therapies that especially minimize damage to healthy tissues while eradicating the body of cancerous tissues. Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that cold plasma induced cell death. In this study, we seek to integrate the medical application of CAP. We proposed and implemented 3 novel ideas to enhance efficacy and selectivity of cancer therapy. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. We determined a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of CAP, including output voltage, treatment time, and gas flow-rate. We varied the characteristics of the cold plasma in order to obtain different major species (such as O, OH, N2+, and N2 lines). "plasma dosage" D ~ Q * V * t. is defined, where D is the entire "plasma dosage"; Q is the flow rate of feeding gas; V is output voltage; t is treatment time. The proper CAP dosage caused 3-fold cell death in the U87 cells compared to the normal human astrocytes E6/E7 cells. We demonstrated there is a synergy between AuNPS and CAP in cancer therapy. Specifically, the concentration of AuNPs plays an important role on plasma therapy. At an optimal concentration, gold nanoparticles can significantly induce U87 cell death up to a 30% overall increase compared to the control group with the same plasma dosage but no AuNPs applied. The ROS intensity of the corresponding conditions has a reversed trend compared to cell viability. This matches with the theory that intracellular ROS accumulation results in oxidative stress, which further changes the intracellular pathways, causing damage to the proteins, lipids and DNA. Our results show that this synergy has great potential in improving the

A standardized method for beam design in neutron capture therapy

International Nuclear Information System (INIS)

Storr, G.J.: Harrington, B.V.

1993-01-01

A desirable end point for a given beam design for Neutron Capture Therapy (NCT) should be quantitative description of tumour control probability and normal tissue damage. Achieving this goal will ultimately rely on data from NCT human clinical trials. Traditional descriptions of beam designs have used a variety of assessment methods to quantify proposed or installed beam designs. These methods include measurement and calculation of open-quotes free fieldclose quotes parameters, such as neutron and gamma flux intensities and energy spectra, and figures-of-merit in tissue equivalent phantoms. The authors propose here a standardized method for beam design in NCT. This method would allow all proposed and existing NCT beam facilities to be compared equally. The traditional approach to determining a quantitative description of tumour control probability and normal tissue damage in NCT research may be described by the following path: Beam design → dosimetry → macroscopic effects → microscopic effects. Methods exist that allow neutron and gamma fluxes and energy dependence to be calculated and measured to good accuracy. By using this information and intermediate dosimetric quantities such as kerma factors for neutrons and gammas, macroscopic effect (absorbed dose) in geometries of tissue or tissue-equivalent materials can be calculated. After this stage, for NCT the data begins to become more sparse and in some areas ambiguous. Uncertainties in the Relative Biological Effectiveness (RBE) of some NCT dose components means that beam designs based on assumptions considered valid a few years ago may have to be reassessed. A standard method is therefore useful for comparing different NCT facilities

Can tDCS enhance item-specific effects and generalization after linguistically motivated aphasia therapy for verbs?

NARCIS (Netherlands)

de Aguiar, Vania; Bastiaanse, Roelien; Capasso, Rita; Gandolfi, Marialuisa; Smania, Nicola; Rossi, Giorgio; Miceli, Gabriele

2015-01-01

Background: Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS) has been shown to enhance item-specific improvement, but its potential to enhance

Irradiation system for neutron capture therapy using the small accelerator

International Nuclear Information System (INIS)

Kobayashi, Tooru; Hoshi, Masaharu

2002-01-01

Neutron capture therapy (NCT) is to kill tumor cells that previously incorporated the stable isotope which generates heavy charged particles with a short range and a high linear energy transfer (LET) on neutron irradiation. Boron-10 is ordinarily used as such an isotope. The tumor tissue is neutron-irradiated at craniotomy after preceding craniotomy for tumor extraction: therefore two surgeries are required for the present NCT in Japan. The reactions 10 B(n, αγ) 7 Li and 7 Li (p, n) 7 Be are thought preferential for patients and doctors if a convenient small accelerator, not the reactor used at present, is available in the hospital because only one craniotomy is sufficient. Authors' examinations of the system for NCT using the small accelerator involve irradiation conditions, desirable energy spectrum of neutron, characterization of thermal and epi-thermal neutrons, social, practical and technical comparison of the reactor and accelerator, and usefulness of the reaction 7 Li (p, n) 7 Be. The system devoted to the NCT is awaited in future. (K.H.)

Enhancing CBT for Chronic Insomnia: A Randomised Clinical Trial of Additive Components of Mindfulness or Cognitive Therapy.

Science.gov (United States)

Wong, Mei Yin; Ree, Melissa J; Lee, Christopher W

2016-09-01

Although cognitive behavioural therapy (CBT) for insomnia has resulted in significant reductions in symptoms, most patients are not classified as good sleepers after treatment. The present study investigated whether additional sessions of cognitive therapy (CT) or mindfulness-based therapy (MBT) could enhance CBT in 64 participants with primary insomnia. All participants were given four sessions of standard CBT as previous research had identified this number of sessions as an optimal balance between therapist guidance and patient independence. Participants were then allocated to further active treatment (four sessions of CT or MBT) or a no further treatment control. The additional treatments resulted in significant improvements beyond CBT on self-report and objective measures of sleep and were well tolerated as evidenced by no dropouts from either treatment. The effect sizes for each of these additional treatments were large and clinically significant. The mean scores on the primary outcome measure, the Insomnia Severity Index, were 5.74 for CT and 6.69 for MBT, which are within the good-sleeper range. Treatment effects were maintained at follow-up. There were no significant differences between CT and MBT on any outcome measure. These results provide encouraging data on how to enhance CBT for treatment of insomnia. Copyright © 2015 John Wiley & Sons, Ltd. CBT treatments for insomnia can be enhanced using recent developments in cognitive therapy. CBT treatments for insomnia can be enhanced using mindfulness-based treatments. Both cognitive therapy and mindfulness produce additional clinically significant change. Copyright © 2015 John Wiley & Sons, Ltd.

Local ablation therapy with contrast-enhanced ultrasonography for hepatocellular carcinoma: a practical review

Directory of Open Access Journals (Sweden)

Tae Kyoung Kim

2015-10-01

Full Text Available A successful program for local ablation therapy for hepatocellular carcinoma (HCC requires extensive imaging support for diagnosis and localization of HCC, imaging guidance for the ablation procedures, and post-treatment monitoring. Contrast-enhanced ultrasonography (CEUS has several advantages over computed tomography/magnetic resonance imaging (CT/MRI, including real-time imaging capability, sensitive detection of arterial-phase hypervascularity and washout, no renal excretion, no ionizing radiation, repeatability, excellent patient compliance, and relatively low cost. CEUS is useful for image guidance for isoechoic lesions. While contrast-enhanced CT/MRI is the standard method for the diagnosis of HCC and post-ablation monitoring, CEUS is useful when CT/MRI findings are indeterminate or CT/MRI is contraindicated. This article provides a practical review of the role of CEUS in imaging algorithms for pre- and post-ablation therapy for HCC.

Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder

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Bieleninik, Łucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J.; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo

2017-01-01

Importance Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. Objective To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Design, Setting, and Participants Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Interventions Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child’s focus of attention, to help children develop affect sharing and joint attention. Main Outcomes and Measures The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Results Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14

Massage Therapy of the Back Using a Real-Time Haptic-Enhanced Telerehabilitation System

Directory of Open Access Journals (Sweden)

Cristina Ramírez-Fernández

2017-01-01

Full Text Available We present the usability evaluation of a haptic-enhanced telerehabilitation system for massage therapy of the back using the Vybe haptic gaming pad and the gesture sensor LEAP motion controller. The evaluated system includes features that allow for (i administering online therapy programs, (ii providing self-adjustable and safety treatment of back massages using a virtual environment, and (iii saving and replaying massage sessions according to a patient’s therapy program. The usability evaluation with 25 older adults and 10 specialists suggests that the haptic telerehabilitation system is perceived with high usability and pleasurable user experience, while providing personalized intensity of haptic therapy in a supervised, real-time, and secure way to treat the patient. Moreover, the specialists totally agree that the system design features, such as save and play, and delimiting therapy zones are the most important for back massage therapy, while the features of regulating feedback intensity and providing/receiving a massage remotely are also important. Finally, based on their comments, five design insights aiming at improving the current version of the system were generated.

A tool to enhance occupational therapy reasoning from ICF perspective: The Hasselt Occupational Performance Profile (H-OPP).

Science.gov (United States)

Ghysels, R; Vanroye, E; Westhovens, M; Spooren, A

2017-03-01

In order to enhance occupational therapy reasoning in clinical practice, different elements such as client-centred approach, evidence-based care and interdisciplinary work should be taken into account, but is a challenge. To describe the development of the digital Hasselt Occupational Performance Profile (H-OPP © ) that enhances occupational therapy reasoning from ICF perspective. A participative qualitative design was used to create the H-OPP © in an iterative way in which occupational therapy lectures, ICF experts, students and occupational therapists in the field were involved. After linking occupational therapy terminology to the ICF, different stages of the H-OPP were identified and elaborated with main features: generating an occupational performance profile based on inventarization of problems and possibilities, formulating an occupational performance diagnosis and enabling to create an intervention plan. In all stages, both the perspectives of the client and the occupational therapist were taken into account. To increase practical use, the tool was further elaborated and digitalized. The H-OPP © is a digital coach that guides and facilitates professional reasoning in (novice) occupational therapists. It augments involvement of the client system. Furthermore, it enhances interdisciplinary communication and evidence-based care.

Workshop on neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Fairchild, R.G.; Bond, V.P. (eds.)

1986-01-01

Potentially optimal conditions for Neutron Capture Therapy (NCT) may soon be in hand due to the anticipated development of band-pass filtered beams relatively free of fast neutron contaminations, and of broadly applicable biomolecules for boron transport such as porphyrins and monoclonal antibodies. Consequently, a number of groups in the US are now devoting their efforts to exploring NCT for clinical application. The purpose of this Workshop was to bring these groups together to exchange views on significant problems of mutual interest, and to assure a unified and effective approach to the solutions. Several areas of preclinical investigation were deemed to be necessary before it would be possible to initiate clinical studies. As neither the monomer nor the dimer of sulfhydryl boron hydride is unequivocally preferable at this time, studies on both compounds should be continued until one is proven superior.

Workshop on neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.; Bond, V.P.

1986-01-01

Potentially optimal conditions for Neutron Capture Therapy (NCT) may soon be in hand due to the anticipated development of band-pass filtered beams relatively free of fast neutron contaminations, and of broadly applicable biomolecules for boron transport such as porphyrins and monoclonal antibodies. Consequently, a number of groups in the US are now devoting their efforts to exploring NCT for clinical application. The purpose of this Workshop was to bring these groups together to exchange views on significant problems of mutual interest, and to assure a unified and effective approach to the solutions. Several areas of preclinical investigation were deemed to be necessary before it would be possible to initiate clinical studies. As neither the monomer nor the dimer of sulfhydryl boron hydride is unequivocally preferable at this time, studies on both compounds should be continued until one is proven superior

Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

Science.gov (United States)

Wang, Sheng; Zhang, Lei; Dong, Chunhong; Su, Lin; Wang, Hanjie; Chang, Jin

2015-01-01

A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

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2012-10-01

life for more able individuals with autism or Asperger syndrome. Autism , 4(1), 63-83. Kanner, L. (1971). Follow-up study of eleven autistic...Enhancement Therapy for Adults with Autism Spectrum Disorders PRINCIPAL INVESTIGATOR: Nancy J. Minshew, M.D. & Shaun M. Each, Ph.D...Therapy for Adults with Autism Spectrum Disorders 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0665 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

TU-H-CAMPUS-TeP3-05: Evaluation of the Microscopic Dose Enhancement in the Nanoparticle-Enhanced Auger Therapy

International Nuclear Information System (INIS)

Sung, W; Jung, S; Ye, S

2016-01-01

Purpose: The aim of this study is to apply Monte Carlo simulations to investigate the nanoparticle dose enhancement for Auger therapy. Methods: Two nanoparticle fabrications were considered: nanoshell and nanosphere. In the first step, a single nanoparticle was irradiated with Auger emitters. The electrons were scored in a phase space at the outer surface of the nanoparticle with Geant4-Penelope. In the second step, the previously recorded phase space was used as a source and placed at the center of a cell-size water phantom. The nanoscale dose was evaluated in water around the nanoparticle with Geant4-DNA. The dose enhancement factor (DEF) is defined as the ratio of doses with and without nanoparticles. The nanoparticles were replaced by corresponding water nanoparticle with the same size and volume source which represents typical situation of Auger emitters without nanoparticle. Various sizes/materials of nanoparticles and isotopes were considered. Results: Nanoshell - Microscopic dose was increased up to 130% at 20 – 100 nm distances from the surface of Au- 125 I nanoshell. However, dose at less than 20 nm distance was reduced due to absorbed low energy electrons in gold nanoshell. The amounts and regions of the dose enhancement were dependent on nanoshell size, materials, and isotopes. Nanosphere - The increased amounts of electrons up to 300% and reduced average energy with nanosphere were observed compared with water nanoparticle. We observed localized dose enhancement (up to a factor 3.6) in the immediate vicinity (< 50 nm) of Au- 125 I nanosphere. The dose enhancement patterns vary according to nanosphere sizes and isotopes. Conclusion: We conclude that Auger therapy with nanoparticles can lead to change of electron energy spectrum and dose enhancements at certain range. The dose enhancement patterns vary according to nanoparticle sizes, materials, and isotopes. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the

Research on neutron capture therapy in the USSR

International Nuclear Information System (INIS)

Ryabukhin, Y.

1988-01-01

Research on neutron capture therapy in the USSR began in 1964. Towards 1975 prime knowledge in physics, pharmacology and radiobiology had been accumulated. It was realized that inherent to NCT is a variety of modalities as to the type and location of the tumor, the energy and source of neutrons, the nature and transportation of the nuclide-carrying agent (NCA), etc. Thus, it became likely that some modalities would turn out to be clinically feasible. At the end of the 70s, studies of boron derivatives began at the All-Union Oncological Research Center, Moscow. These studies were stimulated by the clinical trials in Japan. Still, neutron capturing nuclides (NCN) other than 10 b are regarded as promising. Research was aimed at clinical trials that could ensure sufficient safety, convenience and conclusiveness. Hence, new requirements emerged, such as the pre-clinical modeling of NCT in big animals and the monitoring of tumor response to each fraction of NCT. Usual requirements are also to be met, that is: tailoring neutron beams with an adequate intensity and energy, choosing NCNs and finding suitable NCAs, physical and radiobiological planning including adoption of tentative RBEs and time-fractionation regimen, selecting tumors as candidates for NCT, and developing techniques for monitoring NCNs in vivo

A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

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Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

2011-02-01

Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced

Alcohol Treatment and Cognitive-Behavioral Therapy: Enhancing Effectiveness by Incorporating Spirituality and Religion

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Hodge, David R.

2011-01-01

Cognitive-behavioral therapy (CBT) is an effective modality for the treatment of alcoholism. Given widespread interest in incorporating spirituality into professional treatment, this article orients practitioners to spiritually modified CBT, an approach that may enhance outcomes with some spiritually motivated clients. More specifically, by…

Effects of an immuno-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy.

Science.gov (United States)

Aiko, S; Kumano, I; Yamanaka, N; Tsujimoto, H; Takahata, R; Maehara, T

2012-02-01

Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY

HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand?

OpenAIRE

Whittle, Nigel; Singewald, Nicolas

2014-01-01

A novel strategy to treat anxiety and fear-related disorders such as phobias, panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive behavioural therapy), including extinction-based exposure therapy, with cognitive enhancers. By targeting and boosting mechanisms underlying learning, drug development in this field aims at designing CBT-augmenting compounds that help to overcome extinction learning deficits, promote long-term fear inhibition and thus support relapse prevent...

Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models.

Science.gov (United States)

Xu, Chunxiao; Zhang, Yanping; Rolfe, P Alexander; Hernández, Vivian M; Guzman, Wilson; Kradjian, Giorgio; Marelli, Bo; Qin, Guozhong; Qi, Jin; Wang, Hong; Yu, Huakui; Tighe, Robert; Lo, Kin-Ming; English, Jessie M; Radvanyi, Laszlo; Lan, Yan

2017-10-01

Purpose: To determine whether combination therapy with NHS-muIL12 and the anti-programmed death ligand 1 (PD-L1) antibody avelumab can enhance antitumor efficacy in preclinical models relative to monotherapies. Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt - mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice. Immune cell populations within spleen and tumors were evaluated by FACS and IHC. Immune gene expression in tumor tissue was profiled by NanoString® assay and plasma cytokine levels were determined by multiplex cytokine assay. The frequency of tumor antigen-reactive IFNγ-producing CD8 + T cells was evaluated by ELISpot assay. Results: NHS-muIL12 and avelumab combination therapy enhanced antitumor efficacy relative to either monotherapy in both tumor models. Most EMT-6 tumor-bearing mice treated with combination therapy had complete tumor regression. Combination therapy also induced the generation of tumor-specific immune memory, as demonstrated by protection against tumor rechallenge and induction of effector and memory T cells. Combination therapy enhanced cytotoxic NK and CD8 + T-cell proliferation and T-bet expression, whereas NHS-muIL12 monotherapy induced CD8 + T-cell infiltration into the tumor. Combination therapy also enhanced plasma cytokine levels and stimulated expression of a greater number of innate and adaptive immune genes compared with either monotherapy. Conclusions: These data indicate that combination therapy with NHS-muIL12 and avelumab increased antitumor efficacy in preclinical models, and suggest that combining NHS-IL12 and avelumab may be a promising approach to treating patients with solid tumors. Clin Cancer Res; 23(19); 5869-80. ©2017 AACR . ©2017 American Association for Cancer Research.

Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

Science.gov (United States)

Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

2017-11-01

Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

Polydopamine-coated gold nanostars for CT imaging and enhanced photothermal therapy of tumors

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Li, Du; Shi, Xiangyang; Jin, Dayong

2016-12-01

The advancement of biocompatible nanoplatforms with dual functionalities of diagnosis and therapeutics is strongly demanded in biomedicine in recent years. In this work, we report the synthesis and characterization of polydopamine (pD)-coated gold nanostars (Au NSs) for computed tomography (CT) imaging and enhanced photothermal therapy (PTT) of tumors. Au NSs were firstly formed via a seed-mediated growth method and then stabilized with thiolated polyethyleneimine (PEI-SH), followed by deposition of pD on their surface. The formed pD-coated Au NSs (Au-PEI@pD NSs) were well characterized. We show that the Au-PEI@pD NSs are able to convert the absorbed near-infrared laser light into heat, and have strong X-ray attenuation property. Due to the co-existence of Au NSs and the pD, the light to heat conversion efficiency of the NSs can be significantly enhanced. These very interesting properties allow their uses as a powerful theranostic nanoplatform for efficient CT imaging and enhanced phtotothermal therapy of cancer cells in vitro and the xenografted tumor model in vivo. With the easy functionalization nature enabled by the coated pD shell, the developed pD-coated Au NSs may be developed as a versatile nanoplatform for targeted CT imaging and PTT of different types of cancer.

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy

International Nuclear Information System (INIS)

Fujimoto, T.; Ichikawa, H.; Akisue, T.; Fujita, I.; Kishimoto, K.; Hara, H.; Imabori, M.; Kawamitsu, H.; Sharma, P.; Brown, S.C.; Moudgil, B.M.; Fujii, M.; Yamamoto, T.; Kurosaka, M.; Fukumori, Y.

2009-01-01

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

Cognitive deficits in marijuana users: effects on motivational enhancement therapy plus cognitive behavioral therapy treatment outcome

Science.gov (United States)

Aharonovich, Efrat; Brooks, Adam C; Nunes, Edward V; Hasin, Deborah S

2008-01-01

Clinical variables that affect treatment outcome for marijuana dependent individuals are not yet well understood, including the effects of cognitive functioning. To address this, level of cognitive functioning and treatment outcome were investigated. Twenty marijuana-dependent outpatients were administered a neuropsychological battery at treatment entry. All patients received 12 weekly individual sessions of combined motivational enhancement therapy and cognitive behavioral therapy. The Wilcoxon Exact Test was used to compare cognitive functioning test scores between completers and dropouts, and the Fisher Exact Test was used to compare proportion of negative urines between those with higher and lower scores on the cognitive tests. Marijuana abstinence was unrelated to cognitive functioning. However, dropouts scored significantly lower than completers on measures of abstract reasoning and processing accuracy, providing initial evidence that cognitive functioning plays a role in treatment retention of adult marijuana dependent patients. If supported by further studies, the findings may help inform the development of interventions tailored for cognitively impaired marijuana dependent patients. PMID:18329188

Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy.

Science.gov (United States)

Mi, Peng; Dewi, Novriana; Yanagie, Hironobu; Kokuryo, Daisuke; Suzuki, Minoru; Sakurai, Yoshinori; Li, Yanmin; Aoki, Ichio; Ono, Koji; Takahashi, Hiroyuki; Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2015-06-23

Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.

Phonatory vocal tract stability in stuttering children before and after fluency--enhancing therapy.

Science.gov (United States)

Dehqan, A; Ali Dashti, G; Mirzadeh, M

2010-01-01

Stuttering is a complex disorder. Essentially, it is a neuromuscular disorder whose core consists of tiny lags and disruptions in the timing of the complicated movements required for speech. The purpose of the current study was to collec and comparg jitters and shimmer values in children who stutter before and after fluency--enhancing therapy. Subjects consisted of 15 Iranian preschool girls with stutterg, and 15 Iranial preschool girls without afflictions, matched according to age. Vocal jittering and shimmer measurements of thesphonation of the children were compared before and after therapy. Each subject phonated vowels nine times in a random order. Each phonation was sustained for at least five seconds and was recorded. The middle three-second portion of each recorded vowel phonation was subjected to jitter and shimmer analysis. On shimmer measures between pre-treatment and post treatment, significant differences were found in all sustained vowels of persons who stutter group and means of shimmer in post therapy were significantly lower than pre-treatment. Differences in jitter measurements were not significant between pre-treatment and post-treatment statuses and this parameter did not change after therapy. The findings showed that therapy resulted in decreaseg irregularity in the amplitude of vibrations (shimmer). In other words, the therapy increases the steady-state of the laryngeal system. Moreover, this parameter may be used as an index for the effectiveness of therapy.

The use of genes for performance enhancement: doping or therapy?

Directory of Open Access Journals (Sweden)

R.S. Oliveira

2011-12-01

Full Text Available Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO, vascular endothelial growth factor (VEGF, insulin-like growth factor type 1 (IGF-1, myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.

The use of genes for performance enhancement: doping or therapy?

Science.gov (United States)

Oliveira, R S; Collares, T F; Smith, K R; Collares, T V; Seixas, F K

2011-12-01

Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM) to enhance athletic performance. In such 'gene doping', exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO), vascular endothelial growth factor (VEGF), insulin-like growth factor type 1 (IGF-1), myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products) in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.

Improvement and decline in vision with gene therapy in childhood blindness.

Science.gov (United States)

Jacobson, Samuel G; Cideciyan, Artur V; Roman, Alejandro J; Sumaroka, Alexander; Schwartz, Sharon B; Heon, Elise; Hauswirth, William W

2015-05-14

Retinal gene therapy for Leber's congenital amaurosis, an autosomal recessive childhood blindness, has been widely considered to be safe and efficacious. Three years after therapy, improvement in vision was maintained, but the rate of loss of photoreceptors in the treated retina was the same as that in the untreated retina. Here we describe long-term follow-up data from three treated patients. Topographic maps of visual sensitivity in treated regions, nearly 6 years after therapy for two of the patients and 4.5 years after therapy for the third patient, indicate progressive diminution of the areas of improved vision. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00481546.).

Utilization of RP-10 reactor for neutron therapy

International Nuclear Information System (INIS)

Paucar, R.; Nieto, M.; Parreno, F.; Vela, M.; Pozo, Z.

1997-01-01

In the Nuclear Energy Peruvian Institute, IPEN, a research area has established of Neutron Radiotherapy, know as NCT. This research joins the physics of particles (Neutrons and photons) and Medical Physics, and this one is an applied investigation where in considering the construction of a treatment hall in Huarangal (Peru) Reactor's irradiation facility, it can treat patients with brain tumors. In Neutron Therapy (NCT), it tries to use neutrons to destroy tumor cells where other therapeutic techniques are not effective. This process consist on to incise a neutrons beam of adequate characteristics over the tumor area of the patient. The neutrons used are of thermal energy and therefore irradiations are developed in experimental reactors. For this one, it is used horizontal channels prepared suitably. Before the irradiation, it is injected to the patient a substance which is absorbed by tumoral tissue. The substance components will be B-10, nuclide with an absorption cross section high to thermal neutrons (3837 b). The B-10 irradiate with thermal neutrons produce alpha particles of short reach (10 μm. on soft tissue) and with LET values (lineal energy transference) very high. The result is a cell preferential destruction which have absorbed the substance and it's next neighbors, like the cell size is 10 μm. This process as know as Boron Neutron Capture Therapy (BNCT). This work describes Peruvian RP-10 reactor and recently efforts to assess the design and feasibility of the medical neutron irradiation facility for NCT. (author). 22 refs., 6 tabs

Trajectory of phantom limb pain relief using mirror therapy: Retrospective analysis of two studies.

Science.gov (United States)

Griffin, Sarah C; Curran, Sean; Chan, Annie W Y; Finn, Sacha B; Baker, Chris I; Pasquina, Paul F; Tsao, Jack W

2017-04-01

Research indicates that mirror therapy reduces phantom limb pain (PLP). Objectives were to determine when mirror therapy works in those who respond to treatment, the relevance of baseline PLP to when pain relief occurs, and what pain symptoms respond to mirror therapy. Data from two independent cohorts with unilateral lower limb amputation were analyzed for this study (n=33). Mirror therapy consisted of 15-min sessions in which amputees performed synchronous movements of the phantom and intact legs/feet. PLP was measured using a visual analogue scale and the Short-Form McGill Pain Questionnaire. The severity of PLP at the beginning of treatment predicted when pain relief occurred. Those with low baseline PLP experienced a reduction (ppain relief by session 14 of treatment, and those with high baseline PLP experienced pain relief by session 21 of treatment. Mirror therapy reduced throbbing, shooting, stabbing, sharp, cramping, aching, tender, splitting, tiring/exhausting, and punishing-cruel pain symptoms. The degree of PLP at baseline predicts when mirror therapy relieves pain. This article indicates that the degree of baseline PLP affects when mirror therapy relieves pain: relief occurs by session 7 in patients with low PLP but by session 21 in patients with high PLP. Clinicians should anticipate slower pain relief in patients who begin treatment with high levels of pain. ClinicalTrials.gov numbers:NCT00623818 and NCT00662415. Copyright © 2017 Scandinavian Association for the Study of Pain. All rights reserved.

Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy

International Nuclear Information System (INIS)

Liu Junye; Guo Yao; Guo Guozhen

2006-01-01

Objective: To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods: The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase (BCD). Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine (5-FC). Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results: Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-BCD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion: Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy. (authors)

The efficacy of a brief motivational enhancement education program on CPAP adherence in OSA: a randomized controlled trial.

Science.gov (United States)

Lai, Agnes Y K; Fong, Daniel Y T; Lam, Jamie C M; Weaver, Terri E; Ip, Mary S M

2014-09-01

Poor adherence to CPAP treatment in OSA adversely affects the effectiveness of this therapy. This randomized controlled trial (RCT) examined the efficacy of a brief motivational enhancement education program in improving adherence to CPAP treatment in subjects with OSA. Subjects with newly diagnosed OSA were recruited into this RCT. The control group received usual advice on the importance of CPAP therapy and its care. The intervention group received usual care plus a brief motivational enhancement education program directed at enhancing the subjects' knowledge, motivation, and self-efficacy to use CPAP through the use of a 25-min video, a 20-min patient-centered interview, and a 10-min telephone follow-up. Self-reported daytime sleepiness adherence-related cognitions and quality of life were assessed at 1 month and 3 months. CPAP usage data were downloaded at the completion of this 3-month study. One hundred subjects with OSA (mean ± SD, age 52 ± 10 years; Epworth Sleepiness Scales [ESS], 9 ± 5; median [interquartile range] apnea-hypopnea index, 29 [20, 53] events/h) prescribed CPAP treatment were recruited. The intervention group had better CPAP use (higher daily CPAP usage by 2 h/d [Cohen d = 1.33, P motivational enhancement education in addition to usual care were more likely to show better adherence to CPAP treatment, with greater improvements in treatment self-efficacy and daytime sleepiness. ClinicalTrials.gov; No.: NCT01173406; URL: www.clinicaltrials.gov.

Gadolinium enhances the sensitivity of SW-1573 cells for thermal neutron irradiation

NARCIS (Netherlands)

Franken, N. A. P.; Bergs, J. W. J.; Kok, T. T.; Kuperus, R. R. N.; Stecher-Rasmussen, F.; Haveman, J.; van Bree, C.; Stalpers, L. J. A.

2006-01-01

Gadolinium neutron capture therapy (Gd-NCT) is an experimental cancer treatment based on the physical principal that neutron capture by gadolinium-157 ensures the release of focal high-dose radiation, such as gamma-rays and electrons. Survival and induction of chromosomal aberrations of human

Group treatment for trichotillomania: cognitive-behavioral therapy versus supportive therapy.

Science.gov (United States)

Toledo, Edson Luiz; De Togni Muniz, Enilde; Brito, Antônio Marcelo Cabrita; de Abreu, Cristiano Nabuco; Tavares, Hermano

2015-04-01

Trichotillomania is a psychiatric condition characterized by the chronic pulling and plucking of one's own hair. Cognitive-behavioral therapy shows promise as a treatment for trichotillomania and might be preferable to pharmacotherapy. However, there have been no randomized, controlled studies of the efficacy of group cognitive-behavioral therapy. We evaluated 44 subjects, recruited from April 2009 to May 2010, all of whom met DSM-IV criteria for a diagnosis of trichotillomania. Subjects were randomized to receive 22 sessions of either group cognitive-behavioral therapy or group supportive therapy (control). Treatment evaluation was non-blind and used self-report scales. The primary outcome measure was the improvement of hair-plucking behavior as assessed by the Massachusetts General Hospital Hairpulling Scale. Secondary measures included scores on the Beck Depression Inventory, the Beck Anxiety Inventory, and the Social Adjustment Scale-Self-Report. Both groups showed significant posttreatment improvement in the scores from the Massachusetts General Hospital Hairpulling Scale (F = 23.762, P behavior over time was significantly greater in the study group than in the control group (F = 3.545, P cognitive-behavioral therapy is a valid treatment for trichotillomania. This treatment model should be further revised and expanded to address comorbidities such as anxiety and social maladjustment. ClinicalTrials.gov identifier: NCT01968343. © Copyright 2015 Physicians Postgraduate Press, Inc.

A cluster randomized trial of standard quality improvement versus patient-centered interventions to enhance depression care for African Americans in the primary care setting: study protocol NCT00243425

Directory of Open Access Journals (Sweden)

Ghods Bri K

2010-02-01

Full Text Available Abstract Background Several studies document disparities in access to care and quality of care for depression for African Americans. Research suggests that patient attitudes and clinician communication behaviors may contribute to these disparities. Evidence links patient-centered care to improvements in mental health outcomes; therefore, quality improvement interventions that enhance this dimension of care are promising strategies to improve treatment and outcomes of depression among African Americans. This paper describes the design of the BRIDGE (Blacks Receiving Interventions for Depression and Gaining Empowerment Study. The goal of the study is to compare the effectiveness of two interventions for African-American patients with depression--a standard quality improvement program and a patient-centered quality improvement program. The main hypothesis is that patients in the patient-centered group will have a greater reduction in their depression symptoms, higher rates of depression remission, and greater improvements in mental health functioning at six, twelve, and eighteen months than patients in the standard group. The study also examines patient ratings of care and receipt of guideline-concordant treatment for depression. Methods/Design A total of 36 primary care clinicians and 132 of their African-American patients with major depressive disorder were recruited into a cluster randomized trial. The study uses intent-to-treat analyses to compare the effectiveness of standard quality improvement interventions (academic detailing about depression guidelines for clinicians and disease-oriented care management for their patients and patient-centered quality improvement interventions (communication skills training to enhance participatory decision-making for clinicians and care management focused on explanatory models, socio-cultural barriers, and treatment preferences for their patients for improving outcomes over 12 months of follow

NCT program at Nuclear Medicine, Inc

International Nuclear Information System (INIS)

Noonan, D.J.

1986-01-01

The Neutron Capture Therapy program at Nuclear Medicine, Inc. (NMI) is focused on obtaining Food and Drug Administration (FDA) approval of the treatment for malignant brain tumors. To minimize both the time and expense of the approval process, research efforts have been strictly focused and Orphan Drug sponsorship of the boron compound, Na 2 B 12 H 11 SH, has been obtained. The significance of Orphan Drug sponsorship and NMI's initial meeting with the FDA to discuss preclinical and clinical protocols are discussed. 9 references, 2 figures

Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changes in rectal cancer

International Nuclear Information System (INIS)

Lussanet, Quido G. de; Backes, Walter H.; Griffioen, Arjan W.; Padhani, Anwar R.; Baeten, Coen I.; Baardwijk, Angela van; Lambin, Philippe; Beets, Geerard L.; Engelshoven, Jos van; Beets-Tan, Regina G.H.

2005-01-01

Purpose: Dynamic contrast-enhanced T1-weighted magnetic resonance imaging (DCE-MRI) allows noninvasive evaluation of tumor microvasculature characteristics. This study evaluated radiation therapy related microvascular changes in locally advanced rectal cancer by DCE-MRI and histology. Methods and Materials: Dynamic contrast-enhanced-MRI was performed in 17 patients with primary rectal cancer. Seven patients underwent 25 fractions of 1.8 Gy radiation therapy (RT) (long RT) before DCE-MRI and 10 did not. Of these 10, 3 patients underwent five fractions of 5 Gy RT (short RT) in the week before surgery. The RT treated and nontreated groups were compared in terms of endothelial transfer coefficient (K PS , measured by DCE-MRI), microvessel density (MVD) (scored by immunoreactivity to CD31 and CD34), and tumor cell and endothelial cell proliferation (scored by immunoreactivity to Ki67). Results: Tumor K PS was 77% (p = 0.03) lower in the RT-treated group. Histogram analyses showed that RT reduced both magnitude and intratumor heterogeneity of K PS (p = 0.01). MVD was significantly lower (37%, p 0.03) in tumors treated with long RT than in nonirradiated tumors, but this was not the case with short RT. Endothelial cell proliferation was reduced with short RT (81%, p = 0.02) just before surgery, but not with long RT (p > 0.8). Tumor cell proliferation was reduced with both long (57%, p PS values showed significant radiation therapy related reductions in microvessel blood flow in locally advanced rectal cancer. These findings may be useful in evaluating effects of radiation combination therapies (e.g., chemoradiation or RT combined with antiangiogenesis therapy), to account for effects of RT alone

Influence of contrast-enhanced CT and MRI with or without SPIO particles on therapy and therapy costs for patients with focal liver disease

International Nuclear Information System (INIS)

Helmberger, T.; Gregor, M.; Holzknecht, N.; Scheidler, J.; Reiser, M.; Rau, H.

2000-01-01

Purpose: Evaluation of the diagnostic efficacy and cost-benefit of contrast enhanced CT (CT) and MRI pre- and post-SPIO-particles in focal hepatic disease with consideration of therapeutic outcome. Results: In 34/52 (65.4%) of the cases the correct diagnosis was primarily stated by CT (sensitivity [se.] 85.2%, specificity [sp.] 44.0%). In additional 10/52 of the cases unenhanced MRI (se. 91.4%, sp. 75.0%) enabled correct diagnoses, and in another 6 cases the diagnosis was established only by SPIO-MRI (se. 100%, sp. 86.7%). Considering the possible therapeutic recommendation arising from each modality, CT would have induced needless therapy costs of 191,042 DM, unenhanced MRI of 171,035 DM, and SPIO-MRI of 7,311 DM. In comparison to the real therapy costs of 221,873 DM, this would have corresponded to an unnecessary increase of therapy costs of 86.1%, 77.1%, and 3.3%, respectively. In two cases (91 hemangioma, 1 regenerative nodule) all modalities failed, causing unnecessary surgery in one patient. Discussion: In this problem-oriented scenario unenhanced and SPIO-enhanced MRI proved to be superior to CT regarding diagnostic efficacy. The cost-benefit resulted mainly due to preserving patients from unnecessary surgical procedures. (orig./AJ) [de

Local control of murine melanoma xenografts in nude mice by neutron capture therapy

International Nuclear Information System (INIS)

Allen, B.J.; Corderoy-Buck, S.; Moore, D.E.; Mishima, Y.; Ichihashi, M.

1992-01-01

In recent years considerable progress has been made in the development and implementation of neutron capture therapy (NCT) for the treatment of cancer. In particular, the boron analogue of the melanin precursor phenylalanine, i.e., DL-p-boronophenylalanine (BPA), has been used to demonstrate the regression and cure of Harding-Passey (HP) melanoma in syngeneic mice. However, 18 to 25% cures were obtained for neutron irradiations without boron, suggesting that the neutron dose alone plays an important role. Neutron capture therapy of B-16 melanoma xenografts in nude mice showed substantial tumor regression over 35 days, but the survival rate of NCT treated mice after 7 weeks was only 40-60%. In this paper the authors demonstrate the equivalence of the nude mouse model with a syngeneic model, using the same Harding-Passey murine melanoma line, and delineate the conditions required for maximum differential response between neutron irradiation with and without BPA administration, with complete local control as the end point

Technology-enhanced writing therapy for people with aphasia: results of a quasi-randomized waitlist controlled study.

Science.gov (United States)

Marshall, Jane; Caute, Anna; Chadd, Katie; Cruice, Madeline; Monnelly, Katie; Wilson, Stephanie; Woolf, Celia

2018-05-10

Acquired writing impairment, or dysgraphia, is common in aphasia. It affects both handwriting and typing, and may recover less well than other aphasic symptoms. Dysgraphia is an increasing priority for intervention, particularly for those wishing to participate in online written communication. Effective dysgraphia treatment studies have been reported, but many did not target, or did not achieve, improvements in functional writing. Functional outcomes might be promoted by therapies that exploit digital technologies, such as voice recognition and word prediction software. This study evaluated the benefits of technology-enhanced writing therapy for people with acquired dysgraphia. It aimed to explore the impact of therapy on a functional writing activity, and to examine whether treatment remediated or compensated for the writing impairment. The primary question was: Does therapy improve performance on a functional assessment of writing; and, if so, do gains occur only when writing is assisted by technology? Secondary measures examined whether therapy improved unassisted written naming, functional communication, mood and quality of life. The study employed a quasi-randomized waitlist controlled design. A total of 21 people with dysgraphia received 12 h of writing therapy either immediately or after a 6-week delay. The primary outcome measure was a functional assessment of writing, which was administered in handwriting and on a computer with assistive technology enabled. Secondary measures were: The Boston Naming Test (written version), Communication Activities of Daily Living-2, Visual Analogue Mood Scales (Sad question), and the Assessment of Living with Aphasia. Analyses of variance (ANOVA) were used to examine change on the outcome measures over two time points, between which the immediate group had received therapy but the delayed group had not. Pre-therapy, post-therapy and follow-up scores on the measures were also examined for all participants. Time × group

Development of reference problems for neutron capture therapy treatment planning systems

International Nuclear Information System (INIS)

Albritton, J.R.; Kiger, W.S. III

2006-01-01

Currently, 5 different treatment planning systems (TPSs) are or have been used in clinical trials of Neutron Capture Therapy (NCT): MacNCTPlan, NCTPlan, BNCT Rtpe, SERA, and JCDS. This paper describes work performed to comprehensively test and compare 4 of these NCT treatment planning systems in order to facilitate the pooling of patient data from the different clinical sites for analysis of the clinical results as well as to provide an important quality assurance tool for existing and future TPSs. Two different phantoms were used to evaluate the planning systems: the modified Snyder head phantom and a large water-filled box, similar to that used in the International Dosimetry Exchange for NCT. The comparison of the resulting dose profile, isodose contours, and dose volume histograms to reference calculations performed with the Monte Carlo radiation transport code MCNP5 yielded many interesting differences. Each of the planning systems deviated from the reference calculations, with the newer systems (i.e., SERA and NCTPlan) most often yielding better agreement than their predecessors (i.e., BNCT Rtpe and MacNCTPlan). The combination of simple phantoms and sources with more complicated and realistic planning conditions has produced a well-rounded and useful suite of test problems for NCT treatment planning system analysis. (author)

Motivation Enhancement Therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy?

Science.gov (United States)

Ondersma, Steven J; Winhusen, Theresa; Erickson, Sarah J; Stine, Susan M; Wang, Yun

2009-04-01

Some evidence suggests that motivational approaches are less efficacious--or even counter-productive--with persons who are relatively motivated at baseline. The present study was conducted to examine whether disordinal moderation by baseline motivation could partially explain negative findings in a previous study [Winhusen, T., Kropp, F., Babcock, D., Hague, D., Erickson, S.J., Renz, C., Rau, L., Lewis, D., Leimberger, J., Somoza, E., 2008. Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. J. Subst. Abuse Treat. 35, 161-173]. Analyses also focused on the relative utility of the University of Rhode Island Change Assessment (URICA) scale, vs. a single goal question as potential moderators of Motivation Enhancement Therapy (MET). Participants were 200 pregnant women presenting for substance abuse treatment at one of four sites. Women were randomly assigned to either a three-session MET condition or treatment as usual (TAU). Generalized Estimating Equations (GEE) revealed no significant moderation effects on drug use at post-treatment. At follow-up, contrary to expectations, participants who had not set a clear quit goal at baseline were less likely to be drug-free if randomized to MET (OR=0.48); participants who did set a clear quit goal were more likely to be drug-free if randomized to MET (OR=2.53). No moderating effects were identified via the URICA. Disordinal moderation of MET efficacy by baseline motivation may have contributed somewhat to the negative results of the [Winhusen, T., Kropp, F., Babcock, D., Hague, D., Erickson, S.J., Renz, C., Rau, L., Lewis, D., Leimberger, J., Somoza, E., 2008. Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. J. Subst. Abuse Treat. 35, 161-173] study, but in the opposite direction expected. A simple question regarding intent to quit may be useful in identifying persons who may differentially respond to motivational

Protocolized hyperventilation enhances electroconvulsive therapy.

Science.gov (United States)

de Arriba-Arnau, Aida; Dalmau, Antonia; Soria, Virginia; Salvat-Pujol, Neus; Ribes, Carmina; Sánchez-Allueva, Ana; Menchón, José Manuel; Urretavizcaya, Mikel

2017-08-01

Hyperventilation is recommended in electroconvulsive therapy (ECT) to enhance seizures and to increase patients' safety. However, more evidence is needed regarding its effects and the optimum method of application. This prospective study involving 21 subjects compared two procedures, protocolized hyperventilation (PHV) and hyperventilation as usual (HVau), applied to the same patient in two consecutive sessions. Transcutaneous partial pressure of carbon dioxide (TcPCO 2 ) was measured throughout all sessions. Ventilation parameters, hemodynamic measures, seizure characteristics, and side effects were also explored. PHV resulted in lower TcPCO 2 after hyperventilation (p=.008) and over the whole session (p=.035). The lowest TcPCO 2 was achieved after voluntary hyperventilation. Changes in TcPCO 2 from baseline showed differences between HVau and PHV at each session time-point (all p<.05). Between- and within-subjects factors were statistically significant in a general linear model. Seizure duration was greater in PHV sessions (p=.028), without differences in other seizure quality parameters or adverse effects. Correlations were found between hypocapnia induction and seizure quality indexes. Secondary outcomes could be underpowered. PHV produces hypocapnia before the stimulus, modifies patients' TcPCO 2 values throughout the ECT session and lengthens seizure duration. Voluntary hyperventilation is the most important part of the PHV procedure with respect to achieving hypocapnia. A specific ventilation approach, CO 2 quantification and monitoring may be advisable in ECT. PHV is easy to apply in daily clinical practice and does not imply added costs. Ventilation management has promising effects in terms of optimizing ECT technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

Science.gov (United States)

Minami, Yasunori; Kudo, Masatoshi

2009-12-31

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

A systematic review of randomized controlled trials on curative and health enhancement effects of forest therapy

Directory of Open Access Journals (Sweden)

Kamioka H

2012-07-01

Full Text Available Hiroharu Kamioka,1 Kiichiro Tsutani,2 Yoshiteru Mutoh,3 Takuya Honda,4 Nobuyoshi Shiozawa,5 Shinpei Okada,6 Sang-Jun Park,6 Jun Kitayuguchi,7 Masamitsu Kamada,8 Hiroyasu Okuizumi,9 Shuichi Handa91Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 3Todai Policy Alternatives Research Institute, The University of Tokyo, Tokyo, 4Japanese Society for the Promotion of Science, Tokyo, 5Food Labeling Division, Consumer Affairs Agency, Cabinet Office, Government of Japan, Tokyo, 6Physical Education and Medicine Research Foundation, Nagano, 7Physical Education and Medicine Research Center Unnan, Shimane, 8Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Shimane, 9Mimaki Onsen (Spa Clinic, Tomi City, Nagano, JapanObjective: To summarize the evidence for curative and health enhancement effects through forest therapy and to assess the quality of studies based on a review of randomized controlled trials (RCTs.Study design: A systematic review based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included one treatment group in which forest therapy was applied. The following databases – from 1990 to November 9, 2010 – were searched: MEDLINE via PubMed, CINAHL, Web of Science, and Ichushi-Web. All Cochrane databases and Campbell Systematic Reviews were also searched up to November 9, 2010.Results: Two trials met all inclusion criteria. No specific diseases were evaluated, and both studies reported significant effectiveness in one or more outcomes for health enhancement. However, the results of evaluations with the CONSORT (Consolidated Standards of Reporting Trials 2010 and CLEAR NPT (A Checklist to Evaluate a Report of a Nonpharmacological Trial checklists generally showed a remarkable lack of description in the studies. Furthermore, there was a

Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder: The TIME-A Randomized Clinical Trial.

Science.gov (United States)

Bieleninik, Lucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo; Gold, Christian

2017-08-08

Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents' concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child's focus of attention, to help children develop affect sharing and joint attention. The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14.08 to 13.23 in the music therapy group and from 13.49 to 12.58 in the standard care group (mean difference, 0

Massage Therapy Research

Science.gov (United States)

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

2007-01-01

Massage therapy has been notably effective in preventing prematurity, enhancing growth of infants, increasing attentiveness, decreasing depression and aggression, alleviating motor problems, reducing pain, and enhancing immune function. This review covers massage therapy research from the last decade, as an update to the American Psychologist 1998…

Dynamic contrast-enhanced micro-CT on mice with mammary carcinoma for the assessment of antiangiogenic therapy response

Energy Technology Data Exchange (ETDEWEB)

Eisa, Fabian [University of Erlangen-Nuremberg, Institute of Medical Physics, Erlangen (Germany); University of Erlangen-Nuremberg, Graduate School in Advanced Optical Technologies (SAOT), Erlangen (Germany); Brauweiler, Robert; Hupfer, Martin; Nowak, Tristan; Kalender, Willi A. [University of Erlangen-Nuremberg, Institute of Medical Physics, Erlangen (Germany); Lotz, Laura; Hoffmann, Inge; Dittrich, Ralf; Beckmann, Matthias W. [University of Erlangen-Nuremberg, OB/GYN, University Hospital Erlangen, Erlangen (Germany); Wachter, David [University Hospital Erlangen, Institute of Pathology, Erlangen (Germany); Jost, Gregor; Pietsch, Hubertus [Bayer Pharma AG, Berlin (Germany)

2012-04-15

To evaluate the potential of in vivo dynamic contrast-enhanced micro-computed tomography (DCE micro-CT) for the assessment of antiangiogenic drug therapy response of mice with mammary carcinoma. 20 female mice with implanted MCF7 tumours were split into control group and therapy group treated with a known effective antiangiogenic drug. All mice underwent DCE micro-CT for the 3D analysis of functional parameters (relative blood volume [rBV], vascular permeability [K], area under the time-enhancement curve [AUC]) and morphology. All parameters were determined for total, peripheral and central tumour volumes of interest (VOIs). Immunohistochemistry was performed to characterise tumour vascularisation. 3D dose distributions were determined. The mean AUCs were significantly lower in therapy with P values of 0.012, 0.007 and 0.023 for total, peripheral and central tumour VOIs. K and rBV showed significant differences for the peripheral (P{sub per}{sup K} = 0.032, P{sub per}{sup rBV} = 0.029), but not for the total and central tumour VOIs (P{sub total}{sup K} = 0.108, P{sub central}{sup K} = 0.246, P{sub total}{sup rBV} = 0.093, P{sub central}{sup rBV} = 0.136). Mean tumour volume was significantly smaller in therapy (P{sub in} {sub vivo} = 0.001, P{sub ex} {sub vivo} = 0.005). Histology revealed greater vascularisation in the controls and central tumour necrosis. Doses ranged from 150 to 300 mGy. This study indicates the great potential of DCE micro-CT for early in vivo assessment of antiangiogenic drug therapy response. (orig.)

Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorder: Results of an 18-Month Feasibility Study

Science.gov (United States)

Eack, Shaun M.; Greenwald, Deborah P.; Hogarty, Susan S.; Bahorik, Amber L.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

2013-01-01

Adults with autism experience significant impairments in social and non-social information processing for which few treatments have been developed. This study conducted an 18-month uncontrolled trial of Cognitive Enhancement Therapy (CET), a comprehensive cognitive rehabilitation intervention, in 14 verbal adults with autism spectrum disorder to…

Robot Enhanced Therapy for Children with Autism (DREAM): A Social Model of Autism

OpenAIRE

Richardson, Kathleen; Coecklebergh, M; Wakunuma, Kutoma; Billing, Erik; Ziemke, Tom; Gomez, P; Vanderborght, Bram; Belpaeme, Tony

2017-01-01

Development of Robot-enhanced Therapy for Children with Autism Spectrum Disorders The development of social robots for children with autism has been a growth field in the last 15 years. This paper reviews studies in robots and autism as a neurodevelopmental disorder that impacts on social-communication development and the way in which social robots could help children with autism develop social skills. Drawing on the ethics research from the EU funded DREAM project (framework 7), based on ...

Interleukin-2 therapy in patients with HIV infection.

Science.gov (United States)

Abrams, D; Lévy, Y; Losso, M H; Babiker, A; Collins, G; Cooper, D A; Darbyshire, J; Emery, S; Fox, L; Gordin, F; Lane, H C; Lundgren, J D; Mitsuyasu, R; Neaton, J D; Phillips, A; Routy, J P; Tambussi, G; Wentworth, D

2009-10-15

any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].) 2009 Massachusetts Medical Society

Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

Science.gov (United States)

Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

2017-03-28

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

Effect of Photon Beam Energy, Gold Nanoparticle Size and Concentration on the Dose Enhancement in Radiation Therapy

Directory of Open Access Journals (Sweden)

Nahideh Gharehaghaji

2013-02-01

Full Text Available Introduction: Gold nanoparticles have been used as radiation dose enhancing materials in recent investigations. In the current study, dose enhancement effect of gold nanoparticles on tumor cells was evaluated using Monte Carlo (MC simulation. Methods: We used MCNPX code for MC modeling in the current study. A water phantom and a tumor region with a size of 1×1×1 cm3 loaded with gold nanoparticles were simulated. The macroscopic dose enhancement factor was calculated for gold nanoparticles with sizes of 30, 50, and 100 nm. Also, we simulated different photon beams including mono-energetic beams (50-120 keV, a Cobalt-60 beam, 6 & 18 MV photon beams of a conventional linear accelerator. Results: We found a dose enhancement factor (DEF of from 1.4 to 3.7 for monoenergetic kilovoltage beams, while the DEFs for megavoltage beams were negligible and less than 3% for all GNP sizes and concentrations. The optimum energy for higher DEF was found to be the 90 keV monoenergetic beam. The effect of GNP size was not considerable, but the GNP concentration had a substantial impact on achieved DEF in GNP-based radiation therapy. Conclusion: The results were in close agreement with some previous studies considering the effect of photon energy and GNP concentration on observed DEF. Application of GNP-based radiation therapy using kilovoltage beams is recommended.

Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518)

International Nuclear Information System (INIS)

Jensen, AD; Hoess, A; Haberkorn, U; Huber, PE; Steins, M; Thomas, M; Debus, J; Herfarth, KK; Münter, MW; Bischoff, H; Haselmann, R; Timke, C; Krempien, R; Sterzing, F; Nill, S; Heeger, S

2006-01-01

Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux ® ) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux ® ) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux ® ) and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival

Gene therapy and radionuclides targeting therapy in mammary carcinoma

International Nuclear Information System (INIS)

Song Jinhua

2003-01-01

Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application

Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer.

Directory of Open Access Journals (Sweden)

Hongxin Cao

Full Text Available Small cell lung cancer (SCLC is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality.We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP on SCLC, and tried two drug combinations to improve CP therapy.Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies.

‘Third wave’ cognitive therapy versus mentalization-based therapy for major depressive disorder. A protocol for a randomised clinical trial

Directory of Open Access Journals (Sweden)

Jakobsen Janus Christian

2012-12-01

Full Text Available Abstract Background Most interventions for depression have shown small or no effects. ‘Third wave‘ cognitive therapy and mentalization-based therapy have both gained some ground as treatments of psychological problems. No randomised trial has compared the effects of these two interventions for patients with major depression. Methods/ design We plan a randomised, parallel group, assessor-blinded superiority clinical trial. During two years we will include 84 consecutive adult participants diagnosed with major depressive disorder. The participants will be randomised to either ‘third wave‘ cognitive therapy versus mentalization-based therapy. The primary outcome will be the Hamilton Rating Scale for Depression at cessation of treatment at 18 weeks. Secondary outcomes will be the proportion of patients with remission, Symptom Checklist 90 Revised, Beck’s Depression Inventory, and The World Health Organisation-Five Well-being Index 1999. Discussion Interventions for depression have until now shown relatively small effects. Our trial results will provide knowledge about the effects of two modern psychotherapeutic interventions. Trial registration ClinicalTrials: NCT01070134

Chemotherapy and molecular target therapy combined with radiation therapy

International Nuclear Information System (INIS)

Akimoto, Tetsuo

2012-01-01

Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518

Directory of Open Access Journals (Sweden)

Hoess A

2006-05-01

Full Text Available Abstract Background Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux® which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. Methods/design The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux® plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. Discussion The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux® and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival.

Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

Science.gov (United States)

Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

2018-01-01

This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

Enhancing the Pediatric Drug Development Framework to Deliver Better Pediatric Therapies Tomorrow.

Science.gov (United States)

Bucci-Rechtweg, Christina

2017-10-01

Health care professionals involved in the clinical management of children have long appreciated the limited number of therapies suitably evaluated for their optimal use in the pediatric population. In the past century, advances in regulatory policy significantly evolved adult drug evaluation. The scarcity of available patient populations, practical complexities of drug development research, and minimal financial returns have hampered pharmaceutical investment in the study of therapies for children. More recently, pediatric policy and legislation in the United States and Europe have instituted a system of obligations and incentives to stimulate investment in pediatric drug development. These initiatives, in conjunction with a more sophisticated process of drug discovery and development, have led to significant advancements in the labeling of drugs for pediatric use. Facilitated by the emergence of new targets, precision medicine, and innovations in regulatory science, there is now a subtle shift in focus toward drug development research for children rather than simply in children. Although there has been an increase in pediatric studies of investigational agents and labeling of pediatric information for use, there have been unintended consequences of existing policies. As a result, limited progress has been made in certain therapeutic areas and for off-patent therapies. Future policy reform to enhance the availability and accessibility of pediatric medicines should not only reflect an understanding not only of the successes of existing policy and legislative initiatives but also constructively address failures and unintended consequences. Taken together, policy reform, global cooperation, and innovation in regulatory science will more ably deliver better pediatric therapies tomorrow. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

Science.gov (United States)

De Stasio, Gelsomina; Rajesh, Deepika; Casalbore, Patrizia; Daniels, Matthew J; Erhardt, Robert J; Frazer, Bradley H; Wiese, Lisa M; Richter, Katherine L; Sonderegger, Brandon R; Gilbert, Benjamin; Schaub, Sebastien; Cannara, Rachel J; Crawford, John F; Gilles, Mary K; Tyliszczak, Tolek; Fowler, John F; Larocca, Luigi M; Howard, Steven P; Mercanti, Delio; Mehta, Minesh P; Pallini, Roberto

2005-06-01

Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents. Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA. In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA. Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

CD4+ Count-Guided Interruption of Antiretroviral Treatment. The Strategies for Mangement of Antiretroviral Therapy (SMART) Study Group

DEFF Research Database (Denmark)

El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD

2006-01-01

had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less......BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who...... the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society....

Effectiveness of enhanced cognitive behavioral therapy (CBT-E) for eating disorders : Study protocol for a randomized controlled trial

NARCIS (Netherlands)

de Jong, M.; Korrelboom, C.W.; van der Meer, I.; Deen, M.; Hoek, H.W.; Spinhoven, P.

2016-01-01

Background While eating disorder not otherwise specified (EDNOS) is the most common eating disorder (ED) diagnosis in routine clinical practice, no specific treatment methods for this diagnosis have yet been developed and studied. Enhanced cognitive behavioral therapy (CBT-E) has been described and

Effectiveness of enhanced cognitive behavioral therapy (CBT-E) for eating disorders : study protocol for a randomized controlled trial

NARCIS (Netherlands)

de Jong, Martie; Korrelboom, Kees; van der Meer, Iris; Deen, Mathijs; Hoek, Hans W.; Spinhoven, Philip

2016-01-01

Background: While eating disorder not otherwise specified (EDNOS) is the most common eating disorder (ED) diagnosis in routine clinical practice, no specific treatment methods for this diagnosis have yet been developed and studied. Enhanced cognitive behavioral therapy (CBT-E) has been described and

Parent-Child Interaction Therapy: Enhancing Parent-Child Relationships

Directory of Open Access Journals (Sweden)

Anthony J. Urquiza

2012-07-01

Full Text Available Disruptive child behavior problems are common problems for parents and can be associated with serious delinquent behaviors and aggressive/violent behaviors in adolescence and adulthood. Parenting interventions to address disruptive child behavior problems has gained widespread acceptance. One of these parenting interventions is Parent-Child Interaction Therapy (PCIT. PCIT is a 14- to 20-week, founded on social learning and attachment theories, designed for children between 2 and 7 years of age with disruptive, or externalizing, behavior problems. This article will provide a brief review of the history of PCIT, a description of the basic components of PCIT, and an overview of recent developments that highlight the promise of PCIT with maltreating parent-child relationships, traumatized children, and in developing resilience in young children. In addressing the three basic treatment objectives for PCIT (i.e., reduction in child behavior problems, improving parenting skills, enhancing the quality of parent-child relationships, there is an abundance of research demonstrating very strong treatment effects and therefore, its value to the field. Recent research has also demonstrated the value of PCIT in reducing trauma symptoms in young children.

Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

DEFF Research Database (Denmark)

Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje

2016-01-01

Objective To determine if exercise therapy is superior to arthroscopic partial meniscectomy for knee function in middle aged patients with degenerative meniscal tears. Design Randomised controlled superiority trial. Setting Orthopaedic departments at two public hospitals and two physiotherapy...... clinics in Norway. Participants 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. Interventions 12 week supervised exercise therapy alone or arthroscopic partial....... Our results should encourage clinicians and middle aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option. Trial registration www.clinicaltrials.gov (NCT01002794)....

Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

DEFF Research Database (Denmark)

Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje

2016-01-01

OBJECTIVE: To determine if exercise therapy is superior to arthroscopic partial meniscectomy for knee function in middle aged patients with degenerative meniscal tears. DESIGN: Randomised controlled superiority trial. SETTING: Orthopaedic departments at two public hospitals and two physiotherapy...... clinics in Norway. PARTICIPANTS: 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. INTERVENTIONS: 12 week supervised exercise therapy alone or arthroscopic partial....... Our results should encourage clinicians and middle aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option.Trial registration www.clinicaltrials.gov (NCT01002794)....

Improved evaluation of antivascular cancer therapy using constrained tracer-kinetic modeling for multi-agent dynamic contrast-enhanced MRI

NARCIS (Netherlands)

Hectors, Stefanie; Jacobs, Igor; Lok, Jasper; Peters, Johannes; Bussink, Johan; Hoeben, Freek J. M.; Keizer, Henk; Janssen, Henk M.; Nicolay, Klaas; Schabel, Matthias; Strijkers, Gustav

2018-01-01

Dynamic contrast-enhanced MRI (DCE-MRI) is a promising technique for assessing the response of tumor vasculature to anti-vascular therapies. Multi-agent DCE-MRI employs a combination of low and high molecular weight contrast agents, which potentially improves the accuracy of estimation of tumor

Noise and poise: Enhancement of postural complexity in the elderly with a stochastic-resonance based therapy

Science.gov (United States)

Costa, M.; Priplata, A. A.; Lipsitz, L. A.; Wu, Z.; Huang, N. E.; Goldberger, A. L.; Peng, C.-K.

2007-03-01

Pathologic states are associated with a loss of dynamical complexity. Therefore, therapeutic interventions that increase physiologic complexity may enhance health status. Using multiscale entropy analysis, we show that the postural sway dynamics of healthy young and healthy elderly subjects are more complex than that of elderly subjects with a history of falls. Application of subsensory noise to the feet has been demonstrated to improve postural stability in the elderly. We next show that this therapy significantly increases the multiscale complexity of sway fluctuations in healthy elderly subjects. Quantification of changes in dynamical complexity of biologic variability may be the basis of a new approach to assessing risk and to predicting the efficacy of clinical interventions, including noise-based therapies.

Individual music therapy for managing neuropsychiatric symptoms for people with dementia and their carers: a cluster randomised controlled feasibility study.

Science.gov (United States)

Hsu, Ming Hung; Flowerdew, Rosamund; Parker, Michael; Fachner, Jörg; Odell-Miller, Helen

2015-07-18

Previous research highlights the importance of staff involvement in psychosocial interventions targeting neuropsychiatric symptoms of dementia. Music therapy has shown potential effects, but it is not clear how this intervention can be programmed to involve care staff within the delivery of patients' care. This study reports initial feasibility and outcomes from a five month music therapy programme including weekly individual active music therapy for people with dementia and weekly post-therapy video presentations for their carers in care homes. 17 care home residents and 10 care staff were randomised to the music therapy intervention group or standard care control group. The cluster randomised, controlled trial included baseline, 3-month, 5-month and post-intervention 7-month measures of residents' symptoms and well-being. Carer-resident interactions were also assessed. Feasibility was based on carers' feedback through semi-structured interviews, programme evaluations and track records of the study. The music therapy programme appeared to be a practicable and acceptable intervention for care home residents and staff in managing dementia symptoms. Recruitment and retention data indicated feasibility but also challenges. Preliminary outcomes indicated differences in symptoms (13.42, 95 % CI: [4.78 to 22.07; p = 0.006]) and in levels of wellbeing (-0.74, 95 % CI: [-1.15 to -0.33; p = 0.003]) between the two groups, indicating that residents receiving music therapy improved. Staff in the intervention group reported enhanced caregiving techniques as a result of the programme. The data supports the value of developing a music therapy programme involving weekly active individual music therapy sessions and music therapist-carer communication. The intervention is feasible with modifications in a more rigorous evaluation of a larger sample size. Clinicaltrials.gov, number NCT01744600.

Nanotechnology-driven cancer therapy

International Nuclear Information System (INIS)

Hosmane, Narayan S.

2012-01-01

In recent years, much efforts have been devoted to developing nanomaterials-based boron drugs for neutron capture therapy (NCT) and to date, a majority of the studies have proved reasonably promising. Conversely, further in vivo studies and clinical trails are needed to establish them as appropriate boron carriers; this is especially so with the relatively novel boron nanotubes and magnetic nanoparticles. More advanced forms of boron nanotubes can be anticipated as much interest in their synthesis as their future applications. Thus, boron neutron capture therapy (BNCT) is a promising treatment for malignant brain tumors as well as for other types of cancers, such as, liver, prostate, bladder, breasts, head and neck tumors. Current research focuses on both the design and synthesis of high boron containing compounds as BNCT agents, and the search for suitable delivery vehicles. To be suitable BNCT agents, the problem of their low water-solubility needs to be resolved by chemical modification. In the case of magnetic nanoparticles, strategies are required to counter their tendency of embolization and their unclear cytotoxicity must be resolved

An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

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Felicity C. Stark

2017-10-01

Full Text Available Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1 compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18, significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies.

Intermediate-energy neutron beams from reactors for NCT

International Nuclear Information System (INIS)

Brugger, R.M.; Less, T.J.; Passmore, G.G.

1986-01-01

This paper discusses ways that a beam of intermediate-energy neutrons might be extracted from a nuclear reactor. The challenge is to suppress the fast-neutron component and the gamma-ray component of the flux while leaving enough of the intermediate-energy neutrons in the beam to be able to perform neutron capture therapy in less than an hour exposure time. Moderators, filters, and reflectors are considered. 11 references, 7 figures, 3 tables

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

Science.gov (United States)

Menendez-Castro, Carlos; Zapke, Maren; Fahlbusch, Fabian; von Goessel, Heiko; Rascher, Wolfgang; Jüngert, Jörg

2017-07-06

Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

Local dose enhancement in radiation therapy: Monte Carlo simulation study

International Nuclear Information System (INIS)

Silva, Laura E. da; Nicolucci, Patricia

2014-01-01

The development of nanotechnology has boosted the use of nanoparticles in radiation therapy in order to achieve greater therapeutic ratio between tumor and healthy tissues. Gold has been shown to be most suitable to this task due to the high biocompatibility and high atomic number, which contributes to a better in vivo distribution and for the local energy deposition. As a result, this study proposes to study, nanoparticle in the tumor cell. At a range of 11 nm from the nanoparticle surface, results have shown an absorbed dose 141 times higher for the medium with the gold nanoparticle compared to the water for an incident energy spectrum with maximum photon energy of 50 keV. It was also noted that when only scattered radiation is interacting with the gold nanoparticles, the dose was 134 times higher compared to enhanced local dose that remained significant even for scattered radiation. (author)

The combination of suicide gene therapy and radiation enhances the killing of nasopharyngeal carcinoma xenographs

International Nuclear Information System (INIS)

Xia Jiahui; Xia Kun; Feng Yong

2004-01-01

Nasopharyngeal carcinoma (NPC) is very common in Southern China and Southeast Asian countries. To explore a novel and more effective approach to NPC therapy, a combined strategy of suicide genes and radiation was designed in this study. Five suicide gene expression cassettes, yeast cytosine deaminase (CD), yeast CD/uracil phosphoribosyl-transferase (UPRT), and yeast CDglyTK gene controlled by CMV, and Egr-1 and a synthetic CMV-enhanced Egr-1 promoter (CE) were constructed in an expression vector p11MS. The expression of suicide genes in NPC CNE-2 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The cytotoxicity of suicide gene therapy and radiation were analyzed by MTT assay. An animal study in which yeast CD/UPRT-expressing CNE-2 tumors in nude mice were treated with 5-fluorocytosine (5-FC) and radiation was also developed. Our results revealed that p11MSCEyCD/UPRT and p11MSCEyCDglyTK are superior over three other constructs in the killing of NPC cells in vitro. We combined suicide gene-expressing tumors, 5-FC treatment, and radiation in vivo and found that the tumors greatly regressed, some disappeared completely in 3 nude mice in the yCD/UPRT group, and a significant difference of tumor volumes was observed between this group and the other four groups (p<0.05). Our results indicated that suicide gene therapy and radiation have a synergic effect on NPC therapy, and the combined strategy of radiogene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies. (author)

Effects of horticultural therapy on elderly' health: protocol of a randomized controlled trial.

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Chan, Hui Yu; Ho, Roger Chun-Man; Mahendran, Rathi; Ng, Kheng Siang; Tam, Wilson Wai-San; Rawtaer, Iris; Tan, Chay Hoon; Larbi, Anis; Feng, Lei; Sia, Angelia; Ng, Maxel Kian-Wee; Gan, Goh Lee; Kua, Ee Heok

2017-08-29

Due to a rapidly ageing population in the world, it is increasingly pertinent to promote successful ageing strategies which are cost-effective, easily accessible, and more likely to be acceptable to the elderly. Past research associates exposure to natural environments and horticultural therapy (HT) with positive psychological, social and physical health benefits. This Randomized Controlled Trial (RCT) is designed to evaluate the efficacy of HT in promoting Asian elderly' mental health, cognitive functioning and physical health. 70 elderly participants aged 60 to 85 years old will be randomized to participate in either the active horticultural therapy group or be in the waitlist control. Sessions will be weekly for 12 weeks, and monthly for 3 months. Mental health will be assessed through self-reports of depressive and anxiety symptomatology, life satisfaction, social connectedness and psychological well-being, collaborated with immunological markers. Outcome measures of cognitive functioning and physical health include neuropsychological tests of cognitive function and basic health screening. Outcomes will be assessed at baseline, 3 months and 6 months post-intervention. This RCT comprehensively investigates the efficacy of a non-invasive intervention, HT, in enhancing mental health, cognitive functioning and physical health. The results have tremendous potential for supporting future successful ageing programs and applicability to larger populations. ClinicalTrials.gov NCT02495194 . Trial registration date: July 13, 2015. Retrospectively registered.

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Pierce K H Chow

Full Text Available The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279 was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC not amenable to curative therapies.Sorafenib (400 mg twice-daily was initiated 14 days post-radioembolization with yttrium-90 (90Y resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD] and overall survival (OS.Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC stage B (38% or C (62% HCC received a median of 3.0 GBq (interquartile range, 1.0 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months. Twenty eight patients experienced ≥1 toxicity; 15 (52% grade ≥3. Best ORR was 25%, including 2 (7% CR and 5 (18% PR, and 15 (54% SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7% had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively.This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib.ClinicalTrials.gov NCT00712790.

The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects.

Science.gov (United States)

Narita, Takuya; Shintani, Yasunori; Ikebe, Chiho; Kaneko, Masahiro; Harada, Narumi; Tshuma, Nomathamsanqa; Takahashi, Kunihiko; Campbell, Niall G; Coppen, Steven R; Yashiro, Kenta; Sawa, Yoshiki; Suzuki, Ken

2013-09-20

Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application. Copyright © 2012 Elsevier Ireland Ltd. All rights

Distribution of exogenous porphyrins in vivo; implications for neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.; Gabel, D.; Hillman, M.; Watts, K.

1982-01-01

Endogenous porphyrins (HpD) are already in clinical use for phototherapy, in which red light is used to stimulate a cytotoxic response in tumors. The evident success, at least with superficial cancers, gives biological evidence of selective concentrations of porphyrins in tumors adequate for therapy. The authors have investigated, in addition, the biodistribution of a synthetic porphyrin (tetraphenylporphinesulfonate, or TPPS) in seven different animal tumor models. Their data, as well as those of others, indicate abundant accumulations of TPPS in tumor. If boronated analogs behave in the same way, boron concentrations would be up to 10 times that needed for therapy. Utilization of such porphyrin analogs in the neutron capture therapy (NCT) procedure is similar in concept to phototherapy currently being used clinically, with the distinct advantage of deeper tissue penetration produced by the activating neutrons

Yoga-enhanced cognitive behavioural therapy (Y-CBT) for anxiety management: a pilot study.

Science.gov (United States)

Khalsa, Manjit K; Greiner-Ferris, Julie M; Hofmann, Stefan G; Khalsa, Sat Bir S

2015-01-01

Cognitive behavioural therapy (CBT) is an effective treatment for generalized anxiety disorder, but there is still room for improvement. The aim of the present study was to examine the potential benefit of enriching CBT with kundalini yoga (Y-CBT). Participants consisted of treatment resistant clients at a community mental health clinic. A total of 32 participants enrolled in the study and 22 completed the programme. After the Y-CBT intervention, pre-post comparisons showed statistically significant improvements in state and trait anxiety, depression, panic, sleep and quality of life. Results from this preliminary study suggest that Y-CBT may have potential as a promising treatment for those suffering from generalized anxiety disorder. Yoga-enhanced cognitive behavioural therapy (Y-CBT) may be a promising new treatment for those suffering from generalized anxiety disorder. Y-CBT may also reduce depression in those suffering from generalized anxiety. Y-CBT may reduce depression and anxiety in a clinic population where clients suffer from multiple diagnoses including generalized anxiety disorder. Copyright © 2014 John Wiley & Sons, Ltd.

An open trial of outpatient group therapy for bulimic disorders: combination program of cognitive behavioral therapy with assertive training and self-esteem enhancement.

Science.gov (United States)

Shiina, Akihiro; Nakazato, Michiko; Mitsumori, Makoto; Koizumi, Hiroki; Shimizu, Eiji; Fujisaki, Mihisa; Iyo, Masaomi

2005-12-01

The purposes of this study were to examine the therapeutic efficacy of combined group cognitive behavioral therapy (CGCBT) and to explore the characteristics of the patients who failed to complete it. Our group cognitive behavioral therapy combined with assertiveness training for alexithymia and self-esteem enhancement therapy were attended over a 10-week period. Twenty-five participants were enrolled in the study. The clinical symptoms were assessed before and after treatment, using rating scales including the Eating Disorder Inventory-2, the Bulimic Investigatory Test, Edinburgh, the Toronto Alexithymia Scale, the Rosenberg Self-Esteem Scale, and Global Assessment of Functioning. Sixteen participants (64%) completed the CGCBT program. Completion of the CGCBT resulted in significant improvements in reducing binge-eating behavior and improving social functioning. Eight patients (32%) significantly improved using the Clinical Global Impression Change (CGI-C). Stepwise logistic regression analysis of the results indicated that a lower age (P=0.04) and psychiatric comorbidity (P=0.06) were predictors of dropout from the CGCBT program. Our CGCBT program is a promising first-line treatment for bulimic outpatients. Lower age and the presence of comorbidity had effects on dropout rates.

Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18-month randomized clinical trial.

Science.gov (United States)

Eack, Shaun M; Hogarty, Susan S; Greenwald, Deborah P; Litschge, Maralee Y; Porton, Shannondora A; Mazefsky, Carla A; Minshew, Nancy J

2018-03-01

Cognitive remediation is a promising approach to treating core cognitive deficits in adults with autism, but rigorously controlled trials of comprehensive interventions that target both social and non-social cognition over a sufficient period of time to impact functioning are lacking. This study examined the efficacy of cognitive enhancement therapy (CET) for improving core cognitive and employment outcomes in adult autism. Verbal adult outpatients with autism spectrum disorder (N = 54) were randomized to an 18-month, single-blind trial of CET, a cognitive remediation approach that integrates computer-based neurocognitive training with group-based training in social cognition, or an active enriched supportive therapy (EST) comparison focused on psychoeducation and condition management. Primary outcomes were composite indexes of neurocognitive and social-cognitive change. Competitive employment was a secondary outcome. Intent-to-treat analyses indicated that CET produced significant differential increases in neurocognitive function relative to EST (d = .46, P = .013). Both CET and EST were associated with large social-cognitive improvements, with CET demonstrating an advantage at 9 (d = .58, P = 0.020), but not 18 months (d = .27, P = 0.298). Effects on employment indicated that participants treated with CET were significantly more likely to gain competitive employment than those in EST, OR = 6.21, P = 0.023, which was mediated by cognitive improvement. CET is a feasible and potentially effective treatment for core cognitive deficits in adult autism spectrum disorder. The treatment of cognitive impairments in this population can contribute to meaningful improvements in adult outcomes. Autism Res 2018, 11: 519-530. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Cognitive enhancement therapy (CET), an 18-month cognitive remediation intervention designed to improve thinking and social understanding, was

SU-F-T-666: Molecular-Targeted Gold Nanorods Enhances the RBE of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Khoo, A; Sahoo, N; Krishnan, S; Diagaradjane, P [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: In recent years, proton beam radiation therapy (PBRT) has gained significant attention in the treatment of tumors in anatomically complex locations. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. The purpose of this study is to evaluate whether this limitation can be overcome by artificially enhancing the RBE using molecular-targeted gold nanorods (GNRs). Methods: Molecular-targeting of GNRs was accomplished using Cetuximab (antibody specific to epidermal growth factor receptor that is over-expressed in tumors) conjugated GNRs (cGNRs) and their binding affinity to Head and Neck cancer cells was confirmed using dark field microscopy and Transmission Electron Microscopy (TEM). The radiosensitization potential of cGNRs when irradiated with photon (6MV) and proton (100 and 160 MeV) beams was determined using clonogenic assays. The RBE at 10% surviving fraction (RBE{sub 10}) for proton therapies at central and distal locations of SOBP was calculated with respect to 6 MV photons. IgGconjugated GNRs (iGNRs) were used as controls in all experiments. Results: cGNRs demonstrated significant radiosensitization when compared to iGNRs for 6MV photons (1.14 vs 1.04), 100 MeV protons (1.19 vs 1.04), and 160 MeV protons (1.17 vs 1.04). While RBE10 for proton beams at the center of SOBP revealed similar effects for both 100 and 160 MeV (RBE{sup 10}=1.39 vs 1.38; p>0.05), enhanced radiosensitization was observed at the distal SOBP with 100 MeV beams demonstrating greater effect than 160 MeV beams (RBE{sup 10}=1.79 vs 1.6; p<0.05). Conclusion: EGFR-targeting GNRs significantly enhance the RBE of protons well above the accepted 1.1 value. The enhanced RBE observed for lower energy protons (100 MeV) and at the distal SOBP suggests that low energy components may play a role in the observed radiosensitization effect. This strategy holds promise for clinical translation and could evolve as a paradigm-changing approach

Gadolinium neutron capture therapy for brain tumors. Biological aspects

International Nuclear Information System (INIS)

Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

1994-01-01

This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

A protocol proposition of cell therapy for the treatment of chronic obstructive pulmonary disease.

Science.gov (United States)

Ribeiro-Paes, J T; Stessuk, T; Marcelino, M; Faria, C; Marinelli, T; Ribeiro-Paes, M J

2014-01-01

The main feature of pulmonary emphysema is airflow obstruction resulting from the destruction of the alveolar walls distal to the terminal bronchioles. Existing clinical approaches have improved and extended the quality of life of emphysema patients. However, no treatment currently exists that can change the disease course and cure the patient. The different therapeutic approaches that are available aim to increase survival and/or enhance the quality of life of emphysema patients. In this context, cell therapy is a promising therapeutic approach with great potential for degenerative pulmonary diseases. In this protocol proposition, all patients will be submitted to laboratory tests, such as evaluation of heart and lung function and routine examinations. Stem cells will be harvested by means of 10 punctures on each anterior iliac crest, collecting a total volume of 200mL bone marrow. After preparation, separation, counting and labeling (optional) of the mononuclear cells, the patients will receive an intravenous infusion from the pool of Bone Marrow Mononuclear Cells (BMMC). This article proposes a rational and safe clinical cellular therapy protocol which has the potential for developing new projects and can serve as a methodological reference for formulating clinical application protocols related to the use of cellular therapy in COPD. This study protocol was submitted and approved by the Brazilian National Committee of Ethics in Research (CONEP - Brazil) registration number 14764. It is also registered in ClinicalTrials.gov (NCT01110252). Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

A Randomized Controlled Comparison of Integrative Cognitive-Affective Therapy and Cognitive-Behavioral Therapy-Enhanced for Bulimia Nervosa

Science.gov (United States)

Wonderlich, Stephen A.; Peterson, Carol B.; Crosby, Ross D.; Smith, Tracey L.; Klein, Marjorie H.; Mitchell, James E.; Crow, Scott J.

2016-01-01

Background The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa, Integrative Cognitive-Affective Therapy (ICAT), with an established treatment, Cognitive-Behavioral Therapy-Enhanced (CBT-E). Method Eighty adults with symptoms of bulimia nervosa were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination, were assessed at baseline, end of treatment, and 4-month follow-up. Treatment outcome, as measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety, and self-esteem, was determined using generalized estimating equations, logistic regression, and a general linear model (intent-to-treat). Results Both treatments were associated with significant improvement in bulimic symptoms as well as all measures of outcome, and no statistically significant differences were observed between the two conditions at end of treatment or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at end of treatment, 32.5% at follow-up) and CBT-E (22.5% at both end of treatment and follow-up) were not significantly different. Conclusions ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for bulimia nervosa suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study. PMID:23701891

Enhancing predicted efficacy of tumor treating fields therapy of glioblastoma using targeted surgical craniectomy: A computer modeling study

DEFF Research Database (Denmark)

Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard

2016-01-01

the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one......Objective: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore...... with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic...

An economic analysis of robot-assisted therapy for long-term upper-limb impairment after stroke.

Science.gov (United States)

Wagner, Todd H; Lo, Albert C; Peduzzi, Peter; Bravata, Dawn M; Huang, Grant D; Krebs, Hermano I; Ringer, Robert J; Federman, Daniel G; Richards, Lorie G; Haselkorn, Jodie K; Wittenberg, George F; Volpe, Bruce T; Bever, Christopher T; Duncan, Pamela W; Siroka, Andrew; Guarino, Peter D

2011-09-01

Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. A total of 127 participants were randomized to usual care plus robot therapy (n=49), usual care plus intensive comparison therapy (n=50), or usual care alone (n=28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (Prehabilitation compared with traditional rehabilitation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00372411.

Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3 inhibitor therapy with evolving actionable targets

Directory of Open Access Journals (Sweden)

Pashtoon M. Kasi

2016-01-01

Full Text Available For acute myeloid leukemia (AML, identification of activating mutations in the FMS-like tyrosine kinase-3 (FLT3 has led to the development of several FLT3-inhibitors. Here we present clinical and next generation sequencing data at the time of progression of a patient on a novel FLT3-inhibitor clinical trial (ASP2215 to show that employing therapeutic interventions with these novel targeted therapies can lead to consequences secondary to selective pressure and clonal evolution of cancer. We describe novel findings alongside data on treatment directed towards actionable aberrations acquired during the process. (Clinical Trial: NCT02014558; registered at: 〈https://clinicaltrials.gov/ct2/show/NCT02014558〉

Ultrasound-mediated microbubble enhancement of radiation therapy studied using three-dimensional high-frequency power Doppler ultrasound.

Science.gov (United States)

Kwok, Sheldon J J; El Kaffas, Ahmed; Lai, Priscilla; Al Mahrouki, Azza; Lee, Justin; Iradji, Sara; Tran, William Tyler; Giles, Anoja; Czarnota, Gregory J

2013-11-01

Tumor responses to high-dose (>8 Gy) radiation therapy are tightly connected to endothelial cell death. In the study described here, we investigated whether ultrasound-activated microbubbles can locally enhance tumor response to radiation treatments of 2 and 8 Gy by mechanically perturbing the endothelial lining of tumors. We evaluated vascular changes resulting from combined microbubble and radiation treatments using high-frequency 3-D power Doppler ultrasound in a breast cancer xenograft model. We compared treatment effects and monitored vasculature damage 3 hours, 24 hours and 7 days after treatment delivery. Mice treated with 2 Gy radiation and ultrasound-activated microbubbles exhibited a decrease in vascular index to 48 ± 10% at 24 hours, whereas vascular indices of mice treated with 2 Gy radiation alone or microbubbles alone were relatively unchanged at 95 ± 14% and 78 ± 14%, respectively. These results suggest that ultrasound-activated microbubbles enhance the effects of 2 Gy radiation through a synergistic mechanism, resulting in alterations of tumor blood flow. This novel therapy may potentiate lower radiation doses to preferentially target endothelial cells, thus reducing effects on neighboring normal tissue and increasing the efficacy of cancer treatments. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy

Science.gov (United States)

Zhang, Xin; Yan, Qi; Naer Mulatihan, Di; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

2018-06-01

The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

Manual therapy compared with physical therapy in patients with non-specific neck pain: a randomized controlled trial.

Science.gov (United States)

Groeneweg, Ruud; van Assen, Luite; Kropman, Hans; Leopold, Huco; Mulder, Jan; Smits-Engelsman, Bouwien C M; Ostelo, Raymond W J G; Oostendorp, Rob A B; van Tulder, Maurits W

2017-01-01

Manual therapy according to the School of Manual Therapy Utrecht (MTU) is a specific type of passive manual joint mobilization. MTU has not yet been systematically compared to other manual therapies and physical therapy. In this study the effectiveness of MTU is compared to physical therapy, particularly active exercise therapy (PT) in patients with non-specific neck pain. Patients neck pain, aged between 18-70 years, were included in a pragmatic randomized controlled trial with a one-year follow-up. Primary outcome measures were global perceived effect and functioning (Neck Disability Index), the secondary outcome was pain intensity (Numeric Rating Scale for Pain). Outcomes were measured at 3, 7, 13, 26 and 52 weeks. Multilevel analyses (intention-to-treat) were the primary analyses for overall between-group differences. Additional to the primary and secondary outcomes the number of treatment sessions of the MTU group and PT group was analyzed. Data were collected from September 2008 to February 2011. A total of 181 patients were included. Multilevel analyses showed no statistically significant overall differences at one year between the MTU and PT groups on any of the primary and secondary outcomes. The MTU group showed significantly lower treatment sessions compared to the PT group (respectively 3.1 vs. 5.9 after 7 weeks; 6.1 vs. 10.0 after 52 weeks). Patients with neck pain improved in both groups without statistical significantly or clinically relevant differences between the MTU and PT groups during one-year follow-up. ClinicalTrials.gov Identifier: NCT00713843.

Predicting the prognosis of non-small cell lung cancer patient treated with conservative therapy using contrast-enhanced MR imaging

International Nuclear Information System (INIS)

Ohno, Y.; Adachi, S.; Motoyama, A.; Sugimura, K.; Kono, M.; Kusumoto, M.

2000-01-01

The aim of this study was to evaluate the therapeutic effect more accurately and predict the prognosis of treated non-small cell lung cancer by using contrast-enhanced magnetic resonance imaging (CE-MRI). Contrast-enhanced computed tomography (CE-CT) and CE-MRI were examined 90 non-small cell lung cancer patients treated with conservative therapies. Enhancement patterns of CE-MRI were classified into three types: peripheral; mottled; and homogeneous. Reduction ratio of tumor size (RRT) based on the World Health Organization response criteria and a new response rate; reduction ratio of viable tumor size (RRVT) which evaluates not only the reduction of tumor size but also changes in necrosis and/or cavity size, were evaluated. Changes of enhancement pattern were compared and correlated with pathological diagnosis. The RRTs, RRVTs, and interobserver agreements evaluated by all modalities were compared. The RRTs and RRVTs in each subgroup were correlated and compared with prognoses. Change of enhancement pattern depended on therapy had no tendency (p = 0.06). Enhancement pattern had significant correlation with pathological diagnosis (p < 0.0001). Partial response (PR) case of RRVT had significant difference between imaging techniques (p = 0.04). The RRVT of other cases and RRT had no significant difference. Interobserver agreements of RRT and RRVT were almost perfect (κ≥ 0.93). Prognosis had better correlation with RRVT than with RRT. Differences of relapse-free survival and survival between patients considered as having no change (NC) by RRT and PR by RRVT (NC-PR) and patients considered as having NC by RRT and RRVT were significant (p = 0.03, p = 0.01). There were no significant differences of relapse-free survival and survival between NC-PR patients and patients considered as having PR by RRT and RRVT. The CE-MRI technique could accurately evaluate the therapeutic effect and predict the prognosis of treated non-small cell lung cancer. (orig.)

Epithermal neutron beam design for neutron capture therapy at the Power Burst Facility and the Brookhaven Medical Research Reactor

International Nuclear Information System (INIS)

Wheeler, F.J.; Parsons, D.K.; Rushton, B.L.; Nigg, D.W.

1990-01-01

Nuclear design studies have been performed for two reactor-based epithermal neutron beams for cancer treatment by neutron capture therapy (NCT). An intermediate-intensity epithermal beam has been designed and implemented at the Brookhaven Medical Research Reactor (BMRR). Measurements show that the BMRR design predictions for the principal characteristics of this beam are accurate. A canine program for research into the biological effects of NCT is now under way at BMRR. The design for a high-intensity epithermal beam with minimal contamination from undesirable radiation components has been finalized for the Power Burst Facility (PBF) at the Idaho National Engineering Laboratory. This design will be implemented when it is determined that human NCT trials are advisable. The PBF beam will exhibit approximately an order of magnitude improvement in absolute epithermal flux intensity over that available in the BMRR, and its angular distribution and spectral characteristics will be more advantageous for NCT. The combined effects of beam intensity, angular distribution, spectrum, and contaminant level allow the desired tumor radiation dose to be delivered in much shorter times than are possible with the currently available BMRR beam, with a significant reduction (factor of 3 to 5) in collateral dose due to beam contaminants

Dialectical Behavior Therapy Compared With Enhanced Usual Care for Adolescents With Repeated Suicidal and Self-Harming Behavior: Outcomes Over a One-Year Follow-Up.

Science.gov (United States)

Mehlum, Lars; Ramberg, Maria; Tørmoen, Anita J; Haga, Egil; Diep, Lien M; Stanley, Barbara H; Miller, Alec L; Sund, Anne M; Grøholt, Berit

2016-04-01

We conducted a 1-year prospective follow-up study of posttreatment clinical outcomes in adolescents with recent and repetitive self-harm who had been randomly allocated to receive 19 weeks of either dialectical behavior therapy adapted for adolescents (DBT-A) or enhanced usual care (EUC) at community child and adolescent psychiatric outpatient clinics. Assessments of self-harm, suicidal ideation, depression, hopelessness, borderline symptoms, and global level of functioning were made at the end of the 19-week treatment period and at follow-up 1 year later. Altogether 75 of the 77 (97%) adolescents participated at both time points. Frequencies of hospitalizations, emergency department visits and other use of mental health care during the 1-year follow-up period were recorded. Change analyses were performed using mixed effects linear spline regression and mixed effect Poisson regression with robust variance. Over the 52-week follow-up period, DBT-A remained superior to EUC in reducing the frequency of self-harm. For other outcomes such as suicidal ideation, hopelessness, and depressive or borderline symptoms and for the global level of functioning, inter-group differences apparent at the 19-week assessment were no longer observed, mainly due to participants in the EUC group having significantly improved on these dimensions over the follow-up year, whereas DBT-A participants remained unchanged. A stronger long-term reduction in self-harm and a more rapid recovery in suicidal ideation, depression, and borderline symptoms suggest that DBT-A may be a favorable treatment alternative for adolescents with repetitive self-harming behavior. Treatment for Adolescents With Deliberate Self Harm; http://clinicaltrials.gov/; NCT00675129. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model

Science.gov (United States)

MacLaughlin, Christina M.; Ding, Lili; Jin, Cheng; Cao, Pingjiang; Siddiqui, Iram; Hwang, David M.; Chen, Juan; Wilson, Brian C.; Zheng, Gang; Hedley, David W.

2016-03-01

Local disease control is a major problem in the treatment of pancreatic cancer, because curative-intent surgery is only possible in a minority of patients, and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for ablation of pancreatic tumors, this approach remains under investigated. Using photothermal sensitizers in combination with laser light for PTT can result in more efficient conversion of light energy to heat, and confinement of thermal destruction to the tumor, thus sparing adjacent organs and vasculature. Porphyrins have been previously employed as photosensitizers for PDT and PTT, however their incorporation in to "porphysomes", lipid-based nanoparticles each containing ~80,000 porphyrins through conjugation of pyropheophorbide to phospholipids, carries two distinct advantages: 1) high-density porphyrin packing imparts the nanoparticles with enhanced photonic properties for imaging and phototherapy; 2) the enhanced permeability and retention effect may be exploited for optimal delivery of porphysomes to the tumor region thus high payload porphyrin delivery. The feasibility of porphysome-enhanced PTT for pancreatic cancer treatment was investigated using a patient-derived orthotopic pancreas xenograft tumor model. Uptake of porphysomes at the orthotopic tumor site was validated using ex vivo fluorescence imaging of intact organs of interest. The accumulation of porphysomes in orthotopic tumor microstructure was also confirmed by fluorescence imaging of excised tissue slices. PTT progress was monitored as changes in tumor surface temperature using IR optical imaging. Histological analyses were conducted to examine microstructure changes in tissue morphology, and the viability of remaining tumor tissues following exposure to heat. These studies may also provide insight as to the contribution of heat sink in application of thermal therapies to highly vascularized pancreatic tumors.

Concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy.

Science.gov (United States)

Lee, Dong Hyun; Kim, Moo Hyun; Guo, Long Zhe; De Jin, Cai; Cho, Young Rak; Park, Kyungil; Park, Jong Sung; Park, Tae-Ho; Serebruany, Victor

2016-01-15

Despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (DAPT) in patients undergoing percutaneous coronary interventions (PCI). There is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. Sustained released nitrates (SRN) are commonly used together with clopidogrel in post-PCI setting for mild vasodilatation and nitric oxide-induced platelet inhibition. We prospectively enrolled 458 patients (64.5 ± 9.6 years old, and 73.4% males) following PCI undergoing DAPT with clopidogrel and aspirin. Platelet reactivity was assessed by the VerifyNow™ P2Y12 assay at the maintenance outpatient setting. Concomitant SRN (n=266) significantly (p=0.008) enhanced platelet inhibition after DAPT (251.6 ± 80.9PRU) when compared (232.1 ± 73.5PRU) to the SRN-free (n=192) patients. Multivariate logistic regression analysis with the cut-off value of 253 PRU for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during DAPT and use of SRN (Relative risk=1.675; Odds ratio [1.059-2.648]; p=0.027). In contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ACE-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following DAPT. The synergic ability of SRN to enhance response during DAPT may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Longitudinal functional brain imaging study in early course schizophrenia before and after cognitive enhancement therapy.

Science.gov (United States)

Keshavan, Matcheri S; Eack, Shaun M; Prasad, Konasale M; Haller, Chiara S; Cho, Raymond Y

2017-05-01

Schizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated. We conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed. During the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition (β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function. Copyright © 2017. Published by Elsevier Inc.

Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.

Science.gov (United States)

Hakim, James; Musiime, Victor; Szubert, Alex J; Mallewa, Jane; Siika, Abraham; Agutu, Clara; Walker, Simon; Pett, Sarah L; Bwakura-Dangarembizi, Mutsa; Lugemwa, Abbas; Kaunda, Symon; Karoney, Mercy; Musoro, Godfrey; Kabahenda, Sheila; Nathoo, Kusum; Maitland, Kathryn; Griffiths, Anna; Thomason, Margaret J; Kityo, Cissy; Mugyenyi, Peter; Prendergast, Andrew J; Walker, A Sarah; Gibb, Diana M

2017-07-20

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had

Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

International Nuclear Information System (INIS)

Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

2005-01-01

The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

Enhancing the Therapy Experience Using Principles of Video Game Design.

Science.gov (United States)

Folkins, John Wm; Brackenbury, Tim; Krause, Miriam; Haviland, Allison

2016-02-01

This article considers the potential benefits that applying design principles from contemporary video games may have on enhancing therapy experiences. Six principles of video game design are presented, and their relevance for enriching clinical experiences is discussed. The motivational and learning benefits of each design principle have been discussed in the education literature as having positive impacts on student motivation and learning and are related here to aspects of clinical practice. The essential experience principle suggests connecting all aspects of the experience around a central emotion or cognitive connection. The discovery principle promotes indirect learning in focused environments. The risk-taking principle addresses the uncertainties clients face when attempting newly learned skills in novel situations. The generalization principle encourages multiple opportunities for skill transfer. The reward system principle directly relates to the scaffolding of frequent and varied feedback in treatment. Last, the identity principle can assist clients in using their newly learned communication skills to redefine self-perceptions. These principles highlight areas for research and interventions that may be used to reinforce or advance current practice.

A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles.

Science.gov (United States)

Wang, Mingxin; You, Chaoqun; Gao, Zhiguo; Wu, Hongshuai; Sun, Baiwang; Zhu, Xiaoli; Chen, Renjie

2018-08-01

The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

A novel double-enhanced suicide gene therapy in a colon cancer cell line mediated by gef and apoptin.

Science.gov (United States)

Boulaiz, Houria; Aránega, Antonia; Cáceres, Blanca; Blanca, Cáceres; Alvarez, Pablo; Pablo, Alvarez; Serrano-Rodríguez, Fernando; Fernando, Rodríguez-Serrano; Carrillo, Esmeralda; Esmeralda, Carrillo; Melguizo, Consolación; Consolación, Melguizo; Prados, Jose; Jose, Prados

2014-02-01

Double-suicide gene therapy is a promising strategy for the treatment of advanced cancer. It has become an important research line in the development of gene therapy to overcome the drawbacks of single-gene therapy. The aim of this study was to investigate the usefulness of double-suicide gene therapy with the two suicide genes, gef and apoptin, in colon carcinoma. gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system. Expression of both genes in the DLD-1 cell line was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell viability was determined with the sulforhodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, and the results were confirmed by electron microscopy. The mitochondrial membrane potential was measured by JC-1 assay. Our results showed that the combined expression of gef and apoptin genes was strikingly more effective than the expression of either gene alone. Co-expression of gef and apoptin synergistically enhanced the decrease in cell viability, increasing necrosis and inducing apoptosis in colon cancer cells via the mitochondrial pathway, which can be deficient in advanced or metastatic colon cancer. Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

Cognitive Enhancement for Elderly Facing Dementia with the Use of Cognitive Rehabilitation Therapy Techniques and Psychological Treatment. A Case Study.

Science.gov (United States)

Stratakou, Georgia Dim; Plerou, Antonia

2017-01-01

Psychological therapies in order to provide cognitive enhancement have gained some momentum the last decades. The goal of this case study was to evaluate the effects of a cognitive enhancement training program on daily living activities, cognition, and depression in a demented elderly participant. A 6-month training program was proposed for the participant, whose overall evaluation results suggest significant deficits impairment but whose response rate to the proposed tasks of the treatment was interestingly high. However, additional research is needed to overall evaluate the efficacy of the proposed method to elderly adults.

MR-Guided Pulsed High-Intensity Focused Ultrasound Enhancement of Gene Therapy Combined With Androgen Deprivation and Radiotherapy for Prostate Cancer Treatment

Science.gov (United States)

2009-09-01

ultrasound . J. Acoust. Soc.Am. 72 1926-1932, (1982) (7) Neppiras E A. Acoustic cavitation . Physics reports 61(3): 159-251, (1980) (8) ter Haar G R, Daniels...Guided Pulsed High-Intensity Focused Ultrasound Enhancement of 5b. GRANT NUMBER W81XWH-08-1-0469 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...failing to This work is aimed to study MR guided high intensity focused ultrasound (MRgHIFU) enhancement of gene therapy for Prostate Cancer. The

Jogging the Cogs: Trauma-Focused Art Therapy and Cognitive Behavioral Therapy with Sexually Abused Children

Science.gov (United States)

Pifalo, Terry

2007-01-01

Art therapy in conjunction with cognitive behavioral therapy reduces symptoms and enhances the potential for positive outcomes for sexually abused children in trauma-focused treatment. This article presents a treatment model that utilizes specific art therapy interventions to facilitate treatment, based on research on the effectiveness of combined…

Costs of a motivational enhancement therapy coupled with cognitive behavioral therapy versus brief advice for pregnant substance users.

Directory of Open Access Journals (Sweden)

Xiao Xu

Full Text Available To determine and compare costs of a nurse-administered behavioral intervention for pregnant substance users that integrated motivational enhancement therapy with cognitive behavioral therapy (MET-CBT to brief advice (BA administered by an obstetrical provider. Both interventions were provided concurrent with prenatal care.We conducted a micro-costing study that prospectively collected detailed resource utilization and unit cost data for each of the two intervention arms (MET-CBT and BA within the context of a randomized controlled trial. A three-step approach for identifying, measuring and valuing resource utilization was used. All cost estimates were inflation adjusted to 2011 U.S. dollars.A total of 82 participants received the MET-CBT intervention and 86 participants received BA. From the societal perspective, the total cost (including participants' time cost of the MET-CBT intervention was $120,483 or $1,469 per participant. In contrast, the total cost of the BA intervention was $27,199 or $316 per participant. Personnel costs (nurse therapists and obstetric providers for delivering the intervention sessions and supervising the program composed the largest share of the MET-CBT intervention costs. Program set up costs, especially intervention material design and training costs, also contributed substantially to the overall cost.Implementation of an MET-CBT program to promote drug abstinence in pregnant women is associated with modest costs. Future cost effectiveness and cost benefit analyses integrating costs with outcomes and benefits data will enable a more comprehensive understanding of the intervention in improving the care of substance abusing pregnant women.

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Berbeco, Ross I., E-mail: rberbeco@partners.org; Detappe, Alexandre [Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Tsiamas, Panogiotis [Department of Radiation Oncology, St. Jude Children’s Hospital, Memphis, Tennessee 38105 (United States); Parsons, David; Yewondwossen, Mammo; Robar, James [Department of Radiation Oncology and Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia B3H 1V7 (Canada)

2016-01-15

Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam, (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.

Distribution patterns of Gd-DTPA-enhanced magnetic resonance imaging after intravenous tissue plasminogen activator therapy for acute myocardial infarction

International Nuclear Information System (INIS)

Fukuzawa, Shigeru; Watanabe, Hiroyuki; Shimada, Kazuhiro; Katagiri, Nakoto; Ozawa, Shun

1994-01-01

In patients who received thrombolytic therapy for acute myocardial infarction (AMI), we observed 3 distinct patterns in gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging. To clarify the significance of these distribution patterns of Gd-DTPA, 20 consecutive patients underwent Gd-DTPA-enhanced MR imaging 7-10 days after AMI. All of the patients received intravenous recombinant tissue plasminogen activator (IVTPA) within 6 h of onset. Echocardiograms were obtained prior to and serially over 10 days, and interpreted for regional wall motion. Coronary angiograms were obtained the day before discharge. None of the 6 patients with a closed infarct-related artery, and 9 of the 14 patients with an open artery, demonstrated subendocardial enhancement (p<0.05). All of these latter 9 patients demonstrated a significant improvement in wall motion between days 1 and 10 after AMI. In contrast, only 1 of the 7 patients with transmural enhancement and none of the 4 patients with non-homogeneous enhancement demonstrated improvement of wall motion on day 10 (p<0.05). We concluded that subendocardial enhancement was a fair prognostic sign for restoration of regional cardiac function in patients who received IVTPA during AMI. (author)

HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand?

Science.gov (United States)

Whittle, Nigel; Singewald, Nicolas

2014-04-01

A novel strategy to treat anxiety and fear-related disorders such as phobias, panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive behavioural therapy), including extinction-based exposure therapy, with cognitive enhancers. By targeting and boosting mechanisms underlying learning, drug development in this field aims at designing CBT-augmenting compounds that help to overcome extinction learning deficits, promote long-term fear inhibition and thus support relapse prevention. Progress in revealing the role of epigenetic regulation of specific genes associated with extinction memory generation has opened new avenues in this direction. The present review examines recent evidence from pre-clinical studies showing that increasing histone acetylation, either via genetic or pharmacological inhibition of HDACs (histone deacetylases) by e.g. vorinostat/SAHA (suberoylanilide hydroxamic acid), entinostat/MS-275, sodium butyrate, TSA (trichostatin A) or VPA (valproic acid), or by targeting HATs (histone acetyltransferases), augments fear extinction and, importantly, generates a long-term extinction memory that can protect from return of fear phenomena. The molecular mechanisms and pathways involved including BDNF (brain-derived neurotrophic factor) and NMDA (N-methyl-D-aspartate) receptor signalling are just beginning to be revealed. First studies in healthy humans are in support of extinction-facilitating effects of HDAC inhibitors. Very recent evidence that HDAC inhibitors can rescue deficits in extinction-memory-impaired rodents indicates a potential clinical utility of this approach also for exposure therapy-resistant patients. Important future work includes investigation of the long-term safety aspects of HDAC inhibitor treatment, as well as design of isotype(s)-specific inhibitors. Taken together, HDAC inhibitors display promising potential as pharmacological adjuncts to augment the efficacy of exposure-based approaches in anxiety and trauma therapy.

Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells

OpenAIRE

2009-01-01

Abstract Purpose The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative activity in tumour cells, improved the antitumour effect of chemotherapeutic drugs used as first-line treatment in the management...

Manual Therapy

OpenAIRE

Hakgüder, Aral; Kokino, Siranuş

2002-01-01

Manual therapy has been used in the treatment of pain and dysfunction of spinal and peripheral joints for more than a hundred years. Manual medicine includes manipulation, mobilization, and postisometric relaxation techniques. The aim of manual therapy is to enhance restricted movement caused by blockage of joints keeping postural balance, restore function and maintain optimal body mechanics. Anatomic, biomechanical, and neurophysiological evaluations of the leucomotor system is essential for...

Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

Directory of Open Access Journals (Sweden)

Li-Xia Feng

2014-03-01

Full Text Available Ceramide (CE-based combination therapy (CE combination as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX (CE + DTX and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and combination index (CI assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31 and human breast carcinoma cell (MCF-7, CI = 0.48. The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01. The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment.

Circulating N-Linked Glycoprotein Side-Chain Biomarker, Rosuvastatin Therapy, and Incident Cardiovascular Disease: An Analysis From the JUPITER Trial.

Science.gov (United States)

Akinkuolie, Akintunde O; Glynn, Robert J; Padmanabhan, Latha; Ridker, Paul M; Mora, Samia

2016-07-13

GlycA, a novel protein glycan biomarker of N-acetyl side chains of acute-phase proteins, was recently associated with incident cardiovascular disease (CVD) in healthy women. Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown. In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681), participants with low-density lipoprotein cholesterol 0.20). In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Quinacrine enhances carmustine therapy of experimental rat glioma.

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Reyes, S; Herrera, L A; Ostrosky, P; Sotelo, J

2001-10-01

The high rate of mutagenesis in malignant cells has been considered to be a primary factor in the appearance of chemotherapy-resistant cell clones in glioblastomas. Quinacrine binds strongly to deoxyribonucleic acid, preventing mutagenesis. We investigated whether quinacrine could improve carmustine therapy in C6 cell cultures and in C6 malignant gliomas implanted subcutaneously into Wistar rats. A potential chemopreventive effect of quinacrine on acquired resistance to carmustine therapy was studied in vitro and in vivo. Deoxyribonucleic acid damage was measured in cultured C6 cells by using the micronucleus test. Wistar rats with subcutaneously implanted C6 gliomas were treated with carmustine, quinacrine, or carmustine plus quinacrine, using pharmacological schemes similar to those used for human patients. The addition of quinacrine to cultured C6 cells did not modify carmustine-induced cytotoxicity; however, the deoxyribonucleic acid damage in surviving cells was minor, as indicated by the frequency of micronucleated cells. The surviving cells continued to be susceptible to a second exposure to carmustine, in contrast to non-quinacrine-treated control cells, which developed resistance to carmustine in a subsequent exposure (P < 0.05). The rate of tumor remission was higher for glioma-bearing rats treated with quinacrine plus carmustine, compared with rats treated with carmustine alone (P < 0.01). The addition of quinacrine to carmustine therapy increases the antineoplastic effect of the carmustine therapy. Our results suggest that chemical inhibition of mutagenesis in malignant glial cells during chemotherapy prevents the appearance of resistant clones.

X-ray therapy with enhanced effectiveness

International Nuclear Information System (INIS)

Silberbauer, F.

1989-01-01

The introduction of iodine atoms into a malignant tumor by intravenous injection of a contrast medium that is excreted by way of the kidneys selectively increases the tumor's capacity for the absorption of X-ray photons. This effect is exploited in CCT, but in high-voltage X-ray therapy it leads to an elevated focal dose while the incident dose remains the same. (orig.) [de

Experiential Learning and Therapy.

Science.gov (United States)

Hatala, Elaine

This paper describes the experiential therapy program at the Bowling Green Adolescent Center (New Jersey). This model supports the view that the therapeutic process of addiction treatment is accelerated and enhanced by providing the patients with experiential interventions. Experiential therapy includes goal setting, hands-on participation,…

Changes in intraocular pressure values measured with noncontact tonometer (NCT), ocular response analyzer (ORA) and corvis scheimpflug technology tonometer (CST) in the early phase after small incision lenticule extraction (SMILE).

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Shen, Yang; Su, Xiangjian; Liu, Xiu; Miao, Huamao; Fang, Xuejun; Zhou, Xingtao

2016-11-18

Corneal biomechanical properties are always compromised after corneal refractive surgeries thus leading to underestimated intraocular pressure (IOP) that complicates the management of IOP. We investigated the changes in postoperative baseline of IOP values measured with noncontact tonometer (NCT), ocular response analyzer (ORA) and corvis scheimpflug technology (CST) in the early phase after small incision lenticule extraction (SMILE). Twenty-two eyes (-6.76 ± 1.39D) of 22 moderate and high myopes, (28.36 ± 7.14 years, 12 male and 10 female) were involved in this prospective study. IOP values were measured using a non-contact tomometer (NCT-IOP), an ocular response analyzer (corneal-compensated IOP, IOPcc and Goldmann-correlated IOP, IOPg) and a Corvis scheimpflug technology tonometer (CST-IOP) preoperatively, at 20 min and 24 h, postoperatively. Repeated measures analysis of variance (RM-ANOVA), Pearson's correlation analysis and multiple linear regression models (stepwise) were performed. Cut-off P values were 0.05. Except for IOPcc, NCT-IOP, IOPg, and CST-IOP values significantly decreased after SMILE procedure (All P values 0.05). Multiple linear regression models (stepwise) showed that the practical post-operative IOP value was the main predictor of the theoretical post-operative NCT-IOP, IOPcc and IOPg values (all P values <0.001). The postoperative applanation time 1 (AT1) value (B = 8.079, t = 4.866, P < 0.001), preoperative central corneal thickness (CCT) value (B = 0.035, t = 2.732, P = 0.014) and postoperative peak distance (PD) value (B = 0.515, t = 2.176, P = 0.043) were the main predictors of the theoretical post-operative CST-IOP value. IOP values are underestimated when assessed after SMILE by using NCT-IOP, IOPg and CST-IOP. The practical postoperative IOPcc value and theoretical post-operative CST-IOP value may be more preferable for IOP assessment in the early phase after SMILE. Current Controlled

Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients

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Melillo Paolo

2012-07-01

Full Text Available Abstract Background Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA. In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration. Methods Pupillary light reflexes (PLR were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate, and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison. Results The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye compared to the left (untreated eye at both follow-up time-points, showing stability of

No Effects of D-Cycloserine Enhancement in Exposure With Response Prevention Therapy in Panic Disorder With Agoraphobia : A Double-Blind, Randomized Controlled Trial

NARCIS (Netherlands)

Hofmeijer-Sevink, Mieke Klein; Duits, Puck; Rijkeboer, Marleen M.; Hoogendoorn, Adriaan W.; van Megen, Harold J.; Vulink, Nienke C.; Denys, Damiaan A.; van den Hout, Marcel A.; van Balkom, Anton J.; Cath, Danielle C.

2017-01-01

Purpose/Background: D-cycloserine (DCS) is a partial N-methyl-Daspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the

No Effects of D-Cycloserine Enhancement in Exposure With Response Prevention Therapy in Panic Disorder With Agoraphobia A Double-Blind, Randomized Controlled Trial

NARCIS (Netherlands)

Hofmeijer-Sevink, Mieke Klein; Duits, Puck; Rijkeboer, Marleen M.; Hoogendoorn, Adriaan W.; van Megen, Harold J.; Vulink, Nienke C.; Denys, Damiaan A.; van den Hout, Marcel A.; van Balkom, Anton J.; Cath, Danielle C.

2017-01-01

Purpose/Background: D-cycloserine (DCS) is a partial N-methyl-Daspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the

Rumination-focused cognitive behaviour therapy vs. cognitive behaviour therapy for depression: study protocol for a randomised controlled superiority trial.

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Hvenegaard, Morten; Watkins, Ed R; Poulsen, Stig; Rosenberg, Nicole K; Gondan, Matthias; Grafton, Ben; Austin, Stephen F; Howard, Henriette; Moeller, Stine B

2015-08-11

Cognitive behavioural therapy is an effective treatment for depression. However, one third of the patients do not respond satisfactorily, and relapse rates of around 30 % within the first post-treatment year were reported in a recent meta-analysis. In total, 30-50 % of remitted patients present with residual symptoms by the end of treatment. A common residual symptom is rumination, a process of recurrent negative thinking and dwelling on negative affect. Rumination has been demonstrated as a major factor in vulnerability to depression, predicting the onset, severity, and duration of future depression. Rumination-focused cognitive behavioural therapy is a psychotherapeutic treatment targeting rumination. Because rumination plays a major role in the initiation and maintenance of depression, targeting rumination with rumination-focused cognitive behavioural therapy may be more effective in treating depression and reducing relapse than standard cognitive behavioural therapy. This study is a two-arm pragmatic randomised controlled superiority trial comparing the effectiveness of group-based rumination-focused cognitive behaviour therapy with the effectiveness of group-based cognitive behavioural therapy for treatment of depression. One hundred twenty-eight patients with depression will be recruited from and given treatment in an outpatient service at a psychiatric hospital in Denmark. Our primary outcome will be severity of depressive symptoms (Hamilton Rating Scale for Depression) at completion of treatment. Secondary outcomes will be level of rumination, worry, anxiety, quality of life, behavioural activation, experimental measures of cognitive flexibility, and emotional attentional bias. A 6-month follow-up is planned and will include the primary outcome measure and assessment of relapse. The clinical outcome of this trial may guide clinicians to decide on the merits of including rumination-focused cognitive behavioural therapy in the treatment of depression in

No Effects of D-Cycloserine Enhancement in Exposure with Response Prevention Therapy in Panic Disorder with Agoraphobia : A Double-Blind, Randomized Controlled Trial

NARCIS (Netherlands)

Hofmeijer-Sevink, Mieke Klein; Duits, Puck; Rijkeboer, Marleen M.; Hoogendoorn, Adriaan W; Van Megen, Harold J.; Vulink, Nienke C.; Denys, Damiaan A.; Van Den Hout, Marcel A.; van Balkom, Anton J L M; Cath, Danielle C.

2017-01-01

Purpose/Background D-cycloserine (DCS) is a partial N-methyl-D-aspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the

No Effects of D-Cycloserine Enhancement in Exposure With Response Prevention Therapy in Panic Disorder With Agoraphobia : A Double-Blind, Randomized Controlled Trial

NARCIS (Netherlands)

Hofmeijer-Sevink, Mieke Klein; Duits, Puck; Rijkeboer, Marleen M; Hoogendoorn, Adriaan W; van Megen, Harold J; Vulink, Nienke C; Denys, D.; van den Hout, Marcel A; van Balkom, Anton J L M; Cath, Danielle C

2017-01-01

PURPOSE/BACKGROUND: D-cycloserine (DCS) is a partial N-methyl-D-aspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the

Effectiveness of enhanced communication therapy in the first four months after stroke for aphasia and dysarthria: a randomised controlled trial.

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Bowen, Audrey; Hesketh, Anne; Patchick, Emma; Young, Alys; Davies, Linda; Vail, Andy; Long, Andrew F; Watkins, Caroline; Wilkinson, Mo; Pearl, Gill; Ralph, Matthew A Lambon; Tyrrell, Pippa

2012-07-13

To assess the effectiveness of enhanced communication therapy in the first four months after stroke compared with an attention control (unstructured social contact). Externally randomised, pragmatic, parallel, superiority trial with blinded outcome assessment. Twelve UK hospital and community stroke services. 170 adults (mean age 70 years) randomised within two weeks of admission to hospital with stroke (December 2006 to January 2010) whom speech and language therapists deemed eligible, and 135 carers. Enhanced, agreed best practice, communication therapy specific to aphasia or dysarthria, offered by speech and language therapists according to participants' needs for up to four months, with continuity from hospital to community. Comparison was with similarly resourced social contact (without communication therapy) from employed visitors. Primary outcome was blinded, functional communicative ability at six months on the Therapy Outcome Measure (TOM) activity subscale. Secondary outcomes (unblinded, six months): participants' perceptions on the Communication Outcomes After Stroke scale (COAST); carers' perceptions of participants from part of the Carer COAST; carers' wellbeing on Carers of Older People in Europe Index and quality of life items from Carer COAST; and serious adverse events. Therapist and visitor contact both had good uptake from service users. An average 22 contacts (intervention or control) over 13 weeks were accepted by users. Impairment focused therapy was the approach most often used by the speech and language therapists. Visitors most often provided general conversation. In total, 81/85 of the intervention group and 72/85 of the control group completed the primary outcome measure. Both groups improved on the TOM activity subscale. The estimated six months group difference was not statistically significant, with 0.25 (95% CI -0.19 to 0.69) points in favour of therapy. Sensitivity analyses that adjusted for chance baseline imbalance further reduced

Cognitive behavioural therapy attenuates the enhanced early facial stimuli processing in social anxiety disorders: an ERP investigation.

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Cao, Jianqin; Liu, Quanying; Li, Yang; Yang, Jun; Gu, Ruolei; Liang, Jin; Qi, Yanyan; Wu, Haiyan; Liu, Xun

2017-07-28

Previous studies of patients with social anxiety have demonstrated abnormal early processing of facial stimuli in social contexts. In other words, patients with social anxiety disorder (SAD) tend to exhibit enhanced early facial processing when compared to healthy controls. Few studies have examined the temporal electrophysiological event-related potential (ERP)-indexed profiles when an individual with SAD compares faces to objects in SAD. Systematic comparisons of ERPs to facial/object stimuli before and after therapy are also lacking. We used a passive visual detection paradigm with upright and inverted faces/objects, which are known to elicit early P1 and N170 components, to study abnormal early face processing and subsequent improvements in this measure in patients with SAD. Seventeen patients with SAD and 17 matched control participants performed a passive visual detection paradigm task while undergoing EEG. The healthy controls were compared to patients with SAD pre-therapy to test the hypothesis that patients with SAD have early hypervigilance to facial cues. We compared patients with SAD before and after therapy to test the hypothesis that the early hypervigilance to facial cues in patients with SAD can be alleviated. Compared to healthy control (HC) participants, patients with SAD had more robust P1-N170 slope but no amplitude effects in response to both upright and inverted faces and objects. Interestingly, we found that patients with SAD had reduced P1 responses to all objects and faces after therapy, but had selectively reduced N170 responses to faces, and especially inverted faces. Interestingly, the slope from P1 to N170 in patients with SAD was flatter post-therapy than pre-therapy. Furthermore, the amplitude of N170 evoked by the facial stimuli was correlated with scores on the interaction anxiousness scale (IAS) after therapy. Our results did not provide electrophysiological support for the early hypervigilance hypothesis in SAD to faces, but

Boron thermal/epithermal neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.

1982-01-01

The development of various particle beams for radiotherapy represents an attempt to improve dose distribution, and to provide high LET radiations which are less sensitive to ambient physical and radiobiological factors such as oxygen tension, cell cycle, and dose rate. In general, a compromise is necessary as effective RBE is reduced in order to spread the dose distribution over the anticipated tumor volume. The approach of delivering stable non-toxic isotopes to tumor, and then activating these atoms subsequently via an external radiation beam has mator advantages; problems associated with high uptake of these isotopes in competing cell pools are obviated, and the general tumor volume can be included in the treatment field of the activating beam. As long as the normal tissues supporting tumor show a low uptake of the isotope to be activated, and as long as the range of the reaction products is short, dose will be restricted to tumor, with a consequent high therapeutic ratio. Neutron Capture Therapy (NCT) is generally carried out by activating boron-10 with low energy neutrons. The range of the high LET, low OER particles from the 10 B(n, α) 7 Li reaction is approx. 10μ, or one cell diameter, a situation that is optimal for cell killing. Significant advantages may be gained by using the NCT procedure in conjunction with improved tissue penetration provided with epithermal or filtered beams, and new compounds showing physiological binding to tumor

"How do I say that?": Using communication principles to enhance medication therapy management instruction.

Science.gov (United States)

Denvir, Paul M; Cardone, Katie E; Parker, Wendy M; Cerulli, Jennifer

2018-02-01

Medication therapy management (MTM) is a comprehensive, patient-centered approach to improving medication use, reducing the risk of adverse events and improving medication adherence. Given the service delivery model and required outputs of MTM services, communication skills are of utmost importance. The objectives of this study were to identify and describe communication principles and instructional practices to enhance MTM training. Drawing on formative assessment data from interviews of both pharmacy educators and alumni, this article identifies and describes communication principles and instructional practices that pharmacy educators can use to enhance MTM training initiatives to develop student communication strategies. Analysis revealed five key communication challenges of MTM service delivery, two communication principles that pharmacy teachers and learners can use to address those challenges, and a range of specific strategies, derived from communication principles, that students can use when challenges emerge. Implications of the analysis for pharmacy educators and researchers are described. Proactive communication training provided during MTM advanced pharmacy practice experiences enabled students to apply the principles and instructional strategies to specific patient interactions during the advanced pharmacy practice experiences and in their post-graduation practice settings. Copyright © 2017 Elsevier Inc. All rights reserved.

Photon activation therapy: a Monte Carlo study on dose enhancement by various sources and activation media

International Nuclear Information System (INIS)

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Meigooni, Ali Soleimani

2013-01-01

In the present study, a number of brachytherapy sources and activation media were simulated using MCNPX code and the results were analyzed based on the dose enhancement factor values. Furthermore, two new brachytherapy sources ( 131 Cs and a hypothetical 170 Tm) were evaluated for their application in photon activation therapy (PAT). 125 I, 103 Pd, 131 Cs and hypothetical 170 Tm brachytherapy sources were simulated in water and their dose rate constant and the radial dose functions were compared with previously published data. The sources were then simulated in a soft tissue phantom which was composed of Ag, I, Pt or Au as activation media uniformly distributed in the tumour volume. These simulations were performed using the MCNPX code, and dose enhancement factor (DEF) was obtained for 7, 18 and 30 mg/ml concentrations of the activation media. Each source, activation medium and concentration was evaluated separately in a separate simulation. The calculated dose rate constant and radial dose functions were in agreement with the published data for the aforementioned sources. The maximum DEF was found to be 5.58 for a combination of the 170 Tm source with 30 mg/ml concentration of I. The DEFs for 131 Cs and 170 Tm sources for all the four activation media were higher than those for other sources and activation media. From this point of view, these two sources can be more useful in photon activation therapy with photon emitter sources. Furthermore, 131 Cs and 170 Tm brachytherapy sources can be proposed as new options for use in the field of PAT.

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT

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van Assen Luite

2010-01-01

Full Text Available Abstract Background Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. Methods/Design This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum till one year (maximum will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands. The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy, also for a period of six weeks. Primary outcomes are Global Perceived Effect (GPE and functional status (Neck Disability Index (NDI-DV. Secondary outcomes are neck pain (Numeric Rating Scale (NRS, Eurocol, costs and quality of life (SF36. Discussion This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. Trial registration ClinicalTrials.gov Identifier: NCT00713843

Robust aptamer–polydopamine-functionalized M-PLGA–TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy

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Xu GJ

2016-06-01

Full Text Available Guojun Xu,1–3,* Xinghua Yu,2,* Jinxie Zhang,1,2,* Yingchao Sheng,4 Gan Liu,2 Wei Tao,1,2 Lin Mei1,2 1School of Life Sciences, Tsinghua University, Beijing, 2Graduate School at Shenzhen, Tsinghua University, Shenzhen, 3School of Materials Science and Engineering, Tsinghua University, Beijing, 4Department of Orthopedic Surgery, Changshu Hospital of TCM, Changshu, People’s Republic of China *These authors contributed equally to this work Abstract: One limitation of current biodegradable polymeric nanoparticles (NPs is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer–polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide (M-PLGA–D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS nanoformulation (Apt-pD-NPs for the delivery of docetaxel (DTX with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1 increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA–TPGS; 2 significant active targeting effect caused by conjugated AS1411 aptamers; and 3 excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer–polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures. Keywords: dopamine, AS1411 aptamer, active targeting, polymeric NPs, enhanced cervical chemotherapy

A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa.

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Wonderlich, S A; Peterson, C B; Crosby, R D; Smith, T L; Klein, M H; Mitchell, J E; Crow, S J

2014-02-01

The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' cognitive-behavioral therapy (CBT-E). Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.

BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

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Katja Storch

Full Text Available Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

Enhanced therapeutic effect of multiple injections of HSV-TK + GCV gene therapy in combination with ionizing radiation in a mouse mammary tumor model

International Nuclear Information System (INIS)

Vlachaki, Maria T.; Chhikara, Madhu; Aguilar, Laura; Zhu Xiaohong; Chiu, Kam J.; Woo, Shiao; Teh, Bin S.; Thompson, Timothy C.; Butler, E. Brian; Aguilar-Cordova, Estuardo

2001-01-01

Purpose: Standard therapies for breast cancer lack tumor specificity and have significant risk for recurrence and toxicities. Herpes simplex virus-thymidine kinase (HSV-tk) gene therapy combined with radiation therapy (XRT) may be effective because of complementary mechanisms and distinct toxicity profiles. HSV-tk gene therapy followed by systemic administration of ganciclovir (GCV) enhances radiation-induced DNA damage by generating high local concentrations of phosphorylated nucleotide analogs that increase radiation-induced DNA breaks and interfere with DNA repair mechanisms. In addition, radiation-induced membrane damage enhances the 'bystander effect' by facilitating transfer of nucleotide analogs to neighboring nontransduced cells and by promoting local and systemic immune responses. This study assesses the effect of single and multiple courses of HSV-tk gene therapy in combination with ionizing radiation in a mouse mammary cancer model. Methods and Materials: Mouse mammary TM40D tumors transplanted s.c. in syngeneic immunocompetent BALB-c mice were treated with either adenoviral-mediated HSV-tk gene therapy or local radiation or the combination of gene and radiation therapy. A vector consisting of a replication-deficient (E1-deleted) adenovirus type 5 was injected intratumorally to administer the HSV-tk gene, and GCV was initiated 24 h later for a total of 6 days. Radiation was given as a single dose of 5 Gy 48 h after the HSV-tk injection. A metastatic model was developed by tail vein injection of TM40D cells on the same day that the s.c. tumors were established. Systemic antitumor effect was evaluated by counting the number of lung nodules after treating only the primary tumors with gene therapy, radiation, or the combination of gene and radiation therapy. To assess the therapeutic efficacy of multiple courses of this combinatorial approach, one, two, and three courses of HSV-tk + GCV gene therapy, in combination with radiation, were compared to HSV-tk or

Surface-enhanced Raman scattering study of the healing of radial fractures treated with or without Huo-Xue-Hua-Yu decoction therapy

Science.gov (United States)

Chen, Weiwei; Huang, Hao; Chen, Rong; Feng, Shangyuan; Yu, Yun; Lin, Duo; Lin, Jia

2014-11-01

This study aimed to assess, through surface-enhanced Raman scattering (SERS) spectroscopy, the incorporation of calcium hydroxyapatite (CHA ~960 cm-1) and other biochemical substances in the repair of complete radial fractures in rabbits treated with or without Huo-Xue-Hua-Yu decoction (HXHYD) therapy. A total of 18 rabbits with complete radial fractures were randomly divided into two groups; one group was treated with HXHYD therapy and the other without therapy acted as a control. The animals were sacrificed at 15, 30 and 45 d after surgery. Specimens were routinely prepared for SERS measurement and high quality SERS spectra from a mixture of bone tissues and silver nanoparticles were obtained. The mineral-to-matrix ratios from the control and treated groups were calculated. Results showed that both deposition content of CHA measured by SERS spectroscopy and the mineral-to-matrix ratio in the treated group were always greater than those of the control group during the experiment, demonstrating that HXHYD therapy is effective in improving fracture healing and that SERS spectroscopy might be a novel tool to assess fracture healing.

Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.

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Eric S Rosenberg

2010-05-01

Full Text Available An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation.Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log(10 HIV-1 RNA copies/mL, respectively.The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of

A Newly Designed Mobile-Based Computerized Cognitive Addiction Therapy App for the Improvement of Cognition Impairments and Risk Decision Making in Methamphetamine Use Disorder: Randomized Controlled Trial.

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Zhu, Youwei; Jiang, Haifeng; Su, Hang; Zhong, Na; Li, Runji; Li, Xiaotong; Chen, Tianzhen; Tan, Haoye; Du, Jiang; Xu, Ding; Yan, Huan; Xu, Dawen; Zhao, Min

2018-06-20

Cognitive rehabilitation therapy has been found to improve cognitive deficits and impulse control problems in methamphetamine use disorder (MUD). However, there is limited research regarding this therapy's feasibility when using mobile-based health technologies in supporting recovery from MUD in China. The main aim of this study was to test whether 4 weeks of a newly designed computerized cognitive addiction therapy (CCAT) app can improve cognitive impairments, eliminate drug-related attention bias, and attenuate risk decision-making behaviors in participants with MUD. Forty MUD participants were assigned randomly to either the CCAT group (n=20), who received 4 weeks of CCAT plus regular detoxification treatment as usual, or the control group (n=20), who only received the regular detoxification treatment as usual, in drug rehabilitation centers in Shanghai. The CCAT was designed by combine methamphetamine use-related picture stimuli with cognitive training with the aim of improving cognitive function and eliminating drug-related attention bias. The CogState Battery, Delay Discounting Task (DDT), Iowa Gambling Task (IGT), and Balloon Analog Risk Task (BART) were administered face-to-face to all participants before and after CCAT interventions. Forty male patients were recruited. The mean age was 32.70 (SD 5.27) years in the CCAT group and mean 35.05 (SD 8.02) years in the control group. Compared to the control group, CCAT improved working memory in the CCAT group (P=.01). Group×time interactions were observed among DDT, IGT, and BART tasks, with rates of discounting delayed rewards, IGT, and BART scores (Pcognitive impairment and impulsive control in MUD. Further study is needed to understand the underlying brain mechanisms of the cognitive therapy. ClinicalTrials.gov NCT03318081; https://clinicaltrials.gov/ct2/show/NCT03318081 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT03318081). ©Youwei Zhu, Haifeng Jiang, Hang Su, Na Zhong, Runji Li

Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia: radiation effects and methotrexate leukoencephalopathy

International Nuclear Information System (INIS)

Shalen, P.R.; Ostrow, P.T.; Glass, P.J.

1981-01-01

The authors report a case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice

Pharmacotherapy and group cognitive behavioral therapy enhance follow-up treatment duration in gambling disorder patients.

Science.gov (United States)

Choi, Sam-Wook; Shin, Young-Chul; Youn, HyunChul; Lim, Se-Won; Ha, Juwon

2016-01-01

Longer treatment duration is important for the successful treatment of gambling disorder (GD). This retrospective study investigated the factors and interventions that might enhance treatment duration in GD patients in South Korea. A total of 758 outpatients with a primary diagnosis of GD, who were treated in a clinical practice from 2002 to 2011, were assessed by retrospective chart review. We compared the treatment duration according to pharmacotherapy and group cognitive behavioral therapy (CBT). Pharmacotherapy contributed to a longer duration of treatment maintenance, despite the patients' gambling severity (p gambling severity. The treatment maintenance duration was the longest in those receiving combined antidepressant pharmacotherapy and group CBT (F = 35.79, p prevention and treatment strategies.

Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

Directory of Open Access Journals (Sweden)

Xi Lin

2017-11-01

Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

Facilitating Occupational Therapy Student Learning to Enhance Cross-Cultural Effectiveness

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Gilbertson, Barbara Carol Hooper

2012-01-01

Developing cultural awareness and effectiveness is critical to meaningful and successful occupational therapy practice and of concern to occupational therapists worldwide (World Federation of Occupational Therapists, 2010). Occupational therapy graduates, not fully representative of the demographics of the populations they will meet clinically,…

The ethics of gene therapy.

Science.gov (United States)

Chan, Sarah; Harris, John

2006-10-01

Recent developments have progressed in areas of science that pertain to gene therapy and its ethical implications. This review discusses the current state of therapeutic gene technologies, including stem cell therapies and genetic modification, and identifies ethical issues of concern in relation to the science of gene therapy and its application, including the ethics of embryonic stem cell research and therapeutic cloning, the risks associated with gene therapy, and the ethics of clinical research in developing new therapeutic technologies. Additionally, ethical issues relating to genetic modification itself are considered: the significance of the human genome, the distinction between therapy and enhancement, and concerns regarding gene therapy as a eugenic practice.

Music therapy

DEFF Research Database (Denmark)

Ridder, Hanne Mette Ochsner

alternate with clear and lucid mental states. These states are important as it is here that it is possible to meet the person’s psychosocial needs. Ketil Normann’s conceps of periods of lucidity are presented and connected to clinical music therapy practice and how it is possible to use music in order...... as a consequence of person-centred care. Umeå University Medical Dissertations. New Series. Ridder, H.M. (2005). Music therapy as a way to enhance lucidity in persons with dementia in advanced stages. In: Esch, A.; Frohne-Hagemann, I.; Laqua, M.; Schirmer, H.; Seitz, E. (Eds.) Jahrbuch Musicktherapie. Forschung...... und Entwicklung Music Therapy Annual. Research and Development. 2005 (1), pp. 25-40. Reichert Verlag Wiesbaden....

Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in outpatients with anorexia nervosa (ANTOP study): randomised controlled trial.

Science.gov (United States)

Zipfel, Stephan; Wild, Beate; Groß, Gaby; Friederich, Hans-Christoph; Teufel, Martin; Schellberg, Dieter; Giel, Katrin E; de Zwaan, Martina; Dinkel, Andreas; Herpertz, Stephan; Burgmer, Markus; Löwe, Bernd; Tagay, Sefik; von Wietersheim, Jörn; Zeeck, Almut; Schade-Brittinger, Carmen; Schauenburg, Henning; Herzog, Wolfgang

2014-01-11

Psychotherapy is the treatment of choice for patients with anorexia nervosa, although evidence of efficacy is weak. The Anorexia Nervosa Treatment of OutPatients (ANTOP) study aimed to assess the efficacy and safety of two manual-based outpatient treatments for anorexia nervosa--focal psychodynamic therapy and enhanced cognitive behaviour therapy--versus optimised treatment as usual. The ANTOP study is a multicentre, randomised controlled efficacy trial in adults with anorexia nervosa. We recruited patients from ten university hospitals in Germany. Participants were randomly allocated to 10 months of treatment with either focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual (including outpatient psychotherapy and structured care from a family doctor). The primary outcome was weight gain, measured as increased body-mass index (BMI) at the end of treatment. A key secondary outcome was rate of recovery (based on a combination of weight gain and eating disorder-specific psychopathology). Analysis was by intention to treat. This trial is registered at http://isrctn.org, number ISRCTN72809357. Of 727 adults screened for inclusion, 242 underwent randomisation: 80 to focal psychodynamic therapy, 80 to enhanced cognitive behaviour therapy, and 82 to optimised treatment as usual. At the end of treatment, 54 patients (22%) were lost to follow-up, and at 12-month follow-up a total of 73 (30%) had dropped out. At the end of treatment, BMI had increased in all study groups (focal psychodynamic therapy 0·73 kg/m(2), enhanced cognitive behaviour therapy 0·93 kg/m(2), optimised treatment as usual 0·69 kg/m(2)); no differences were noted between groups (mean difference between focal psychodynamic therapy and enhanced cognitive behaviour therapy -0·45, 95% CI -0·96 to 0·07; focal psychodynamic therapy vs optimised treatment as usual -0·14, -0·68 to 0·39; enhanced cognitive behaviour therapy vs optimised treatment as usual -0·30

Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

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Castano, Ana P.; Hamblin, Michael R.

2006-02-01

One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.

Science.gov (United States)

Motoya, Satoshi; Watanabe, Mamoru; Kim, Hyo Jong; Kim, Young Ho; Han, Dong Soo; Yuasa, Hirotoshi; Tabira, Junichi; Isogawa, Naoki; Arai, Shoko; Kawaguchi, Isao; Hibi, Toshifumi

2018-04-01

Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID. We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain. A total of 121 East Asian (Japan, Korea, and Taiwan) patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95), and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21). At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95) achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26) with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22), 47.6% (10/21), and 15.0% (3/20) with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib. In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

Rational Design of Branched Nanoporous Gold Nanoshells with Enhanced Physico-Optical Properties for Optical Imaging and Cancer Therapy.

Science.gov (United States)

Song, Jibin; Yang, Xiangyu; Yang, Zhen; Lin, Lisen; Liu, Yijing; Zhou, Zijian; Shen, Zheyu; Yu, Guocan; Dai, Yunlu; Jacobson, Orit; Munasinghe, Jeeva; Yung, Bryant; Teng, Gao-Jun; Chen, Xiaoyuan

2017-06-27

Reported procedures on the synthesis of gold nanoshells with smooth surfaces have merely demonstrated efficient control of shell thickness and particle size, yet no branch and nanoporous features on the nanoshell have been implemented to date. Herein, we demonstrate the ability to control the roughness and nanoscale porosity of gold nanoshells by using redox-active polymer poly(vinylphenol)-b-(styrene) nanoparticles as reducing agent and template. The porosity and size of the branches on this branched nanoporous gold nanoshell (BAuNSP) material can be facilely adjusted by control of the reaction speed or the reaction time between the redox-active polymer nanoparticles and gold ions (Au 3+ ). Due to the strong reduction ability of the redox-active polymer, the yield of BAuNSP was virtually 100%. By taking advantage of the sharp branches and nanoporous features, BAuNSP exhibited greatly enhanced physico-optical properties, including photothermal effect, surface-enhanced Raman scattering (SERS), and photoacoustic (PA) signals. The photothermal conversion efficiency can reach as high as 75.5%, which is greater than most gold nanocrystals. Furthermore, the nanoporous nature of the shells allows for effective drug loading and controlled drug release. The thermoresponsive polymer coated on the BAuNSP surface serves as a gate keeper, governing the drug release behavior through photothermal heating. Positron emission tomography imaging demonstrated a high passive tumor accumulation of 64 Cu-labeled BAuNSP. The strong SERS signal generated by the SERS-active BAuNSP in vivo, accompanied by enhanced PA signals in the tumor region, provide significant tumor information, including size, morphology, position, and boundaries between tumor and healthy tissues. In vivo tumor therapy experiments demonstrated a highly synergistic chemo-photothermal therapy effect of drug-loaded BAuNSPs, guided by three modes of optical imaging.

Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

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Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

2016-01-01

neurons of the degenerating brain retain the ability to respond to growth factors, with axonal sprouting, cell hypertrophy and activation of functional markers. NGF-induced sprouting persists over ten years. Growth factor therapy appears safe over extended time periods and merits continued testing as a means of treating neurodegenerative disorders. Trial Registration: NCT00087789 and NCT00017940 PMID:26302439

Dialectical behavior therapy for adolescents with repeated suicidal and self-harming behavior: a randomized trial.

Science.gov (United States)

Mehlum, Lars; Tørmoen, Anita J; Ramberg, Maria; Haga, Egil; Diep, Lien M; Laberg, Stine; Larsson, Bo S; Stanley, Barbara H; Miller, Alec L; Sund, Anne M; Grøholt, Berit

2014-10-01

We examined whether a shortened form of dialectical behavior therapy, dialectical behavior therapy for adolescents (DBT-A) is more effective than enhanced usual care (EUC) to reduce self-harm in adolescents. This was a randomized study of 77 adolescents with recent and repetitive self-harm treated at community child and adolescent psychiatric outpatient clinics who were randomly allocated to either DBT-A or EUC. Assessments of self-harm, suicidal ideation, depression, hopelessness, and symptoms of borderline personality disorder were made at baseline and after 9, 15, and 19 weeks (end of trial period), and frequency of hospitalizations and emergency department visits over the trial period were recorded. Treatment retention was generally good in both treatment conditions, and the use of emergency services was low. DBT-A was superior to EUC in reducing self-harm, suicidal ideation, and depressive symptoms. Effect sizes were large for treatment outcomes in patients who received DBT-A, whereas effect sizes were small for outcomes in patients receiving EUC. Total number of treatment contacts was found to be a partial mediator of the association between treatment and changes in the severity of suicidal ideation, whereas no mediation effects were found on the other outcomes or for total treatment time. DBT-A may be an effective intervention to reduce self-harm, suicidal ideation, and depression in adolescents with repetitive self-harming behavior. Clinical trial registration information-Treatment for Adolescents With Deliberate Self Harm; http://ClinicalTrials.gov/; NCT00675129. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy.

Science.gov (United States)

Hatlebakk, Jan G; Zerbib, Frank; Bruley des Varannes, Stanislas; Attwood, Stephen E; Ell, Christian; Fiocca, Roberto; Galmiche, Jean-Paul; Eklund, Stefan; Långström, Göran; Lind, Tore; Lundell, Lars R

2016-05-01

We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes. We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole. In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P acidity was stable in both groups. Patients who required a dose increase to 40 mg/d had more severe supine reflux at baseline, and decreased esophageal acid exposure (P acidity after dose escalation. Esophageal and intragastric pH parameters, off and on therapy, did not predict long-term symptom breakthrough. In a prospective study of patients with chronic GERD, esophageal acid reflux was reduced greatly by LARS or esomeprazole therapy. However, patients receiving LARS had significantly greater reductions in 24-hour esophageal acid exposure after 6 months and 5 years. Esophageal and gastric pH, off and on therapy, did not predict long-term outcomes of patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show/NCT

Photon activation therapy with 127I-deoxyuridine: measurement of dose enhancement in cultured mammalian cells

International Nuclear Information System (INIS)

Fairchild, R.G.; Laster, B.H.; Commerford, S.L.; Furcinitti, P.S.; Sylvester, B.; Gabel, D.; Popenoe, E.; Foster, S.

1985-01-01

A technique for radiation enhancement of conventional photon radiotherapy is outlined which has been called photon activation therapy (PAT) (6). High linear energy transfer (LET) radiations in the form of Auger electron distributions are generated by photons of appropriate energies, through photon activation of stable iodine incorporated as an analog of thymidine (Tyd) in DNA. Of the several halogenated deoxyribonucleosides evaluated, iodinated deoxyuridine (IdUrd) has been chosen as the only Tyd analog providing effective photon activation. This mechanism is combined with radiation sensitization produced by IdUrd to produce an overall radiation enhancement. Calculations show that at 5% replacement (IdUrd for Tyd) therapeutic (TG) will vary from ∼2 (single acute dose) to ∼17 (low dose rates associated with permanent implant brachytherapy). Parameters used in the calculation of TG have been evaluated in cell culture; dose enhancements obtained with x-rays (including photon activation) were found to be significantly higher than values measured with γ-rays (no photon activation). Comparison is made between theoretical and measured values. Because of the evident lack of repair of damage produced by both sensitization and photon activation, significant gains are expected to be realized following protracted irradiations. Exchanges (IdUrd for Tyd) for 105 have been obtained in vivo (murine tumors). The authors believe that the application of PAT would be most advantageous in the treatment of brain tumors (grade IV astrocytomas) with implanted 145 Sm sources

Surface-enhanced Raman scattering study of the healing of radial fractures treated with or without Huo–Xue–Hua–Yu decoction therapy

International Nuclear Information System (INIS)

Chen, Weiwei; Huang, Hao; Yu, Yun; Lin, Duo; Chen, Rong; Feng, Shangyuan; Lin, Jia

2014-01-01

This study aimed to assess, through surface-enhanced Raman scattering (SERS) spectroscopy, the incorporation of calcium hydroxyapatite (CHA ∼960 cm −1 ) and other biochemical substances in the repair of complete radial fractures in rabbits treated with or without Huo–Xue–Hua–Yu decoction (HXHYD) therapy. A total of 18 rabbits with complete radial fractures were randomly divided into two groups; one group was treated with HXHYD therapy and the other without therapy acted as a control. The animals were sacrificed at 15, 30 and 45 d after surgery. Specimens were routinely prepared for SERS measurement and high quality SERS spectra from a mixture of bone tissues and silver nanoparticles were obtained. The mineral-to-matrix ratios from the control and treated groups were calculated. Results showed that both deposition content of CHA measured by SERS spectroscopy and the mineral-to-matrix ratio in the treated group were always greater than those of the control group during the experiment, demonstrating that HXHYD therapy is effective in improving fracture healing and that SERS spectroscopy might be a novel tool to assess fracture healing. (letter)

Using feminist, emotion-focused, and developmental approaches to enhance cognitive-behavioral therapies for posttraumatic stress disorder related to childhood sexual abuse.

Science.gov (United States)

Cohen, Jacqueline N

2008-06-01

A body of research indicates the efficacy of cognitive-behavioral interventions for the treatment of posttraumatic stress disorder (PTSD) subsequent to sexual assault in adulthood. The generalizability of these treatments to women who present with trauma symptoms associated with childhood sexual abuse (CSA) has yet to be shown, however. A number of characteristics and dynamics of CSA that make it unique from sexual assault in adulthood are described, specifically its disruption of normal childhood development, its impact on attachment style and interpersonal relationships, its inescapability, and the stigma attached to it. Then, drawing on the developmental, emotion-focused, and feminist literatures, a number of considerations that would enhance the application of cognitive- behavioral trauma therapies to the treatment of women with PTSD related to CSA are delineated. These considerations relate to providing clients with corrective interpersonal experiences, creating new relationship events, enhancing affect regulation skills before initiating exposure therapy, considering the time elapsed since the abuse, addressing themes of power, betrayal, self-blame, stigma, and sex-related cognitions and emotions, and helping clients develop a feminist consciousness. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Does enhanced cognitive behaviour therapy for eating disorders improve quality of life?

Science.gov (United States)

Watson, Hunna J; Allen, Karina; Fursland, Anthea; Byrne, Susan M; Nathan, Paula R

2012-09-01

Quality of life (QOL) is the degree of enjoyment and satisfaction experienced in life, and embraces emotional well-being, physical health, economic and living circumstances, and work satisfaction. QOL recovery with eating disorder treatment has received sparse attention, and until now, no study has investigated QOL recovery with enhanced cognitive behaviour therapy (CBT-E). Patients (n = 196) admitted to a specialist eating disorders outpatient programme and receiving CBT-E completed measures of QOL, eating disorder psychopathology, depression, anxiety and self-esteem, before and after treatment. QOL at intake was compared with community norms, and QOL below the norm was predicted from sociodemographic and clinical correlates with logistic regression. Baseline QOL below the norm was associated with depression and anxiety Axis I comorbidity, and severity of depressive symptoms. Predictors of post-treatment QOL were baseline QOL and level of depressive symptoms and self-esteem at post-treatment. CBT-E was associated with gains in QOL over the course of treatment, in addition to eating disorder symptom relief. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.

Making Cross-Racial Therapy Work: A Phenomenological Study of Clients' Experiences of Cross-Racial Therapy

Science.gov (United States)

Chang, Doris F.; Berk, Alexandra

2009-01-01

A phenomenological and consensual qualitative study of clients' lived experiences of cross-racial therapy was conducted to enhance the understanding of whether, how, and under what conditions race matters in the therapy relationship. The sample consisted of 16 racial and/or ethnic minority clients who received treatment from 16 White, European…

Therapy optimization in multiple sclerosis: a prospective observational study of therapy compliance and outcomes.

Science.gov (United States)

Coyle, Patricia K; Cohen, Bruce A; Leist, Thomas; Markowitz, Clyde; Oleen-Burkey, MerriKay; Schwartz, Marc; Tullman, Mark J; Zwibel, Howard

2014-03-13

-based MS samples, and the sample appears to be representative of DMT users in the US. TOP MS data can be used to explore the associations between disease-modifying therapy compliance and health outcomes. ClinicalTrials.gov (NCT00819000).

Cancer nanomedicine: gold nanoparticle mediated combined cancer therapy

Science.gov (United States)

Yang, C.; Bromma, Kyle; Chithrani, B. D.

2018-02-01

Recent developments in nanotechnology has provided new tools for cancer therapy and diagnosis. Among other nanomaterial systems, gold nanoparticles are being used as radiation dose enhancers and anticancer drug carriers in cancer therapy. Fate of gold nanoparticles within biological tissues can be probed using techniques such as TEM (transmission electron microscopy) and SEM (Scanning Electron Microscopy) due to their high electron density. We have shown for the first time that cancer drug loaded gold nanoparticles can reach the nucleus (or the brain) of cancer cells enhancing the therapeutic effect dramatically. Nucleus of the cancer cells are the most desirable target in cancer therapy. In chemotherapy, smart delivery of highly toxic anticancer drugs through packaging using nanoparticles will reduce the side effects and improve the quality and care of cancer patients. In radiation therapy, use of gold nanoparticles as radiation dose enhancer is very promising due to enhanced localized dose within the cancer tissue. Recent advancement in nanomaterial characterization techniques will facilitate mapping of nanomaterial distribution within biological specimens to correlate the radiobiological effects due to treatment. Hence, gold nanoparticle mediated combined chemoradiation would provide promising tools to achieve personalized and tailored cancer treatments in the near future.

Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.

Directory of Open Access Journals (Sweden)

Xiaofang Yu

Full Text Available Mesenchymal stem cell (MSC administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP. MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC, HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.

Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis

Directory of Open Access Journals (Sweden)

Vyas D

2014-06-01

Full Text Available Dinesh Vyas, Gieric Laput, Arpitak K Vyas College of Human Medicine, Michigan State University, East Lansing, MI, USA Abstract: The lack of therapy and the failure of existing therapy has been a challenge for clinicians in treating various cancers. Doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel are the first-line therapy in various cancers; however, toxicity, resistance, and treatment failure limit their clinical use. Their status leads us to discover and investigate more targeted therapy with more efficacy. In this article, we dissect literature from the patient perspective, the tumor biology perspective, therapy-induced metastasis, and cell data generated in the laboratory. Keywords: chemotherapy, cancer, inflammation

BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma.

Science.gov (United States)

Rossi, Adriana; Mark, Tomer; Jayabalan, David; Christos, Paul; Zafar, Faiza; Pekle, Karen; Pearse, Roger; Chen-Kiang, Selina; Coleman, Morton; Niesvizky, Ruben

2013-03-14

The combination of clarithromycin, lenalidomide, and dexamethasone (BiRd) was evaluated as therapy for treatment-naive symptomatic multiple myeloma (MM), with overall response at 2 years of 90%. We reviewed the long-term follow-up of initial BiRd therapy. Seventy-two patients were given dexamethasone 40 mg weekly, clarithromycin 500 mg twice daily, and lenalidomide 25 mg daily on days 1 to 21 of a 28-day cycle. After a median follow-up of 6.6 years, overall response rates were 93%, with a very good partial response or better of 68%. Median progression-free survival was 49 months. Evaluation for the development of second primary malignancies (SPMs) was conducted, and no increase in incidence was noted in our cohort of patients who received frontline immunomodulatory therapy. BiRd remains a highly potent and safe regimen for frontline therapy in patients with MM without apparent increase in risk of SPMs. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

Comparing systemic therapy and cognitive behavioral therapy for social anxiety disorders: study protocol for a randomized controlled pilot trial.

Science.gov (United States)

Hunger, Christina; Hilzinger, Rebecca; Koch, Theresa; Mander, Johannes; Sander, Anja; Bents, Hinrich; Schweitzer, Jochen

2016-03-31

Social anxiety disorders are among the most prevalent anxiety disorders in the general population. The efficacy of cognitive behavioral therapy (CBT) for social anxiety disorders is well demonstrated. However, only three studies point to the efficacy of systemic therapy (ST) in anxiety disorders, and only two of them especially focus on social anxiety disorders. These ST studies either do not use a good comparator but minimal supportive therapy, they do not use a multi-person ST but a combined therapy, or they do not especially focus on social anxiety disorders but mood and anxiety disorders in general. Though ST was approved as evidence based in Germany for a variety of disorders in 2008, evidence did not include anxiety disorders. This is the first pilot study that will investigate multi-person ST, integrating a broad range of systemic methods, specifically for social anxiety disorders and that will compare ST to the "gold standard" CBT. This article describes the rationale and protocol of a prospective, open, interventive, balanced, bi-centric, pilot randomized controlled trial (RCT). A total of 32 patients with a primary SCID diagnosis of social anxiety disorder will be randomized to either CBT or ST. Both treatments will be manualized. The primary outcome will include social anxiety symptoms at the end of therapy. Therapy will be restricted to no more than 26 hours (primary endpoint). Secondary outcomes will include psychological, social systems and interpersonal functioning, symptom adjustment, and caregiver burden, in addition to change measures, therapist variables and treatment adherence. At the secondary endpoints, 9 and 12 months after the beginning of therapy, we will again assess all outcomes. The study is expected to pilot test a RCT which will be the first to directly compare CBT and multi-person ST, integrating a broad range of systemic methods, for social anxiety disorders, and it will provide empirical evidence for the calculation of the number of

Music Therapy and Avatars: Reflections on Virtual Learning Environments for Music Therapy Students

DEFF Research Database (Denmark)

Story, Maya

2014-01-01

Music therapy students have expressed concerns regarding their general preparedness for practicum and working with new populations. Simulations in the immersive virtual world, Second Life, may provide a platform to assist in training music therapy students and enhance preparedness. This project...... examined the feasibility of utilizing Second Life to assist in training music therapists. Music therapy practicum students enrolled in a music therapy equivalency program participated in weekly one hour virtual class meetings in Second Life, which included 5 sessions of music therapy simulations....... At the end of the semester, students were interviewed in relation to their experiences, and interviews were analyzed qualitatively. Common themes among students were limitations of Second Life software, student’s knowledge of software, emotional reactions (both positive and negative), and distance learning....

Hyper-thermal neutron irradiation field for neutron capture therapy

International Nuclear Information System (INIS)

Sakurai, Yoshinori; Kobayashi, Tooru; Kanda, Keiji

1994-01-01

The utilization of hyper-thermal neutrons, which have an energy spectrum of a Maxwell distribution higher than the room temperature of 300 K, has been studied in order to improve the thermal neutron flux distribution in a living body for a deep-seated tumor in neutron capture therapy (NCT). Simulation calculations using MCNP-V3 were carried out in order to investigate the characteristics of the hyper-thermal neutron irradiation field. From the results of simulation calculations, the following were confirmed: (i) The irradiation field of the hyper-thermal neutrons is feasible by using some scattering materials with high temperature, such as Be, BeO, C, SiC and ZrH 1.7 . Especially, ZrH 1.7 is thought to be the best material because of good characteristics of up-scattering for thermal neutrons. (ii) The ZrH 1.7 of 1200 K yields the hyper-thermal neutrons of a Maxwell-like distribution at about 2000 K and the treatable depth is about 1.5 cm larger comparing with the irradiation of the thermal neutrons of 300 K. (iii) The contamination by the secondary gamma-rays from the scattering materials can be sufficiently eliminated to the tolerance level for NCT through the bismuth layer, without the larger change of the energy spectrum of hyper-thermal neutrons. ((orig.))

Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers

OpenAIRE

Deng-Fu Yang; Jeng-Woei Lee; Hsin-Ming Chen; Yih-Chih Hsu

2014-01-01

Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Methods: Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical A...

Heidelberg Neuro-Music Therapy Enhances Task-Negative Activity in Tinnitus Patients

Directory of Open Access Journals (Sweden)

Christoph M. Krick

2017-07-01

Full Text Available Background: Suffering from tinnitus causes mental distress in most patients. Recent findings point toward a diminished activity of the brain's default-mode network (DMN in subjects with mental disorders including depression or anxiety and also recently in subjects with tinnitus-related distress. We recently developed a therapeutic intervention, namely the Heidelberg Neuro-Music Therapy (HNMT, which shows an effective reduction of tinnitus-related distress following a 1-week short-term treatment. This approach offers the possibility to evaluate the neural changes associated with the improvements in tinnitus distress. We previously reported gray matter (GM reorganization in DMN regions and in primary auditory areas following HNMT in cases of recent-onset tinnitus. Here we evaluate on the same patient group, using functional MRI (fMRI, the activity of the DMN following the improvements tinnitus-related distress related to the HNMT intervention.Methods: The DMN activity was estimated by the task-negative activation (TNA during long inter-trial intervals in a word recognition task. The level of TNA was evaluated twice, before and after the 1-week study period, in 18 treated tinnitus patients (“treatment group,” TG, 21 passive tinnitus controls (PTC, and 22 active healthy controls (AC. During the study, the participants in TG and AC groups were treated with HNMT, whereas PTC patients did not receive any tinnitus-specific treatment. Therapy-related effects on DMN activity were assessed by comparing the pairs of fMRI records from the TG and PTC groups.Results: Treatment of the TG group with HNMT resulted in an augmented DMN activity in the PCC by 2.5% whereas no change was found in AC and PTC groups. This enhancement of PCC activity correlated with a reduction in tinnitus distress (Spearman Rho: −0.5; p < 0.005.Conclusion: Our findings show that an increased DMN activity, especially in the PCC, underlies the improvements in tinnitus

Is dignity therapy feasible to enhance the end of life experience for people with motor neurone disease and their family carers?

Directory of Open Access Journals (Sweden)

Bentley Brenda

2012-09-01

Full Text Available Abstract Background Development of interventions that address psychosocial and existential distress in people with motor neurone disease (MND or that alleviate caregiver burden in MND family carers have often been suggested in the research literature. Dignity therapy, which was developed to reduce psychosocial and existential distress at the end of life, has been shown to benefit people dying of cancer and their families. These results may not be transferable to people with MND. The objectives of this study are to assess the feasibility, acceptability and potential effectiveness of dignity therapy to enhance the end of life experience for people with motor neurone disease and their family carers. Methods/design This is a cross-sectional study utilizing a single treatment group and a pre/post test design. The study population will comprise fifty people diagnosed with MND and their nominated family carers. Primarily quantitative outcomes will be gathered through measures assessed at baseline and at approximately one week after the intervention. Outcomes for participants include hopefulness, spirituality and dignity. Outcomes for family carers include perceived caregiver burden, hopefulness and anxiety/depression. Feedback and satisfaction with the intervention will be gathered through a questionnaire. Discussion This detailed research will explore if dignity therapy has the potential to enhance the end of life experience for people with MND and their family carers, and fill a gap for professionals who are called on to address the spiritual, existential and psychosocial needs of their MND patients and families. Trial registration ACTRN Trial Number: ACTRN12611000410954

A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders.

Science.gov (United States)

Minshawi, Noha F; Wink, Logan K; Shaffer, Rebecca; Plawecki, Martin H; Posey, David J; Liu, Hai; Hurwitz, Sarah; McDougle, Christopher J; Swiezy, Naomi B; Erickson, Craig A

2016-01-01

Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. ClinicalTrials.govNCT01086475.

Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

International Nuclear Information System (INIS)

Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus; Gilbertz, Klaus-Peter; Baumgart, Anja; Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K.; Bruchertseifer, Frank; Morgenstern, Alfred

2012-01-01

Targeted therapy with α-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the α-emitter 213 Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined 213 Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either 213 Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with 213 Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined 213 Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either 213 Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with 213 Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 μg) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with 213 Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either 213 Bi-DTPA-F3 or paclitaxel alone. Combined treatment with 213 Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

Strategies for combinational cancer therapies

International Nuclear Information System (INIS)

Khleif, Samir

2014-01-01

The countless pre-clinical studies and many clinical trials that have applied tumor antigen-based therapies for the cancer treatment, and although the necessary tumor-specific immune response may be elicited in tumor-bearing hosts, this was not sufficient for the positive therapeutic outcome since there are multiple mechanisms that tumors develop to escape immune surveillance. The tumor-mediated inhibitory mechanisms involve co-inhibitory receptor-ligand interactions, such as PD-1/ PD-L1, secretion of inhibitory molecules, such as TGFb, and recruitment of suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), etc. Therefore, we hypothesized that successful cancer immunotherapy requires not only induction and enhancement of effector immune response but also simultaneous targeting of suppressor arm of immune system, thus in addition to enhancing antigen-specific immunity using vaccines or radiation therapy, one should also target tumor-mediated immune suppression to improve the overall efficacy of therapy. We developed multiple strategies to target various tumor-mediated immune inhibitory mechanisms that can enhance anti-tumor immunity and restructure tumor microenvironment to allow effector cells generated due to vaccination or radiation therapy to function potently. We evaluated the immune and therapeutic efficacy of multiple combinational therapies, including blocking and agonist antibodies to co-inhibitory/co-stimulatory molecules, such as PD-1, PD-L1, OX40, CTLA-4, GITR, inhibitors and neutralizing antibodies to inhibitory cytokines/molecules, such as IL-10, TGFb, IDO, and small molecules for selective inhibition of Tregs. In addition to evaluation of anti-tumor efficacy we are also investigated cellular and molecular mechanisms of action for these agents when combined with vaccine or radiation therapy and exploring the interactions between compounds within combinational therapies in animal tumor models. We are

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies

Directory of Open Access Journals (Sweden)

Satoshi Motoya

2018-04-01

Full Text Available Background/Aims : Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC. In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID. Methods : We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain. Results : A total of 121 East Asian (Japan, Korea, and Taiwan patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95, and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21. At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95 achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26 with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22, 47.6% (10/21, and 15.0% (3/20 with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib. Conclusion : In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

Impediments to Enhancement of CPT-11 Anticancer Activity by E. coli Directed Beta-Glucuronidase Therapy

Science.gov (United States)

Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R.

2015-01-01

CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti

Contrast enhancement kinetics of normal breast parenchyma in dynamic MR mammography: effects of menopausal status, oral contraceptives, and postmenopausal hormone therapy

International Nuclear Information System (INIS)

Hegenscheid, Katrin; Seipel, Rebecca; Laqua, Rene; Hosten, Norbert; Puls, Ralf; Schmidt, Carsten O.; Ohlinger, Ralf

2012-01-01

To investigate effects of menopausal status, oral contraceptives (OC), and postmenopausal hormone therapy (HT) on normal breast parenchymal contrast enhancement (CE) and non-mass-like enhancing areas in magnetic resonance mammography (MRM). A total of 459 female volunteers (mean age 49.1 ± 12.5 years) underwent T1-weighted 3D MRM 1-5 min after bolus injection of gadobutrol. Quantitative analysis was performed in normal breast parenchyma by manually tracing regions of interest and calculating percentage CE. Semiquantitative analysis was performed in non-mass-like enhancing areas, and signal intensity changes were characterised by five predefined kinetic curve types. The influence of OC (n = 69) and HT (n = 24) on CE was studied using random effects models. Breast parenchymal enhancement was significantly higher in premenopausal than in postmenopausal women (P < 0.001). CE decreased significantly with the use of OC (P = 0.01), while HT had negligible effects (P = 0.52). Prevalence of kinetic curve types of non-mass-like enhancement differed strongly between pre- and postmenopausal women (P < 0.0001), but was similar in OC users and non-OC users (P = 0.61) as well as HT users and non-HT users (P = 0.77). Normal breast parenchymal enhancement and non-mass-like enhancing areas were strongly affected by menopausal status, while they were not affected by HT use and only moderately by OC use. (orig.)

Contrast enhancement kinetics of normal breast parenchyma in dynamic MR mammography: effects of menopausal status, oral contraceptives, and postmenopausal hormone therapy

Energy Technology Data Exchange (ETDEWEB)

Hegenscheid, Katrin; Seipel, Rebecca; Laqua, Rene; Hosten, Norbert; Puls, Ralf [Ernst-Moritz-Arndt University Medical Center Greifswald, Department of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Schmidt, Carsten O. [Ernst-Moritz-Arndt University Medical Center Greifswald, Institute for Community Medicine, Greifswald (Germany); Ohlinger, Ralf [Ernst-Moritz-Arndt University Medical Center Greifswald, Department of Gynecology and Obstetrics, Greifswald (Germany)

2012-12-15

To investigate effects of menopausal status, oral contraceptives (OC), and postmenopausal hormone therapy (HT) on normal breast parenchymal contrast enhancement (CE) and non-mass-like enhancing areas in magnetic resonance mammography (MRM). A total of 459 female volunteers (mean age 49.1 {+-} 12.5 years) underwent T1-weighted 3D MRM 1-5 min after bolus injection of gadobutrol. Quantitative analysis was performed in normal breast parenchyma by manually tracing regions of interest and calculating percentage CE. Semiquantitative analysis was performed in non-mass-like enhancing areas, and signal intensity changes were characterised by five predefined kinetic curve types. The influence of OC (n = 69) and HT (n = 24) on CE was studied using random effects models. Breast parenchymal enhancement was significantly higher in premenopausal than in postmenopausal women (P < 0.001). CE decreased significantly with the use of OC (P = 0.01), while HT had negligible effects (P = 0.52). Prevalence of kinetic curve types of non-mass-like enhancement differed strongly between pre- and postmenopausal women (P < 0.0001), but was similar in OC users and non-OC users (P = 0.61) as well as HT users and non-HT users (P = 0.77). Normal breast parenchymal enhancement and non-mass-like enhancing areas were strongly affected by menopausal status, while they were not affected by HT use and only moderately by OC use. (orig.)

Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial.

Science.gov (United States)

Pulido, Federico; Ribera, Esteban; Lagarde, María; Pérez-Valero, Ignacio; Palacios, Rosario; Iribarren, José A; Payeras, Antoni; Domingo, Pere; Sanz, José; Cervero, Miguel; Curran, Adrián; Rodríguez-Gómez, Francisco J; Téllez, María J; Ryan, Pablo; Barrufet, Pilar; Knobel, Hernando; Rivero, Antonio; Alejos, Belén; Yllescas, María; Arribas, José R

2017-11-29

Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively. Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. NCT02159599. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Creative art therapy to enhance rehabilitation for stroke patients: a randomized controlled trial.

Science.gov (United States)

Kongkasuwan, Ratcharin; Voraakhom, Kotchakorn; Pisolayabutra, Prim; Maneechai, Pichai; Boonin, Jiraporn; Kuptniratsaikul, Vilai

2016-10-01

To examine the efficacy of creative art therapy plus conventional physical therapy, compared with physical therapy only, in increasing cognitive ability, physical functions, psychological status and quality of life of stroke patients. Randomized controlled trial with blinded assessor. An in-patient setting PARTICIPANTS: One hundred and eighteen stroke patients aged ⩾50 years who could communicate verbally. All participants received conventional physical therapy five days per week. An intervention group received additional creative art therapy, twice a week for four weeks, in a rehabilitation ward. Cognitive function, anxiety and depression, physical performance and quality of life were measured with the Abbreviated Mental Test, the Hospital Anxiety and Depression Scale, the modified Barthel Index scale and the pictorial Thai Quality of Life questionnaire, respectively. Mean differences for the intervention group were significantly greater than the control group for depression (-4.5, 95% CI -6.5, -2.5, part therapy and most reported improved concentration (68.5%), emotion (79.6%), self-confidence (72.2%) and motivation (74.1%). Creative art therapy combined with conventional physical therapy can significantly decrease depression, improve physical functions and increase quality of life compared with physical therapy alone. © The Author(s) 2015.

Attitudes Toward Combining Psychological, Mind-Body Therapies and Nutritional Approaches for the Enhancement of Mood.

Science.gov (United States)

Lores, Taryn Jade; Henke, Miriam; Chur-Hansen, Anna

2016-01-01

Context • Interest has been rising in the use of complementary and alternative medicine (CAM) for the promotion of health and treatment of disease. To date, the majority of CAM research has focused on exploring the demographic characteristics, attitudes, and motivations of CAM users and on the efficacy of different therapies and products. Less is known with respect to the psychological characteristics of people who use CAM. Previous research has not investigated the usefulness of integrating mind-body therapies with natural products in a combined mood intervention. Objective • The study intended to investigate attitudes toward a proposed new approach to the treatment of mood, one that integrates psychological mind-body therapies and natural nutritional products. Design • Participants completed an online survey covering demographics, personality traits, locus of control, use of CAM, attitudes toward the proposed psychonutritional approach, and mood. Setting • This study was conducted at the University of Adelaide School of Psychology (Adelaide, SA, Australia). Participants • Participants were 333 members of the Australian general public, who were recruited online via the social-media platform Facebook. The majority were women (83.2%), aged between 18 and 81 y. Outcome Measures • Measures included the Multidimensional Health Locus of Control Scale Form B, the Ten-Item Personality Inventory, and the Depression, Anxiety and Stress Scale. Results • Participants were positive about the proposed approach and were likely to try it to enhance their moods. The likeliness of use of the combined approach was significantly higher in the female participants and was associated with higher levels of the personality trait openness and an internal health locus of control, after controlling for all other variables. Conclusions • Interest exists for an intervention for mood that incorporates both psychological and nutritional approaches. Further research into the

Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial.

Science.gov (United States)

Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

2009-05-21

Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. http://www.clinicaltrials.gov identifier NCT00847769.

[Dance/movement therapy in oncological rehabilitation].

Science.gov (United States)

Mannheim, Elana G; Helmes, Almut; Weis, Joachim

2013-01-01

Dance/movement therapy may be defined as a psychosocial and body-oriented art therapy, which uses dance for the expression of emotional and cognitive issues. Dance/movement therapy is an important intervention for cancer patients to enhance coping strategies. There are only few studies investigating dance therapy with cancer patients. The present study investigates effects of dance/movement therapy (n = 115) in the setting of inpatient rehabilitation based on a pre-post design with a control group as well as a follow-up 3 months later. Standardized questionnaires measuring quality of life, anxiety and depression, and self-concept (EORTC QLQ-C30, HADS, FSKN) were used. In addition, at the end of the inpatient rehabilitation program subjective expectations of the dance/movement therapy and the patients' subjective evaluation of the benefits of the intervention were measured by a new developed questionnaire. As process factors of dance/movement therapy, expression of emotions, enhancement of self-esteem, development of the personality, vitality, getting inner balance, and getting in touch with the body have been identified. In terms of quality of life and psychological well-being, the results showed significant improvements with medium to large effect sizes. Even though those effects may not be attributed to the intervention alone, the analysis of the data and the patients' subjective statements help to reveal therapeutic factors and process characteristics of dance/movement therapy within inpatient rehabilitation. Copyright © 2013 S. Karger AG, Basel.

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation.

Science.gov (United States)

Cannon, Christopher P; Bhatt, Deepak L; Oldgren, Jonas; Lip, Gregory Y H; Ellis, Stephen G; Kimura, Takeshi; Maeng, Michael; Merkely, Bela; Zeymer, Uwe; Gropper, Savion; Nordaby, Matias; Kleine, Eva; Harper, Ruth; Manassie, Jenny; Januzzi, James L; Ten Berg, Jurrien M; Steg, P Gabriel; Hohnloser, Stefan H

2017-10-19

lower among those who received dual therapy with dabigatran and a P2Y 12 inhibitor than among those who received triple therapy with warfarin, a P2Y 12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).

Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

International Nuclear Information System (INIS)

Postiglione, Ilaria; Chiaviello, Angela; Palumbo, Giuseppe

2011-01-01

Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors

Animal-assisted therapy: evaluation and implementation of a complementary therapy to improve the psychological and physiological health of critically ill patients.

Science.gov (United States)

DeCourcey, Mary; Russell, Anne C; Keister, Kathy J

2010-01-01

Animal-assisted therapy has gained widespread support in a variety of health care settings, including critical care units. This article seeks to review some of the current animal-assisted therapy, define a structured program, and evaluate the potential ability of the therapy to enhance the progress and health of our patients.

Adaptation and implementation of family-based treatment enhanced with dialectical behavior therapy skills for anorexia nervosa in community-based specialist clinics.

Science.gov (United States)

Accurso, Erin C; Astrachan-Fletcher, Ellen; O'Brien, Setareh; McClanahan, Susan F; Le Grange, Daniel

2018-01-01

Although family-based therapy (FBT) is a well-established treatment for anorexia nervosa, its implementation and effectiveness in clinical settings has been neglected. A group of seven therapists at a community-based eating disorders clinic were trained in skills-enhanced FBT and provided treatment to 11 youth with anorexia nervosa. Family-based skills training, which borrowed heavily from dialectical behavior therapy, was introduced in four additional sessions and then integrated throughout the remainder of FBT. FBT was perceived as appropriate and acceptable by all participants. Therapists reported high treatment fidelity. There was a large improvement in weight and moderate improvement in caregiver-reported eating disorder psychopathology but no clinically significant change by youth report. This study provides preliminary data on the implementation and effectiveness of FBT in the community.

Cancer suicide gene therapy: a patent review.

Science.gov (United States)

Navarro, Saúl Abenhamar; Carrillo, Esmeralda; Griñán-Lisón, Carmen; Martín, Ana; Perán, Macarena; Marchal, Juan Antonio; Boulaiz, Houria

2016-09-01

Cancer is considered the second leading cause of death worldwide despite the progress made in early detection and advances in classical therapies. Advancing in the fight against cancer requires the development of novel strategies, and the suicide gene transfer to tumor cells is providing new possibilities for cancer therapy. In this manuscript, authors present an overview of suicide gene systems and the latest innovations done to enhance cancer suicide gene therapy strategies by i) improving vectors for targeted gene delivery using tissue specific promoter and receptors; ii) modification of the tropism; and iii) combining suicide genes and/or classical therapies for cancer. Finally, the authors highlight the main challenges to be addressed in the future. Even if many efforts are needed for suicide gene therapy to be a real alternative for cancer treatment, we believe that the significant progress made in the knowledge of cancer biology and characterization of cancer stem cells accompanied by the development of novel targeted vectors will enhance the effectiveness of this type of therapeutic strategy. Moreover, combined with current treatments, suicide gene therapy will improve the clinical outcome of patients with cancer in the future.

Enhanced efficacy of combined {sup 213}Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

Energy Technology Data Exchange (ETDEWEB)

Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Gilbertz, Klaus-Peter [German Armed Forces, Institute of Radiobiology, Munich (Germany); Baumgart, Anja [Technische Universitaet Muenchen, III. Medical Department, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K. [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

2012-12-15

Targeted therapy with {alpha}-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the {alpha}-emitter {sup 213}Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined {sup 213}Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with {sup 213}Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined {sup 213}Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with {sup 213}Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 {mu}g) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with {sup 213}Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either {sup 213}Bi-DTPA-F3 or paclitaxel alone. Combined treatment with {sup 213}Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

Science.gov (United States)

Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

2018-01-01

This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual art therapy. PTSD Checklist–Military Version and Beck Depression Inventory–II scores improved with treatment in both groups with no significant difference in improvement between the experimental and control groups. Art therapy in conjunction with CPT was found to improve trauma processing and veterans considered it to be an important part of their treatment as it provided healthy distancing, enhanced trauma recall, and increased access to emotions. PMID:29332989

Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

Energy Technology Data Exchange (ETDEWEB)

Piludu, Francesca; Vidiri, Antonello [Regina Elena National Cancer Institute, Radiology and Diagnostic Imaging Department, Rome (Italy); Marzi, Simona [Regina Elena National Cancer Institute, Medical Physics Laboratory, Rome (Italy); Pace, Andrea; Villani, Veronica [Regina Elena National Cancer Institute, Neurology Division, Rome (Italy); Fabi, Alessandra [Regina Elena National Cancer Institute, Oncology Department, Rome (Italy); Carapella, Carmine Maria [Regina Elena National Cancer Institute, Oncologic Surgery Department, Rome (Italy); Terrenato, Irene [Regina Elena National Cancer Institute, Biostatistics-Scientific Direction, Rome (Italy); Antenucci, Anna [Regina Elena National Cancer Institute, Clinical Pathology, Rome (Italy)

2015-12-15

The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V{sub tot}), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V{sub CE-T1} and V{sub NON-CE-T1}, respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K{sup trans} maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. Responding patients showed a larger reduction in V{sub NON-CE-T1} after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K{sup trans}, after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V{sub tot} was predictive of overall survival (OS), while V{sub CE-T1} showed a tendency of correlation with OS. Tumor subvolumes with increased nIAUGC and K{sup trans} showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation. (orig.)

Mindfulness in occupational therapy education.

Science.gov (United States)

Gura, Shira Taylor

2010-07-01

ABSTRACT The purpose of this paper is to explore the value of mindfulness and its role in occupational therapy education. The plethora of research on mindfulness-based stress reduction programs has shown consistent and positive results to enhance quality of life in clinical and nonclinical populations. Offering students the opportunities to learn and experience mindfulness could lead to enhanced self-awareness and care, focus and empathy, and a decrease of client judgment enhancing the success of clinical interventions.

Reactor-moderated intermediate-energy neutron beams for neutron-capture therapy

International Nuclear Information System (INIS)

Less, T.J.

1987-01-01

One approach to producing an intermediate energy beam is moderating fission neutrons escaping from a reactor core. The objective of this research is to evaluate materials that might produce an intermediate beam for NCT via moderation of fission neutrons. A second objective is to use the more promising moderator material in a preliminary design of an NCT facility at a research reactor. The evaluations showed that several materials or combinations of materials could produce a moderator source for an intermediate beam for NCT. The best neutron spectrum for use in NCT is produced by Al 2 O 3 , but mixtures of Al metal and D 2 O are also attractive. Using the best moderator materials, results were applied to the design of an NCT moderator at the Georgia Institute of Technology Research Reactor's bio-medical facility. The amount of photon shielding and thermal neutron absorber were optimized with respect to the desired photon dose rate and intermediate neutron flux at the patient position

Complications of cancer therapy

International Nuclear Information System (INIS)

Moskowitz, P.S.; Parker, B.R.

1985-01-01

The purpose of this chapter is to review systematically the toxicity of contemporary chemotherapy and irradiation on normal tissues of growing children. Whenever possible, the separate toxicity of chemotherapy, irradiation, and combination therapy is addressed. However, it is not always possible to quantitate specifically such reactions in the face of multiple drug therapy, which may enhance radiation injury or reactivate prior radiation injury. Prior detailed reviews have provided important sources of information concerning radiation injury for this more general discussion. The information provided will assist both the clinician and the radiologist in the recognition of early and late complications of therapy in pediatric oncology

Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and pgk promoter: an in vitro and in vivo study

International Nuclear Information System (INIS)

Li, Wei; Tao, Min; Li, Dao-Ming; Chen, Kai; Chen, Zheng; Zong, Yang; Yin, Hong; Xu, Ze-Kuan; Zhu, Yi; Gong, Fei-Ran

2012-01-01

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A) may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (AFP) promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk) gene can generate a strong and HCC-selective promoter. We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo. AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B), but did not affect AFP-negative human hepatoma cells (SK-HEP-1) or normal human liver cells (L-02). Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors. The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC

Post-operative benefits of animal-assisted therapy in pediatric surgery: a randomised study.

Science.gov (United States)

Calcaterra, Valeria; Veggiotti, Pierangelo; Palestrini, Clara; De Giorgis, Valentina; Raschetti, Roberto; Tumminelli, Massimiliano; Mencherini, Simonetta; Papotti, Francesca; Klersy, Catherine; Albertini, Riccardo; Ostuni, Selene; Pelizzo, Gloria

2015-01-01

Interest in animal-assisted therapy has been fuelled by studies supporting the many health benefits. The purpose of this study was to better understand the impact of an animal-assisted therapy program on children response to stress and pain in the immediate post-surgical period. Forty children (3-17 years) were enrolled in the randomised open-label, controlled, pilot study. Patients were randomly assigned to the animal-assisted therapy-group (n = 20, who underwent a 20 min session with an animal-assisted therapy dog, after surgery) or the standard-group (n = 20, standard postoperative care). The study variables were determined in each patient, independently of the assigned group, by a researcher unblinded to the patient's group. The outcomes of the study were to define the neurological, cardiovascular and endocrinological impact of animal-assisted therapy in response to stress and pain. Electroencephalogram activity, heart rate, blood pressure, oxygen saturation, cerebral prefrontal oxygenation, salivary cortisol levels and the faces pain scale were considered as outcome measures. After entrance of the dog faster electroencephalogram diffuse beta-activity (> 14 Hz) was reported in all children of the animal-assisted therapy group; in the standard-group no beta-activity was recorded (100% vs 0%, panimal-assisted therapy, though a higher variability in diastolic pressure was observed. Salivary cortisol levels did not show different behaviours over time between groups (p=0.70). Lower pain perception was noted in the animal-assisted group in comparison with the standard-group (p = 0.01). Animal-assisted therapy facilitated rapid recovery in vigilance and activity after anaesthesia, modified pain perception and induced emotional prefrontal responses. An adaptative cardiovascular response was also present. ClinicalTrials.gov NCT02284100.

Red blood cell membrane-camouflaged melanin nanoparticles for enhanced photothermal therapy.

Science.gov (United States)

Jiang, Qin; Luo, Zimiao; Men, Yongzhi; Yang, Peng; Peng, Haibao; Guo, Ranran; Tian, Ye; Pang, Zhiqing; Yang, Wuli

2017-10-01

Photothermal therapy (PTT) has represented a promising noninvasive approach for cancer treatment in recent years. However, there still remain challenges in developing non-toxic and biodegradable biomaterials with high photothermal efficiency in vivo. Herein, we explored natural melanin nanoparticles extracted from living cuttlefish as effective photothermal agents and developed red blood cell (RBC) membrane-camouflaged melanin (Melanin@RBC) nanoparticles as a platform for in vivo antitumor PTT. The as-obtained natural melanin nanoparticles demonstrated strong absorption at NIR region, higher photothermal conversion efficiency (∼40%) than synthesized melanin-like polydopamine nanoparticles (∼29%), as well as favorable biocompatibility and biodegradability. It was shown that RBC membrane coating on melanin nanoparticles retained their excellent photothermal property, enhanced their blood retention and effectively improved their accumulation at tumor sites. With the guidance of their inherited photoacoustic imaging capability, optimal accumulation of Melanin@RBC at tumors was achieved around 4 h post intravenous injection. Upon irradiation by an 808-nm laser, the developed Melanin@RBC nanoparticles exhibited significantly higher PTT efficacy than that of bare melanin nanoparticles in A549 tumor-bearing mice. Given that both melanin nanoparticles and RBC membrane are native biomaterials, the developed Melanin@RBC platform could have great potential in clinics for anticancer PTT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical considerations for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr.

1990-01-01

The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the US in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should not be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam cases gamma rays to be generated when it interacts with tissue, they think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue

Enhancement effect of irradiation by methotrexate

International Nuclear Information System (INIS)

Shehata, W.M.; Meyer, R.L.

1980-01-01

Three cases are described in which complications developed which were believed to be due to the enhancement effect of irradiation by methotrexate during the course of therapy for lung, kidney, and bladder cancer. These included esophageal and large bowel complications. In two of these cases, the patients improved with conservative therapy

Prophylactic Groin Wound Vacuum-assisted Therapy in Vascular Surgery Patients at Enhanced Risk for Postoperative Wound Infection.

Science.gov (United States)

Pesonen, Luke O; Halloran, Brian G; Aziz, Abdulhameed

2018-01-01

Vascular groin wounds have higher than expected surgical site infection (SSI) rates and some patients are at enhanced risk. The Wiseman et al. paper suggests an objective scoring system that identifies patients at enhanced risk of postdischarge SSI. We hypothesize that prophylactic groin wound vacuum-assisted closure (VAC) therapy in enhanced risk patients will decrease SSI and readmission and the Wiseman model provides potential evidence that enhanced risk patients can be objectively identified. A single institution, retrospective analysis was conducted from January 2013 to September 2016 utilizing procedure codes to identify patients with wound VACs placed in the operating room. Two distinct groups were identified. The first was a wound complication patient group with 15 limbs (13 patients) with a groin wound VAC placed within 45 days postoperatively for groin wound complications. Eleven of these limbs had the VAC placed at readmission. The second group was a prophylactic patient group that included 8 limbs (7 patients) who received a VAC prophylactically placed in the enhanced risk wounds. These wounds were determined to be enhanced risk based on clinical criteria judged by the operating surgeon such as a large overhanging panniculus and/or one of several ongoing medical issues. We calculated a Wiseman score for all patients, determined total cost of the readmissions, and determined 30-day postsurgical SSI incidence for the prophylactic VAC group. Per the Wiseman scores, 9 limbs with postoperative complications were high risk and 3 limbs were moderate/high risk. Eleven limbs had a VAC placed at readmission with an average readmission cost of $8876.77. For the prophylactic group, 8 limbs were high risk with no observed postdischarge SSI in the first 30 days from surgery. The Wiseman scores showed close correlation between the retrospective high and moderate/high risk groups versus the prophylactic VAC group (31.5 ± 7.3 vs. 32 ± 5.5, P = 0.87). The Wiseman

Mixed P25 nanoparticles and large rutile particles as a top scattering layer to enhance performance of nanocrystalline TiO{sub 2} based dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Sun, Xiaohua, E-mail: mksxh@163.com; Zhou, Xin; Xu, Yalong; Sun, Panpan; Huang, Niu; Sun, Yihua

2015-05-15

Graphical abstract: - Highlights: • Mixed P25 nanoparticles and large rutile particles were employed to form a top scattering layer. • The top scattering layer exhibits superior light scattering effect. • The bottom nanocrystalline TiO{sub 2} layer can make good use of the back-scattered light. • Bilayer TiO{sub 2} photoanode shows faster interfacial electron transfer and slower charge recombination process. • Bilayer photoanode enhances the DSSC efficiency by a factor of 25%. - Abstract: Herein, we report a bilayer TiO{sub 2} photoanode composed of nanocrystalline TiO{sub 2} (NCT) bottom layer and mixed P25 nanoparticles and large rutile particles (PR) top scattering layer. The present structure performs well in solar light harvesting which is mainly attributed to the fact that the top scattering layer exhibits superior light scattering effect and meanwhile the NCT bottom layer with large dye-loading capacity can make better use of the back-scattered light. Moreover, electrochemical impedance spectroscopy and open circuit voltage decay measurements demonstrate that DSSC based on bilayer photoanode shows faster interfacial electron transfer and slower charge recombination process than that based on NCT monolayer photoanode. These advantages render the DSSCs based on NCT-PR bilayer photoanode exhibiting superior performance under AM1.5G simulated solar irradiation. As an example, by tuning mass ratio between P25 nanoparticles and large rutile particles in the top scattering layer, the DSSC based on NCT-PR bilayer photoanode exhibits an optimum solar energy conversion efficiency of 9.0%, which is about 1.25 times higher than that of monolayer NCT device (7.2%) with the same film thickness.

Development and validation of Monte Carlo dose computations for contrast-enhanced stereotactic synchrotron radiation therapy

International Nuclear Information System (INIS)

Vautrin, M.

2011-01-01

Contrast-enhanced stereotactic synchrotron radiation therapy (SSRT) is an innovative technique based on localized dose-enhancement effects obtained by reinforced photoelectric absorption in the tumor. Medium energy monochromatic X-rays (50 - 100 keV) are used for irradiating tumors previously loaded with a high-Z element. Clinical trials of SSRT are being prepared at the European Synchrotron Radiation Facility (ESRF), an iodinated contrast agent will be used. In order to compute the energy deposited in the patient (dose), a dedicated treatment planning system (TPS) has been developed for the clinical trials, based on the ISOgray TPS. This work focuses on the SSRT specific modifications of the TPS, especially to the PENELOPE-based Monte Carlo dose engine. The TPS uses a dedicated Monte Carlo simulation of medium energy polarized photons to compute the deposited energy in the patient. Simulations are performed considering the synchrotron source, the modeled beamline geometry and finally the patient. Specific materials were also implemented in the voxelized geometry of the patient, to consider iodine concentrations in the tumor. The computation process has been optimized and parallelized. Finally a specific computation of absolute doses and associated irradiation times (instead of monitor units) was implemented. The dedicated TPS was validated with depth dose curves, dose profiles and absolute dose measurements performed at the ESRF in a water tank and solid water phantoms with or without bone slabs. (author) [fr

Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema

Directory of Open Access Journals (Sweden)

Martínez Helena

2011-03-01

Full Text Available Abstract Background Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology. Methods A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garnments. The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment. The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less atractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image. Discussion The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients. Trial registration ClinicalTrials (NCT: NCT01152099

Nanotechnology Cancer Therapy and Treatment

Science.gov (United States)

Nanotechnology offers the means to target therapies directly and selectively to cancerous cells and neoplasms. With these tools, clinicians can safely and effectively deliver chemotherapy, radiotherapy, and the next generation of immuno- and gene therapies to the tumor. Futhermore, surgical resection of tumors can be guided and enhanced by way of nanotechnology tools. Find out how nanotechnology will offer the next generation of our therapeutic arsenal to the patient.

Power Burst Reactor Facility as an epithermal neutron source for brain cancer therapy

International Nuclear Information System (INIS)

Wheeler, F.J.

1986-01-01

The Power Burst Facility (PBF) reactor is considered for modification to provide an intense, clean source of intermediate-energy (epithermal) neutrons desirable for clinical studies of neutron capture therapy (NCT) for malignant tumors. The modifications include partial replacement of the reflector, installation of a neutron-moderating, shifting region, additional shielding, and penetration of the present concrete shield with a collimating (and optionally) filtering region. The studies have indicated that the reactor, after these modifications, will be safely operable at full power (28 MW) within the acceptable limits of the plant protection systems. The neutron beam exiting from the collimator port is predicted to be of sufficient intensity (approx.10 10 neutrons/cm 2 -s) to provide therapeutic doses in very short irradiation times. The beam would be relatively free of undesirable fast neutrons, thermal neutrons and gamma rays. The calculated neutron energy spectrum and associated gamma rays in the beam were provided as input in simulation studies that used a computer model of a patient with a brain tumor to determine predicted dose rates to the tumor and healthy tissue. The results of this conceptual study indicate an intense, clean beam of epithermal neutrons for NCT clinical trials is attainable in the PBF facility with properly engineered design modifications. 9 refs., 11 figs., 3 tabs

High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

Directory of Open Access Journals (Sweden)

Tahereh Safari

2015-01-01

Full Text Available Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R- mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7±1.9% in estradiol-treated rats but only by 27.3±5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen.

Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

Directory of Open Access Journals (Sweden)

Jessica Ann Wojtalik

2016-01-01

Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

Novel ICD Programming and Inappropriate ICD Therapy in CRT-D Versus ICD Patients: A MADIT-RIT Sub-Study.

Science.gov (United States)

Kutyifa, Valentina; Daubert, James P; Schuger, Claudio; Goldenberg, Ilan; Klein, Helmut; Aktas, Mehmet K; McNitt, Scott; Stockburger, Martin; Merkely, Bela; Zareba, Wojciech; Moss, Arthur J

2016-01-01

The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate therapy (MADIT-RIT) trial showed a significant reduction in inappropriate implantable cardioverter defibrillator (ICD) therapy in patients programmed to high-rate cut-off (Arm B) or delayed ventricular tachycardia therapy (Arm C), compared with conventional programming (Arm A). There is limited data on the effect of cardiac resynchronization therapy with a cardioverter defibrillator (CRT-D) on the effect of ICD programming. We aimed to elucidate the effect of CRT-D on ICD programming to reduce inappropriate ICD therapy in patients implanted with CRT-D or an ICD, enrolled in MADIT-RIT. The primary end point of this study was the first inappropriate ICD therapy. Secondary end points were inappropriate anti-tachycardia pacing and inappropriate ICD shock. The study enrolled 742 (49%) patients with an ICD and 757 (51%) patients with a CRT-D. Patients implanted with a CRT-D had 62% lower risk of inappropriate ICD therapy than those with an ICD only (hazard ratio [HR] =0.38, 95% confidence interval: 0.25-0.57; Pprogramming significantly reduced the risk of inappropriate ICD therapy compared with conventional ICD programming in ICD (HR=0.14 [B versus A]; HR=0.21 [C versus A]) and CRT-D patients (HR=0.15 [B versus A]; HR=0.23 [C versus A]; Pprogramming significantly reduces the risk of inappropriate ICD therapy in both ICD and CRT-D patients. http://clinicaltrials.gov; Unique identifier: NCT00947310. © 2016 American Heart Association, Inc.

Development of a theory- and evidence-based intervention to enhance implementation of physical therapy guidelines for the management of low back pain

OpenAIRE

Rutten, Geert M; Harting, Janneke; Bartholomew, Leona K; Braspenning, Jozé C; van Dolder, Rob; Heijmans, Marcel FGJ; Hendriks, Erik JM; Kremers, Stef PJ; van Peppen, Roland PS; Rutten, Steven TJ; Schlief, Angelique; de Vries, Nanne K; Oostendorp, Rob AB

2014-01-01

Background Systematic planning could improve the generally moderate effectiveness of interventions to enhance adherence to clinical practice guidelines. The aim of our study was to demonstrate how the process of Intervention Mapping was used to develop an intervention to address the lack of adherence to the national CPG for low back pain by Dutch physical therapists. Methods We systematically developed a program to improve adherence to the Dutch physical therapy guidelines for low back pain. ...

Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy

Science.gov (United States)

Deng, Xiaoran; Chen, Yinyin; Cheng, Ziyong; Deng, Kerong; Ma, Ping'an; Hou, Zhiyao; Liu, Bei; Huang, Shanshan; Jin, Dayong; Lin, Jun

2016-03-01

Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of ``killing three birds with one stone'', that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation

Cognitive and Neurophysiological Recovery Following Electroconvulsive Therapy: A Study Protocol

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Ben J. A. Palanca

2018-05-01

Full Text Available Electroconvulsive therapy (ECT employs the elective induction of generalizes seizures as a potent treatment for severe psychiatric illness. As such, ECT provides an opportunity to rigorously study the recovery of consciousness, reconstitution of cognition, and electroencephalographic (EEG activity following seizures. Fifteen patients with major depressive disorder refractory to pharmacologic therapy will be enrolled (Clinicaltrials.gov, NCT02761330. Adequate seizure duration will be confirmed following right unilateral ECT under etomidate anesthesia. Patients will then undergo randomization for the order in which they will receive three sequential treatments: etomidate + ECT, ketamine + ECT, and ketamine + sham ECT. Sessions will be repeated in the same sequence for a total of six treatments. Before each session, sensorimotor speed, working memory, and executive function will be assessed through a standardized cognitive test battery. After each treatment, the return of purposeful responsiveness to verbal command will be determined. At this point, serial cognitive assessments will begin using the same standardized test battery. The presence of delirium and changes in depression severity will also be ascertained. Sixty-four channel EEG will be acquired throughout baseline, ictal, and postictal epochs. Mixed-effects models will correlate the trajectories of cognitive recovery, clinical outcomes, and EEG metrics over time. This innovative research design will answer whether: (1 time to return of responsiveness will be prolonged with ketamine + ECT compared with ketamine + sham ECT; (2 time of restoration to baseline function in each cognitive domain will take longer after ketamine + ECT than after ketamine + sham ECT; (3 postictal delirium is associated with delayed restoration of baseline function in all cognitive domains; and (4 the sequence of reconstitution of cognitive domains following the three treatments in this study is similar to that

A mass merchandiser's role in enhancing pharmacy students' business plan development skills for medication therapy management services.

Science.gov (United States)

Moultry, Aisha Morris

2011-09-10

To develop a relationship between a pharmacy management course and a mass merchandiser and to determine whether involving pharmacy managers from the mass merchandiser in the course would enhance student skills in developing a business plan for medication therapy management services. The pharmacy managers from the mass merchandiser participated in lectures, provided panel discussions, and conducted a business plan competition. Learning was assessed by means of 4 examinations and 1 project (ie, the business plan). At the conclusion of the semester, surveys were administered to solicit student input and gain insight from pharmacy managers on the perceived value of this portion of the course. Students' average grade on the business plan assignment, which included the oral presentation, the peer assessment, and the written proposal, was 92.2%. Approximately 60% (n=53) of surveyed students agreed or strongly agreed that their management skills had improved because of the participation of pharmacy managers from the mass merchandiser. All of the managers enjoyed participating in the experience. The involvement of pharmacy managers from a mass merchandiser enhanced student learning in the classroom, and managers felt that their participation was an important contribution to the development of future pharmacists.

Massage therapy research review.

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Field, Tiffany

2016-08-01

In this review, massage therapy has been shown to have beneficial effects on varying conditions including prenatal depression, preterm infants, full-term infants, autism, skin conditions, pain syndromes including arthritis and fibromyalgia, hypertension, autoimmune conditions including asthma and multiple sclerosis, immune conditions including HIV and breast cancer and aging problems including Parkinson's and dementia. Although many of the studies have involved comparisons between massage therapy and standard treatment control groups, several have compared different forms of massage (e.g. Swedish versus Thai massage), and different active therapies such as massage versus exercise. Typically, the massage therapy groups have experienced more positive effects than the control or comparison groups. This may relate to the massage therapy providing more stimulation of pressure receptors, in turn enhancing vagal activity and reducing cortisol levels. Some of the researchers have assessed physical, physiological and biochemical effects, although most have relied exclusively on self-report measures. Despite these methodological problems and the dearth of research from the U.S., the massage therapy profession has grown significantly and massage therapy is increasingly practiced in traditional medical settings, highlighting the need for more rigorous research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive behavioral therapy for insomnia in posttraumatic stress disorder: a randomized controlled trial.

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Talbot, Lisa S; Maguen, Shira; Metzler, Thomas J; Schmitz, Martha; McCaslin, Shannon E; Richards, Anne; Perlis, Michael L; Posner, Donn A; Weiss, Brandon; Ruoff, Leslie; Varbel, Jonathan; Neylan, Thomas C

2014-02-01

Examine whether cognitive behavioral therapy for insomnia (CBT-I) improves sleep in posttraumatic stress disorder (PTSD) as well as nightmares, nonsleep PTSD symptoms, depression symptoms, and psychosocial functioning. RANDOMIZED CONTROLLED TRIAL WITH TWO ARMS: CBT-I and monitor-only waitlist control. Department of Veterans Affairs (VA) Medical Center. Forty-five adults (31 females: [mean age 37 y (22-59 y)] with PTSD meeting research diagnostic criteria for insomnia, randomly assigned to CBT-I (n = 29; 22 females) or monitor-only waitlist control (n = 16; nine females). Eight-session weekly individual CBT-I delivered by a licensed clinical psychologist or a board-certified psychiatrist. Measures included continuous monitoring of sleep with diary and actigraphy; prepolysomnography and postpolysomnography and Clinician-Administered PTSD Scale (CAPS); and pre, mid, and post self-report questionnaires, with follow-up of CBT-I participants 6 mo later. CBT-I was superior to the waitlist control condition in all sleep diary outcomes and in polysomnography-measured total sleep time. Compared to waitlist participants, CBT-I participants reported improved subjective sleep (41% full remission versus 0%), disruptive nocturnal behaviors (based on the Pittsburgh Sleep Quality Index-Addendum), and overall work and interpersonal functioning. These effects were maintained at 6-mo follow-up. Both CBT-I and waitlist control participants reported reductions in PTSD symptoms and CAPS-measured nightmares. Cognitive behavioral therapy for insomnia (CBT-I) improved sleep in individuals with posttraumatic stress disorder, with durable gains at 6 mo. Overall psychosocial functioning improved following CBT-I. The initial evidence regarding CBT-I and nightmares is promising but further research is needed. Results suggest that a comprehensive approach to treatment of posttraumatic stress disorder should include behavioral sleep medicine. TRIAL NAME: Cognitive Behavioral Treatment Of Insomnia

Phase II Pragmatic Randomized Controlled Trial of Patient-Led Therapies (Mirror Therapy and Lower-Limb Exercises) During Inpatient Stroke Rehabilitation.

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Tyson, Sarah; Wilkinson, Jack; Thomas, Nessa; Selles, Ruud; McCabe, Candy; Tyrrell, Pippa; Vail, Andy

2015-10-01

Patient-led therapy has the potential to increase the amount of therapy patients undertake during stroke rehabilitation and to enhance recovery. Our objective was to assess the feasibility and acceptability of 2 patient-led therapies during the acute stages of stroke care: mirror therapy for the upper limb and lower-limb exercises for the lower limb. This was a blind assessed, multicenter, pragmatic randomized controlled trial of patient-led upper-limb mirror therapy and patient-led lower leg exercises. Stroke survivors with upper and lower limb limitations, undergoing inpatient rehabilitation and able to consent were recruited at least 1 week poststroke. Both interventions proved feasible, with >90% retention. No serious adverse events were reported. Both groups did less therapy than recommended; typically 5 to 15 minutes for 7 days or less. Participants receiving mirror therapy (n = 63) tended to do less practice than those doing lower-limb exercises (n = 31). Those with neglect did 69% less mirror therapy than those without (P = .02), which was not observed in the exercise group. Observed between-group differences were modest but neglect, upper-limb strength, and dexterity showed some improvement in the mirror therapy group. No changes were seen in the lower-limb group. Both patient-led mirror therapy and lower-limb exercises during inpatient stroke care are safe, feasible, and acceptable and warrant further investigation. Practice for 5 to 15 minutes for 7 days is a realistic prescription unless strategies to enhance adherence are included. © The Author(s) 2015.

About neutron capture therapy method development at WWR-SM reactor in institute of Nuclear Physics of Uzbekistan Academy of Sciences

International Nuclear Information System (INIS)

Abdullaeva, G.A.; Baytelesov, S.A.; Dosimbaev, A.A.; Koblik, Yu.N.; Gritsay, O.O.

2006-01-01

Full text: Neutron capture therapy (NCT) is developing method of swellings treatment, on which specialists set one's serious hopes, as at its realization the practical possibilities of the effect on any swellings open. The essence of method is simple and lies in the fact that to the swelling enter preparation containing boron or gadolinium, which one have a large capture cross-section of the thermal and slow neutrons. Then the swelling is irradiated once with the slow (epithermal) neutron beam with fluency about 10 9 neutrons /sm 2 s for a short time and single. As a result of thermal neutrons capture by the boron (or gadolinium) nuclei secondary radiation which affecting swelling cells is emitted. NCT of oncologic diseases makes the specific demands to physical parameters of neutron beams. Now research reactors are often used for NCT. However, research reactor WWR-SM (INP, Uzbekistan AS, Tashkent) doesn't provide with the epithermal neutron beams and to develop this technique the reactor, first of all, needs for obtaining the epithermal neutron beams with energy spectrum in range from 1 eV up to 10 keV and with intensity ∼ 10 9 neutron /sm 2 s. Practically it is connected with upgrade of at least one of existed reactor channels, namely with equipping with the special equipment (filters), forming from the reactor spectrum the beam of necessary energy neutrons. It requires realization of preliminary model calculations, including calculations of capture cross-sections, of filters types and their geometrical parameters on the basis of optimal selected materials. Such calculations, as a rule, are carried out on the basis of Monte-Carlo method and designed software for calculation of nuclear reactor physical and technical characteristics [1]. In this work the calculation results of devices variants and problems discussion, related with possibility of WWR-SM reactor using for NCT are presented. (author)

Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial

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Kulig Kornelia

2009-05-01

Full Text Available Abstract Background Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology. Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. Methods/Design We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. Discussion This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. Trial Registration http://www.clinicaltrials.gov identifier NCT00847769.

Bothersome tics in patients with chronic tic disorders: Characteristics and individualized treatment response to behavior therapy.

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McGuire, Joseph F; Piacentini, John; Scahill, Lawrence; Woods, Douglas W; Villarreal, Robert; Wilhelm, Sabine; Walkup, John T; Peterson, Alan L

2015-07-01

This report examined the most frequently reported bothersome tics among individuals with chronic tic disorders and evaluated the improvement and remission of tics and their associated characteristics. Youths and adults (N = 240) were randomly assigned to receive the comprehensive behavioral intervention for tics (CBIT) or psychoeducation and supportive therapy (PST). At baseline, motor tics and tics with an urge were rated as more bothersome relative to vocal tics and tics without premonitory urges. The five most common bothersome tics included eye blinking, head jerks, sniffing, throat clearing, and other complex motor tics. While CBIT outperformed PST across tic type and urge presence, tics preceded by premonitory urges at baseline had higher severity at posttreatment across treatment condition. Six individual tic types had lower severity at posttreatment following CBIT relative to PST. Baseline urge presence was associated with tic remission for CBIT but not PST. Specific bothersome tics were more likely to remit with CBIT relative to PST. Findings suggest that individual tics respond and remit differently to CBIT relative to PST, with implications highlighting the negative reinforcement hypothesis in tic symptom maintenance. CLINICALTRIALS. NCT00218777; NCT00231985. Published by Elsevier Ltd.

Neutron capture therapy of ocular melanoma: dosimetry and microdosimetry approaches

International Nuclear Information System (INIS)

Pignol, J.P.; Methlin, G.; Abbe, J.C.; Lefebvre, O.; Sahel, J.

1994-01-01

Neutron capture therapy (NCT) aims at destroying cancerous cells with the α and 7 Li particles produced by the neutron capture reaction on 10 B. This note reports on the study of the boron distribution in tissues on an animal model (nude mice) xenografted with a human ocular melanoma after an i.p.injection of 2g/kg of 10 B-BPA and in cells cultured in the presence of 530 μmol/l of 10 B-BPA. A concentration of 64 ppm of 10 B in the active part of the tumour with a ratio of concentrations versus the skin of 3.7 are observed. Investigations on cells reveal the presence of boron in the cytoplasm. The biological, dosimetric and microdosimetric consequences of these findings are discussed. (authors). 15 refs., 2 tabs., 2 figs

Brief cognitive behavioral therapy in primary care: a hybrid type 2 patient-randomized effectiveness-implementation design

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Cully Jeffrey A

2012-07-01

qualitative methods (e.g., focus interviews and surveys from patients and providers. Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. Conclusions Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. Trial registration NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT01149772

Brief cognitive behavioral therapy in primary care: a hybrid type 2 patient-randomized effectiveness-implementation design.

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Cully, Jeffrey A; Armento, Maria E A; Mott, Juliette; Nadorff, Michael R; Naik, Aanand D; Stanley, Melinda A; Sorocco, Kristen H; Kunik, Mark E; Petersen, Nancy J; Kauth, Michael R

2012-07-11

and surveys from patients and providers). Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT01149772.

Preparation of new boron compounds with potential for application in 10B NCT: Derivatives of monocarbon carboranes

International Nuclear Information System (INIS)

Morris, J.H.; Khan, S.A.; Mair, F.; Peters, G.

1992-01-01

In order to extend the range and versatility of boron clusters appropriate to NCT the authors have studied routes to derivatives of the anions 1-carba-closo-dodecahydrododecaborate-1, [CB 11 H 12 ] - , (1), and its synthetic precursor, 7-carba-nido-tridecahydroundecaborate-1, [CB 10 H 13 ] - , (2). Substitution chemistry of closo-[CB 11 H 12 ] - and its derivatives had been examined previously primarily with respect to substituents at the C-atom. The different isomeric sites of boron substitution, which have been much less studied, offer potential scope for subtle modification of properties of the substituted species. They have sought to prepare thiol substituted derivatives analogous to the widely studied species [B 12 H 11 SH] 2- . The preliminary experiments to introduce the thiol substituent by routes analogous to those for the preparation of [B 12 H 11 SH] 2- or 1- and 2-[B 10 H 9 SH] 2- were unsuccessful. Therefore they considered routes involving prior substitution of either the precursor nido-[CB 10 H 13 ] - and its derivatives, or the monoboron species used for boron insertion

Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent

Energy Technology Data Exchange (ETDEWEB)

Barth, Rolf F. E-mail: barth.1@osu.edu; Wu Gong; Yang Weilian; Binns, Peter J.; Riley, Kent J.; Patel, Hemant; Coderre, Jeffrey A.; Tjarks, Werner; Bandyopadhyaya, A.K.; Thirumamagal, B.T.S.; Ciesielski, Michael J.; Fenstermaker, Robert A

2004-11-01

Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.t.) administration of boronated cetuximab (C225-G5-B{sub 1100}), the mean boron concentration in rats bearing either F98{sub EGFR} or F98{sub WT} gliomas were 92.3{+-}23.3 {mu}g/g and 36.5{+-}18.8 {mu}g/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B{sub 1000}) was 6.7{+-}3.6 {mu}g/g. Based on its favorable in vivo uptake, C225-G5-B{sub 1100} was evaluated as a delivery agent for BNCT in F98{sub EGFR} glioma bearing rats. The mean survival time (MST) of rats that received C225-G5-B{sub 1100}, administered by convection enhanced delivery (CED), was 45{+-}3 d compared to 25{+-}3 d for untreated control animals. A further enhancement in MST to >59 d was obtained by administering C225-G5-B{sub 1100} in combination with i.v. boronophenylalanine (BPA). These data are the first to demonstrate the efficacy of a boronated MoAb for BNCT of an intracerebral (i.c.) glioma and are paradigmatic for future studies using a combination of boronated MoAbs and low molecular weight delivery agents.

Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: A randomized controlled trial.

Science.gov (United States)

Zhou, Tian-Hang; Dang, Wei-Min; Ma, Yan-Tao; Hu, Chang-Qing; Wang, Ning; Zhang, Guo-Yi; Wang, Gang; Shi, Chuan; Zhang, Hua; Guo, Bin; Zhou, Shu-Zhe; Feng, Lei; Geng, Shu-Xia; Tong, Yu-Zhen; Tang, Guan-Wen; He, Zhong-Kai; Zhen, Long; Yu, Xin

2018-02-01

Bright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown. The aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371). This was a multi-center, single blind, randomized clinical trial. Seventy-four participants were randomized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary outcome measures were rates of switch into hypomania or mania and adverse events. 1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control, with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side effects: No serious adverse events were reported. BLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced cognitive behaviour therapy for adolescents with anorexia nervosa: An alternative to family therapy?

Science.gov (United States)

Dalle Grave, Riccardo; Calugi, Simona; Doll, Helen A.; Fairburn, Christopher G.

2013-01-01

A specific form of family therapy (family-based treatment) is the leading treatment for adolescents with anorexia nervosa. As this treatment has certain limitations, alternative approaches are needed. “Enhanced” cognitive behaviour therapy (CBT-E) is a potential candidate given its utility as a treatment for adults with eating disorder psychopathology. The aim of the present study was to establish, in a representative cohort of patients with marked anorexia nervosa, the immediate and longer term outcome following CBT-E. Forty-nine adolescent patients were recruited from consecutive referrals to a community-based eating disorder clinic. Each was offered 40 sessions of CBT-E over 40 weeks from a single therapist. Two-thirds completed the full treatment with no additional input. In these patients there was a substantial increase in weight together with a marked decrease in eating disorder psychopathology. Over the 60-week post-treatment follow-up period there was little change despite minimal subsequent treatment. These findings suggest that CBT-E may prove to be a cost-effective alternative to family-based treatment. PMID:23123081

Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

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Rianne A. de Kleine

2013-10-01

Full Text Available There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD. Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: D-cycloserine, MDMA, hydrocortisone, and propranolol.

Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review.

Science.gov (United States)

de Kleine, Rianne A; Rothbaum, Barbara O; van Minnen, Agnes

2013-10-17

There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.

Effectiveness of Aquatic Therapy vs Land-based Therapy for Balance and Pain in Women with Fibromyalgia: a study protocol for a randomised controlled trial.

Science.gov (United States)

Rivas Neira, Sabela; Pasqual Marques, Amélia; Pegito Pérez, Irene; Fernández Cervantes, Ramón; Vivas Costa, Jamile

2017-01-19

Fibromyalgia is a disease with an increasing incidence. It impairs the quality of life of patients and decreases their functional capacity. Aquatic therapy has already been used for managing the symptoms of this syndrome. However, aquatic therapy has only recently been introduced as a treatment modality for improving proprioception in fibromyalgia. The main objective of this study is to determine the effectiveness of two physiotherapy protocols, one in and one out of water, for improving balance and decreasing pain in women with fibromyalgia. The study protocol will be a single-blind randomised controlled trial. Forty women diagnosed with fibromyalgia will be randomly assigned into 2 groups: Aquatic Therapy (n = 20) or Land-based Therapy (n = 20). Both interventions include 60-min therapy sessions, structured into 4 sections: Warm-up, Proprioceptive Exercises, Stretching and Relaxation. These sessions will be carried out 3 times a week for 3 months. Primary outcomes are balance (static and dynamic) and pain (intensity and threshold). Secondary outcomes include functional balance, quality of life, quality of sleep, fatigue, self-confidence in balance and physical ability. Outcome measures will be evaluated at baseline, at the end of the 3-month intervention period, and 6-weeks post-treatment. Statistical analysis will be carried out using the SPSS 21.0 program for Windows and a significance level of p ≤ 0.05 will be used for all tests. This study protocol details two physiotherapy interventions in women with fibromyalgia to improve balance and decrease pain: aquatic therapy and land-based therapy. In current literature there is a lack of methodological rigour and a limited number of studies that describe physiotherapy protocols to manage fibromyalgia symptoms. High-quality scientific works are required to highlight physiotherapy as one of the most recommended treatment options for this syndrome. Date of publication in ClinicalTrials.gov: 18

Well-Being Therapy in Dutch mental health care

NARCIS (Netherlands)

Meulenbeek, Petrus Antonius Maria

2017-01-01

Relapse after treatment of mental disorders is a major problem. Enhancing psychological well-being and resilience may reduce the risk of relapse in patients with mental disorders. Well-being therapy tries to address these factors. The original model of well-being therapy was developed by the Italian

Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus.

Science.gov (United States)

Cucchiarini, M; McNulty, A L; Mauck, R L; Setton, L A; Guilak, F; Madry, H

2016-08-01

Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis (OA). Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Experiential Learning in Occupational Therapy: Can It Enhance Readiness for Clinical Practice?

Science.gov (United States)

Knecht-Sabres, Lisa Jean

2013-01-01

This mixed method study examined the effectiveness of experiential learning opportunities near the end of the occupational therapy students' didactic education. A pretest/posttest design with a gain score approach was used to determine whether there was a significant improvement in the occupational therapy students' self-perception of their…

Randomized Controlled Trial of Nurse-Delivered Cognitive Behavioral Therapy Versus Supportive Psychotherapy Telehealth Interventions for Chronic Back Pain.

Science.gov (United States)

Rutledge, Thomas; Atkinson, J Hampton; Holloway, Rachael; Chircop-Rollick, Tatiana; D'Andrea, John; Garfin, Steven R; Patel, Shetal; Penzien, Donald B; Wallace, Mark; Weickgenant, Anne L; Slater, Mark

2018-04-16

This study evaluated a nurse-delivered, telehealth intervention of cognitive behavioral therapy versus supportive psychotherapy for chronic back pain. Participants (N=61) had chronic back pain (pain "daily" ≥ 6 months at an intensity ≥4/10 scale) and were randomized to an 8-week, 12-session, Cognitive Behavioral Therapy (CBT) or to Supportive Care (SC) matched for frequency, format, and time, with each treatment delivered by a primary care nurse. The primary outcome was the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included the Numerical Rating Scale (NRS) and the Patient Global Impressions Scale (CGI). CBT participants (n=30) showed significant improvements on the RMDQ (means=11.4[5.9] vs. 9.4[6.1] at baseline and post-treatment, respectively, p.10). The results suggest that telehealth, nurse-delivered CBT and SC treatments for chronic back pain can offer significant and relatively comparable benefits. ClinicalTrials.gov: NCT00608530. This article describes the benefits of training primary care nurses to deliver evidence-based behavioral therapies for low back pain. Due to the high prevalence of chronic pain and the growing emphasis on non-opioid therapies, training nurses to provide behavior therapies could be a cost-effective way to improve pain management. Copyright © 2018. Published by Elsevier Inc.

Negative Pressure Wound Therapy in Maxillofacial Applications

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Adam J. Mellott

2016-09-01

Full Text Available Negative pressure wound therapy has greatly advanced the field of wound healing for nearly two decades, by providing a robust surgical adjunct technique for accelerating wound closure in acute and chronic wounds. However, the application of negative pressure wound therapy in maxillofacial applications has been relatively under utilized as a result of the physical articulations and contours of the head and neck that make it challenging to obtain an airtight seal for different negative pressure wound therapy systems. Adapting negative pressure wound therapies for maxillofacial applications could yield significant enhancement of wound closure in maxillofacial applications. The current review summarizes the basic science underlying negative pressure wound therapy, as well as specific maxillofacial procedures that could benefit from negative pressure wound therapy.

[Acceptance and mindfulness-based cognitive-behavioral therapies].

Science.gov (United States)

Ngô, Thanh-Lan

2013-01-01

achieve specific goals. They focus on the present moment rather than on historical causes. However, they also present significant differences: control vs acceptance of thoughts, focus on cognition vs behavior, focus on the relationship between the individual and his thoughts vs cognitive content, goal of modifying dysfunctional beliefs vs metacognitive processes, use of experiential vs didactic methods, focus on symptoms vs quality of life, strategies used before vs after the unfolding of full emotional response. The main interventions based on mindfulness meditation and acceptance are: Acceptance and Commitment Therapy, Functional Analytic Therapy, the expanded model of Behavioral Activation, Metacognitive Therapy, Mindfulness based Cognitive Therapy, Dialectic Behavior Therapy, Integrative Behavioral Couples Therapy and Compassionate Mind Training. These are described in this article. They offer concepts and techniques which might enhance therapeutic efficacy. They teach a new way to deploy attention and to enter into a relationship with current experience (for example, defusion) in order to diminish cognitive reactivity, a maintenance factor for psychopathology, and to enhance psychological flexibility. The focus on cognitive process, metacognition as well as cognitive content might yield additional benefits in therapy. It is possible to combine traditional CBT with third wave approaches by using psychoeducation and cognitive restructuring in the beginning phases of therapy in order to establish thought bias and to then encourage acceptance of internal experiences as well as exposure to feared stimuli rather than to continue to use cognitive restructuring techniques. Traditional CBT and third wave approaches seem to impact different processes: the former enhance the capacity to observe and describe experiences and the latter diminish experiential avoidance and increase conscious action as well as acceptance. The identification of personal values helps to motivate the

Efficacy of perceptual vision therapy in enhancing visual acuity and contrast sensitivity function in adult hypermetropic anisometropic amblyopia

Directory of Open Access Journals (Sweden)

Yalcin E

2013-12-01

Full Text Available Elvan Yalcin, Ozlem BalciWorld Eye Hospital, Department of Pediatric Ophthalmology, Istanbul, TurkeyBackground: The purpose of this study was to evaluate the efficacy of neural vision therapy, also termed perceptual vision therapy, in enhancing best corrected visual acuity (BCVA and contrast sensitivity function in amblyopic patients.Methods: This prospective study enrolled 99 subjects previously diagnosed with unilateral hypermetropic amblyopia aged 9–50 years. The subjects were divided into two groups, with 53 subjects (53 eyes in the perceptual vision therapy group and 46 subjects (46 eyes in the control group. Because the nature of the treatment demands hard work and strict compliance, we enrolled the minimal number of subjects required to achieve statistically significant results. Informed consent was obtained from all subjects. Study phases included a baseline screening, a series of 45 training sessions with perceptual vision therapy, and an end-of-treatment examination. BCVA and contrast sensitivity function at 1.5, 3, 6, 12, and 18 cycles per degree spatial frequencies were obtained for statistical analysis in both groups. All subjects had follow-up examinations within 4–8 months. With the exception of one subject from the study group and two subjects from the control group, all subjects had occlusion during childhood. The study was not masked.Results: The results for the study group demonstrated a mean improvement of 2.6 logarithm of the minimum angle of resolution (logMAR lines in visual acuity (from 0.42 to 0.16 logMAR. Contrast sensitivity function improved at 1.5, 3, 6, 12, and 18 cycles per degree spatial frequencies. The control group did not show any significant change in visual acuity or contrast sensitivity function. None of the treated eyes showed a drop in visual acuity. Manifest refractions remained unchanged during the study.Conclusion: The results of our study demonstrate the efficacy of perceptual vision therapy in

Sequential gadolinium-DTPA enhanced MRI studies in neuro-Behcet's disease

International Nuclear Information System (INIS)

Kazui, S.; Naritomi, H.; Ogawa, M.; Sawada, T.; Imakita, S.; Yamada, N.

1991-01-01

Sequential gadolinium-DTPA (Gd-DTPA) enhanced MR images were obtained before and after steroid therapy in a case of neuro-Behcet's disease. Multiple scattered lesions, which could not be detected on pre- and post-contrast CT, were demonstrated mainly in the white matter of the pons and/or the cerebrum with both T1- and T2-weighted images. Some of these lesions, however, were not enhanced at all by infusion of Gd-DTPA. The Gd-DTPA infusion study demonstrated marked enhancement in the white matter of the pons and cerebrum. Some lesions not seen with T2-weighted images were also strongly enhanced by Gd-DTPA infusion at the acute stage. After steroid therapy, the symptoms and abnormal laboratory findings were resolved. The pontine and cerebral lesions on plain MR images remained unchanged even after resolution of the symptoms, suggesting that they were inactive old foci. On the other hand, the lesions detected in the enhancement study before steroid therapy disappeared with the repeat Gd-DTPA enhanced MR images which were performed after resolution of the symptoms. Some active inflammatory lesions in neuro-Behcet's disease may be demonstrated only on Gd-DTPA enhanced MR images. Gd-DTPA enhanced MR imaging appears to be potentially useful for detecting active inflammatory lesions in neuro-Behcet's disease and for evaluating the efficacy of treatment. (orig.)

Anorexia nervosa and childhood sexual abuse: Treatment outcomes of intensive enhanced cognitive behavioural therapy.

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Calugi, Simona; Franchini, Cecilia; Pivari, Silvia; Conti, Maddalena; El Ghoch, Marwan; Dalle Grave, Riccardo

2018-04-01

Sexual abuse has been widely studied as a risk factor in anorexia nervosa, but data on its influence on treatment outcomes are scarce. Hence, we compared short- and long-term outcomes of inpatient enhanced cognitive-behavioural therapy (CBT-E) in patients with anorexia nervosa who had and had not suffered sexual abuse. Eighty-one patients were recruited, and body mass index (BMI), Eating Disorder Examination, Brief Symptom Inventory, and Work and Social Adjustment Scale scores were recorded before and after treatment, and at 6- and 12-month follow-ups. Twenty patients (24.7%) reported experiencing childhood sexual abuse before anorexia nervosa onset, while 61 (75.3%) reported none. Both groups displayed similar characteristics before treatment, and similarly large increases in BMI, eating-disorder, general psychopathology, and work and social functioning from baseline to 12-month follow-up. Based on these findings, childhood sexual abuse does not appear to compromise outcomes in patients with anorexia nervosa treated via intensive CBT-E. Copyright © 2017 Elsevier B.V. All rights reserved.

Music therapy as an adjunct to standard treatment for obsessive compulsive disorder and co-morbid anxiety and depression: A randomized clinical trial.

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Shiranibidabadi, Shahrzad; Mehryar, Amirhooshang

2015-09-15

Previous studies have highlighted the potential therapeutic benefits of music therapy as an adjunct to standard care, in a variety of psychiatric ailments including mood and anxiety disorders. However, the role of music in the treatment of obsessive-compulsive disorder (OCD) have not been investigated to date. In a single-center, parallel-group, randomized clinical trial (NCT02314195) 30 patients with OCD were randomly assigned to standard treatment (pharmacotherapy and cognitive-behavior therapy) plus 12 sessions of individual music therapy (n = 15) or standard treatment only (n = 15) for one month. Maudsley Obsessive-Compulsive Inventory, Beck Anxiety Inventory, and Beck Depression Inventory-Short Form were administered baseline and after one month. Thirty patients completed the study. Music therapy resulted in a greater decrease in total obsessive score (post-intervention score: music therapy+standard treatment: 12.4 ± 1.9 vs standard treatment only: 15.1 ± 1.7, p Music therapy was significantly more effective in reducing anxiety (post-intervention score: music therapy + standard treatment: 16.9 ± 7.4 vs standard treatment only: 22.9 ± 4.6, p music therapy + standard treatment: 10.8 ± 3.8 vs standard treatment: 17.1 ± 3.7, p music therapy, as an adjunct to standard care, seems to be effective in reducing obsessions, as well as co-morbid anxiety and depressive symptoms. Copyright © 2015. Published by Elsevier B.V.

Folk Hero Modeling Therapy for Puerto Rican Adolescents.

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Costantino, Guiseppe; And Others

1988-01-01

Describes development of a new modality for Puerto Rican adolescents which presents Puerto Rican folk heros and heroines in modeling therapy targeted towards enhancing adolescents' pride in their ethnic heritage. Evaluation of therapy using 21 adolescents indicated subjects increased in self-disclosure and self-confidence, gained pride, learned…

SECOND-STAGE TREATMENTS FOR RELATIVE NONRESPONDERS TO COGNITIVE BEHAVIORAL THERAPY (CBT) FOR PANIC DISORDER WITH OR WITHOUT AGORAPHOBIA-CONTINUED CBT VERSUS SSRI: A RANDOMIZED CONTROLLED TRIAL.

Science.gov (United States)

Payne, Laura A; White, Kamila S; Gallagher, Matthew W; Woods, Scott W; Shear, M Katherine; Gorman, Jack M; Farchione, Todd J; Barlow, David H

2016-05-01

Cognitive behavioral therapy (CBT) and pharmacotherapy are efficacious for the short-term treatment of panic disorder. Less is known about the efficacy of these therapies for individuals who do not respond fully to short-term CBT. The current trial is a second-step stratified randomized design comparing two treatment conditions-selective serotonin reuptake inhibitor (SSRI; paroxetine or citalopram; n = 34) and continued CBT (n = 24)-in a sample of individuals classified as treatment nonresponders to an initial course of CBT for panic disorder. Participants were randomized to 3 months of treatment and then followed for an additional 9 months. Only treatment responders after 3 months were maintained on the treatment until 12-month follow-up. Data analysis focused on panic disorder symptoms and achievement of response status across the first 3 months of treatment. Final follow-up data are presented descriptively. Participants in the SSRI condition showed significantly lower panic disorder symptoms as compared to continued CBT at 3 months. Results were similar when excluding individuals with comorbid major depression or analyzing the entire intent-to-treat sample. Group differences disappeared during 9-month naturalistic follow-up, although there was significant attrition and use of nonstudy therapies in both arms. These data suggest greater improvement in panic disorder symptoms when switching to SSRI after failure to fully respond to an initial course of CBT. Future studies should further investigate relapse following treatment discontinuation for nonresponders who became responders. Clinicaltrials.gov Identifier: NCT00000368; https://clinicaltrials.gov/show/NCT00000368. © 2015 Wiley Periodicals, Inc.

Cognitive Behavioral Therapy for Insomnia in Posttraumatic Stress Disorder: A Randomized Controlled Trial

Science.gov (United States)

Talbot, Lisa S.; Maguen, Shira; Metzler, Thomas J.; Schmitz, Martha; McCaslin, Shannon E.; Richards, Anne; Perlis, Michael L.; Posner, Donn A.; Weiss, Brandon; Ruoff, Leslie; Varbel, Jonathan; Neylan, Thomas C.

2014-01-01

disorder should include behavioral sleep medicine. Clinical Trial Information: Trial Name: Cognitive Behavioral Treatment Of Insomnia In Posttraumatic Stress Disorder. URL: http://clinicaltrials.gov/ct2/show/NCT00881647. Registration Number: NCT00881647. Citation: Talbot LS; Maguen S; Metzler TJ; Schmitz M; McCaslin SE; Richards A; Perlis ML; Posner DA; Weiss B; Ruoff L; Varbel J; Neylan TC. Cognitive behavioral therapy for insomnia in posttraumatic stress disorder: a randomized controlled trial. SLEEP 2014;37(2):327-341. PMID:24497661

Optimal Neutron Source and Beam Shaping Assembly for Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Vujic, J.; Greenspan, E.; Kastenber, W.E.; Karni, Y.; Regev, D.; Verbeke, J.M.; Leung, K.N.; Chivers, D.; Guess, S.; Kim, L.; Waldron, W.; Zhu, Y.

2003-01-01

There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly

Pharmacological enhancement of treatment for amblyopia

Science.gov (United States)

Rashad, Mohammad A

2012-01-01

Background The purpose of this study was to compare a weight-adjusted dose of carbidopa- levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia. Methods This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks. Results The mean logarithm of the minimal angle of resolution (logMAR) of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51) than in the pharmacological enhancement group (0.58, 0.49, and 0.56) at three follow-up visits (at months 1, 3, and 12, respectively). There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51) and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56) at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively). The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5%) than in the occlusion group (30%). The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3%) than in the occlusion group (22%). Conclusion Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add to the effect of occlusion in severe amblyopia and bilateral amblyopia. PMID:22536029

Second-Line Therapy for Advanced NSCLC.

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Weiss, Jared M; Stinchcombe, Thomas E

2013-01-01

Most patients with lung cancer have non-small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first-line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second-line trials is approximately 9 months, and many patients receive further therapy after second-line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second-line therapies. For patients with EGFR mutation, a TKI is the favored second-line therapy if not already used in first-line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.

Macrophage membrane-coated iron oxide nanoparticles for enhanced photothermal tumor therapy

Science.gov (United States)

Meng, Qian-Fang; Rao, Lang; Zan, Minghui; Chen, Ming; Yu, Guang-Tao; Wei, Xiaoyun; Wu, Zhuhao; Sun, Yue; Guo, Shi-Shang; Zhao, Xing-Zhong; Wang, Fu-Bing; Liu, Wei

2018-04-01

Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should have long blood circulation times and active cancer targeting. Additionally, they should be harmless and invisible to the immune system. Here, we developed a biomimetic nanoplatform with the above properties for cancer therapy. Macrophage membranes were reconstructed into vesicles and then coated onto magnetic iron oxide nanoparticles (Fe3O4 NPs). Inherited from the Fe3O4 core and the macrophage membrane shell, the resulting Fe3O4@MM NPs exhibited good biocompatibility, immune evasion, cancer targeting and light-to-heat conversion capabilities. Due to the favorable in vitro and in vivo properties, biomimetic Fe3O4@MM NPs were further used for highly effective photothermal therapy of breast cancer in nude mice. Surface modification of synthetic nanomaterials with biomimetic cell membranes exemplifies a novel strategy for designing an ideal nanoplatform for translational medicine.

Virtual Reality-Enhanced Cognitive-Behavioral Therapy for Morbid Obesity: A Randomized Controlled Study with 1 Year Follow-Up.

Science.gov (United States)

Manzoni, Gian Mauro; Cesa, Gian Luca; Bacchetta, Monica; Castelnuovo, Gianluca; Conti, Sara; Gaggioli, Andrea; Mantovani, Fabrizia; Molinari, Enrico; Cárdenas-López, Georgina; Riva, Giuseppe

2016-02-01

It is well known that obesity has a multifactorial etiology, including biological, environmental, and psychological causes. For this reason, obesity treatment requires a more integrated approach than the standard behavioral treatment based on dietary and physical activity only. To test the long-term efficacy of an enhanced cognitive-behavioral therapy (CBT) of obesity, including a virtual reality (VR) module aimed at both unlocking the negative memory of the body and to modify its behavioral and emotional correlates, 163 female morbidly obese inpatients (body mass index >40) were randomly assigned to three conditions: a standard behavioral inpatient program (SBP), SBP plus standard CBT, and SBP plus VR-enhanced CBT. Patients' weight, eating behavior, and body dissatisfaction were measured at the start and upon completion of the inpatient program. Weight was assessed also at 1 year follow-up. All measures improved significantly at discharge from the inpatient program, and no significant difference was found among the conditions. However, odds ratios showed that patients in the VR condition had a greater probability of maintaining or improving weight loss at 1 year follow-up than SBP patients had (48% vs. 11%, p = 0.004) and, to a lesser extent, than CBT patients had (48% vs. 29%, p = 0.08). Indeed, only the VR-enhanced CBT was effective in further improving weight loss at 1 year follow-up. On the contrary, participants who received only the inpatient program regained back, on average, most of the weight they had lost. Findings support the hypothesis that a VR module addressing the locked negative memory of the body may enhance the long-term efficacy of standard CBT.

Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting.

Science.gov (United States)

Natarajan, Pradeep; Young, Robin; Stitziel, Nathan O; Padmanabhan, Sandosh; Baber, Usman; Mehran, Roxana; Sartori, Samantha; Fuster, Valentin; Reilly, Dermot F; Butterworth, Adam; Rader, Daniel J; Ford, Ian; Sattar, Naveed; Kathiresan, Sekar

2017-05-30

burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration. © 2017 American Heart Association, Inc.

Photon-activation therapy

International Nuclear Information System (INIS)

Fairchild, R.G.; Bond, V.P.

1982-01-01

Photon Activation Therapy (PAT) is a technique in which radiation dose to tumor is enhanced via introduction of stable 127 I in the form of iodinated deoxyuridine (IdUrd). Stimulation of cytotoxic effects from IdUrd is accomplished by activation with external (or implanted) radiation sources. Thus, accumulations of this nucleoside in actively competing cellpools do not preclude therapy in so far as such tissues can be excluded from the radiation field. Calculations show that 5% replacement of thymidine (Tyd) in tumor DNA should enhance the biological effectiveness of a given photon radiotherapy dose by a factor of approx. 3. Proportionally higher gains would result from higher replacements of Tyd and IdUrd. In addition, biological response is enhanced by chemical sensitization with IdUrd. The data indicate that damage from photon activation as well as chemical sensitization does not repair. Thus, at low dose rates, a further increase in therapeutic gain should accrue as normal tissues are allowed to repair and regenerate. A samarium-145 source has been developed for PAT, with activating x-ray energies of from 38 to 45 keV. Favorable clinical results can be expected through the use of IdUrd and protracted irradiations with low energy x-rays. In particular, PAT may provide unique advantages at selected sites such as brain, or head and neck tumors

Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

Science.gov (United States)

Reagan-Shaw, Shannon; Mukhtar, Hasan; Ahmad, Nihal

2008-01-01

Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

Effectiveness of Implant Therapy Analyzed in a Swedish Population: Prevalence of Peri-implantitis.

Science.gov (United States)

Derks, J; Schaller, D; Håkansson, J; Wennström, J L; Tomasi, C; Berglundh, T

2016-01-01

Peri-implantitis is an inflammatory disease affecting soft and hard tissues surrounding dental implants. As the global number of individuals that undergo restorative therapy through dental implants increases, peri-implantitis is considered as a major and growing problem in dentistry. A randomly selected sample of 588 patients who all had received implant-supported therapy 9 y earlier was clinically and radiographically examined. Prevalence of peri-implantitis was assessed and risk indicators were identified by multilevel regression analysis. Forty-five percent of all patients presented with peri-implantitis (bleeding on probing/suppuration and bone loss >0.5 mm). Moderate/severe peri-implantitis (bleeding on probing/suppuration and bone loss >2 mm) was diagnosed in 14.5%. Patients with periodontitis and with ≥4 implants, as well as implants of certain brands and prosthetic therapy delivered by general practitioners, exhibited higher odds ratios for moderate/severe peri-implantitis. Similarly, higher odds ratios were identified for implants installed in the mandible and with crown restoration margins positioned ≤1.5 mm from the crestal bone at baseline. It is suggested that peri-implantitis is a common condition and that several patient- and implant-related factors influence the risk for moderate/severe peri-implantitis (ClinicalTrials.gov NCT01825772). © International & American Associations for Dental Research 2015.

Improving access to psychological therapies in voice disorders: a cognitive behavioural therapy model.

Science.gov (United States)

Miller, Tracy; Deary, Vincent; Patterson, Jo

2014-06-01

The improving access to psychological therapies initiative has highlighted the importance of managing mental health problems effectively, and research has shown excellent outcomes from cognitive behavioural therapy (CBT) interventions. Patients presenting with functional dysphonia will often also describe psychological distress including anxiety, depression and reduced general well-being, and it is felt that effective voice therapy needs to include the management of psychological well-being. The evidence for the use of CBT enhanced voice therapy is limited to date. Recent research has only started to identify the benefits of this approach and questions regarding how to achieve and maintain competence are essential. Voice therapy outcomes are positive and patients receiving CBT with voice therapy have shown more improvement in their general well-being and distress. CBT is a very well evidenced therapy and recommended by The National Institute for Health and Care Excellence (NICE) as the treatment of choice for mental health difficulties and medically unexplained symptoms. Allied health professionals are increasingly being trained to use CBT skills in the management of a number of symptoms/illnesses, and this should be considered for the management of functional dysphonia. However, there is a need for more research and detailed consideration of how therapists should be trained and supervised and how cost-effective this approach may be.

Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

Science.gov (United States)

Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

2015-08-01

Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

A Mass Merchandiser's Role in Enhancing Pharmacy Students’ Business Plan Development Skills for Medication Therapy Management Services

Science.gov (United States)

2011-01-01

Objectives. To develop a relationship between a pharmacy management course and a mass merchandiser and to determine whether involving pharmacy managers from the mass merchandiser in the course would enhance student skills in developing a business plan for medication therapy management services. Design. The pharmacy managers from the mass merchandiser participated in lectures, provided panel discussions, and conducted a business plan competition. Learning was assessed by means of 4 examinations and 1 project (ie, the business plan). At the conclusion of the semester, surveys were administered to solicit student input and gain insight from pharmacy managers on the perceived value of this portion of the course. Assessment. Students’ average grade on the business plan assignment, which included the oral presentation, the peer assessment, and the written proposal, was 92.2%. Approximately 60% (n = 53) of surveyed students agreed or strongly agreed that their management skills had improved because of the participation of pharmacy managers from the mass merchandiser. All of the managers enjoyed participating in the experience. Conclusions. The involvement of pharmacy managers from a mass merchandiser enhanced student learning in the classroom, and managers felt that their participation was an important contribution to the development of future pharmacists. PMID:21969719

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE" study: a double-blind randomised controlled multicenter clinical trial

Directory of Open Access Journals (Sweden)

Lee Myoungsook

2011-01-01

Full Text Available Abstract Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT: NCT01031667

Enhancement of exposure therapy in participants with specific phobia: A randomized controlled trial comparing yohimbine, propranolol and placebo.

Science.gov (United States)

Meyerbröker, K; Morina, N; Emmelkamp, P M G

2018-05-04

Recent research indicates that pharmacological agents may enhance psychotherapeutic outcome. Yet, empirical results have not been conclusive with respect to two pharmacological agents, yohimbine hydrochloride (YOH) and propranolol. YOH is suggested to enhance emotional memory by elevating norepinephrine, whereas the β-adrenergic receptor antagonist propranolol might help better cope with feared situations by reducing accompanying bodily sensations. In this controlled trial, fifty-six participants with specific phobia were randomly assigned to either 1) virtual reality exposure therapy (VRET) plus YOH, 2) VRET plus Propranolol, or 3) VRET plus placebo. Participants in all conditions received three sessions of VRET over a period of two weeks. We conducted 2 × 3 repeated measures MANOVA's. Results showed a significant effect for time, with partial eta squared ranging from ηp2 = 0.647 to ηp2 = 0.692, for specific phobia, yet no significant interaction effects were found. No significant differences were found when VRET with YOH or a beta-blocker was compared to VRET with a non-active placebo. Implications for clinical practice and future research are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Narrative exposure therapy for PTSD increases top-down processing of aversive stimuli - evidence from a randomized controlled treatment trial

Directory of Open Access Journals (Sweden)

Adenauer Hannah

2011-12-01

Full Text Available Abstract Background Little is known about the neurobiological foundations of psychotherapy for Posttraumatic Stress Disorder (PTSD. Prior studies have shown that PTSD is associated with altered processing of threatening and aversive stimuli. It remains unclear whether this functional abnormality can be changed by psychotherapy. This is the first randomized controlled treatment trial that examines whether narrative exposure therapy (NET causes changes in affective stimulus processing in patients with chronic PTSD. Methods 34 refugees with PTSD were randomly assigned to a NET group or to a waitlist control (WLC group. At pre-test and at four-months follow-up, the diagnostics included the assessment of clinical variables and measurements of neuromagnetic oscillatory brain activity (steady-state visual evoked fields, ssVEF resulting from exposure to aversive pictures compared to neutral pictures. Results PTSD as well as depressive symptom severity scores declined in the NET group, whereas symptoms persisted in the WLC group. Only in the NET group, parietal and occipital activity towards threatening pictures increased significantly after therapy. Conclusions Our results indicate that NET causes an increase of activity associated with cortical top-down regulation of attention towards aversive pictures. The increase of attention allocation to potential threat cues might allow treated patients to re-appraise the actual danger of the current situation and, thereby, reducing PTSD symptoms. Registration of the clinical trial Number: NCT00563888 Name: "Change of Neural Network Indicators Through Narrative Treatment of PTSD in Torture Victims" ULR: http://www.clinicaltrials.gov/ct2/show/NCT00563888

Value of Single-Dose Contrast-Enhanced Magnetic Resonance Angiography Versus Intraarterial Digital Subtraction Angiography in Therapy Indications in Abdominal and Iliac Arteries

International Nuclear Information System (INIS)

Schaefer, Philipp J.; Schaefer, Fritz K. W.; Mueller-Huelsbeck, Stefan; Both, Markus; Heller, Martin; Jahnke, Thomas

2007-01-01

The objective of the study was to prove the value of single-dose contrast-enhanced magnetic resonance angiography [three-dimensional (3D) ceMRA] in abdominal and iliac arteries versus the reference standard intra-arterial digital subtraction angiography (i.a.DSA) when indicating a therapy. Patients suspected of having abdominal or iliac artery stenosis were included in this study. A positive vote of the local Ethics Committee was given. After written informed consent was obtained, 37 patients were enrolled, of which 34 were available for image evaluation. Both 3D ceMRA and i.a. DSA were performed for each patient. The dosage for 3D ceMRA was 0.1 mmol/kg body weight in a 1.5-T scanner with a phased-array coil. The parameters of the 3D-FLASH sequence were as follows: TR/TE 4.6/1.8 ms, effective thickness 3.5 mm, matrix 512 x 200, flip angle 30 o , field of view 420 mm, TA 23 s, coronal scan orientation. Totally, 476 vessel segments were evaluated for stenosis degree by two radiologists in a consensus fashion in a blinded read. For each patient, a therapy was proposed, if clinically indicated. Sensitivity, specificity, positive and negative predictive values, and accuracy for stenoses ≥50% were 68%, 92%, 44%, 97%, and 90%, respectively. In 13/34 patients, a discrepancy was found concerning therapy decisions based on MRA findings versus therapy decisions based on the reference standard DSA. The results showed that the used MRA imaging technique of abdominal and iliac arteries is not competitive to i.a. DSA, with a high rate of misinterpretation of the MRAs resulting in incorrect therapies

Gene therapy and its implications in Periodontics

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Mahale, Swapna; Dani, Nitin; Ansari, Shumaila S.; Kale, Triveni

2009-01-01

Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense mechanism against infection by transfecting host cells with an antimicrobial peptide protein-encoding gene. -Periodontal vaccination. Gene therapy is one of the recent entrants and its applications in the field of periodontics are reviewed in general here. PMID:20376232

Psychosocial Impact of Personalized Therapies in Oncology.

Science.gov (United States)

Schilling, Georgia; Schulz-Kindermann, Frank

2018-01-01

Personalized medicine is a keyword in modern oncology summarizing biomarker-driven targeted therapies. Those novel agents enhance our therapeutic portfolio and offer new options for our patients. But the term is often misleading and implicates a tailored therapy to the individual person, but it rather means a treatment stratified on genetic characteristics of the tumor. Molecular therapies raise expectations of curability or long-term treatments making former life-threatening diseases to more chronic ones but this is true only for some patients. So we have to carefully communicate with our patients about the options and limitations of those modern therapies not to trigger disappointments.

Anxiety reduction through group instruction in rational therapy.

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Maxwell, J W; Wilkerson, J

1982-09-01

This study investigated the effects of group Rational Therapy in promoting rational thinking and self-enhancing emotions among 24 college students. Each subject was administered the Sixteen Personality Factor Questionnaire as a pre- and post-test measurement. Results reveal that some aspects of personality are affected by Rational Therapy group programs while others are not.

A 5-Year follow-up of internet-based cognitive behavior therapy for social anxiety disorder.

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Hedman, Erik; Furmark, Tomas; Carlbring, Per; Ljótsson, Brjánn; Rück, Christian; Lindefors, Nils; Andersson, Gerhard

2011-06-15

Internet-based cognitive behavior therapy (CBT) has been shown to be a promising method to disseminate cognitive behavior therapy for social anxiety disorder (SAD). Several trials have demonstrated that Internet-based CBT can be effective for SAD in the shorter term. However, the long-term effects of Internet-based CBT for SAD are less well known. Our objective was to investigate the effect of Internet-based CBT for SAD 5 years after completed treatment. We conducted a 5-year follow-up study of 80 persons with SAD who had undergone Internet-based CBT. The assessment comprised a diagnostic interview and self-report questionnaires. The main outcome measure was the Liebowitz Social Anxiety Scale-Self-Report (LSAS-SR). Additional measures of social anxiety were the Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS). Attrition rates were low: 89% (71/80) of the participants completed the diagnostic interview and 80% (64/80) responded to the questionnaires. Mixed-effect models analysis showed a significant effect of time on the three social anxiety measures, LSAS-SR, SIAS, and SPS (F(3,98-102) = 16.05 - 29.20, P < .001) indicating improvement. From baseline to 5-year follow-up, participants' mean scores on the LSAS-SR were reduced from 71.3 (95% confidence interval [CI] 66.1-76.5) to 40.3 (95% CI 35.2 - 45.3). The effect sizes of the LSAS-SR were large (Cohen's d range 1.30 - 1.40, 95% CI 0.77 - 1.90). Improvements gained at the 1-year follow-up were sustained 5 years after completed treatment. Internet-based CBT for SAD is a treatment that can result in large and enduring effects. Clinicaltrials.gov NCT01145690; http://clinicaltrials.gov/ct2/show/NCT01145690 (Archived by WebCite at http://www.webcitation.org/5ygRxDLfK).

Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive-behavioural therapy in out-patients with anorexia nervosa.

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Egger, N; Wild, B; Zipfel, S; Junne, F; Konnopka, A; Schmidt, U; de Zwaan, M; Herpertz, S; Zeeck, A; Löwe, B; von Wietersheim, J; Tagay, S; Burgmer, M; Dinkel, A; Herzog, W; König, H-H

2016-12-01

Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

Exploring play therapy in pediatric oncology: a preliminary endeavour.

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Chari, Uttara; Hirisave, Uma; Appaji, L

2013-04-01

To discuss the benefits and feasibility of play therapy in pediatric oncology. This is highlighted through the use of a case report of non-directive play therapy with a 4 y- old girl, diagnosed with Acute Lymphoblastic Leukemia. The outcome of play therapy was examined using a combination of qualitative and quantitative assessments. The benefits of play therapy with this child were manifested in better illness adjustment and general mental well-being, enhanced coping, and normalization. Having illustrated benefits of play therapy in pediatric oncology, this paper discusses its feasibility and proposes avenues for clinical practice and research endeavours.

Vitamin D enhances the efficacy of photodynamic therapy in a murine model of breast cancer

International Nuclear Information System (INIS)

Rollakanti, Kishore R; Anand, Sanjay; Maytin, Edward V

2015-01-01

Cutaneous metastasis occurs more frequently in breast cancer than in any other malignancy in women, causing significant morbidity. Photodynamic therapy (PDT), which combines a porphyrin-based photosensitizer and activation by light, can be employed for breast cancer (especially cutaneous metastases) but tumor control after PDT has not surpassed traditional treatments methods such as surgery, radiation, and chemotherapy up to now. Here, we report that breast cancer nodules in mice can be effectively treated by preconditioning the tumors with 1α, 25-dihydroxyvitamin D 3 (calcitriol; Vit D) prior to administering 5-aminolevulinate (ALA)-based PDT. Breast carcinoma tumors (MDA-MB-231 cells implanted subcutaneously in nude mice) received systemic Vit D (1 μg/kg) for 3 days prior to receiving ALA. The addition of Vit D increased intratumoral accumulation of protoporphyrin IX (PpIX) by 3.3 ± 0.5-fold, relative to mice receiving ALA alone. Bioluminescence imaging in vivo and immunohistochemical staining confirmed that tumor-specific cell death after ALA-PDT was markedly enhanced (36.8 ± 7.4-fold increase in TUNEL-positive nuclei; radiance decreased to 14% of control) in Vit D pretreated tumors as compared to vehicle-pretreated tumors. Vit D stimulated proliferation (10.7 ± 2.8-fold) and differentiation (9.62 ± 1.7-fold) in tumor cells, underlying an augmented cellular sensitivity to ALA-PDT. The observed enhancement of tumor responses to ALA-PDT after low, nontoxic doses of Vit D supports a new combination approach that deserves consideration in the clinical setting, and offers potential for improved remission of cutaneous breast cancer metastases

Impact of educational outreach intervention on enhancing health care providers' knowledge about statin therapy prescribing in Malaysian patients with type 2 diabetes mellitus.

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Elnaem, Mohamed Hassan; Nik Mohamed, Mohamad Haniki; Zaman Huri, Hasniza; Azarisman, Shah M

2018-03-06

Previous research reported underutilization of statin therapy among patients with type 2 diabetes mellitus. Improving health care providers' awareness and understanding of the benefits and risks of statin treatment could be of assistance in optimizing the statin prescribing process. This study aimed to assess health care providers' knowledge related to statin therapy and the impact of educational outreach intervention based on the perceived knowledge. This was a cross-sectional study based on educational outreach intervention targeting physicians and pharmacists in 1 major tertiary hospital in the state of Pahang, Malaysia. Participants responded to a 12-item, validated questionnaire both prior to and after the outreach educational program. Two sessions were conducted separately for 2 cohorts of pharmacists and physicians. The knowledge scores prior to and after the educational intervention were calculated and compared using a paired-samples t-test. The response rate to both pre-and post-educational outreach questionnaires was 91% (40/44). Prior to the intervention, around 84% (n37) of the participants decided to initiate statin therapy for both pre-assessment clinical case scenarios; however, only 27% (n12) could state the clinical benefits of statin therapy. Forty-five percent (n20) could state the drug to drug interactions, and 52.3% (n23) could identify the statin therapy that can be given at any time day/evening. The educational outreach program increased participants' knowledge scores of 1.450 (95% CI, 0.918 to 1.982) point, P health care providers' knowledge and beliefs about statin therapy. This type of intervention is considered effective for short-term knowledge enhancement. Further research is needed to test the long-term efficacy of such intervention. © 2018 John Wiley & Sons, Ltd.

Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 gy) and intraoperative radiation therapy (15 gy) in patients with primarily resectable pancreatic cancer - NEOPANC

International Nuclear Information System (INIS)

Roeder, Falk; Debus, Juergen; Huber, Peter E; Werner, Jens; Timke, Carmen; Saleh-Ebrahimi, Ladan; Schneider, Lutz; Hackert, Thilo; Hartwig, Werner; Kopp-Schneider, Annette; Hensley, Frank W; Buechler, Markus W

2012-01-01

The current standard treatment, at least in Europe, for patients with primarily resectable tumors, consists of surgery followed by adjuvant chemotherapy. But even in this prognostic favourable group, long term survival is disappointing because of high local and distant failure rates. Postoperative chemoradiation has shown improved local control and overalls survival compared to surgery alone but the value of additional radiation has been questioned in case of adjuvant chemotherapy. However, there remains a strong rationale for the addition of radiation therapy considering the high rates of microscopically incomplete resections after surgery. As postoperative administration of radiation therapy has some general disadvantages, neoadjuvant and intraoperative approaches theoretically offer benefits in terms of dose escalation, reduction of toxicity and patients comfort especially if hypofractionated regimens with highly conformal techniques like intensity-modulated radiation therapy are considered. The NEOPANC trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant short course intensity-modulated radiation therapy (5 × 5 Gy) in combination with surgery and intraoperative radiation therapy (15 Gy), followed by adjuvant chemotherapy according to the german treatment guidelines, in patients with primarily resectable pancreatic cancer. The aim of accrual is 46 patients. The primary objectives of the NEOPANC trial are to evaluate the general feasibility of this approach and the local recurrence rate after one year. Secondary endpoints are progression-free survival, overall survival, acute and late toxicity, postoperative morbidity and mortality and quality of life. http://www.clinicaltrials.gov/ct2/show/NCT01372735

Contrast-Enhanced Ultrasound with VEGFR2-Targeted Microbubbles for Monitoring Regorafenib Therapy Effects in Experimental Colorectal Adenocarcinomas in Rats with DCE-MRI and Immunohistochemical Validation.

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Ralf Stefan Eschbach

Full Text Available To investigate contrast-enhanced ultrasound (CEUS with VEGFR2-targeted microbubbles for monitoring therapy effects of regorafenib on experimental colon carcinomas in rats with correlation to dynamic contrast-enhanced MRI (DCE-MRI and immunohistochemistry.Human colorectal adenocarcinoma xenografts (HT-29 were implanted subcutaneously in n = 21 (n = 11 therapy group; n = 10 control group female athymic nude rats (Hsd: RH-Foxn1rnu. Animals were imaged at baseline and after a one-week daily treatment with regorafenib or a placebo (10 mg/kg bodyweight, using CEUS with VEGFR2-targeted microbubbles and DCE-MRI. In CEUS tumor perfusion was assessed during an early vascular phase (wash-in area under the curve = WiAUC and VEGFR2-specific binding during a late molecular phase (signal intensity after 8 (SI8min and 10 minutes (SI10min, using a conventional 15L8 linear transducer (transmit frequency 7 MHz, dynamic range 80 dB, depth 25 mm. In DCE-MRI functional parameters plasma flow (PF and plasma volume (PV were quantified. For validation purposes, CEUS parameters were correlated with DCE-MRI parameters and immunohistochemical VEGFR2, CD31, Ki-67 and TUNEL stainings.CEUS perfusion parameter WiAUC decreased significantly (116,989 ± 77,048 a.u. to 30,076 ± 27,095a.u.; p = 0.005 under therapy with no significant changes (133,932 ± 65,960 a.u. to 84,316 ± 74,144 a.u.; p = 0.093 in the control group. In the therapy group, the amount of bound microbubbles in the late phase was significantly lower in the therapy than in the control group on day 7 (SI8min: 283 ± 191 vs. 802 ± 460 a.u.; p = 0.006; SI10min: 226 ± 149 vs. 645 ± 461 a.u.; p = 0.009. PF and PV decreased significantly (PF: 147 ± 58 mL/100 mL/min to 71 ± 15 mL/100 mL/min; p = 0.003; PV: 13 ± 3% to 9 ± 4%; p = 0.040 in the therapy group. Immunohistochemistry revealed significantly fewer VEGFR2 (7.2 ± 1.8 vs. 17.8 ± 4.6; p < 0.001, CD31 (8.1 ± 3.0 vs. 20.8 ± 5.7; p < 0.001 and Ki-67 (318.7 �

The mechanisms of inter-effect about gene therapy and radiotherapy to tumor and the prospect of therapeutic alliance

International Nuclear Information System (INIS)

Zhao Yanzhi; Li Jin; Wang Qin; Mu Chuanjie

2006-01-01

The way about therapy include radio therapy and gene therapy in the recent years there are some improve about the therapy alliance, by the mechanism of improving the efficiency of the gene transfering, the recombination and conform of the DNA and induction the expression of the gene et. The radiotherapy can enhance the effect of the gene therapy. By the mechanism of improving of radiosensitivity some, reducing the radiation damage of radiotherapy, repairing the radiation impaired gene the gene therapy can enhance the effect of the radiotherapy. (authors)

Computer games supporting cognitive behaviour therapy in children.

Science.gov (United States)

Brezinka, Veronika

2014-01-01

Therapeutic computer games might enhance children's motivation for psychotherapy, facilitate their understanding of important therapeutic concepts, structure therapy sessions, enhance treatment of migrant children and disseminate evidence-based treatment approaches. The game Treasure Hunt was developed to support cognitive behaviour therapy with children who come into treatment for various mental health problems. To evaluate the applicability and appropriateness of the game, 124 therapists answered a questionnaire on their impression of Treasure Hunt three months after download. Of these, 42 consented to participate in the further evaluation and sent questionnaires of 218 children in whose therapy Treasure Hunt had been used. A limitation of these data is an eventual positive bias, as therapists with a positive attitude towards therapeutic computer games may have been more likely to participate. Data show that the vast majority of children were satisfied their therapist had used the game during treatment. Therapists used Treasure Hunt for a broad range of diagnoses. They judged the game as helpful in the explanation of cognitive-behavioural concepts, used it as reinforcement and reported it enhanced child motivation for psychotherapy and strengthened the therapeutic relationship with the child.

Enhanced CAR T cell therapy: A novel approach for head and neck cancers.

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Wang, Songlin; Zhu, Zhao

2018-05-05

Head and neck cancer that presents in locally advanced stages often results in a bad prognosis with an increased recurrence rate even after curative resections. Radiation therapy is then applied, with multiple side effects, as adjuvant regional therapy. Because of the high rate of recurrence and mortality, new therapies are needed for patients suffering from head and neck malignant tumors.CAR (chimeric antigen receptor) T cell therapy, which was first devised about 25 years ago, causes the killing or apoptosis of target tumor cells through inducing the secretion of cytokines and granzymes by T cells (Cheadle et al., 2014). CARs are comprised of three canonical domains for antigen recognition, T cell activation, and co-stimulation, and are synthetic receptors that reprogram immune cells for therapeutic treatment of multiple tumors (Sadelain, 2017). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Waiting-List Controlled Trial of Cognitive Marital Therapy in Severe Marital Discord.

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Waring, Edward M.; And Others

1991-01-01

Evaluated effectiveness of marital therapy designed to enhance intimacy through self-disclosure of personal constructs. Couples in therapy (n=22) and controls (n=19) showed significant reduction in symptoms of nonpsychotic emotional illness. Couples in therapy subjectively reported improvement. Found significant pattern of improvement for wives in…

WE-G-BRE-07: Proton Therapy Enhanced by Tumor-Targeting Gold Nanoparticles: A Pilot in Vivo Experiment at The Proton Therapy Center at MD Anderson Cancer Center

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Wolfe, T; Grant, J; Wolfe, A; Gillin, M; Krishnan, S [MD Anderson Cancer Ctr., Houston, TX (United States)

2014-06-15

Purpose: Assess tumor-growth delay and survival in a mouse model of prostate cancer treated with tumor-targeting gold nanoparticles (AuNPs) and proton therapy. Methods: We first examined the accumulation of targeting nanoparticles within prostate tumors by imaging AuNPs with ultrasound-guided photoacoustics at 24h after the intravenous administration of goserelin-conjugated AuNPs (gAuNP) in three mice. Nanoparticles were also imaged at the cellular level with TEM in PC3 cells incubated with gAuNP for 24h. Pegylated AuNPs (pAuNP) were also imaged in vivo and in vitro for comparison. PC3 cells were then implanted subcutaneously in nude mice; 51mice with 8–10mm tumors were included. AuNPs were injected intravenously at 0.2%w/w final gold concentration 24h before irradiation. A special jig was designed to facilitate tumor irradiation perpendicular to the proton beam. Proton energy was set to 180MeV, the radiation field was 18×18cm{sup 2}, and 9cm or 13.5cm thick solid-water compensators were used to position the tumors at either the beam entrance (BE) or the SOBP. Physical doses of 5Gy were delivered to all tumors on a patient beam line at MD Anderson's Proton Therapy Center. Results: The photoacoustic experiment reveled that our nanoparticles leak from the tumor-feeding vasculature and accumulate within the tumor volume over time. Additionally, TEM images showed gAuNP are internalized in cancer cells, accumulating within the cytoplasm, whereas pAuNP are not. Tumor-growth was delayed by 11 or 32days in mice receiving gAuNP irradiated at the BE or the SOBP, relative to proton radiation alone. Survival curves (ongoing experiment) reveal that gAuNPs improved survival by 36% or 74% for tumors irradiated at the BE or SOBP. Conclusion: These important, albeit preliminary, in vivo findings reveal nanoparticles to be potent sensitizers to proton therapy. Further, conjugation of AuNPs to tumor-specific antigens that promote enhanced cellular internalization improved

Primed Physical Therapy Enhances Recovery of Upper Limb Function in Chronic Stroke Patients.

Science.gov (United States)

Ackerley, Suzanne J; Byblow, Winston D; Barber, P Alan; MacDonald, Hayley; McIntyre-Robinson, Andrew; Stinear, Cathy M

2016-05-01

Recovery of upper limb function is important for regaining independence after stroke. To test the effects of priming upper limb physical therapy with intermittent theta burst stimulation (iTBS), a form of noninvasive brain stimulation. Eighteen adults with first-ever chronic monohemispheric subcortical stroke participated in this randomized, controlled, triple-blinded trial. Intervention consisted of priming with real or sham iTBS to the ipsilesional primary motor cortex immediately before 45 minutes of upper limb physical therapy, daily for 10 days. Changes in upper limb function (Action Research Arm Test [ARAT]), upper limb impairment (Fugl-Meyer Scale), and corticomotor excitability, were assessed before, during, and immediately, 1 month and 3 months after the intervention. Functional magnetic resonance images were acquired before and at one month after the intervention. Improvements in ARAT were observed after the intervention period when therapy was primed with real iTBS, but not sham, and were maintained at 1 month. These improvements were not apparent halfway through the intervention, indicating a dose effect. Improvements in ARAT at 1 month were related to balancing of corticomotor excitability and an increase in ipsilesional premotor cortex activation during paretic hand grip. Two weeks of iTBS-primed therapy improves upper limb function at the chronic stage of stroke, for at least 1 month postintervention, whereas therapy alone may not be sufficient to alter function. This indicates a potential role for iTBS as an adjuvant to therapy delivered at the chronic stage. © The Author(s) 2015.

Blending online therapy into regular face-to-face therapy for depression: content, ratio and preconditions according to patients and therapists using a Delphi study.

NARCIS (Netherlands)

van der Vaart, R.; Witting, M.; Riper, H.; Kooistra, L.C.; Bohlmeijer, E.T.; van Gemert-Pijnen, L.

2014-01-01

Background: Blending online modules into face-to-face therapy offers perspectives to enhance patient self-management and to increase the (cost-)effectiveness of therapy, while still providing the support patients need. The aim of this study was to outline optimal usage of blended care for

Combined passive acoustic mapping and magnetic resonance thermometry for monitoring phase-shift nanoemulsion enhanced focused ultrasound therapy

Science.gov (United States)

Crake, Calum; Meral, F. Can; Burgess, Mark T.; Papademetriou, Iason T.; McDannold, Nathan J.; Porter, Tyrone M.

2017-08-01

Focused ultrasound (FUS) has the potential to enable precise, image-guided noninvasive surgery for the treatment of cancer in which tumors are identified and destroyed in a single integrated procedure. However, success of the method in highly vascular organs has been limited due to heat losses to perfusion, requiring development of techniques to locally enhance energy absorption and heating. In addition, FUS procedures are conventionally monitored using MRI, which provides excellent anatomical images and can map temperature, but is not capable of capturing the full gamut of available data such as the acoustic emissions generated during this inherently acoustically-driven procedure. Here, we employed phase-shift nanoemulsions (PSNE) embedded in tissue phantoms to promote cavitation and hence temperature rise induced by FUS. In addition, we incorporated passive acoustic mapping (PAM) alongside simultaneous MR thermometry in order to visualize both acoustic emissions and temperature rise, within the bore of a full scale clinical MRI scanner. Focal cavitation of PSNE could be resolved using PAM and resulted in accelerated heating and increased the maximum elevated temperature measured via MR thermometry compared to experiments without nanoemulsions. Over time, the simultaneously acquired acoustic and temperature maps show translation of the focus of activity towards the FUS transducer, and the magnitude of the increase in cavitation and focal shift both increased with nanoemulsion concentration. PAM results were well correlated with MRI thermometry and demonstrated greater sensitivity, with the ability to detect cavitation before enhanced heating was observed. The results suggest that PSNE could be beneficial for enhancement of thermal focused ultrasound therapies and that PAM could be a critical tool for monitoring this process.

Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

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Suellen M. Andrade

2017-01-01

Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

The effects of reminiscence therapy on depressive symptoms of Chinese elderly: study protocol of a randomized controlled trial

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Chen Ting-ji

2012-11-01

Full Text Available Abstract Background Depression is one of the most common mental disorders with a high prevalence among the older adults. In recent years, after realizing some side effects of the antidepressants, non-pharmacological psychological treatments begin to attract accruing attention. Reminiscence therapy is one of the psychological treatments that specially designed for the elderly to improve their mental health status by recalling and assessing their existing memory. Though some studies indicate reminiscence therapy can be effective and beneficial for the mental health of elderly, the conclusions are not consistent yet. The aim of this research is to assess the effectiveness of reminiscence therapy for Chinese elderly. Methods Sixty older adults (≥60 years of age with mild to moderate depression will be randomly assigned to an experimental or a control condition. The participants in the experiment group will receive the reminiscence therapy under the Watt’s protocol with adaptation to Chinese Culture which consists of six weekly sessions of 90 minutes each. The control group will be treated as before. An assessor who is blind to intervention will conduct the measures before treatment, after treatment immediately, and three months after treatment. Discussion This study will provide the evidence whether the reminiscence therapy is effective to treat depressive symptoms of Chinese elderly. This research has been registered in the clinicaltrials.gov (NCT01553669.

Functional strength training and movement performance therapy produce analogous improvement in sit-to-stand early after stroke: early-phase randomised controlled trial.

Science.gov (United States)

Kerr, A; Clark, A; Cooke, E V; Rowe, P; Pomeroy, V M

2017-09-01

Restoring independence in the sit-to-stand (STS) task is an important objective for stroke rehabilitation. It is not known if a particular intervention, strength training or therapy focused on movement performance is more likely to improve STS recovery. This study aimed to compare STS outcomes from functional strength training, movement performance therapy and conventional therapy. Randomised controlled trial. Acute stroke units. Medically well patients (n=93) with recent (movement performance therapy. Subjects were allocated to groups on a random basis. STS ability, timing, symmetry, co-ordination, smoothness and knee velocity were measured at baseline, outcome (after 6 weeks of intervention) and follow-up (3 months after outcome). No significant differences were found between the groups. All three groups improved their STS ability, with 88% able to STS at follow-up compared with 56% at baseline. Few differences were noted in quality of movement, with only symmetry when rising showing significantly greater improvement in the movement performance therapy group; this benefit was not evident at follow-up. Recovery of the STS movement is consistently good during stroke rehabilitation, irrespective of the type of therapy experienced. Changes in quality of movement did not differ according to group allocation, indicating that the type of therapy is less important. Clinical trial registration number NCT00322192. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Blending online therapy into regular face-to-face therapy for depression: content, ratio and preconditions according to patients and therapists using a Delphi study

NARCIS (Netherlands)

van der Vaart, R.; Witting, Marjon; Riper, Heleen; Kooistra, L.C.; Bohlmeijer, Ernst Thomas; van Gemert-Pijnen, Julia E.W.C.

2014-01-01

Background Blending online modules into face-to-face therapy offers perspectives to enhance patient self-management and to increase the (cost-)effectiveness of therapy, while still providing the support patients need. The aim of this study was to outline optimal usage of blended care for depression,

Pharmacological enhancement of treatment for amblyopia

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Rashad MA

2012-03-01

Full Text Available Mohammad A RashadOphthalmology Department, Faculty of Medicine, Ain Shams University, Cairo, EgyptBackground: The purpose of this study was to compare a weight-adjusted dose of carbidopa-levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia.Methods: This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks.Results: The mean logarithm of the minimal angle of resolution (logMAR of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51 than in the pharmacological enhancement group (0.58, 0.49, and 0.56 at three follow-up visits (at months 1, 3, and 12, respectively. There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51 and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56 at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively. The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5% than in the occlusion group (30%. The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3% than in the occlusion group (22%.Conclusion: Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy.

Science.gov (United States)

Ganesan, Palanivel; Choi, Dong-Kug

2016-01-01

Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty-based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care. Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy.

Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

Science.gov (United States)

Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

2011-01-01

The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Brain-specific enhancers for cell-based therapy

Science.gov (United States)

Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun; Pennacchio, Len A.; Vogt, Daniel; Nicholas, Cory; Kriegstein, Arnold

2018-04-24

Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

Gene therapy for ocular diseases.

Science.gov (United States)

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Gamblers anonymous and cognitive-behavioral therapies for pathological gamblers.

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Petry, Nancy M

2005-01-01

Numerous types of treatments for pathological gambling have been described, but two of the most common are Gamblers Anonymous (GA) and cognitive-behavioral therapy. This paper describes some outcome data associated with the two approaches. It also reviews evidence suggesting that a combined intervention may enhance therapy engagement and reduce relapse rates.

Future directions for ICT in aphasia therapy for older adults: enhancing current practices through interdisciplinary perspectives

OpenAIRE

Kötteritzsch, Anna; Gerling, Kathrin

2015-01-01

Growing numbers of older adults requiring aphasia therapy create challenges for the health care system. Information and communication technology (ICT) has the potential to provide computer-mediated, self-administered aphasia therapy that complements conventional therapy. We explore overlaps in ICT for older adults and aphasia therapy applications with the goal of integrating innovative ICT in aphasia therapy. Based on a case study, we explain how results of different disciplines developing IC...

Acidity-Triggered Tumor Retention/Internalization of Chimeric Peptide for Enhanced Photodynamic Therapy and Real-Time Monitoring of Therapeutic Effects.

Science.gov (United States)

Han, Kai; Zhang, Wei-Yun; Ma, Zhao-Yu; Wang, Shi-Bo; Xu, Lu-Ming; Liu, Jia; Zhang, Xian-Zheng; Han, He-You

2017-05-17

Photodynamic therapy (PDT) holds great promise in tumor treatment. Nevertheless, it remains highly desirable to develop easy-to-fabricated PDT systems with improved tumor accumulation/internalization and timely therapeutic feedback. Here, we report a tumor-acidity-responsive chimeric peptide for enhanced PDT and noninvasive real-time apoptosis imaging. Both in vitro and in vivo studies revealed that a tumor mildly acidic microenvironment could trigger rapid protonation of carboxylate anions in chimeric peptide, which led to increased ζ potential, improved hydrophobicity, controlled size enlargement, and precise morphology switching from sphere to spherocylinder shape of the chimeric peptide. All of these factors realized superfast accumulation and prolonged retention in the tumor region, selective cellular internalization, and enhanced PDT against the tumor. Meanwhile, this chimeric peptide could further generate reactive oxygen species and initiate cell apoptosis during PDT. The subsequent formation of caspase-3 enzyme hydrolyzed the chimeric peptide, achieving a high signal/noise ratio and timely fluorescence feedback. Importantly, direct utilization of the acidity responsiveness of a biofunctional Asp-Glu-Val-Asp-Gly (DEVDG, caspase-3 enzyme substrate) peptide sequence dramatically simplified the preparation and increased the performance of the chimeric peptide furthest.

Single-session gamified virtual reality exposure therapy for spider phobia vs. traditional exposure therapy: study protocol for a randomized controlled non-inferiority trial.

Science.gov (United States)

Miloff, Alexander; Lindner, Philip; Hamilton, William; Reuterskiöld, Lena; Andersson, Gerhard; Carlbring, Per

2016-02-02

Traditional one-session exposure therapy (OST) in which a patient is gradually exposed to feared stimuli for up to 3 h in a one-session format has been found effective for the treatment of specific phobias. However, many individuals with specific phobia are reluctant to seek help, and access to care is lacking due to logistic challenges of accessing, collecting, storing, and/or maintaining stimuli. Virtual reality (VR) exposure therapy may improve upon existing techniques by facilitating access, decreasing cost, and increasing acceptability and effectiveness. The aim of this study is to compare traditional OST with in vivo spiders and a human therapist with a newly developed single-session gamified VR exposure therapy application with modern VR hardware, virtual spiders, and a virtual therapist. Participants with specific phobia to spiders (N = 100) will be recruited from the general public, screened, and randomized to either VR exposure therapy (n = 50) or traditional OST (n = 50). A behavioral approach test using in vivo spiders will serve as the primary outcome measure. Secondary outcome measures will include spider phobia questionnaires and self-reported anxiety, depression, and quality of life. Outcomes will be assessed using a non-inferiority design at baseline and at 1, 12, and 52 weeks after treatment. VR exposure therapy has previously been evaluated as a treatment for specific phobias, but there has been a lack of high-quality randomized controlled trials. A new generation of modern, consumer-ready VR devices is being released that are advancing existing technology and have the potential to improve clinical availability and treatment effectiveness. The VR medium is also particularly suitable for taking advantage of recent phobia treatment research emphasizing engagement and new learning, as opposed to physiological habituation. This study compares a market-ready, gamified VR spider phobia exposure application, delivered using consumer VR hardware, with

Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

International Nuclear Information System (INIS)

Chen Bin; Pogue, Brian W.; Hoopes, P. Jack; Hasan, Tayyaba

2005-01-01

Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm 2 ) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm 2 ) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments

Cognitive Behavioral Therapy for Eating Disorders

OpenAIRE

Murphy, Rebecca; Straebler, Suzanne; Cooper, Zafra; Fairburn, Christopher G.

2010-01-01

Cognitive behavioral therapy (CBT) is the leading evidence-based treatment for bulimia nervosa. A new ?enhanced? version of the treatment appears to be more potent and has the added advantage of being suitable for all eating disorders, including anorexia nervosa and eating disorder not otherwise specified. This article reviews the evidence supporting CBT in the treatment of eating disorders and provides an account of the ?transdiagnostic? theory that underpins the enhanced form of the treatme...

Post-operative benefits of animal-assisted therapy in pediatric surgery: a randomised study.

Directory of Open Access Journals (Sweden)

Valeria Calcaterra

Full Text Available Interest in animal-assisted therapy has been fuelled by studies supporting the many health benefits. The purpose of this study was to better understand the impact of an animal-assisted therapy program on children response to stress and pain in the immediate post-surgical period.Forty children (3-17 years were enrolled in the randomised open-label, controlled, pilot study. Patients were randomly assigned to the animal-assisted therapy-group (n = 20, who underwent a 20 min session with an animal-assisted therapy dog, after surgery or the standard-group (n = 20, standard postoperative care. The study variables were determined in each patient, independently of the assigned group, by a researcher unblinded to the patient's group. The outcomes of the study were to define the neurological, cardiovascular and endocrinological impact of animal-assisted therapy in response to stress and pain. Electroencephalogram activity, heart rate, blood pressure, oxygen saturation, cerebral prefrontal oxygenation, salivary cortisol levels and the faces pain scale were considered as outcome measures.After entrance of the dog faster electroencephalogram diffuse beta-activity (> 14 Hz was reported in all children of the animal-assisted therapy group; in the standard-group no beta-activity was recorded (100% vs 0%, p<0.001. During observation, some differences in the time profile between groups were observed for heart rate (test for interaction p = 0.018, oxygen saturation (test for interaction p = 0.06 and cerebral oxygenation (test for interaction p = 0.09. Systolic and diastolic blood pressure were influenced by animal-assisted therapy, though a higher variability in diastolic pressure was observed. Salivary cortisol levels did not show different behaviours over time between groups (p=0.70. Lower pain perception was noted in the animal-assisted group in comparison with the standard-group (p = 0.01.Animal-assisted therapy facilitated rapid recovery in vigilance and

Effects of atomoxetine with and without behavior therapy on the school and home functioning of children with attention-deficit/hyperactivity disorder.

Science.gov (United States)

Waxmonsky, James G; Waschbusch, Daniel A; Pelham, William E; Draganac-Cardona, Lillian; Rotella, Bryan; Ryan, Lynn

2010-11-01

To evaluate the effects of atomoxetine alone and in combination with behavior therapy on the school functioning of children with attention-deficit/hyperactivity disorder (ADHD). Most atomoxetine studies have not assessed school functioning other than by measuring the change in ADHD symptoms. Combining behavior therapy with atomoxetine may be particularly beneficial for the academic domain as medication has not been found to produce sustained benefits in this realm. However, there is little research examining the effects of combining atomoxetine and behavior therapy. In an 8-week open-label trial, 56 children aged 6-12 years with ADHD diagnosed according to DSM-IV-TR were randomly assigned to receive atomoxetine and behavior therapy or atomoxetine alone. Behavior therapy consisted of an 8-week parenting course, a child social skills course, and a teacher-implemented daily report card of classroom behavior. The primary outcome was direct observation of the subject's classroom behavior. Secondary outcomes included change in ADHD symptoms and functioning at home and school. All data were collected between March 2007 and May 2008. Classroom observations showed that atomoxetine decreased rule violations (P parent-rated symptoms of inattention (P parents, teachers, and direct observation. The addition of behavior therapy led to further improvements at home but not at school. clinicaltrials.gov Identifier: NCT00918567. © Copyright 2010 Physicians Postgraduate Press, Inc.

Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial

Science.gov (United States)

Forestier, R; Desfour, H; Tessier, J-M; Françon, A; Foote, A M; Genty, C; Rolland, C; Roques, C-F; Bosson, J-L

2010-01-01

Objective To determine whether spa therapy, plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment, in the management of knee osteoarthritis. Methods Large multicentre randomised prospective clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria, attending French spa resorts as outpatients between June 2006 and April 2007. Zelen randomisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating. The main endpoint criteria were patient self-assessed. All patients continued usual treatments and performed daily standardised home exercises. The spa therapy group also received 18 days of spa therapy (massages, showers, mud and pool sessions). Main Endpoint The number of patients achieving minimal clinically important improvement (MCII) at 6 months, defined as ≥19.9 mm on the visual analogue pain scale and/or ≥9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery. Results The intention to treat analysis included 187 controls and 195 spa therapy patients. At 6 months, 99/195 (50.8%) spa group patients had MCII and 68/187 (36.4%) controls (χ2=8.05; df=1; p=0.005). However, no improvement in quality of life (Short Form 36) or patient acceptable symptom state was observed at 6 months. Conclusion For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone, and is well tolerated. Trial registration number NCT00348777. PMID:19734131

Reflections on Clinical Learning in Novice Speech-Language Therapy Students

Science.gov (United States)

Hill, Anne E.; Davidson, Bronwyn J.; Theodoros, Deborah G.

2012-01-01

Background: Reflective practice is reported to enhance clinical reasoning and therefore to maximize client outcomes. The inclusion of targeted reflective practice in academic programmes in speech-language therapy has not been consistent, although providing opportunities for speech-language therapy students to reflect during their clinical practice…

Additive effect of BPA and Gd-DTPA for application in accelerator-based neutron source

International Nuclear Information System (INIS)

Yoshida, F.; Yamamoto, T.; Nakai, K.; Zaboronok, A.; Matsumura, A.

2015-01-01

Because of its fast metabolism gadolinium as a commercial drug was not considered to be suitable for neutron capture therapy. We studied additive effect of gadolinium and boron co-administration using colony forming assay. As a result, the survival of tumor cells with additional 5 ppm of Gd-DTPA decreased to 1/10 compared to the cells with boron only. Using gadolinium to increase the effect of BNCT instead of additional X-ray irradiation might be beneficial, as such combination complies with the short-time irradiation regimen at the accelerator-based neutron source. - Highlights: • Gd-DTPA is widely clinically used as a contrast medium for MRI. • Shift to an accelerator-based neutron source is advantageous for gadolinium NCT. • Boron–gadolinium NCT effects on tumor cell lines were significant. • Additional administration of Gd-DTPA might enhance the effect of BPA–BNCT.

Moderators and predictors of response to behavior therapy for tics in Tourette syndrome.

Science.gov (United States)

Sukhodolsky, Denis G; Woods, Douglas W; Piacentini, John; Wilhelm, Sabine; Peterson, Alan L; Katsovich, Lily; Dziura, James; Walkup, John T; Scahill, Lawrence

2017-03-14

To examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders. Data from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9-69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression-Improvement score assessed by masked evaluators. The presence of tic medication significantly moderated response to CBIT vs PST ( p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity ( p = 0.005) and positive participant expectancy ( p = 0.01) predicted greater tic improvement. Anxiety disorders ( p = 0.042) and premonitory urge severity ( p = 0.005) predicted lower tic reduction. Presence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication. The child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respectively). This study provides Class I evidence that

Near-infrared light-triggered theranostics for tumor-specific enhanced multimodal imaging and photothermal therapy

Directory of Open Access Journals (Sweden)

Wu B

2017-06-01

Full Text Available Bo Wu,1,* Bing Wan,2,* Shu-Ting Lu,1 Kai Deng,3 Xiao-Qi Li,1 Bao-Lin Wu,1 Yu-Shuang Li,1 Ru-Fang Liao,1 Shi-Wen Huang,3 Hai-Bo Xu1,2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Department of Radiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 3Department of Chemistry, Key Laboratory of Biomedical Polymers, Ministry of Education, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: The major challenge in current clinic contrast agents (CAs and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed “bomb-like” light-triggered CAs (LTCAs for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration. This will result in protection and fluorescence quenching. Then, the release of CAs was triggered by near-infrared (NIR light laser irradiation, which will lead to fluorescence and MRI activation and enable imaging of inflammation. In vitro and in vivo experiments demonstrated that LTCAs with 808 nm laser irradiation have shorter T1 relaxation time in MRI and stronger intensity in FI compared to those without irradiation. Additionally, due to the high photothermal conversion efficiency of IR820, the injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice up to 17 days after NIR laser irradiation. The results indicate that the LTCAs can serve as a promising platform for NIR-activated multimodal imaging and photothermal therapy. Keywords: light triggered, near-infrared light, tumor-specific, multimodal imaging, photothermal therapy, contrast agents

Genetic engineering of stem cells for enhanced therapy.

Science.gov (United States)

Nowakowski, Adam; Andrzejewska, Anna; Janowski, Miroslaw; Walczak, Piotr; Lukomska, Barbara

2013-01-01

Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.

The Use of Dialectical Behavior Therapy (DBT) in Music Therapy: A Sequential Explanatory Study.

Science.gov (United States)

Chwalek, Carolyn M; McKinney, Cathy H

2015-01-01

There are published examples of how dialectical behavior therapy (DBT) and music therapy are effectively being used as separate therapies in the treatment of individuals with a variety of mental health disorders. However, research examining DBT-informed music therapy is limited. The purpose of this study was to determine whether music therapists working in mental health settings are implementing components of DBT in their work, and if so, how and why; and if not, why not and what is their level of interest in such work. We used a sequential explanatory mixed-methods research design implemented in two phases. Phase 1 was a quantitative survey of board-certified music therapists (n=260). Due to a low survey response rate (18%), and to enhance the validity of the findings, Phase 2, an embedded qualitative procedure in the form of interviews with clinicians experienced in the DBT approach, was added to the study. Both survey and interviews inquired about DBT training, use of DBT-informed music therapy, music therapy experiences used to address DBT skills, and experiences of implementing DBT-informed music therapy. Respondents indicating they implement DBT-informed music therapy (38.3%) are using components and adaptations of the standard DBT protocol. Advantages of implementing DBT-informed music therapy were identified, and more than half of the respondents who do not implement DBT in their music therapy practice also perceived this work as at least somewhat important. Disadvantages were also identified and support the need for further research. Components of DBT are used in music therapy and are valued, but there is a lack of empirical evidence to inform, refine, and guide practice. © the American Music Therapy Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Oculomotor biofeedback therapy for exotropia.

Science.gov (United States)

Goldrich, S G

1982-04-01

Twelve exotropes of various types received oculomotor biofeedback therapy at State College of New York (SUNY) University Optometric Center. Feedback of a variable pitch tone which reflected changes in ocular vergence reinforced motor control of eye posture. Patients were trained to achieve and sustain alignment in a variety of viewing situations. The six intermittent exotropes in the study who did not have amblyopia or prior history of unsuccessful surgical or orthoptic therapy achieved the highest recovery rating after training. The amblyope and those who had orthoptic training learned to voluntarily correct their eye position, although they did not achieve as acute a sensitivity to loss of alignment as did the others. Therapy restored eye control at near in a young constant exotrope whose condition resulted from severe neurological dysfunction. A constant postsurgical exotrope who had no ability for sensory fusion made little progress. Advantages of oculomotor biofeedback therapy are shorter treatment time, elimination of lengthy home training exercises, and enhanced patient motivation.

A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458).

Science.gov (United States)

Shaib, Walid L; Hawk, Natalyn; Cassidy, Richard J; Chen, Zhengjia; Zhang, Chao; Brutcher, Edith; Kooby, David; Maithel, Shishir K; Sarmiento, Juan M; Landry, Jerome; El-Rayes, Bassel F

2016-10-01

A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials. Copyright © 2016 Elsevier Inc. All rights reserved.

A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)

International Nuclear Information System (INIS)

Shaib, Walid L.; Hawk, Natalyn; Cassidy, Richard J.; Chen, Zhengjia; Zhang, Chao; Brutcher, Edith; Kooby, David; Maithel, Shishir K.; Sarmiento, Juan M.; Landry, Jerome; El-Rayes, Bassel F.

2016-01-01

Purpose: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials: A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results: Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion: The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.

A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)

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Shaib, Walid L.; Hawk, Natalyn [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Cassidy, Richard J. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Chen, Zhengjia; Zhang, Chao [Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Brutcher, Edith [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Kooby, David; Maithel, Shishir K.; Sarmiento, Juan M. [Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Landry, Jerome [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); El-Rayes, Bassel F., E-mail: bassel.el-rayes@emoryhealthcare.org [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

2016-10-01

Purpose: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials: A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results: Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion: The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.

Time to reconsider nonsurgical therapy of benign nontoxic multinodular goitre. Focus on recombinant human TSH (rhTSH) augmented radioiodine therapy

DEFF Research Database (Denmark)

Fast, Søren; Nielsen, Viveque; Bonnema, Steen

2009-01-01

alternatives are needed. Until recently, levothyroxine therapy was the preferred non-surgical alternative, but due to low efficacy and potential side-effects, it is not recommended for routine use in recent international guidelines. Conventional radioiodine (131I)-therapy has been used for two decades......, which makes 131I-therapy less feasible. Another challenge is the negative correlation between initial goitre size and goitre volume reduction (GVR). With its ability to more than double the thyroid 131I-uptake, recombinant human TSH (rhTSH) increases the absorbed radiation dose and thus enhances the GVR...... efficacy. Thus, although in its infancy, and still experimental, rhTSH-augmented 131I-therapy may profoundly alter the nonsurgical treatment of benign non-toxic MNG....

Photodynamic therapy in endodontics: a literature review.

Science.gov (United States)

Trindade, Alessandra Cesar; De Figueiredo, José Antônio Poli; Steier, Liviu; Weber, João Batista Blessmann

2015-03-01

Recently, several in vitro and in vivo studies demonstrated promising results about the use of photodynamic therapy during root canal system disinfection. However, there is no consensus on a standard protocol for its incorporation during root canal treatment. The purpose of this study was to summarize the results of research on photodynamic therapy in endodontics published in peer-reviewed journals. A review of pertinent literature was conducted using the PubMed database, and data obtained were categorized into sections in terms of relevant topics. Studies conducted in recent years highlighted the antimicrobial potential of photodynamic therapy in endodontics. However, most of these studies were not able to confirm a significant improvement in root canal disinfection for photodynamic therapy as a substitute for current disinfection methods. Its indication as an excellent adjunct to conventional endodontic therapy is well documented, however. Data suggest the need for protocol adjustments or new photosensitizer formulations to enhance photodynamic therapy predictability in endodontics.

Periosteal Electrical Dry Needling as an Adjunct to Exercise and Manual Therapy for Knee Osteoarthritis: A Multi-Center Randomized Clinical Trial.

Science.gov (United States)

Dunning, James; Butts, Raymond; Young, Ian; Mourad, Firas; Galante, Victoria; Bliton, Paul; Tanner, Michelle; Fernández-de-Las-Peñas, César

2018-05-28

To compare the effects of adding electrical dry needling into a manual therapy and exercise program on pain, stiffness, function, and disability in individuals with painful knee osteoarthritis (OA). Two hundred and forty-two participants (n=242) with painful knee OA were randomized to receive 6 weeks of electrical dry needling, manual therapy and exercise (n=121) or manual therapy and exercise (n=121). The primary outcome was related-disability as assessed by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 3 months. Individuals receiving the combination of electrical dry needling, manual therapy and exercise experienced significantly greater improvements in related-disability (WOMAC: F=35.504; P0.82) for all outcome measures in favor of the electrical dry needling group at 3 months. The inclusion of electrical dry needling into a manual therapy and exercise program was more effective for improving pain, function and related-disability than the application of manual therapy and exercise alone in individuals with painful knee OA. Therapy, Level 1b. Prospectively registered February 10, 2015 on http://www.clinicaltrials.gov (NCT02373631)This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Quality management and accreditation of research tissue banks: experience of the National Center for Tumor Diseases (NCT) Heidelberg.

Science.gov (United States)

Herpel, Esther; Röcken, Christoph; Manke, Heike; Schirmacher, Peter; Flechtenmacher, Christa

2010-12-01

Tissue banks are key resource and technology platforms in biomedical research that address the molecular pathogenesis of diseases as well as disease prevention, diagnosis, and treatment. Due to the central role of tissue banks in standardized collection, storage, and distribution of human tissues and their derivatives, quality management and its external assessment is becoming increasingly relevant for the maintenance, acceptance, and funding of tissue banks. Little experience exists regarding formalized external evaluation of tissue banks, especially regarding certification and accreditation. Based on the accreditation of the National Center of Tumor Diseases (NCT) tissue bank in Heidelberg (Germany), criteria, requirements, processes, and implications were compiled and evaluated. Accreditation formally approved professional competence and performance of the tissue bank in all steps involved in tissue collection, storage, handling as well as macroscopic and histologic examination and final (exit) examination of the tissue and transfer supervised by board-certified competent histopathologists. Thereby, accreditation provides a comprehensive measure to evaluate and document the quality standard of tissue research banks and may play a significant role in the future assessment of tissue banks. Furthermore, accreditation may support harmonization and standardization of tissue banking for biomedical research purposes.

A randomised controlled trial evaluating family mediated exercise (FAME therapy following stroke

Directory of Open Access Journals (Sweden)

Stokes Emma

2008-06-01

Full Text Available Abstract Background Stroke is a leading cause of disability among adults worldwide. Evidence suggests that increased duration of exercise therapy following stroke has a positive impact on functional outcome following stroke. The main objective of this randomised controlled trial is to evaluate the impact of additional family assisted exercise therapy in people with acute stroke. Methods/Design A prospective multi-centre single blind randomised controlled trial will be conducted. Forty patients with acute stroke will be randomised into either an experimental or control group. The experimental group will receive routine therapy and additional lower limb exercise therapy in the form of family assisted exercises. The control group will receive routine therapy with no additional formal input from their family members. Participants will be assessed at baseline, post intervention and followed up at three months using a series of standardised outcome measures. A secondary aim of the project is to evaluate the impact of the family mediated exercise programme on the person with stroke and the individual(s assisting in the delivery of exercises using a qualitative methodology. The study has gained ethical approval from the Research Ethics Committees of each of the clinical sites involved in the study. Discussion This study will evaluate a structured programme of exercises that can be delivered to people with stroke by their 'family members/friends'. Given that the progressive increase in the population of older people is likely to lead to an increased prevalence of stroke in the future, it is important to reduce the burden of this illness on the individual, the family and society. Family mediated exercises can maximise the carry over outside formal physiotherapy sessions, giving patients the opportunity for informal practice. Trial Registration The protocol for this study is registered with the US NIH Clinical trials registry (NCT00666744

Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial.

Science.gov (United States)

Vazquez, Jose; Reboli, Annette C; Pappas, Peter G; Patterson, Thomas F; Reinhardt, John; Chin-Hong, Peter; Tobin, Ellis; Kett, Daniel H; Biswas, Pinaki; Swanson, Robert

2014-02-21

Hospitalized patients are at increased risk for candidemia and invasive candidiasis (C/IC). Improved therapeutic regimens with enhanced clinical and pharmacoeconomic outcomes utilizing existing antifungal agents are still needed. An open-label, non-comparative study evaluated an intravenous (i.v.) to oral step-down strategy. Patients with C/IC were treated with i.v. anidulafungin and after 5 days of i.v. therapy had the option to step-down to oral azole therapy (fluconazole or voriconazole) if they met prespecified criteria. The primary endpoint was the global response rate (clinical + microbiological) at end of treatment (EOT) in the modified intent-to-treat (MITT) population (at least one dose of anidulafungin plus positive Candida within 96 hours of study entry). Secondary endpoints included efficacy at other time points and in predefined patient subpopulations. Patients who stepped down early (≤ 7 days' anidulafungin) were identified as the "early switch" subpopulation. In total, 282 patients were enrolled, of whom 250 were included in the MITT population. The MITT global response rate at EOT was 83.7% (95% confidence interval, 78.7-88.8). Global response rates at all time points were generally similar in the early switch subpopulation compared with the MITT population. Global response rates were also similar across multiple Candida species, including C. albicans, C. glabrata, and C. parapsilosis. The most common treatment-related adverse events were nausea and vomiting (four patients each). A short course of i.v. anidulafungin, followed by early step-down to oral azole therapy, is an effective and well-tolerated approach for the treatment of C/IC. ClinicalTrials.gov: NCT00496197.

Long-term effect of gene therapy on Leber's congenital amaurosis.

Science.gov (United States)

Bainbridge, James W B; Mehat, Manjit S; Sundaram, Venki; Robbie, Scott J; Barker, Susie E; Ripamonti, Caterina; Georgiadis, Anastasios; Mowat, Freya M; Beattie, Stuart G; Gardner, Peter J; Feathers, Kecia L; Luong, Vy A; Yzer, Suzanne; Balaggan, Kamaljit; Viswanathan, Ananth; de Ravel, Thomy J L; Casteels, Ingele; Holder, Graham E; Tyler, Nick; Fitzke, Fred W; Weleber, Richard G; Nardini, Marko; Moore, Anthony T; Thompson, Debra A; Petersen-Jones, Simon M; Michaelides, Michel; van den Born, L Ingeborgh; Stockman, Andrew; Smith, Alexander J; Rubin, Gary; Ali, Robin R

2015-05-14

Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

Co-expression of interleukin 12 enhances antitumor effects of a novel chimeric promoter-mediated suicide gene therapy in an immunocompetent mouse model

International Nuclear Information System (INIS)

Xu, Yu; Liu, Zhengchun; Kong, Haiyan; Sun, Wenjie; Liao, Zhengkai; Zhou, Fuxiang; Xie, Conghua

2011-01-01

Highlights: → A novel chimeric promoter consisting of CArG element and hTERT promoter was developed. → The promoter was characterized with radiation-inducibility and tumor-specificity. → Suicide gene system driven by the promoter showed remarkable cytotoxicity in vitro. → Co-expression of IL12 enhanced the promoter mediated suicide gene therapy in vivo. -- Abstract: The human telomerase reverse transcriptase (hTERT) promoter has been widely used in target gene therapy of cancer. However, low transcriptional activity limited its clinical application. Here, we designed a novel dual radiation-inducible and tumor-specific promoter system consisting of CArG elements and the hTERT promoter, resulting in increased expression of reporter genes after gamma-irradiation. Therapeutic and side effects of adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter were evaluated in mice bearing Lewis lung carcinoma, combining with or without adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus promoter. The combination treatment showed more effective suppression of tumor growth than those with single agent alone, being associated with pronounced intratumoral T-lymphocyte infiltration and minor side effects. Our results suggest that the combination treatment with HRP/IAA system driven by the novel chimeric promoter and the co-expression of IL12 might be an effective and safe target gene therapy strategy of cancer.

Co-expression of interleukin 12 enhances antitumor effects of a novel chimeric promoter-mediated suicide gene therapy in an immunocompetent mouse model

Energy Technology Data Exchange (ETDEWEB)

Xu, Yu, E-mail: xuyu1001@gmail.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Liu, Zhengchun, E-mail: l135027@126.com [Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Kong, Haiyan, E-mail: suppleant@163.com [Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Sun, Wenjie, E-mail: wendy11240325@163.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Liao, Zhengkai, E-mail: fastbeta@gmail.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Zhou, Fuxiang, E-mail: happyzhoufx@sina.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Xie, Conghua, E-mail: chxie_65@hotmail.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); and others

2011-09-09

Highlights: {yields} A novel chimeric promoter consisting of CArG element and hTERT promoter was developed. {yields} The promoter was characterized with radiation-inducibility and tumor-specificity. {yields} Suicide gene system driven by the promoter showed remarkable cytotoxicity in vitro. {yields} Co-expression of IL12 enhanced the promoter mediated suicide gene therapy in vivo. -- Abstract: The human telomerase reverse transcriptase (hTERT) promoter has been widely used in target gene therapy of cancer. However, low transcriptional activity limited its clinical application. Here, we designed a novel dual radiation-inducible and tumor-specific promoter system consisting of CArG elements and the hTERT promoter, resulting in increased expression of reporter genes after gamma-irradiation. Therapeutic and side effects of adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter were evaluated in mice bearing Lewis lung carcinoma, combining with or without adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus promoter. The combination treatment showed more effective suppression of tumor growth than those with single agent alone, being associated with pronounced intratumoral T-lymphocyte infiltration and minor side effects. Our results suggest that the combination treatment with HRP/IAA system driven by the novel chimeric promoter and the co-expression of IL12 might be an effective and safe target gene therapy strategy of cancer.

Cognitive-behavior therapy singly and combined with medication for persistent insomnia: Impact on psychological and daytime functioning.

Science.gov (United States)

Morin, Charles M; Beaulieu-Bonneau, Simon; Bélanger, Lynda; Ivers, Hans; Sánchez Ortuño, Montserrat; Vallières, Annie; Savard, Josée; Guay, Bernard; Mérette, Chantal

2016-12-01

While impairment of daytime functioning due to poor sleep is often the main determinant for seeking treatment, few studies have examined the clinical impact of insomnia therapies on daytime outcomes. The main objective of this study was to evaluate the impact of cognitive-behavior therapy (CBT), alone and combined with medication, on various indices of daytime and psychological functioning. Participants were 160 individuals with chronic insomnia who received CBT alone or CBT plus medication (zolpidem) for an initial six-week therapy, followed by an extended six-month therapy. Participants treated with CBT initially received maintenance CBT or no additional treatment and those treated with combined therapy initially continued with CBT plus intermittent medication (prn) or CBT without medication (taper). Measures of anxiety and depressive symptoms, fatigue, quality of life, and perceived impact of sleep difficulties on various indices of daytime functioning were completed at baseline, after each treatment stage, and at six-month follow-up. Following acute treatment, significant improvements of fatigue, quality of life (mental component), anxiety, and depression were obtained in the CBT alone condition but not in the combined CBT plus medication condition. Following extended treatment, further improvements were noted for the subgroup receiving extended CBT relative to that with no additional treatment, and for the subgroup receiving CBT and intermittent medication relative to that with CBT but no medication. Improvements were well maintained at the 6-month follow-up. These findings indicate that insomnia-specific therapy is effective at improving daytime and psychological functioning in the short term, and that maintenance therapy produces an added value to optimize long-term outcomes. www.clinicaltrials.gov (#NCT 00042146). Copyright © 2016 Elsevier Ltd. All rights reserved.

A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT and intraoperative radiation therapy (IORT in patients with retroperitoneal soft tissue sarcoma

Directory of Open Access Journals (Sweden)

Roeder Falk

2012-07-01

Full Text Available Abstract Background Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT are considered. Methods/design The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy followed by surgery and IORT (10–12 Gy in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. Discussion The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. Trial registration NCT01566123

A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma

International Nuclear Information System (INIS)

Roeder, Falk; Hensley, Frank W; Buechler, Markus W; Debus, Juergen; Koch, Moritz; Weitz, Juergen; Bischof, Marc; Schulz-Ertner, Daniela; Nikoghosyan, Anna V; Huber, Peter E; Edler, Lutz; Habl, Gregor; Krempien, Robert; Oertel, Susanne; Saleh-Ebrahimi, Ladan

2012-01-01

Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered. The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy) followed by surgery and IORT (10–12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. NCT01566123

Development of a manualized protocol of massage therapy for clinical trials in osteoarthritis

Directory of Open Access Journals (Sweden)

Ali Ather

2012-10-01

Full Text Available Abstract Background Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. Methods The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists’ clinical judgment and maintaining consistency with a prior pilot study. Results The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. Conclusions The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Trial registration Clinicaltrials.gov NCT00970008 (18 August 2009

Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study

International Nuclear Information System (INIS)

Nikoghosyan, Anna V; Rauch, Geraldine; Münter, Marc W; Jensen, Alexandra D; Combs, Stephanie E; Kieser, Meinhard; Debus, Jürgen

2010-01-01

Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours. The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial. Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points. Up to now it was impossible to compare two different

Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.

Science.gov (United States)

Liu, Zheng; Gao, Shunji; Zhao, Yang; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

2012-02-01

Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Ultrasound-enhanced delivery of doxorubicin/all-trans retinoic acid-loaded nanodiamonds into tumors.

Science.gov (United States)

Li, Huanan; Zeng, Deping; Wang, Zhenyu; Fang, Liaoqiong; Li, Faqi; Wang, Zhibiao

2018-03-14

To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm 2 . Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. DOX-ATRA-NDs demonstrate great potential in clinical applications.

Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

Science.gov (United States)

Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Silberg, Debra G

2013-04-01

Approximately 20-30% of patients with gastroesophageal reflux disease (GERD) do not experience complete symptom resolution during proton pump inhibitor (PPI) therapy. The aim of this study was to determine the prevalence of esophageal mucosal breaks among patients who have a partial response to PPI therapy. This was an analysis of data from a phase 2b clinical trial carried out to assess the efficacy and safety of a reflux inhibitor, lesogaberan (AZD3355), as an add-on to PPI therapy in this patient population (clinicaltrials.gov reference: NCT01005251). A total of 661 patients with persistent GERD symptoms who had received a minimum of 4 weeks of PPI therapy were included in the study. The prevalence of esophageal mucosal breaks was assessed according to (i) the most recent endoscopy results from within the previous 24 months, if available ("historical" endoscopies), and (ii) the results of endoscopies performed at study baseline ("baseline" endoscopies). Baseline endoscopies were not carried out in patients who had a historical endoscopy showing an absence of esophageal mucosal breaks. Historical endoscopy results were available for 244 patients, of whom 48 (19.7%) had esophageal mucosal breaks. Baseline endoscopies were carried out in 465 patients, of whom 146 (31.4%) had esophageal mucosal breaks. Sensitivity analyses showed a prevalence of esophageal mucosal breaks of 20-30%. In both the historical and baseline endoscopies, most esophageal mucosal breaks were Los Angeles grades A or B. In patients with GERD symptoms partially responsive to PPI therapy, mild-to-moderate severity esophageal mucosal breaks are common (prevalence 20-30%), and may contribute to symptom etiology.

Does multi-modal cervical physical therapy improve tinnitus in patients with cervicogenic somatic tinnitus?

Science.gov (United States)

Michiels, S; Van de Heyning, P; Truijen, S; Hallemans, A; De Hertogh, W

2016-12-01

Tinnitus can be related to many different aetiologies such as hearing loss or a noise trauma, but it can also be related to the somatosensory system of the cervical spine, called cervicogenic somatic tinnitus (CST). Case studies suggest a positive effect of cervical spine treatment on tinnitus complaints in patients with CST, but no experimental studies are available. To investigate the effect of a multimodal cervical physical therapy treatment on tinnitus complaints in patients with CST. Randomized controlled trial. Patients with a combination of severe subjective tinnitus (Tinnitus Functional Index (TFI): 25-90 points) and neck complaints (Neck Bournemouth Questionnaire (NBQ) > 14 points). All patients received cervical physical therapy for 6 weeks (12 sessions). Patients were randomized in an immediate-start therapy group (n = 19) and a 6-week delayed-start therapy group (n = 19). TFI and NBQ-scores were documented at baseline, after the wait-and-see period in the delayed-start group, after treatment and after 6 weeks follow-up. The Global Perceived Effect (GPE) was documented at all measuring moments, except at baseline. In all patients (n = 38) TFI and NBQ-scores decreased significantly after treatment (p = 0.04 and p tinnitus. This effect was maintained in 24% of patients after follow-up at six weeks. Cervical physical therapy can have a positive effect on subjective tinnitus complaints in patients with a combination of tinnitus and neck complaints. Larger studies, using more responsive outcome measures, are however necessary to prove this effect. NCT02016313. Copyright © 2016 Elsevier Ltd. All rights reserved.

Treating Post-traumatic Stress Disorder in Patients with Multiple Sclerosis: A Randomized Controlled Trial Comparing the Efficacy of Eye Movement Desensitization and Reprocessing and Relaxation Therapy

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Carletto, Sara; Borghi, Martina; Bertino, Gabriella; Oliva, Francesco; Cavallo, Marco; Hofmann, Arne; Zennaro, Alessandro; Malucchi, Simona; Ostacoli, Luca

2016-01-01

Objective: Multiple Sclerosis (MS) is a demyelinating autoimmune disease that imposes a significant emotional burden with heavy psychosocial consequences. Several studies have investigated the association between MS and mental disorders such as depression and anxiety, and recently researchers have focused also on Post-traumatic Stress Disorder (PTSD). This is the first study that investigates the usefulness of proposing a treatment for PTSD to patients with MS. Methods: A randomized controlled trial with patients with MS diagnosed with PTSD comparing Eye Movement Desensitization and Reprocessing (EMDR; n = 20) and Relaxation Therapy (RT; n = 22). The primary outcome measure was the proportion of participants that no longer meet PTSD diagnosis as measured with Clinician Administered PTSD Scale 6-months after the treatment. Results: The majority of patients were able to overcome their PTSD diagnosis after only 10 therapy sessions. EMDR treatment appears to be more effective than RT in reducing the proportion of patients with MS suffering from PTSD. Both treatments are effective in reducing PTSD severity, anxiety and depression symptoms, and to improve Quality of Life. Conclusion: Although our results can only be considered preliminary, this study suggests that it is essential that PTSD symptoms are detected and that brief and cost-effective interventions to reduce PTSD and associated psychological symptoms are offered to patients, in order to help them to reduce the psychological burden associated with their neurological condition. Trial registration: NCT01743664, https://clinicaltrials.gov/ct2/show/NCT01743664 PMID:27148134

Treating Post-traumatic Stress Disorder in patients with Multiple Sclerosis: a randomized controlled trial comparing the efficacy of Eye Movement Desensitization and Reprocessing and Relaxation Therapy.

Directory of Open Access Journals (Sweden)

Sara eCarletto

2016-04-01

Full Text Available Objective: Multiple Sclerosis (MS is a demyelinating autoimmune disease that imposes a significant emotional burden with heavy psychosocial consequences. Several studies have investigated the association between MS and mental disorders such as depression and anxiety, and recently researchers have focused also on Post-traumatic Stress Disorder (PTSD. This is the first study that investigates the usefulness of proposing a treatment for PTSD to patients with MS. Methods: A randomized controlled trial with patients with MS diagnosed with PTSD comparing Eye Movement Desensitization and Reprocessing (EMDR; n = 20 and Relaxation Therapy (RT; n = 22. The primary outcome measure was the proportion of participants that no longer meet PTSD diagnosis as measured with Clinician Administered PTSD Scale six-months after the treatment.Results: The majority of patients were able to overcome their PTSD diagnosis after only 10 therapy sessions. EMDR treatment appears to be more effective than RT in reducing the proportion of patients with MS suffering from PTSD. Both treatments are effective in reducing PTSD severity, anxiety symptoms and to improve Quality of Life (QoL. Conclusions: Although our results can only be considered preliminary, this study suggests that it is essential that PTSD symptoms are detected and that brief and cost-effective interventions to reduce PTSD and associated psychological symptoms are offered to patients, in order to help them to reduce the psychological burden associated with their neurological condition.Trail registration: NCT01743664, https://clinicaltrials.gov/ct2/show/NCT01743664

In vivo evaluation of the 3-carboranyl thymidine analogue (3-CTA), N5-2OH, for neutron capture therapy

International Nuclear Information System (INIS)

Barth, Rolf F.; Yang, Weilian; Wu, Gong; Byun, Youngjoo; Tjarks, Werner; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

2006-01-01

The purpose of the present study was to evaluate a 3 CTA, designated N5-2OH, as a boron delivery agent for NCT. Target validation was established using the thymidine kinase 1 (+) wild type L929 cell line and its TK1(-) counterpart, which were implanted subcutaneously into NIH nu/nu mice. 10 B-enriched N5-2OH, solubilized in DMSO (50μg 10 B in 15μl), was administered by 2 intratumoral (i.t.) injections at 2 h intervals. Two hours later the animals were irradiated at the MITR-II Research Reactor, following which tumor volumes were determined over a period of 30 days. Mice bearing TK1(+) wild type tumors, which had received N5-2OH, had a 15 fold inhibition in tumor growth compared to TK1(-) controls (247 versus 3,603 mm 3 ). Based on these data, biodistribution and therapy studies were initiated in F98 glioma bearing rats. Animals received 500μg of N5-2OH, administered intracerebrally (i.c.) by convection enhanced delivery (CED) using ALZET pumps (8μl/h for 24 h). The tumor boron concentration was 17.3μg/g compared to undetectable amounts in normal brain and blood. BNCT was carried out 14 d following i.c. implantation of 10 3 F98 glioma cells and 24 h following CED of N5-2OH (500μg/200μl). The mean survival time (MST) of these animals was 38 d compared to 31 d and 25 d, respectively, for irradiated and untreated controls. Studies are planned to optimize the delivery and formulation of N5-2OH and additional therapy studies will be carried out using N5-2OH in combination with BPA and BSH. (author)

Effects of a music therapy group intervention on enhancing social skills in children with autism.

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LaGasse, A Blythe

2014-01-01

Research indicates that music therapy can improve social behaviors and joint attention in children with Autism Spectrum Disorder (ASD); however, more research on the use of music therapy interventions for social skills is needed to determine the impact of group music therapy. To examine the effects of a music therapy group intervention on eye gaze, joint attention, and communication in children with ASD. Seventeen children, ages 6 to 9, with a diagnosis of ASD were randomly assigned to the music therapy group (MTG) or the no-music social skills group (SSG). Children participated in ten 50-minute group sessions over a period of 5 weeks. All group sessions were designed to target social skills. The Social Responsiveness Scale (SRS), the Autism Treatment Evaluation Checklist (ATEC), and video analysis of sessions were used to evaluate changes in social behavior. There were significant between-group differences for joint attention with peers and eye gaze towards persons, with participants in the MTG demonstrating greater gains. There were no significant between-group differences for initiation of communication, response to communication, or social withdraw/behaviors. There was a significant interaction between time and group for SRS scores, with improvements for the MTG but not the SSG. Scores on the ATEC did not differ over time between the MTG and SSG. The results of this study support further research on the use of music therapy group interventions for social skills in children with ASD. Statistical results demonstrate initial support for the use of music therapy social groups to develop joint attention. © the American Music Therapy Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

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Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

2015-04-01

Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

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Maytin, Edward V.; Anand, Sanjay

2016-03-01

In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

A Conceptual Model and Clinical Framework for Integrating Mindfulness into Family Therapy with Adolescents.

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Brody, Janet L; Scherer, David G; Turner, Charles W; Annett, Robert D; Dalen, Jeanne

2017-06-07

Individual and group-based psychotherapeutic interventions increasingly incorporate mindfulness-based principles and practices. These practices include a versatile set of skills such as labeling and attending to present-moment experiences, acting with awareness, and avoiding automatic reactivity. A primary motivation for integrating mindfulness into these therapies is compelling evidence that it enhances emotion regulation. Research also demonstrates that family relationships have a profound influence on emotion regulation capacities, which are central to family functioning and prosocial behavior more broadly. Despite this evidence, no framework exists to describe how mindfulness might integrate into family therapy. This paper describes the benefits of mindfulness-based interventions, highlighting how and why informal mindfulness practices might enhance emotion regulation when integrated with family therapy. We provide a clinical framework for integrating mindfulness into family therapy, particularly as it applies to families with adolescents. A brief case example details sample methods showing how incorporating mindfulness practices into family therapy may enhance treatment outcomes. A range of assessment modalities from biological to behavioral demonstrates the breadth with which the benefits of a family-based mindfulness intervention might be evaluated. © 2017 The Authors. Family Process published by Wiley Periodicals, Inc. on behalf of Family Process Institute.

The Environmental Impact on Occupational Therapy Interventions.

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Skubik-Peplaski, Camille Louise; Howell, Dana; Hunter, Elizabeth

2016-01-01

The purpose of this study was to investigate how the environment influenced the intervention choices occupational therapists made for patients recovering from a stroke in an inpatient rehabilitation hospital. Three occupational therapists were observed providing intervention for six patients over a 16-month period. Treatment spaces included a therapy gym, gym with kitchen combination, and a home-like space. Furniture was added to the therapy gym to be more home-like midway through the study. Observations included therapist selection of treatment location and interventions, and observational data of the environment and interactions among therapists and patients. This study found that inpatient rehabilitation environments did influence interventions. The occupational therapists provided therapy in the standard therapy gym environment most often, whether it was enhanced to be more home-like or not, and predominately used preparatory methods.

Molecular targeting of gene therapy and radiotherapy

International Nuclear Information System (INIS)

Weichselbaum, R.R.; Kufe, D.W.; Advani, S.J.; Roizman, B.

2001-01-01

The full promise of gene therapy has been limited by the lack of specificity of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. In this paper we review our studies investigating two modifications of gene therapy combined with radiotherapy. The first investigations described include studies of radiation inducible gene therapy. In this paradigm, radio-inducible DNA sequences from the CarG elements of the Egr-1 promoter are cloned upstream of a cDNA encoding TNFa. The therapeutic gene (TNFa) is induced by radiation within the tumor microenvironment. In the second paradigm, genetically engineered herpes simplex virus (HSV-1) is induced by ionizing radiation to proliferate within the tumor volume. These modifications of radiotherapy and gene therapy may enhance the efficacy of both treatments

New advances in amblyopia therapy I: binocular therapies and pharmacologic augmentation.

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Kraus, Courtney L; Culican, Susan M

2018-05-18

Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence, mostly from the Pediatric Eye Disease Investigator Group, has validated both number of hours a day of patching and days per week of atropine use. The use of glasses alone has also been established as a good first-line therapy for both anisometropic and strabismic amblyopia. Unfortunately, visual acuity equalisation or even improvement is not always attainable with these methods. Additionally, non-compliance with prescribed therapies contributes to treatment failures, with data supporting difficulty adhering to full treatment sessions. Interest in alternative therapies for amblyopia treatment has long been a topic of interest among researchers and clinicians alike. Incorporating new technology with an understanding of the biological basis of amblyopia has led to enthusiasm for binocular treatment of amblyopia. Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy. No new treatment has emerged from currently available evidence as superior to the traditional therapies in common practice today. But ongoing investigation into the use of both new technology and the understanding of the neural basis of amblyopia promises alternate or perhaps better cures in the future. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Music therapy in pediatric palliative care: family-centered care to enhance quality of life.

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Lindenfelser, Kathryn J; Hense, Cherry; McFerran, Katrina

2012-05-01

Research into the value of music therapy in pediatric palliative care (PPC) has identified quality of life as one area of improvement for families caring for a child in the terminal stages of a life-threatening illness. This small-scale investigation collected data in a multisite, international study including Minnesota, USA, and Melbourne, Australia. An exploratory mixed method design used the qualitative data collected through interviews with parents to interpret results from the PedsQL Family Impact Module of overall parental quality of life. Parents described music therapy as resulting in physical improvements of their child by providing comfort and stimulation. They also valued the positive experiences shared by the family in music therapy sessions that were strength oriented and family centered. This highlighted the physical and communication scales within the PedsQL Family Impact Module, where minimal improvements were achieved in contrast to some strong results suggesting diminished quality of life in cognitive and daily activity domains. Despite the significant challenges faced by parents during this difficult time, parents described many positive experiences in music therapy, and the overall score for half of the parents in the study did not diminish. The value of music therapy as a service that addresses the family-centered agenda of PPC is endorsed by this study.

Effects of endocrine therapy on the primary lesion in patients with prostatic cancer. Evaluation with Gd-dynamic subtraction MRI

International Nuclear Information System (INIS)

Yoshizako, Takeshi; Watanabe, Yuji; Dohke, Masako

2000-01-01

The effects of endocrine therapy on prostate cancer were assessed by using Gd-dynamic subtraction MRI (DSMRI). The 36 lesions showed early enhancement before therapy were treated with endocrine therapy. The criteria used for the assessment of therapeutic effect was; the degree of early enhancement could decrease with the viability of cancer reduced by treatment. According to this criteria, the sensitivity, specificity, and accuracy were 35.7% (5/14), 81.8% (18/22), and 58.3% (21/36). In conclusion, interval decrease of early enhancement could be a indicator of therapeutic effect. (author)

Indirect vs Direct Voice Therapy for Children With Vocal Nodules: A Randomized Clinical Trial.

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Hartnick, Christopher; Ballif, Catherine; De Guzman, Vanessa; Sataloff, Robert; Campisi, Paolo; Kerschner, Joseph; Shembel, Adrianna; Reda, Domenic; Shi, Helen; Sheryka Zacny, Elinore; Bunting, Glenn

2018-02-01

latter two-thirds of participants (Cohen d = 0.46). Vocal fold nodules reduced in size in 31% (22 of 70) and completely resolved in 11% (8 of 70) of participants who consented to a second set of images after going through the recruitment process. Both direct and indirect voice therapy improved voice-related quality of life in children with vocal fold nodules, although there was no significant difference between approaches. Future studies may focus upon which voice therapy approaches are effective in treating age-defined populations. clinicaltrials.gov Identifier: NCT01255735.

"Music Therapy Helped Me Get Back Doing": Perspectives of Music Therapy Participants in Mental Health Services.

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McCaffrey, Tríona; Edwards, Jane

2016-01-01

Mental health service development internationally is increasingly informed by the collaborative ethos of recovery. Service user evaluation of experiences within music therapy programs allows new phenomena about participation in services to be revealed that might otherwise remain unnoticed. The aim of this study was to demonstrate how asking service users about their experience of music therapy can generate useful information, and to reflect upon the feedback elicited from such processes in order to gain a deeper understanding of how music therapy is received among service users in mental health. Six mental health service users described their experiences of music therapy in one or two individual interviews. Transcripts of interviews were analyzed using the procedures and techniques of Interpretative Phenomenological Analysis. Interviews with mental health service users provided rich, in-depth accounts reflecting the complex nature of music therapy participation. Super-ordinate themes refer to the context in which music therapy was offered, the rich sound world of music in music therapy, the humanity of music therapy, and the strengths enhancing opportunities experienced by service users. Participants indicated that they each experienced music therapy in unique ways. Opinions about the value of music therapy were revealed through an interview process in which the researcher holds an open attitude, welcoming all narrative contributions respectfully. These findings can remind practitioners of the importance of closely tuning into the perspectives and understandings of those who have valuable expertise to share about their experience of music therapy services in mental health. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Outcomes of implementation of enhanced goal directed therapy in high-risk patients undergoing abdominal surgery

Directory of Open Access Journals (Sweden)

Lakshmi Kumar

2015-01-01

Full Text Available Background and Aims: Advanced monitoring targeting haemodynamic and oxygenation variables can improve outcomes of surgery in high-risk patients. We aimed to assess the impact of goal directed therapy (GDT targeting cardiac index (CI and oxygen extraction ratio (O 2 ER on outcomes of high-risk patients undergoing abdominal surgery. Methods: In a prospective randomised trial, forty patients (American Society of Anaesthesiologists II and III undergoing major abdominal surgeries were randomised into two groups. In-Group A mean arterial pressure ≥ 65 mmHg, central venous pressure ≥ 8-10 mmHg, urine output ≥ 0.5 mL/kg/h and central venous oxygen saturation ≥ 70% were targeted intra-operatively and 12 h postoperatively. In-Group-B (enhanced GDT, in addition to the monitoring in-Group-A, CI ≥ 2.5 L/min/m 2 and O 2 ER ≤ 27% were targeted. The end-points were lactate levels and base deficit during and after surgery. The secondary end points were length of Intensive Care Unit (ICU and hospital stay and postoperative complications. Wilcoxon Mann Whitney and Chi-square tests were used for statistical assessment. Results: Lactate levels postoperatively at 4 and 8 h were lower in-Group-B (P < 0.05. The mean base deficit at 3, 4, 5 and 6 h intra-operatively and postoperatively after 4, 8 and 12 h were lower in-Group-B (P < 0.05. There were no significant differences in ICU stay (2.10 ± 1.52 vs. 2.90 ± 2.51 days or hospital stay (10.85 + 4.39 vs. 13.35 + 6.77 days between Group A and B. Conclusions: Implementation of enhanced GDT targeting CI and OER was associated with improved tissue oxygenation.

Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy

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Drappatz, Jan; de Groot, John; Prados, Michael D; Reardon, David A; Schiff, David; Chamberlain, Marc; Mikkelsen, Tom; Desjardins, Annick; Holland, Jaymes; Ping, Jerry; Weitzman, Ron; Cloughesy, Timothy F

2018-01-01

Abstract Background Cabozantinib is a tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM). Methods Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by an independent radiology facility using modified Response Assessment in Neuro-Oncology criteria. Additional endpoints included duration of response, 6-month and median progression-free survival, overall survival, and safety. Results Among 152 patients naive to prior antiangiogenic therapy, the objective response rate was 17.6% and 14.5% in the 140 mg/day and 100 mg/day groups, respectively, which did not meet the predefined statistical target for success. The proportions of patients alive and progression free at 6 months were 22.3% and 27.8%, respectively. Median progression-free survival was 3.7 months in both groups, and median overall survival was 7.7 months and 10.4 months, respectively. The incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140 mg/day and 100 mg/day groups, respectively, and dose reductions due to AEs were experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. Conclusions Cabozantinib showed evidence of clinical activity in patients with recurrent GBM naive to antiangiogenic therapy, although the predefined statistical target for success was not met. At the starting doses assessed, AEs were frequently managed with dose reductions. Clinical Trials Registration Number NCT00704288 (https://www.clinicaltrials.gov/ct2/show/NCT00704288) PMID

Predictive Biomarkers for Asthma Therapy.

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Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

2017-09-19

Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

Inducement of radionuclides targeting therapy by gene transfection

International Nuclear Information System (INIS)

Luo Quanyong

2001-01-01

The author presents an overview of gene transfection methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to intake radiolabeled antibody and peptide targeting and thus increase their therapeutic effect in radiotherapy. The current research include inducement of radioimmunotherapy through CEA gene transfection, inducement of iodine-131 therapy by sodium iodide symporter gene transfection and inducement of MIBG therapy by noradrenaline transporter gene transfection. These studies raise the prospect that gene-therapy techniques could be used to enable the treatment of a wide range of tumors with radiopharmaceuticals of established clinical acceptability

Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy

International Nuclear Information System (INIS)

Kim, Dong Wook; Huamani, Jessica; Fu, Allie; Hallahan, Dennis E.

2006-01-01

The tumor microenvironment, in particular, the tumor vasculature, as an important target for the cytotoxic effects of radiation therapy is an established paradigm for cancer therapy. We review the evidence that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated in endothelial cells exposed to ionizing radiation (IR) and is a molecular target for the development of novel radiation sensitizing agents. On the basis of this premise, several promising preclinical studies that targeted the inhibition of the PI3K/Akt activation as a potential method of sensitizing the tumor vasculature to the cytotoxic effects of IR have been conducted. An innovative strategy to guide cytotoxic therapy in tumors treated with radiation and PI3K/Akt inhibitors is presented. The evidence supports a need for further investigation of combined-modality therapy that involves radiation therapy and inhibitors of PI3K/Akt pathway as a promising strategy for improving the treatment of patients with cancer

Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

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Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

2009-02-01

This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

[Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

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Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

2018-02-01

The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

Imaging-therapy computed tomography with quasi-monochromatic X-rays.

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Jost, Gregor; Golfier, Sven; Lawaczeck, Ruediger; Weinmann, Hanns-Joachim; Gerlach, Martin; Cibik, Levent; Krumrey, Michael; Fratzscher, Daniel; Rabe, Johannis; Arkadiev, Vladimir; Haschke, Michael; Langhoff, Norbert; Wedell, Reiner; Luedemann, Lutz; Wust, Peter; Pietsch, Hubertus

2008-12-01

Computed tomography (CT) is a widespread and highly precise technique working in the energy range around 50-100 keV. For radiotherapy, however, the MeV energy range enables a better dose distribution. This gap between diagnosis and therapy can be overcome by the use of a modified CT machine in combination with heavy elements targeted to the tumour and used as photoelectric radiation enhancer. The experimental setup consists of an X-ray optical module mounted at the exit of the X-ray tube of a clinical CT. The module converts the standard fan-shaped beam into a high intensity, monochromatized and focused beam. The radiation was characterized using an energy-dispersive detection system calibrated by synchrotron radiation and gel dosimetry. The photoelectric radiation enhancement for different elements was calculated and experimentally verified. The X-ray optical module filters selectively the energy of the tungsten K alpha-emission line (59.3 keV) with a full width at half maximum (FWHM) of 5 keV and focused the radiation onto a focal spot which coincides with the isocentre of the gantry. This results in a steep dose gradient at the centre of rotation qualified for locoregional radiation therapy. The photon energy of the quasi-monochromatic radiation agrees with the energy range of maximal photoelectric dose enhancement for gadolinium and iodine. An additional X-ray optical module optimized for targeted therapy and photoelectric dose enhancement allows the combination of diagnosis and radiotherapy on a clinical CT.

Efficacy and Safety of an Herbal Therapy in Patients with Amnestic Mild Cognitive Impairment: A 24-Week Randomized Phase III Trial

Directory of Open Access Journals (Sweden)

Jinzhou Tian

2017-01-01

Full Text Available Objective. In the 24-week randomized, double-blind, double-placebo, parallel-controlled trial, we aimed to test the effects of herbal therapy with amnestic mild cognitive impairment (aMCI. Methods. A total of 324 patients with aMCI entered a 2-week placebo run-in period followed by 24 weeks’ treatment of either (a herbal capsule (5 shenwu capsules/administration, 3 times/day and placebo identical to donepezil tablets (n=216 or (b donepezil (5 mg/day and placebo identical to herbal capsule (n=108. Results. Herbal therapy showed a significant improvement on the primary efficacy measure, measured by Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog, and showed a mean decrease from baseline of 4.23 points at the endpoint, without a significant difference from the donepezil group. Secondary efficacy measurement of the Logical Memory II Delayed Story Recall subtest (DSR showed modest improvement in those taking herbal capsule compared to baseline, and there was no significant difference from donepezil group. The frequency of adverse events was much less in the herbal therapy group than the donepezil. Conclusion. Herbal therapy demonstrated a significant improvement in cognition and memory, which were similar to the donepezil in patients with aMCI. Herbal therapy was safe and well tolerated. Trial Registration. This study is registered with clinicaltrials.gov NCT01451749.

Challenges in economic modeling of anticancer therapies: an example of modeling the survival benefit of olaparib maintenance therapy for patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer.

Science.gov (United States)

Hettle, Robert; Posnett, John; Borrill, John

2015-01-01

The aim of this paper is to describe a four health-state, semi-Markov model structure with health states defined by initiation of subsequent treatment, designed to make best possible use of the data available from a phase 2 clinical trial. The approach is illustrated using data from a sub-group of patients enrolled in a phase 2 clinical trial of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (NCT00753545). A semi-Markov model was developed with four health states: progression-free survival (PFS), first subsequent treatment (FST), second subsequent treatment (SST), and death. Transition probabilities were estimated by fitting survival curves to trial data for time from randomization to FST, time from FST to SST, and time from SST to death. Survival projections generated by the model are broadly consistent with the outcomes observed in the clinical trial. However, limitations of the trial data (small sample size, immaturity of the PFS and overall survival [OS] end-points, and treatment switching) create uncertainty in estimates of survival. The model framework offers a promising approach to evaluating cost-effectiveness of a maintenance therapy for patients with cancer, which may be generalizable to other chronic diseases.

Non-toxic approach for treatment of breast cancer and its cutaneous metastasis: Capecitabine (Xeloda) enhanced photodynamic therapy in a murine tumor model

Science.gov (United States)

Anand, Sanjay; Denisyuk, Anton; Bullock, Taylor; Govande, Mukul; Maytin, Edward V.

2018-02-01

Breast cancer (BCA) is the most frequently diagnosed cancer in women, with distant metastases to lung, liver, bone and skin occurring in approximately 40% of cases. Radiation therapy (RT) has been successfully employed for the treatment of BCA; however, multiple rounds of RT are associated with undesirable cutaneous side effects. This study explores PDT as a therapeutic alternative, to be given alone or in combination with RT and chemotherapy. Earlier, we had developed differentiation-enhanced combination photodynamic therapy (cPDT) using a neoadjuvant (5-fluorouracil; 5FU) prior to PDT. The neoadjuvant increases the levels of PpIX, leading to better efficacy following aminolevulinate (ALA)- based PDT. Here, to avoid the toxicity of systemic 5FU, we used a nontoxic 5FU precursor (Capecitabine; CPBN) in a new cPDT regimen. CBPN, a standard chemotherapeutic for BCA, is metabolized to 5FU specifically within tumor tissue. Murine (4T1) BCA cells were injected into breast fat pads of nude mice. CPBN was administered by oral gavage followed by intraperitoneal ALA and red light for PDT. CPBN pretreatment of 4T1 tumors led to increased tumor cell differentiation (3.5 fold), homogenous elevation of intratumoral PpIX levels (4.5 fold), and enhanced tumor cell death post-PDT (5 fold), relative to vehicle control. Using an in vivo imaging system (IVIS), a decline in tumor growth following CPBN-PDT was observed. Results showing the effect of CPBN-PDT on distant metastases of BCA to lung, lymph nodes and skin will be presented. In summary, CPBN-PDT, a novel combination approach, has a significant potential for translation into the clinic.

Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies.

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Prins, Martin H; Lensing, Anthonie Wa; Bauersachs, Rupert; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Decousus, Hervé; Raskob, Gary E; Berkowitz, Scott D; Wells, Philip S

2013-09-20

Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66-1.19; pnoninferiority EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193.

Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure

Directory of Open Access Journals (Sweden)

Tojo Katsuyoshi

2008-05-01

Full Text Available Abstract Background The large clinical trials proved that Basal-Bolus (BB insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy. Methods In PROBE (Prospective, Randomized, Open, Blinded-Endpoint design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range age: 64.5(56.8~71.0years with secondary failure of sulfonylurea (SU were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group, and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups. Results After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3 → 7.4(6.9~8.7%, p Conclusion Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure. Trial registration Current Controlled Trials number, NCT00348231

Effect of Prolonged Exposure Therapy Delivered Over 2 Weeks vs 8 Weeks vs Present-Centered Therapy on PTSD Symptom Severity in Military Personnel: A Randomized Clinical Trial.

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Foa, Edna B; McLean, Carmen P; Zang, Yinyin; Rosenfield, David; Yadin, Elna; Yarvis, Jeffrey S; Mintz, Jim; Young-McCaughan, Stacey; Borah, Elisa V; Dondanville, Katherine A; Fina, Brooke A; Hall-Clark, Brittany N; Lichner, Tracey; Litz, Brett T; Roache, John; Wright, Edward C; Peterson, Alan L

2018-01-23

). At 2 weeks posttreatment, mean PSS-I score was 18.03 for spaced therapy (decrease, 7.29; difference in means vs massed therapy, 0.79 [1-sided 95% CI, -∞ to 2.29; P = .049 for noninferiority]) and at 12 weeks posttreatment was 18.88 for massed therapy (decrease, 6.32) and 18.34 for spaced therapy (decrease, 6.97; difference, 0.55 [1-sided 95% CI, -∞ to 2.05; P = .03 for noninferiority]). At posttreatment, PSS-I scores for PCT were 18.65 (decrease, 7.31; difference in decrease vs spaced therapy, 0.10 [95% CI, -2.48 to 2.27]; P = .93). Among active duty military personnel with PTSD, massed therapy (10 sessions over 2 weeks) reduced PTSD symptom severity more than MCC at 2-week follow-up and was noninferior to spaced therapy (10 sessions over 8 weeks), and there was no significant difference between spaced therapy and PCT. The reductions in PTSD symptom severity with all treatments were relatively modest, suggesting that further research is needed to determine the clinical importance of these findings. clinicaltrials.gov Identifier: NCT01049516.

Behavior therapy for children with Tourette disorder: a randomized controlled trial.

Science.gov (United States)

Piacentini, John; Woods, Douglas W; Scahill, Lawrence; Wilhelm, Sabine; Peterson, Alan L; Chang, Susanna; Ginsburg, Golda S; Deckersbach, Thilo; Dziura, James; Levi-Pearl, Sue; Walkup, John T

2010-05-19

Tourette disorder is a chronic and typically impairing childhood-onset neurologic condition. Antipsychotic medications, the first-line treatments for moderate to severe tics, are often associated with adverse effects. Behavioral interventions, although promising, have not been evaluated in large-scale controlled trials. To determine the efficacy of a comprehensive behavioral intervention for reducing tic severity in children and adolescents. Randomized, observer-blind, controlled trial of 126 children recruited from December 2004 through May 2007 and aged 9 through 17 years, with impairing Tourette or chronic tic disorder as a primary diagnosis, randomly assigned to 8 sessions during 10 weeks of behavior therapy (n = 61) or a control treatment consisting of supportive therapy and education (n = 65). Responders received 3 monthly booster treatment sessions and were reassessed at 3 and 6 months following treatment. Comprehensive behavioral intervention. Yale Global Tic Severity Scale (range 0-50, score >15 indicating clinically significant tics) and Clinical Global Impressions-Improvement Scale (range 1 [very much improved] to 8 [very much worse]). Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale (24.7 [95% confidence interval {CI}, 23.1-26.3] to 17.1 [95% CI, 15.1-19.1]) from baseline to end point compared with the control treatment (24.6 [95% CI, 23.2-26.0] to 21.1 [95% CI, 19.2-23.0]) (P tic worsening was reported by 4% of children (5/126). Treatment gains were durable, with 87% of available responders to behavior therapy exhibiting continued benefit 6 months following treatment. A comprehensive behavioral intervention, compared with supportive therapy and education, resulted in greater improvement in symptom severity among children with Tourette and chronic tic disorder. clinicaltrials.gov Identifier: NCT00218777.

Remodeling of Tumor Stroma and Response to Therapy

Energy Technology Data Exchange (ETDEWEB)

Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

2012-03-27

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

Remodeling of Tumor Stroma and Response to Therapy

International Nuclear Information System (INIS)

Johansson, Anna; Ganss, Ruth

2012-01-01

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

Gene and cell therapy for children--new medicines, new challenges?

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Buckland, Karen F; Bobby Gaspar, H

2014-06-01

The range of possible gene and cell therapy applications is expanding at an extremely rapid rate and advanced therapy medicinal products (ATMPs) are currently the hottest topic in novel medicines, particularly for inherited diseases. Paediatric patients stand to gain enormously from these novel therapies as it now seems plausible to develop a gene or cell therapy for a vast number of inherited diseases. There are a wide variety of potential gene and cell therapies in various stages of development. Patients who received first gene therapy treatments for primary immune deficiencies (PIDs) are reaching 10 and 15 years post-treatment, with robust and sustained immune recovery. Cell therapy clinical trials are underway for a variety of tissues including corneal, retinal and muscle repair and islet cell transplantation. Various cell therapy approaches are also being trialled to enhance the safety of bone marrow transplants, which should improve survival rates in childhood cancers and PIDs. Progress in genetic engineering of lymphocyte populations to target and kill cancerous cells is also described. If successful these ATMPs may enhance or replace the existing chemo-ablative therapy for several paediatric cancers. Emerging applications of gene therapy now include skin and neurological disorders such as epidermolysis bullosa, epilepsy and leukodystrophy. Gene therapy trials for haemophilia, muscular dystrophy and a range of metabolic disorders are underway. There is a vast array of potential advanced therapy medicinal products (ATMPs), and these are likely to be more cost effective than existing medicines. However, the first clinical trials have not been without setbacks and some of the key adverse events are discussed. Furthermore, the arrival of this novel class of therapies brings many new challenges for the healthcare industry. We present a summary of the key non-clinical factors required for successful delivery of these potential treatments. Technological advances

The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.

Science.gov (United States)

Rasmussen, M; Espelund, U S; Juul, N; Yoo, A J; Sørensen, L H; Sørensen, K E; Johnsen, S P; Andersen, G; Simonsen, C Z

2018-06-01

Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure blood pressure blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. Procedural average mean and systolic blood pressures were higher in the conscious sedation group (Pblood pressure blood pressure blood pressure variability, and use of vasopressors were all higher in the GA group (Pblood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. NCT 02317237. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Add-on Therapy With the α-Blockers Tamsulosin and Naftopidil Improves Voiding Function by Enhancing Neuronal Activity in Prostatic Hyperplasia Rats.

Science.gov (United States)

Ko, Il-Gyu; Hwang, Lakkyong; Jin, Jun-Jang; Kim, Sang-Hoon; Han, Jin Hee; Jeon, Jung Won; Cho, Sung Tae

2018-03-01

Benign prostatic hyperplasia (BPH) impacts quality of life in men by causing lower urinary tract symptoms. α1-Adrenoceptor (α1-AR) blockers improve lower urinary tract symptoms. We investigated the efficacy of add-on therapy with α1-AR blockers on BPH rats. Rats in the drug-treated groups were orally administered each drug once a day for 30 days after orchiectomy. To induce BPH, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days. Cystometry was conducted to measure voiding contraction pressure and the interval contraction time, immunohistochemistry was performed to measure c-Fos and nerve growth factor (NGF) expression in the neuronal voiding centers, and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry was used to measure nitric oxide synthase (NOS) expression. Orchiectomy and testosterone injection decreased voiding contraction pressure and the interval contraction time, suggesting BPH symptoms. Voiding contraction pressure and the interval contraction time were greater in the group that received the combination treatment (tamsulosin with naftopidil) than in the tamsulosin monotherapy or naftopidil monotherapy groups. c-Fos, NGF, and NOS expression in the neuronal voiding centers was enhanced by BPH induction. c-Fos, NGF, and NOS expression was suppressed by the combination treatment (tamsulosin with naftopidil) to a greater extent than was the case for tamsulosin monotherapy or naftopidil monotherapy. Combination therapy of tamsulosin and naftopidil showed greater efficacy for the treatment of BPH than tamsulosin monotherapy or naftopidil monotherapy; therefore, combination therapy can be considered as a novel therapeutic method for BPH.

Effect of enhanced external counterpulsation therapy on myeloperoxidase in lowering cardiovascular events of patients with chronic heart failure

Directory of Open Access Journals (Sweden)

Starry H. Rampengan

2013-08-01

Full Text Available Background: Chronic heart failure (CHF is a slowly progressive disease with high morbidity and mortality; therefore, the management using pharmacological treatments frequently fails to improve outcome. Enhanced external counterpulsation (EECP, a non-invasive treatment, may serve as alternative treatment for heart failure. This study was aimed to evaluate the influence of EECP on myeloperoxidase (MPO as inflammatory marker as well as cardiac events outcome.Methods: This was an open randomized controlled clinical trial on 66 CHF patients visiting several cardiovascular clinics in Manado between January-December 2012. The subjects were randomly divided into two groups, i.e. the group who receive EECP therapy and those who did not receive EECP therapy with 33 patients in each group. Myeloperoxidase (MPO as inflammatory marker was examined at baseline and after 6 months of observation. Cardiovascular events were observed as well after 6 months of observation. Unpaired t-test was use to analyze the difference of MPO between the two groups, and chi-square followed by calculation of relative risk were used for estimation of cardiovascular event outcomes.Results: MPO measurement at baseline and after 6 months in EECP group were 643.16 ± 239.40 pM and 422.31 ± 156.26 pM, respectively (p < 0.001. Whereas in non EECP group, the MPO values were 584.69 ± 281.40 pM and 517.64 ± 189.68 pM, repectively (p = 0.792. MPO reduction was observed in all patients of EECP group and in 13 patients (48% of non-EECP group (p < 0.001. Cardiovascular events were observed in 7 (21.21% and 15 (45.45% of patients in EECP and non-EECP groups, respectively (p = 0.037.Conclusion: EECP therapy significantly decreased the level of MPO as inflammatory marker and this decrease was correlated with the reduction of cardiovascular events in CHF patients. (Med J Indones. 2013;22:152-60. doi: 10.13181/mji.v22i3.584Keywords: CHF, cardiovascular events, EECP, myeloperoxidase

* Tissue-Specific Extracellular Matrix Enhances Skeletal Muscle Precursor Cell Expansion and Differentiation for Potential Application in Cell Therapy.

Science.gov (United States)

Zhang, Deying; Zhang, Yong; Zhang, Yuanyuan; Yi, Hualin; Wang, Zhan; Wu, Rongpei; He, Dawei; Wei, Guanghui; Wei, Shicheng; Hu, Yun; Deng, Junhong; Criswell, Tracy; Yoo, James; Zhou, Yu; Atala, Anthony

2017-08-01

Skeletal muscle precursor cells (MPCs) are considered a key candidate for cell therapy in the treatment of skeletal muscle dysfunction due to injury, disease, or age. However, expansion of a sufficient number of functional skeletal muscle cells in vitro from a small tissue biopsy has been challenging due to changes in phenotypic expression of these cells under traditional culture conditions. Thus, the aim of the study was to develop a better culture system for the expansion and myo-differentiation of MPCs that could further be used for therapy. For this purpose, we developed an ideal method of tissue decellularization and compared the ability of different matrices to support MPC growth and differentiation. Porcine-derived skeletal muscle and liver and kidney extracellular matrix (ECM) were generated by decellularization methods consisting of distilled water, 0.2 mg/mL DNase, or 5% fetal bovine serum. Acellular matrices were further homogenized, dissolved, and combined with a hyaluronic acid-based hydrogel decorated with heparin (ECM-HA-HP). The cell proliferation and myogenic differentiation capacity of human MPCs were assessed when grown on gel alone, ECM, or each ECM-HA-HP substrate. Human MPC proliferation was significantly enhanced when cultured on the ECM-HA-HP substrates compared to the other substrates tested, with the greatest proliferation on the muscle ECM-HA-HP (mECM-HA-HP) substrate. The number of differentiated myotubes was significantly increased on the mECM-HA-HP substrate compared to the other gel-ECM substrates, as well as the numbers of MPCs expressing specific myogenic cell markers (i.e., myosin, desmin, myoD, and myf5). In conclusion, skeletal mECM-HA-HP as a culture substrate provided an optimal culture microenvironment potentially due to its similarity to the in vivo environment. These data suggest a potential use of skeletal muscle-derived ECM gel for the expansion and differentiation of human MPCs for cell-based therapy for skeletal muscle

Late effects from hadron therapy

Energy Technology Data Exchange (ETDEWEB)

Blakely, Eleanor A.; Chang, Polly Y.

2004-06-01

Successful cancer patient survival and local tumor control from hadron radiotherapy warrant a discussion of potential secondary late effects from the radiation. The study of late-appearing clinical effects from particle beams of protons, carbon, or heavier ions is a relatively new field with few data. However, new clinical information is available from pioneer hadron radiotherapy programs in the USA, Japan, Germany and Switzerland. This paper will review available data on late tissue effects from particle radiation exposures, and discuss its importance to the future of hadron therapy. Potential late radiation effects are associated with irradiated normal tissue volumes at risk that in many cases can be reduced with hadron therapy. However, normal tissues present within hadron treatment volumes can demonstrate enhanced responses compared to conventional modes of therapy. Late endpoints of concern include induction of secondary cancers, cataract, fibrosis, neurodegeneration, vascular damage, and immunological, endocrine and hereditary effects. Low-dose tissue effects at tumor margins need further study, and there is need for more acute molecular studies underlying late effects of hadron therapy.

Exploring a neuroplasticity model of music therapy.

Science.gov (United States)

Stegemöller, Elizabeth L

2014-01-01

Given that music therapists work across a wide range of disabilities, it is important that therapists have at least a fundamental understanding of the neurophysiology associated with the client/patient populations that they serve. Yet, there is a large gap of evidence regarding the neurophysiological changes associated with applying music as therapy. The purpose of this article is to provide music therapists with a general background in neuroplasticity principles that can be applied to the use of music therapy with multiple populations. This article will review literature on neuroplasticity and literature supporting the specific attributes of music therapy that apply to neuroplasticity. Finally, examples of how to use neuroplasticity principles to explain and support clinical music therapy will be provided. Using the material presented in this review, music therapists will be equipped with information to effectively communicate why music therapy works using three neuroplasticity principles; increase in dopamine, neural synchrony, and a clear signal. Music therapy is a powerful tool to enhance neuroplasticity in the brain. © the American Music Therapy Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Drivers of costs associated with reperfusion therapy in acute stroke: the Interventional Management of Stroke III Trial.

Science.gov (United States)

Simpson, Kit N; Simpson, Annie N; Mauldin, Patrick D; Hill, Michael D; Yeatts, Sharon D; Spilker, Judith A; Foster, Lydia D; Khatri, Pooja; Martin, Renee; Jauch, Edward C; Kleindorfer, Dawn; Palesch, Yuko Y; Broderick, Joseph P

2014-06-01

The Interventional Management of Stroke (IMS) III study tested the effect of intravenous tissue-type plasminogen activator (tPA) alone when compared with intravenous tPA followed by endovascular therapy and collected cost data to assess the economic implications of the 2 therapies. This report describes the factors affecting the costs of the initial hospitalization for acute stroke subjects from the United States. Prospective cost analysis of the US subjects was treated with intravenous tPA alone or with intravenous tPA followed by endovascular therapy in the IMS III trial. Results were compared with expected Medicare payments. The adjusted cost of a stroke admission in the study was $35 130 for subjects treated with endovascular therapy after intravenous tPA treatment and $25 630 for subjects treated with intravenous tPA alone (P<0.0001). Significant factors related to costs included treatment group, baseline National Institutes of Health Stroke Scale, time from stroke onset to intravenous tPA, age, stroke location, and comorbid diabetes mellitus. The mean cost for subjects who had routine use of general anesthesia as part of endovascular therapy was $46 444 when compared with $30 350 for those who did not have general anesthesia. The costs of embolectomy for IMS III subjects and patients from the National Inpatient Sample cohort exceeded the Medicare diagnosis-related group payment in ≥75% of patients. Minimizing the time to start of intravenous tPA and decreasing the use of routine general anesthesia may improve the cost-effectiveness of medical and endovascular therapy for acute stroke. http://www.clinicaltrials.gov. Unique identifier: NCT00359424. © 2014 American Heart Association, Inc.

MRI contrast enhancement using Magnetic Carbon Nanoparticles

Science.gov (United States)

Chaudhary, Rakesh P.; Kangasniemi, Kim; Takahashi, Masaya; Mohanty, Samarendra K.; Koymen, Ali R.; Department of Physics, University of Texas at Arlington Team; University of Texas Southwestern Medical Center Team

2014-03-01

In recent years, nanotechnology has become one of the most exciting forefront fields in cancer diagnosis and therapeutics such as drug delivery, thermal therapy and detection of cancer. Here, we report development of core (Fe)-shell (carbon) nanoparticles with enhanced magnetic properties for contrast enhancement in MRI imaging. These new classes of magnetic carbon nanoparticles (MCNPs) are synthesized using a bottom-up approach in various organic solvents, using the electric plasma discharge generated in the cavitation field of an ultrasonic horn. Gradient echo MRI images of well-dispersed MCNP-solutions (in tube) were acquired. For T2 measurements, a multi echo spin echo sequence was performed. From the slope of the 1/T2 versus concentration plot, the R2 value for different CMCNP-samples was measured. Since MCNPs were found to be extremely non-reactive, and highly absorbing in NIR regime, development of carbon-based MRI contrast enhancement will allow its simultaneous use in biomedical applications. We aim to localize the MCNPs in targeted tissue regions by external DC magnetic field, followed by MRI imaging and subsequent photothermal therapy.

Nontraditional Therapies (Traditional Chinese Veterinary Medicine and Chiropractic) in Exotic Animals.

Science.gov (United States)

Marziani, Jessica A

2018-05-01

The nontraditional therapies of Traditional Chinese Veterinary Medicine and chiropractic care are adjunct treatments that can be used in conjunction with more conventional therapies to treat a variety of medical conditions. Nontraditional therapies do not need to be alternatives to Western medicine but, instead, can be used simultaneously. Exotic animal practitioners should have a basic understanding of nontraditional therapies for both client education and patient referral because they can enhance the quality of life, longevity, and positive outcomes for various cases across multiple taxa. Copyright © 2018 Elsevier Inc. All rights reserved.

Male emotional intimacy: how therapeutic men's groups can enhance couples therapy.

Science.gov (United States)

Garfield, Robert

2010-03-01

Men's difficulty with emotional intimacy is a problem that therapists regularly encounter in working with heterosexual couples in therapy. The first part of this article describes historical and cultural factors that contribute to this dilemma in men's marriages and same-sex friendships. Therapeutic men's groups can provide a corrective experience for men, helping them to develop emotional intimacy skills while augmenting their work in couples therapy. A model for such groups is presented, including guidelines for referral, screening, and collaboration with other therapists. Our therapeutic approach encourages relationship-based learning through direct emotional expression and supportive feedback. We emphasize the development of friendship skills, core attributes of friendship (connection, communication, commitment, and cooperation) that contribute to emotional intimacy in men's relationships. Case examples are included to illustrate how this model works in clinical practice, as well as specific suggestions for further study that could lead to a more evidence-based practice.

Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

Science.gov (United States)

Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

2013-05-01

Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

Applications of Nanotechnology in Bladder Cancer Therapy

Directory of Open Access Journals (Sweden)

Jong-Wei Hsu

2012-01-01

Full Text Available Effective therapies can prevent superficial bladder cancer from developing into muscle-invasive stage or more severe stages which require radical cystectomy and negatively affect life quality. In terms of therapeutic approaches against superficial bladder cancer, intravesical (regional therapy has several advantages over oral (systemic therapy. Though urologists can directly deliver drugs to bladder lesions by intravesical instillation after transurethral resection, the efficacy of conventional drug delivery is usually low due to the bladder permeability barrier and bladder periodical discharge. Nanoparticles have been well developed as pharmaceutical carriers. By their versatile properties, nanoparticles can greatly improve the interactions between urothelium and drugs and also enhance the penetration of drugs into urothelium with lesions, which dramatically improves therapeutic efficacy. In this review, we discuss the advances of nanotechnology in bladder cancer therapy by different types of nanoparticles with different encapsulating materials.

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

National Research Council Canada - National Science Library

Wang, Zhou

2004-01-01

.... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

National Research Council Canada - National Science Library

Wang, Zhou

2005-01-01

.... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

National Research Council Canada - National Science Library

Wang, Zhou

2003-01-01

.... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

Prevailing public perceptions of the ethics of gene therapy.

Science.gov (United States)

Robillard, Julie M; Roskams-Edris, Dylan; Kuzeljevic, Boris; Illes, Judy

2014-08-01

Gene therapy research is advancing rapidly, and hopes of treating a large number of brain disorders exist alongside ethical concerns. Most surveys of public attitudes toward these ethical issues are already dated and the content of these surveys has been researcher-driven. To examine current public perceptions, we developed an online instrument that is responsive and relevant to the latest research about ethics, gene therapy, and the brain. The 16-question survey was launched with the platform Amazon Mechanical Turk and was made available to residents of Canada and the United States. The survey was divided into six themes: (1) demographic information, (2) general opinions about gene therapy, (3) medical applications of gene therapy, (4) identity and moral/belief systems, (5) enhancement, and (6) risks. We received and analyzed responses from a total of 467 participants. Our results show that a majority of respondents (>90%) accept gene therapy as a treatment for severe illnesses such as Alzheimer disease, but this receptivity decreases for conditions perceived as less severe such as attention deficit hyperactivity disorder (79%), and for nontherapeutic applications (47%). The greatest area of concern for the application of gene therapy to brain conditions is the fear of not receiving sufficient information before undergoing the treatment. The main ethical concerns with enhancement were the potential for disparities in resource allocation, access to the procedure, and discrimination. When comparing these data with those from the 1990s, our findings suggest that the acceptability of gene therapy is increasing and that this trend is occurring despite lingering concerns over ethical issues. Providing the public and patients with up-to-date information and opportunities to engage in the discourse about areas of research in gene therapy is a priority.

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

National Research Council Canada - National Science Library

Wang, Zhou

2006-01-01

.... Intermittent androgen ablation therapy (IAAT) may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

Novel strategies for enhancing myocardial infarction

NARCIS (Netherlands)

Liu, J.

2011-01-01

Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Massive cell loss initiated a series of cascade events upon ischemic injury. Enourmous effort has been put to investigate strategies for enhancing myocardial healing. Cell therapy emerges as a promising strategy for

Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

Science.gov (United States)

Shi, Bin; Wang, Li-Fang; Meng, Wen-Shu; Chen, Liang; Meng, Zi-Li

2017-06-01

Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, which is generated by many species from Lamiaceae family. Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different vegetables and fruits. Fisetin has been reported to have various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Lung cancer is reported as the most common neoplasm in human world-wide. In the present study, the possible benefits of carnosic acid combined with fisetin on lung cancer in vitro and in vivo was explored. Carnosic acid and fisetin combination led to apoptosis in lung cancer cells. Caspase-3 signaling pathway was promoted in carnosic acid and fisetin co-treatment, which was accompanied by anti-apoptotic proteins of Bcl-2 and Bcl-xl decreasing and pro-apoptotic signals of Bax and Bad increasing. The death receptor (DR) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was enhanced in carnosic acid and fisetin combined treatment. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and fisetin combined treatment inhibited lung cancer growth in comparison to the carnosic acid or fisetin monotherapy. This study supplies a novel therapy to induce apoptosis to inhibit lung cancer through caspase-3 activation.

RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy.

Science.gov (United States)

Pritzker, Kenneth; Pritzker, Laura; Generali, Daniele; Bottini, Alberto; Cappelletti, Maria Rosa; Guo, Baoqing; Parissenti, Amadeo; Trudeau, Maureen

2015-05-01

As there is now evidence that switching clinical nonresponders early in primary systemic therapy to alternate treatment regimens can enhance survival in some breast cancer patients, the need for a robust intermediate endpoint that can guide treatment response across all tumor subtypes is urgent. Recently, chemotherapy drugs have been shown to induce a decrease in RNA quality in tumor cells from breast cancer biopsies in some patients at midtherapy, and that this has been associated with subsequent achievement of pathological complete response (pCR). The decrease in RNA quality has been shown to be associated with RNA disruption; aberrant RNA bands visualized by RNA electrophoresis have been associated with subsequent tumor cell death. The objectives of these studies are to show that a new assay based on induction of RNA disruption in tumor cells by chemotherapy can stratify at midtherapy, pCR responders from non-pCR responders irrespective of clinical response and to present early evidence that clinically useful RNA disruption can be detected as early as 14 days after initiation of treatment. RNA disruption in tumor cells was quantified by analysis of the RNA electrophoresis banding pattern and expressed as an RNA disruption index (RDI). To develop the RNA disruption assay (RDA), RDI was correlated with clinical outcome (pCR) from the NCIC-CTG MA.22 breast cancer clinical trial (ClinicalTrials.gov NCT00066443). RDA Zones were established by stratifying patients using RDI values into Zone 1, Zone 2, and Zone 3. Zone 3 included seven out of eight pCR responders, whereas Zone 1 contained no pCR responders. An intermediate zone (Zone 2) was established which contained one pCR. Subsequently, to determine early drug response, RNA disruption was examined by RDI after 14 days exposure to trastuzumab, zoledronic acid, or letrozole + cyclophosphamide ± sorafenib therapy. In MA.22, RDA stratified 23 of 85 patients in Zone 1 as pCR nonresponders, 24 patients in Zone 2, an

Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.

Directory of Open Access Journals (Sweden)

Akhirunnesa Mily

Full Text Available Development of new tuberculosis (TB drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3 and 4-phenyl butyrate (PBA are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.Adult TB patients (n = 288 were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OHD3 in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OHD3.At week 4, 71% (46/65 of the patients in the PBA+vitD3-group (p = 0.001 and 61.3% (38/62 in the vitD3-group (p = 0.032 were culture negative compared to 42.2% (27/64 in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001 and 2.2 times higher in vitD3-group (p = 0.032 compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034. Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01.Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB

Within-trial economic evaluation of diabetes-specific cognitive behaviour therapy in patients with type 2 diabetes and subthreshold depression

Directory of Open Access Journals (Sweden)

Ohmann Christian

2010-10-01

Full Text Available Abstract Background Despite the high prevalence of subthreshold depression in patients with type 2 diabetes, evidence on cost-effectiveness of different therapy options for these patients is currently lacking. Methods/Design Within-trial economic evaluation of the diabetes-specific cognitive behaviour therapy for subthreshold depression. Patients with diabetes and subthreshold depression are randomly assigned to either 2 weeks of diabetes-specific cognitive behaviour group therapy (n = 104 or to standard diabetes education programme only (n = 104. Patients are followed for 12 months. During this period data on total health sector costs, patient costs and societal productivity costs are collected in addition to clinical data. Health related quality of life (the SF-36 and the EQ-5D is measured at baseline, immediately after the intervention, at 6 and at 12 months after the intervention. Quality adjusted life years (QALYs, and cumulative costs will be estimated for each arm of the trial. Cost-effectiveness of the diabetes-specific cognitive behaviour group therapy will be analysed from the perspective of the German statutory health insurance and from the societal perspective. To this end, incremental cost-effectiveness ratio (ICER in terms of cost per QALY gained will be calculated. Discussion Some methodological issues of the described economic evaluation are discussed. Trial registration The trial has been registered at the Clinical Trials Register (NCT01009138.

Cognitive Enhancers for Facilitating Drug Cue Extinction: Insights from Animal Models

OpenAIRE

Nic Dhonnchadha, Bríd Áine; Kantak, Kathleen M.

2011-01-01

Given the success of cue exposure (extinction) therapy combined with a cognitive enhancer for reducing anxiety, it is anticipated that this approach will prove more efficacious than exposure therapy alone in preventing relapse in individuals with substance use disorders. Several factors may undermine the efficacy of exposure therapy for substance use disorders, but we suspect that neurocognitive impairments associated with chronic drug use are an important contributing factor. Numerous insigh...

Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

Science.gov (United States)

Tsai, Y-S; Shiau, A-L; Chen, Y-F; Tsai, H-T; Tzai, T-S; Wu, C-L

2010-01-01

The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

A randomized factorial trial of disulfiram and contingency management to enhance cognitive behavioral therapy for cocaine dependence.

Science.gov (United States)

Carroll, Kathleen M; Nich, Charla; Petry, Nancy M; Eagan, Dorothy A; Shi, Julia M; Ball, Samuel A

2016-03-01

This study evaluated the extent to which the addition of disulfiram and contingency management for adherence and abstinence (CM), alone and in combination, might enhance the effects of cognitive behavioral therapy (CBT) for cocaine use disorders. Factorial randomized double blind (for medication condition) clinical trial where CBT served as the platform and was delivered in weekly individual sessions in a community-based outpatient clinic. 99 outpatients who met DSM-IV criteria for current cocaine dependence were assigned to receive either disulfiram or placebo, and either CM or no CM. Cocaine and other substance use was assessed via a daily calendar with thrice weekly urine sample testing for 12 weeks with a one-year follow-up (80% interviewed at one year). The primary hypothesis that CM and disulfiram would produce the best cocaine outcomes was not confirmed, nor was there a main effect for disulfiram. For the primary outcome (percent days of abstinence, self report), there was a significant interaction, with the best cocaine outcomes were seen for the combination of CM and placebo, with the two groups assigned to disulfiram associated with intermediate outcomes, and poorest cocaine outcome among those assigned to placebo and no CM. The secondary outcome (urinalysis) indicated a significant effect favoring CM over no CM but the interaction effect was not significant. One year follow-up data indicated sustained treatment effects across conditions. CM enhances outcomes for CBT treatment of cocaine dependence, but disulfiram provided no added benefit to the combination of CM and CBT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hyperbaric oxygen therapy. Promoting healing in difficult cases

International Nuclear Information System (INIS)

Cohn, G.H.

1986-01-01

Inhalation of pressurized 100% oxygen is a helpful adjunctive treatment for certain patients, because the increased oxygen carried by the blood to the tissue enhances new growth of microcirculation and, thus, healing. Patients with tissue breakdown after radiation therapy, refractory osteomyelitis, gas gangrene, soft-tissue infection with necrosis from mixed aerobic and anaerobic organisms, crush injuries resulting in acute ischemia, and compromised skin grafts or non-healing wounds are likely to benefit from hyperbaric oxygen therapy

Clinical trial experience using erythropoietin during radiation therapy

International Nuclear Information System (INIS)

Lavey, R.S.

1998-01-01

Oncologists have several reasons for trying to maintain or increase hemoglobin levels in their patients during therapy. Relief of the symptoms of anemia, including fatigue and dyspnea, are traditional, well-accepted indications. A newer rationale is to enhance the efficacy of radiation therapy and/or chemotherapy in controlling tumors. A laboratory animal study found that administration of recombinant human erythropoietin (rHuEPO) increased intratumoral median oxygen levels and diminished the proportion of measurements in the very low ( [de

Practice comparisons between accelerated resolution therapy, eye movement desensitization and reprocessing and cognitive processing therapy with case examples.

Science.gov (United States)

Hernandez, Diego F; Waits, Wendi; Calvio, Lisseth; Byrne, Mary

2016-12-01

Recent outcomes for Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) therapy indicate that as many as 60-72% of patients retain their PTSD diagnosis after treatment with CPT or PE. One emerging therapy with the potential to augment existing trauma focused therapies is Accelerated Resolution Therapy (ART). ART is currently being used along with evidence based approaches at Fort Belvoir Community Hospital and by report has been both positive for clients as well as less taxing on professionals trained in ART. The following is an in-practice theoretical comparison of CPT, EMDR and ART with case examples from Fort Belvoir Community Hospital. While all three approaches share common elements and interventions, ART distinguishes itself through emphasis on the rescripting of traumatic events and the brevity of the intervention. While these case reports are not part of a formal study, they suggest that ART has the potential to augment and enhance the current delivery methods of mental health care in military environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and Safety of Antiretroviral Therapy Initiated One Week after Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/μL: TB-HAART Study, a Randomized Clinical Trial.

Directory of Open Access Journals (Sweden)

Wondwossen Amogne

Full Text Available Given the high death rate the first two months of tuberculosis (TB therapy in HIV patients, it is critical defining the optimal time to initiate combination antiretroviral therapy (cART.A randomized, open-label, clinical trial comparing efficacy and safety of efavirenz-based cART initiated one week, four weeks, and eight weeks after TB therapy in patients with baseline CD4 count < 200 cells/μL was conducted. The primary endpoint was all-cause mortality rate at 48 weeks. The secondary endpoints were hepatotoxicity-requiring interruption of TB therapy, TB-associated immune reconstitution inflammatory syndrome, new AIDS defining illnesses, CD4 counts, HIV RNA levels, and AFB smear conversion rates. All analyses were intention-to-treat.We studied 478 patients with median CD4 count of 73 cells/μL and 5.2 logs HIV RNA randomized to week one (n = 163, week four (n = 160, and week eight (n = 155. Sixty-four deaths (13.4% occurred in 339.2 person-years. All-cause mortality rates at 48 weeks were 25 per 100 person-years in week one, 18 per 100 person-years in week four and 15 per 100 person-years in week eight (P = 0.2 by the log-rank test. All-cause mortality incidence rate ratios in subgroups with CD4 count below 50 cells/μL versus above were 2.8 in week one (95% CI 1.2-6.7, 3.1 in week four (95% CI 1.2-8.6 and 5.1 in week eight (95% CI 1.8-16. Serum albumin < 3 gms/dL (adjusted HR, aHR = 2.3 and CD4 < 50 cells/μL (aHR = 2.7 were independent predictors of mortality. Compared with similar subgroups from weeks four and eight, first-line TB treatment interruption was high in week one deaths (P = 0.03 and in the CD4 subgroup <50 cells/μL (P = 0.02.Antiretroviral therapy one week after TB therapy doesn't improve overall survival. Despite increased mortality with CD4 < 50 cells/μL, we recommend cART later than the first week of TB therapy to avoid serious hepatotoxicity and treatment interruption.ClinicalTrials.gov NCT 01315301.

Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

Science.gov (United States)

Nevins, Marc L; Said, Sherif

2017-12-28

Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

Imaging-therapy computed tomography with quasi-monochromatic X-rays

International Nuclear Information System (INIS)

Jost, Gregor; Golfier, Sven; Lawaczeck, Ruediger; Weinmann, Hanns-Joachim; Gerlach, Martin; Cibik, Levent; Krumrey, Michael; Fratzscher, Daniel; Rabe, Johannis; Arkadiev, Vladimir; Haschke, Michael; Langhoff, Norbert; Wedell, Reiner

2008-01-01

Introduction: Computed tomography (CT) is a widespread and highly precise technique working in the energy range around 50-100 keV. For radiotherapy, however, the MeV energy range enables a better dose distribution. This gap between diagnosis and therapy can be overcome by the use of a modified CT machine in combination with heavy elements targeted to the tumour and used as photoelectric radiation enhancer. Materials and methods: The experimental setup consists of an X-ray optical module mounted at the exit of the X-ray tube of a clinical CT. The module converts the standard fan-shaped beam into a high intensity, monochromatized and focused beam. The radiation was characterized using an energy-dispersive detection system calibrated by synchrotron radiation and gel dosimetry. The photoelectric radiation enhancement for different elements was calculated and experimentally verified. Results: The X-ray optical module filters selectively the energy of the tungsten Kα-emission line (59.3 keV) with a full width at half maximum (FWHM) of 5 keV and focused the radiation onto a focal spot which coincides with the isocentre of the gantry. This results in a steep dose gradient at the centre of rotation qualified for locoregional radiation therapy. The photon energy of the quasi-monochromatic radiation agrees with the energy range of maximal photoelectric dose enhancement for gadolinium and iodine. Conclusion: An additional X-ray optical module optimized for targeted therapy and photoelectric dose enhancement allows the combination of diagnosis and radiotherapy on a clinical CT

Imaging-therapy computed tomography with quasi-monochromatic X-rays

Energy Technology Data Exchange (ETDEWEB)

Jost, Gregor [Bayer Schering Pharma AG, Contrast Media Research, Muellerstrasse 178, 13353 Berlin (Germany)], E-mail: gregor.jost@bayerhealthcare.com; Golfier, Sven [Bayer Schering Pharma AG, Contrast Media Research, Muellerstrasse 178, 13353 Berlin (Germany)], E-mail: sven.golfier@bayerhealthcare.com; Lawaczeck, Ruediger [Bayer Schering Pharma AG, Contrast Media Research, Muellerstrasse 178, 13353 Berlin (Germany)], E-mail: ruediger.lawaczeck@bayerhealthcare.com; Weinmann, Hanns-Joachim [Bayer Schering Pharma AG, Contrast Media Research, Muellerstrasse 178, 13353 Berlin (Germany)], E-mail: hanns-joachim.weinmann@bayerhealthcare.com; Gerlach, Martin [Physikalisch-Technische Bundesanstalt, Abbestrasse 2-12, 10587 Berlin (Germany)], E-mail: martin.gerlach@ptb.de; Cibik, Levent [Physikalisch-Technische Bundesanstalt, Abbestrasse 2-12, 10587 Berlin (Germany)], E-mail: levent.cibik@ptb.de; Krumrey, Michael [Physikalisch-Technische Bundesanstalt, Abbestrasse 2-12, 10587 Berlin (Germany)], E-mail: michael.krumrey@ptb.de; Fratzscher, Daniel [Institute for Scientific Instruments GmbH, Rudower Chaussee 29/31, 12489 Berlin (Germany)], E-mail: Fratzscher@ifg-adlershof.de; Rabe, Johannis [Institute for Scientific Instruments GmbH, Rudower Chaussee 29/31, 12489 Berlin (Germany)], E-mail: Rabe@ifg-adlershof.de; Arkadiev, Vladimir [Institute for Scientific Instruments GmbH, Rudower Chaussee 29/31, 12489 Berlin (Germany)], E-mail: Arkadiev@ifg-adlershof.de; Haschke, Michael [Institute for Scientific Instruments GmbH, Rudower Chaussee 29/31, 12489 Berlin (Germany)], E-mail: Haschke@ifg-adlershof.de; Langhoff, Norbert [Institute for Scientific Instruments GmbH, Rudower Chaussee 29/31, 12489 Berlin (Germany)], E-mail: Langhoff@ifg-adlershof.de; Wedell, Reiner [Institut fuer angewandte Photonik e.V., Rudower Chaussee 29/31, 12489 Berlin (Germany)], E-mail: wedell-iap@ifg-adlershof.de (and others)

2008-12-15

Introduction: Computed tomography (CT) is a widespread and highly precise technique working in the energy range around 50-100 keV. For radiotherapy, however, the MeV energy range enables a better dose distribution. This gap between diagnosis and therapy can be overcome by the use of a modified CT machine in combination with heavy elements targeted to the tumour and used as photoelectric radiation enhancer. Materials and methods: The experimental setup consists of an X-ray optical module mounted at the exit of the X-ray tube of a clinical CT. The module converts the standard fan-shaped beam into a high intensity, monochromatized and focused beam. The radiation was characterized using an energy-dispersive detection system calibrated by synchrotron radiation and gel dosimetry. The photoelectric radiation enhancement for different elements was calculated and experimentally verified. Results: The X-ray optical module filters selectively the energy of the tungsten K{alpha}-emission line (59.3 keV) with a full width at half maximum (FWHM) of 5 keV and focused the radiation onto a focal spot which coincides with the isocentre of the gantry. This results in a steep dose gradient at the centre of rotation qualified for locoregional radiation therapy. The photon energy of the quasi-monochromatic radiation agrees with the energy range of maximal photoelectric dose enhancement for gadolinium and iodine. Conclusion: An additional X-ray optical module optimized for targeted therapy and photoelectric dose enhancement allows the combination of diagnosis and radiotherapy on a clinical CT.

Learning from dying patients during their final days: life reflections gleaned from dignity therapy.

Science.gov (United States)

Hack, Thomas F; McClement, Susan E; Chochinov, Harvey M; Cann, Beverley J; Hassard, Thomas H; Kristjanson, Linda J; Harlos, Mike

2010-10-01

Dignity therapy is a novel therapeutic approach designed to decrease suffering, enhance quality of life and bolster a sense of dignity for patients approaching death. The benefits of dignity therapy were previously documented in a sample of 100 terminally ill patients. One of the products of dignity therapy is a transcript of the edited therapy session(s). In this qualitative study, 50 of the 100 (17 from Winnipeg, Manitoba, Canada, and 33 from Perth, Australia) dignity therapy transcripts were randomly drawn, and independently coded and analysed by three investigators using a grounded theory approach. The transcripts revealed that dignity therapy serves to provide a safe, therapeutic environment for patients to review the most meaningful aspects of their lives in such a manner that their core values become apparent. The most common values expressed by the patients included 'Family', 'Pleasure', 'Caring', 'A Sense of Accomplishment', 'True Friendship', and 'Rich Experience'. Exemplars of each of these values illustrate the pervasive, defining role of values in our lives. The findings are discussed in terms of values theory, the role of dignity therapy, and consideration of values clarification in clinicians' efforts to enhance the dignity of terminally ill patients.

Alterations in renal morphology and function after ESWL therapy: evaluation with dynamic contrast-enhanced MRI

International Nuclear Information System (INIS)

Krestin, G.P.; Fischbach, R.; Vorreuther, R.; Schulthess, G.K. von