WorldWideScience

Sample records for targeting manual therapy

  1. 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...

  2. Does targeting manual therapy and/or exercise improve patient outcomes in nonspecific low back pain? A systematic review

    DEFF Research Database (Denmark)

    Kent, Peter; Mjøsund, Hanne L; Petersen, Ditte H D

    2010-01-01

    A central element in the current debate about best practice management of non-specific low back pain (NSLBP) is the efficacy of targeted versus generic (non-targeted) treatment. Many clinicians and researchers believe that tailoring treatment to NSLBP subgroups positively impacts on patient outco...... outcomes. Despite this, there are no systematic reviews comparing the efficacy of targeted versus non-targeted manual therapy and/or exercise. This systematic review was undertaken in order to determine the efficacy of such targeted treatment in adults with NSLBP....

  3. Does targeting manual therapy and/or exercise improve patient outcomes in nonspecific low back pain? A systematic review

    Directory of Open Access Journals (Sweden)

    Mjøsund Hanne L

    2010-04-01

    Full Text Available Abstract Background A central element in the current debate about best practice management of non-specific low back pain (NSLBP is the efficacy of targeted versus generic (non-targeted treatment. Many clinicians and researchers believe that tailoring treatment to NSLBP subgroups positively impacts on patient outcomes. Despite this, there are no systematic reviews comparing the efficacy of targeted versus non-targeted manual therapy and/or exercise. This systematic review was undertaken in order to determine the efficacy of such targeted treatment in adults with NSLBP. Method MEDLINE, EMBASE, Current Contents, AMED and the Cochrane Central Register of Controlled Trials were electronically searched, reference lists were examined and citation tracking performed. Inclusion criteria were randomized controlled trials of targeted manual therapy and/or exercise for NSLPB that used trial designs capable of providing robust information on targeted treatment (treatment effect modification for the outcomes of activity limitation and pain. Included trials needed to be hypothesis-testing studies published in English, Danish or Norwegian. Method quality was assessed using the criteria recommended by the Cochrane Back Review Group. Results Four high-quality randomized controlled trials of targeted manual therapy and/or exercise for NSLBP met the inclusion criteria. One study showed statistically significant effects for short-term outcomes using McKenzie directional preference-based exercise. Research into subgroups requires much larger sample sizes than traditional two-group trials and other included studies showed effects that might be clinically important in size but were not statistically significant with their samples sizes. Conclusions The clinical implications of these results are that they provide very cautious evidence supporting the notion that treatment targeted to subgroups of patients with NSLBP may improve patient outcomes. The results of the

  4. Reconceptualising manual therapy skills in contemporary practice

    DEFF Research Database (Denmark)

    Rabey, Martin; Hall, Toby; Hebron, Clair

    2017-01-01

    With conflicting evidence regarding the effectiveness of manual therapy calls have arisen within some quarters of the physiotherapy profession challenging the continued use of manual skills for assessment and treatment. A reconceptualisation of the importance of manual examination findings is put...

  5. Effects of manual therapy and exercise targeting the hips in patients with low-back pain-A randomized controlled trial.

    Science.gov (United States)

    Bade, Michael; Cobo-Estevez, Manuel; Neeley, Darren; Pandya, Jeevan; Gunderson, Travis; Cook, Chad

    2017-08-01

    The benefits of providing manual therapy and exercise targeting the hips in individuals with mechanical low-back pain (LBP) are not well established. The objective in this study is to determine whether a formal prescriptive treatment protocol for the hips improves outcomes in patients with a primary complaint of mechanical LBP. Eighty-four (84) subjects (50 males, 46.1 ± 16.2 years) were randomized to 1 of 2 groups: pragmatic treatment of the lumbar spine only (LBP) (n = 39) or pragmatic treatment of the lumbar spine and prescriptive treatment of bilateral hips (LBP + HIP) (n = 45). Pragmatic treatment of the lumbar spine was based upon published clinical guidelines. Prescriptive treatment of the hips involved the use of 3 hip exercises targeting the gluteal musculature and 3 mobilization techniques targeting the hips. Subjects were assessed at baseline, 2 weeks, and at discharge with the following measures: Modified Oswestry Disability Index, Numeric Pain Rating Scale, a global rating of change (GRoC) score, the patient acceptable symptom state (PASS), and patient satisfaction. At 2 weeks, significant differences between groups differences were found in GRoC and patient satisfaction (P < .05) favoring the LBP + HIP group. At discharge, there were significant differences on the Modified Oswestry Disability Index, numeric pain rating scale, GRoC, and patient satisfaction favoring the LBP + HIP group (P < .05). Effect sizes were small to medium. Our findings suggest that a prescriptive treatment of the hips may be of clinical value to individuals presenting with the primary complaint of mechanical LBP. © 2017 John Wiley & Sons, Ltd.

  6. Physical Therapy and Manual Physical Therapy: Differences in Patient Characteristics.

    NARCIS (Netherlands)

    van Ravensberg, C. D. Dorine; Oostendorp, Rob A B; van Berkel, Lonneke M.; Scholten-Peeters, Gwendolijne G M; Pool, Jan J.M.; Swinkels, Raymond A. H. M.; Huijbregts, Peter A.

    2005-01-01

    This study compared socio-demographic characteristics, health problem characteristics, and primary process data between database samples of patients referred to physical therapy (PT) versus a sample of patients referred to manual physical therapy (MPT) in the Netherlands. Statistical analysis

  7. Physical therapy and manual physical therapy: Differences in patient characteristics

    NARCIS (Netherlands)

    van Ravensberg, C. D. Dorine; Oostendorp, R.A.B.; van Berkel, Lonneke M.; Scholten-Peeters, G.G.M.; Pool, J.J.M.; Swinkels, Raymond A. H. M.; Huijbregts, Peter A.

    2005-01-01

    This study compared socio-demographic characteristics, health problem characteristics, and primary process data between database samples of patients referred to physical therapy (PT) versus a sample of patients referred to manual physical therapy (MPT) in the Netherlands. Statistical analysis

  8. Physical Therapy and Manual Physical Therapy: Differences in Patient Characteristics

    NARCIS (Netherlands)

    van Ravensberg, C. D. Dorine; Oostendorp, Rob A B; van Berkel, Lonneke M.; Scholten-Peeters, Gwendolijne G. M.; Pool, Jan J.M.; Swinkels, Raymond A. H. M.; Huijbregts, Peter A.

    2005-01-01

    This study compared socio-demographic characteristics, health problem characteristics, and primary process data between database samples of patients referred to physical therapy (PT) versus a sample of patients referred to manual physical therapy (MPT) in the Netherlands. Statistical analysis

  9. Reconceptualising manual therapy skills in contemporary practice.

    Science.gov (United States)

    Rabey, Martin; Hall, Toby; Hebron, Clair; Palsson, Thorvaldur Skuli; Christensen, Steffan Wittrup; Moloney, Niamh

    2017-06-01

    With conflicting evidence regarding the effectiveness of manual therapy calls have arisen within some quarters of the physiotherapy profession challenging the continued use of manual skills for assessment and treatment. A reconceptualisation of the importance of manual examination findings is put forward, based upon a contemporary understanding of pain science, rather than considering these skills only in terms of how they should "guide" manual therapy interventions. The place for manual examination findings within complex, multidimensional presentations is considered using vignettes describing the presentations of five people with low back pain. As part of multidimensional, individualised management, the balance of evidence relating to the effectiveness, mechanisms of action and rationale for manual skills is discussed. It is concluded that if manual examination and therapeutic skills are used in a manner consistent with a contemporary understanding of pain science, multidimensional patient profiles and a person-centred approach, their selective and judicious use still has an important role. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Targeted enzyme prodrug therapies.

    Science.gov (United States)

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  11. Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    David Cheng

    2011-10-01

    Full Text Available Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

  12. Targeted Radionuclide Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ersahin, Devrim, E-mail: devrimersahin@yahoo.com; Doddamane, Indukala; Cheng, David [Department of Diagnostic Radiology, School of Medicine, Yale University, 333 Cedar St., New Haven, CT 06520 (United States)

    2011-10-11

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

  13. Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Ersahin, Devrim; Doddamane, Indukala; Cheng, David

    2011-01-01

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose

  14. Athletes’ Shoulder Joints Traumas Manual Therapy Rehabilitation

    Directory of Open Access Journals (Sweden)

    A.N. Sykhorychko

    2012-06-01

    Full Text Available The examination of 60 athletes, aged 18-30, suffering from chronic pains in shoulder joints was conducted. So, 20 women and 20 men were engaged in track and field and team sports, 15 in weightlifting and strength sports, 5 women in strength sports. Shoulder Joints Traumas Manual Therapy enables to reduce pain syndrome, restore shoulder joint flexibility, normalize trophism after trauma and normalize cervicothoracic transition biomechanics.

  15. Athletes’ Shoulder Joints Traumas Manual Therapy Rehabilitation

    OpenAIRE

    A.N. Sykhorychko; Т.G. Kovalenko; М.А. Sykhorychko

    2012-01-01

    The examination of 60 athletes, aged 18-30, suffering from chronic pains in shoulder joints was conducted. So, 20 women and 20 men were engaged in track and field and team sports, 15 in weightlifting and strength sports, 5 women in strength sports. Shoulder Joints Traumas Manual Therapy enables to reduce pain syndrome, restore shoulder joint flexibility, normalize trophism after trauma and normalize cervicothoracic transition biomechanics.

  16. Manual therapy for plantar heel pain.

    Science.gov (United States)

    Pollack, Yosefa; Shashua, Anat; Kalichman, Leonid

    2018-03-01

    Manual therapy employed in the treatment of plantar heel pain includes joint or soft tissue mobilizations. Efficacy of these methods is still under debate. To determine whether manual therapy, consisting of deep massage, myofascial release or joint mobilization is effective in treating plantar heel pain. A critical review of all available studies with an emphasis on randomized controlled trials (RCTs) was performed. PubMed, PEDro, and Google Scholar databases were searched for keywords relating to plantar heel pain, joint, and soft tissue mobilizations. There were no search limitations or language restrictions. The reference lists of all retrieved articles were searched. The PEDro score was used to assess the quality of the reviewed papers. A total of six relevant RCTs were found: two examined the effectiveness of joint mobilization on plantar heel pain and four the effectiveness of soft tissue techniques. Five studies showed a positive short-term effect after manual therapy treatment, mostly soft tissue mobilizations, with or without stretching exercises for patients with plantar heel pain, compared to other treatments. One study observed that adding joint mobilization to the treatment of plantar heel pain was not effective. The quality of all studies was moderate to high. According to reviewed moderate and high-quality RCTs, soft tissue mobilization is an effective modality for treating plantar heel pain. Outcomes of joint mobilizations are controversial. Further studies are needed to evaluate the short and long-term effect of different soft tissue mobilization techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  18. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  19. Labelling of 90Y- and 177Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated, and Fully Automated Synthesis

    Directory of Open Access Journals (Sweden)

    Michele Iori

    2017-01-01

    Full Text Available In spite of the hazard due to the radiation exposure, preparation of 90Y- and 177Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177Lu- and 90Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617 was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90Y- and 177Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90Y-DOTATOC were 96.2±4.9%, 90.3±5.6%, and 82.0±8.4%, while for 177Lu-DOTATOC they were 98.3%  ± 0.6, 90.8%  ± 8.3, and 83.1±5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15±0.4 mSv/GBq, 0.04±0.1 mSv/GBq, and 0.11±0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02±0.008 mSv/GBq, 0.01±0.03 mSv/GBq, and 0.01±0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system.

  20. Unraveling the Mechanisms of Manual Therapy: Modeling an Approach.

    Science.gov (United States)

    Bialosky, Joel E; Beneciuk, Jason M; Bishop, Mark D; Coronado, Rogelio A; Penza, Charles W; Simon, Corey B; George, Steven Z

    2018-01-01

    Synopsis Manual therapy interventions are popular among individual health care providers and their patients; however, systematic reviews do not strongly support their effectiveness. Small treatment effect sizes of manual therapy interventions may result from a "one-size-fits-all" approach to treatment. Mechanistic-based treatment approaches to manual therapy offer an intriguing alternative for identifying patients likely to respond to manual therapy. However, the current lack of knowledge of the mechanisms through which manual therapy interventions inhibit pain limits such an approach. The nature of manual therapy interventions further confounds such an approach, as the related mechanisms are likely a complex interaction of factors related to the patient, the provider, and the environment in which the intervention occurs. Therefore, a model to guide both study design and the interpretation of findings is necessary. We have previously proposed a model suggesting that the mechanical force from a manual therapy intervention results in systemic neurophysiological responses leading to pain inhibition. In this clinical commentary, we provide a narrative appraisal of the model and recommendations to advance the study of manual therapy mechanisms. J Orthop Sports Phys Ther 2018;48(1):8-18. doi:10.2519/jospt.2018.7476.

  1. Manual therapy and exercise for neck pain: A systematic review

    NARCIS (Netherlands)

    Miller, Jordan; Gross, Anita; D'Sylva, Jonathan; Burnie, Stephen J.; Goldsmith, Charles H.; Graham, Nadine; Haines, Ted; Brønfort, Gert; Hoving, Jan L.

    2010-01-01

    Manual therapy is often used with exercise to treat neck pain. This cervical overview group systematic review update assesses if manual therapy, including manipulation or mobilisation, combined with exercise improves pain, function/disability, quality of life, global perceived effect, and patient

  2. Thoracic manual therapy is not more effective than placebo thoracic manual therapy in patients with shoulder dysfunctions: A systematic review with meta-analysis.

    Science.gov (United States)

    Bizzarri, Paolo; Buzzatti, Luca; Cattrysse, Erik; Scafoglieri, Aldo

    2018-02-01

    Manual treatments targeting different regions (shoulder, cervical spine, thoracic spine, ribs) have been studied to deal with patients complaining of shoulder pain. Thoracic manual treatments seem able to produce beneficial effects on this group of patients. However, it is not clear whether the patient improvement is a consequence of thoracic manual therapy or a placebo effect. To compare the efficacy of thoracic manual therapy and placebo thoracic manual treatment for patients with shoulder dysfunction. Electronic databases (MEDLINE, CENTRAL, PEDro, CINAHL, WoS, EMBASE, ERIC) were searched through November 2016. Randomized Controlled Trials assessing pain, mobility and function were selected. The Cochrane bias estimation tool was applied. Outcome results were either extracted or computed from raw data. Meta-analysis was performed for outcomes with low heterogeneity. Four studies were included in the review. The methodology of the included studies was generally good except for one study that was rated as high risk of bias. Meta-analysis showed no significant effect for "pain at present" (SMD -0.02; 95% CI: -0.35, 0.32) and "pain during movement" (SMD -0.12; 95% CI: -0.45, 0.21). There is very low to low quality of evidence that a single session of thoracic manual therapy is not more effective than a single session of placebo thoracic manual therapy in patients with shoulder dysfunction at immediate post-treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  4. The use of manual therapy in paediatric physiotherapy

    OpenAIRE

    Skoutelis V

    2016-01-01

    Introduction: Manual therapy is the most common complementary or alternative treatment approach for orthopedic and non-musculoskeletal conditions in adult patients. In recent years, manual therapy techniques are increasingly used by physiotherapists in therapeutic programmes for children with neurological and orthopedic impairments. There is also a continuous increase in the number of children visits to alternative therapies, especially joint manipulation procedures. The purpose o...

  5. Polarized proton target-IV. Operations manual

    International Nuclear Information System (INIS)

    Hill, D.; Fletcher, O.; Moretti, A.; Onesto, F.

    1976-01-01

    Standard operating procedures are presented for the vacuum, cryogenic, and electronic systems of a polarized proton target. The systems are comprised of (1) a target cryostat; (2) a 4 He pumping system; (3) a 3 He pumping system; (4) a microwave system; (5) a magnet and power supply; (6) a computerized polarization monitor; and (7) miscellaneous auxiliary equipment

  6. Targeted radionuclide therapy

    African Journals Online (AJOL)

    target for which a speci c treatment/drug is intended (Fig. 1). eranostics .... Using an anti-CD20 antibody as a delivery device to target the follicular ... systems combine diagnostic imaging (Ga-68-DOTATATE PET/CT) .... Intra-articular injected ...

  7. Targeted Cancer Therapies

    Science.gov (United States)

    ... are sometimes referred to as the product of "rational" drug design.) One approach to identify potential targets ... molecules that stimulate new blood vessel growth. Immunotherapies trigger the immune system to destroy cancer cells. Some ...

  8. Molecular Targets for Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Mather, S.J.

    2009-01-01

    Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

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

    NARCIS (Netherlands)

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

    2017-01-01

    Background: 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

  10. Targeted therapy for sarcomas

    Directory of Open Access Journals (Sweden)

    Forscher C

    2014-03-01

    Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

  11. Polarized proton Target-III operators manual, revision A

    International Nuclear Information System (INIS)

    Hill, D.; Moretti, A.; Onesto, F.; Rynes, P.

    1976-04-01

    A revision is given of a manual containing standard operating procedures for the vacuum, cryogenic, and electronic systems of a polarized proton target. The discussion includes the target cryostat, the 3 He and 4 He pumping systems, remote monitors and controls, the microwave system, the magnet and power supply, the computerized polarization monitor, the 4 He liquifier and gas recovery system, and miscellaneous auxiliary equipment

  12. Manual therapy and exercise for rotator cuff disease.

    Science.gov (United States)

    Page, Matthew J; Green, Sally; McBain, Brodwen; Surace, Stephen J; Deitch, Jessica; Lyttle, Nicolette; Mrocki, Marshall A; Buchbinder, Rachelle

    2016-06-10

    Management of rotator cuff disease often includes manual therapy and exercise, usually delivered together as components of a physical therapy intervention. This review is one of a series of reviews that form an update of the Cochrane review, 'Physiotherapy interventions for shoulder pain'. To synthesise available evidence regarding the benefits and harms of manual therapy and exercise, alone or in combination, for the treatment of people with rotator cuff disease. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE (January 1966 to March 2015), Ovid EMBASE (January 1980 to March 2015), CINAHL Plus (EBSCO, January 1937 to March 2015), ClinicalTrials.gov and the WHO ICTRP clinical trials registries up to March 2015, unrestricted by language, and reviewed the reference lists of review articles and retrieved trials, to identify potentially relevant trials. We included randomised and quasi-randomised trials, including adults with rotator cuff disease, and comparing any manual therapy or exercise intervention with placebo, no intervention, a different type of manual therapy or exercise or any other intervention (e.g. glucocorticoid injection). Interventions included mobilisation, manipulation and supervised or home exercises. Trials investigating the primary or add-on effect of manual therapy and exercise were the main comparisons of interest. Main outcomes of interest were overall pain, function, pain on motion, patient-reported global assessment of treatment success, quality of life and the number of participants experiencing adverse events. Two review authors independently selected trials for inclusion, extracted the data, performed a risk of bias assessment and assessed the quality of the body of evidence for the main outcomes using the GRADE approach. We included 60 trials (3620 participants), although only 10 addressed the main comparisons of interest. Overall risk of bias was low in three, unclear in 14 and high in

  13. Considerations to improve the safety of cervical spine manual therapy.

    Science.gov (United States)

    Hutting, Nathan; Kerry, Roger; Coppieters, Michel W; Scholten-Peeters, Gwendolijne G M

    2018-02-01

    Manipulation and mobilisation of the cervical spine are well established interventions in the management of patients with headache and/or neck pain. However, their benefits are accompanied by potential, yet rare risks in terms of serious adverse events, including neurovascular insult to the brain. A recent international framework for risk assessment and management offers directions in the mitigation of this risk by facilitating sound clinical reasoning. The aim of this article is to critically reflect on and summarize the current knowledge about cervical spine manual therapy and to provide guidance for clinical reasoning for cervical spine manual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Polarized proton target-III. Operations manual, revision B

    International Nuclear Information System (INIS)

    Hill, D.; Moretti, A.; Onesto, F.; Rynes, P.

    1978-01-01

    The manual presented contains certain standard operating procedures for the vacuum, cryogenic, and electronic systems of PPT-III. In total, these systems comprise the following major divisions: (1) the target cryostat; (2) the 4 He pumping system; (3) the 3 He pumping system; (4) the remote monitors and controls; (5) the microwave system; (6) the magnet and power supply; (7) the computerized polarization monitor; (8) the 4 He liquefier and gas recovery system; and (9) miscellaneous auxiliary equipment

  15. Manual Therapy With Cryotherapy Versus Manual Therapy With Kinesio Taping for Males With Lumbar Discopathy: A Pilot Randomized Trial.

    Science.gov (United States)

    Lizis, Pawel; Kobza, Wojciech

    2017-06-23

    Context • Numerous modalities of therapeutic interventions exist for lumbar discopathy. Manual therapy is one option, although its effectiveness remains controversial. The addition of cryotherapy to manual therapy may enhance the health benefits in patients with lumbar discopathy.  Objective • The study intended to evaluate the efficacy of manual therapy combined with cryotherapy vs manual therapy combined with Kinesio taping for males with lumbar discopathy. Design • The research team designed a pilot randomized trial with concealed allocation, assessor blinding, and intention-to-treat analysis. Setting • The study occurred in the Physiotherapy Outpatient Department of the Regional Hospital (Zywiec, Poland). Participants • The participants were 40 males with lumbar discopathy, aged 30-75 y, who were patients in the department at the hospital. Intervention • The participants were randomly assigned to an intervention group that received Kaltenborn-Evjenth orthopedic manual therapy (KEOMT) combined with cryotherapy, the KEOMT-C group (n = 20), or to a control group that received KEOMT combined with Kinesio taping, the KEOMT-K group (n = 20). The participants in both groups received 10 treatments, 2 per wk for 5 wk. Outcome Measures • The primary outcome was measured using a visual analog scale and the Laitinen scale pain ratings. The secondary outcome measured the quality of life using the short form-36 questionnaire. The participants completed the tests at baseline and postintervention. Results • After the treatments, the intervention group had significantly lower scores than the control group for pain as well as significantly higher scores for quality of life. Conclusions • Patients achieved better health benefits from manual therapy when it was combined with cryotherapy.

  16. Targeted therapies for bone sarcomas

    International Nuclear Information System (INIS)

    Mudry, P.

    2011-01-01

    Therapy success in bone sarcoma is significantly better compared to history cohorts with 60 - 70 % overall survival to date. Unfortunately, there is yet no shift and movement in better survival of patients with relapsed and refractory bone sarcomas during last twenty years. This article reviews targeted therapeutics for bone sarcomas which are under investigation and which could give chance to patients suffering from relapsed and chemo resistant bone sarcomas. Majority of the targeted drugs are given as part of phase 1 or 2 studies. (author)

  17. Targeted Therapies for Lung Cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    Targeted therapies have become standard therapies for patients with non-small cell lung cancer (NSCLC). A phase III trial of carboplatin and paclitaxel with and without bevacizumab in patients with advanced NSCLC with non-squamous histology demonstrated a statistically significant improvement in efficacy. In patients with NSCLC with an activating epidermal growth factor receptor (EGFR) mutation (defined as exon 19 deletion and exon 21 L858R point mutation), phase III trials of EGFR tyrosine kinase inhibitors (TKI) compared to platinum-based chemotherapy have demonstrated superior efficacy in the first-line setting. In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting. A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib. Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation. The oncogenic mutations that are susceptible to targeted therapy are mainly found in non-squamous NSCLC. The development of targeted therapy in patients with squamous NSCLC has been more challenging due to the genomic complexity observed in the squamous histology and the low prevalence of EGFR, ALK, and ROS1 molecular alterations. A phase III trial of cisplatin and gemcitabine with and without necitumumab in patients with advanced NSCLC with squamous histology demonstrated a statistically significant improvement in progression-free and overall survival.

  18. Comparison of manual therapy and exercise therapy in osteoarthritis of the hip: a randomized clinical trial.

    NARCIS (Netherlands)

    Hoeksma, H.L.; Dekker, J.; Ronday, H.K.; Heering, A.; Lubbe, N. van der; Vel, C.; Breedveld, F.C.; Ende, C.H.M. van den

    2004-01-01

    OBJECTIVE: To determine the effectiveness of a manual therapy program compared with an exercise therapy program in patients with osteoarthritis (OA) of the hip. METHODS: A single-blind, randomized clinical trial of 109 hip OA patients was carried out in the outpatient clinic for physical therapy of

  19. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  20. Targeted drugs in radiation therapy

    International Nuclear Information System (INIS)

    Favaudon, V.; Hennequin, C.; Hennequin, C.

    2004-01-01

    New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neo-angiogenesis promoters, TGF-β, cyclooxygenase or the transcription factor NF-κB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms. (authors)

  1. The working mechanism of manual therapy in participants with chronic tension-type headache

    NARCIS (Netherlands)

    Castien, R.F.; Blankenstein, A.H.; van der Windt, D.; Heijmans, M.W.; Dekker, J.

    2013-01-01

    STUDY DESIGN: Prospective longitudinal study.OBJECTIVE: To explore the working mechanism of manual therapy, we investigated whether 3 cervical spine variables were mediators of the effect of manual therapy on headache frequency.BACKGROUND: Manual therapy has been shown to reduce headache frequency

  2. Manual therapy treatment of lumbar radiculopathy: A single case report

    Directory of Open Access Journals (Sweden)

    J.A. Riley

    2011-01-01

    Full Text Available Patients  with  lumbar  radiculopathy  are  often  managed with  manual therapy.  The  aim  of  this  single  case  study  was  to  describe  the outcome of manual therapy treatment of a patient with lumbar radiculopathy.  A 47-year-old female presented with acute, severe left buttock and postero-lateral thigh pain.  Symptom provocation occurred during lumbar flexion, coughing, sneezing, driving and prolonged sitting. her left straight leg raise neurodynamic test was limited and reproduced her pain, as did trigger points in the left lumbar and gluteal muscles. clinical neuro-conduction testing revealed weakness of the big and other toe extensors, as well as eversion and plantar flexion of the left ankle, and a diminished left ankle reflex. This indicated possible involvement of both the l5 and S1 nerve roots.   A  manual  therapy  treatment  approach including  lumbar rotation mobilisations (Maitland approach, massage, trigger point pressure release  and  Transversus  Abdominus muscle activation  was  used.   The  patient  was  symptom  free,  had  full pain-free  range  of  all  lumbar  movements,  a full  pain-free  left  straight leg  raise  neurodynamic  test  and  normal  neurological  conduction  six weeks  after  onset, following seven manual therapy treatments.  Although the results of this case report cannot be generalised, it describes the successful outcome of a patient with severe radicular pain and neurological deficits, whose signs and symptoms  had completely resolved following manual therapy treatment.

  3. Targeted therapy of multiple myeloma.

    Science.gov (United States)

    Dolloff, Nathan G; Talamo, Giampaolo

    2013-01-01

    Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

  4. EFFECTIVENESS OF MANUAL THERAPY VERSUS EXERCISE THERAPY FOR THE MANAGEMENT OF KNEE OSTEOARTHRITIS IN KARACHI PAKISTAN

    Directory of Open Access Journals (Sweden)

    Ayesha Zakir

    2016-02-01

    Full Text Available Introduction: Among musculoskeletal disorders knee Osteoarthritis (OA is exceedingly prevailing articular disorder affecting people and it is a major cause of disability and socioeconomic burden. It is more common in women than men. Entities with knee OA must often undergo a variety of problems, such as pain and tenderness in joints, movement limitation, crepitus on movement, swelling, recurrent effusion, and local inflammation which ultimately leads to limitation in physical function, like lack of ability to perform Activities of Daily Living (ADL or Instrumental Activities of Daily Living (IADL. For reducing knee pain in osteoarthritis several conventional treatment methods are used world widely but most extensively used in our country are pharmacologic and physical therapy. The objective of the study is to find out the effectiveness of Manual therapy verses Exercise therapy for the management of knee osteoarthritis. Methods: Sixty patients including both male and female with mean age (51years and SD of (5.1 were enrolled in the study and divided randomly in to two groups. Those who were assigned as group A had received Manual therapy and those who were assigned as group B had received Exercise therapy. Participants had received three treatment sessions of 30 min per week for consecutive 4 weeks. OUTCOME MEASURE: WOMAC index score for pain, stiffness and physical function was used to evaluate the baseline score and treatment effects after 12 therapy sessions. Results: Study showed significant improvement in both groups before and after the treatment but in comparison manual therapy group showed significant results with respect to pain subscale (p=0.003 and physical function subscale (p=0.004. Conclusion: Significant difference found between manual therapy and exercise therapy treatment approaches in treating knee osteoarthritis. Findings of this study revealed the fact that short term treatment sessions of manual therapy were superior to

  5. 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

  6. Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain: a randomized, controlled trial.

    NARCIS (Netherlands)

    Hoving, J.L.; Koes, B.W.; Vet, H.C.W. de; Windt, D.A.W.M. van der; Assendelft, W.J.J.; Mameren, H. van; Devillé, W.L.J.M.; Pool, J.J.M.; Scholten, R.J.P.M.; Bouter, L.M.

    2002-01-01

    BACKGROUND: Neck pain is a common problem, but the effectiveness of frequently applied conservative therapies has never been directly compared. OBJECTIVE: To determine the effectiveness of manual therapy, physical therapy, and continued care by a general practitioner. DESIGN: Randomized, controlled

  7. Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial

    NARCIS (Netherlands)

    Hoving, Jan Lucas; Koes, Bart W.; de Vet, Henrica C. W.; van der Windt, Danielle A. W. M.; Assendelft, Willem J. J.; van Mameren, Henk; Devillé, Walter L. J. M.; Pool, Jan J. M.; Scholten, Rob J. P. M.; Bouter, Lex M.

    2002-01-01

    BACKGROUND: Neck pain is a common problem, but the effectiveness of frequently applied conservative therapies has never been directly compared. OBJECTIVE: To determine the effectiveness of manual therapy, physical therapy, and continued care by a general practitioner. DESIGN: Randomized, controlled

  8. Targeted Therapy of Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Vivek Subbiah

    2011-01-01

    Full Text Available Refractory and/or recurrent Ewing's sarcoma (EWS remains a clinical challenge because the disease's resistance to therapy makes it difficult to achieve durable results with standard treatments that include chemotherapy, radiation, and surgery. Recently, insulin-like-growth-factor-1-receptor (IGF1R antibodies have been shown to have a modest single-agent activity in EWS. Patient selection using biomarkers and understanding response and resistance mechanisms in relation to IGF1R and mammalian target of rapamycin pathways are areas of active research. Since EWS has a unique tumor-specific EWS-FLI1 t(11;22 translocation and oncogenic fusion protein, inhibition of EWS-FLI1 transcription, translation, and/or protein function may be key to eradicating EWS at the stem-cell level. Recently, a small molecule that blocks the protein-protein interaction of EWS-FLI1 with RNA helicase A has been shown in preclinical models to inhibit EWS growth. The successful application of this first-in-class protein-protein inhibitor in the clinic could become a model system for translocation-associated cancers such as EWS.

  9. Placebo Mechanisms of Manual Therapy: A Sheep in Wolf's Clothing?

    Science.gov (United States)

    Bialosky, Joel E; Bishop, Mark D; Penza, Charles W

    2017-05-01

    When a physical therapist provides a manual therapy (MT) intervention for a patient presenting with pain and the patient experiences a positive clinical outcome, we cannot answer as to why this occurs. Would we continue to devote valuable time and financial resources to learning and improving our skills in providing MT interventions if the related clinical outcomes were placebo responses? In this Viewpoint, the authors conceptualize placebo as an active and important mechanism of MT and argue that placebo mechanisms deserve consideration as an important component of the treatment effect. J Orthop Sports Phys Ther 2017;47(5):301-304. doi:10.2519/jospt.2017.0604.

  10. Validation of an educative manual for patients with head and neck cancer submitted to radiation therapy

    Directory of Open Access Journals (Sweden)

    Flávia Oliveira de Almeida Marques da Cruz

    2016-01-01

    Full Text Available Abstract Objective: develop the content and face validation of an educative manual for patients with head and neck cancer submitted to radiation therapy. Method: descriptive methodological research. The Theory of Psychometrics was used for the validation process, developed by 15 experts in the theme area of the educative manual and by two language and publicity professionals. A minimum agreement level of 80% was considered to guarantee the validity of the material. Results: the items addressed in the assessment tool of the educative manual were divided in three blocks: objectives, structure and format, and relevance. Only one item, related to the sociocultural level of the target public, obtained an agreement rate <80%, and was reformulated based on the participants' suggestions. All other items were considered appropriate and/or complete appropriate in the three blocks proposed: objectives - 92.38%, structure and form - 89.74%, and relevance - 94.44%. Conclusion: the face and content validation of the educative manual proposed were attended to. This can contribute to the understanding of the therapeutic process the head and neck cancer patient is submitted to during the radiation therapy, besides supporting clinical practice through the nursing consultation.

  11. Validation of an educative manual for patients with head and neck cancer submitted to radiation therapy 1

    Science.gov (United States)

    da Cruz, Flávia Oliveira de Almeida Marques; Ferreira, Elaine Barros; Vasques, Christiane Inocêncio; da Mata, Luciana Regina Ferreira; dos Reis, Paula Elaine Diniz

    2016-01-01

    Abstract Objective: develop the content and face validation of an educative manual for patients with head and neck cancer submitted to radiation therapy. Method: descriptive methodological research. The Theory of Psychometrics was used for the validation process, developed by 15 experts in the theme area of the educative manual and by two language and publicity professionals. A minimum agreement level of 80% was considered to guarantee the validity of the material. Results: the items addressed in the assessment tool of the educative manual were divided in three blocks: objectives, structure and format, and relevance. Only one item, related to the sociocultural level of the target public, obtained an agreement rate manual proposed were attended to. This can contribute to the understanding of the therapeutic process the head and neck cancer patient is submitted to during the radiation therapy, besides supporting clinical practice through the nursing consultation. PMID:27305178

  12. Target motion measurement without implanted markers and its validation by comparison with manually obtained data

    International Nuclear Information System (INIS)

    Vences, Lucia; Wulf, Joern; Vordermark, Dirk; Sauer, Otto; Berlinger, Kajetan; Roth, Michael

    2005-01-01

    For an effective radiotherapy the exact tumor location must be determined. The localization has to take into account patient's setup position as well as internal organ motion. Among the different localization methods, the use of a computer tomography (CT) scanner in the therapy room has been proposed recently. Achieving a CT with the patient on the therapy couch, a patient's treatment position is captured. We present a method to locate tumor considering internal organ motion and displacements due to respiration. We tested the method with prostate and lung patients. The method found the most probable tumor position as well as, for high-mobility tumors located in the lung, its trajectory during the respiratory cycle. The results of this novel method were validated by comparison with manually determined target position

  13. Clinical presentation and manual therapy for lower quadrant musculoskeletal conditions.

    Science.gov (United States)

    Courtney, Carol A; Clark, Jeffrey D; Duncombe, Alison M; O'Hearn, Michael A

    2011-11-01

    Chronic lower quadrant injuries constitute a significant percentage of the musculoskeletal cases seen by clinicians. While impairments may vary, pain is often the factor that compels the patient to seek medical attention. Traumatic injury from sport is one cause of progressive chronic joint pain, particularly in the lower quarter. Recent studies have demonstrated the presence of peripheral and central sensitization mechanisms in different lower quadrant pain syndromes, such as lumbar spine related leg pain, osteoarthritis of the knee, and following acute injuries such as lateral ankle sprain and anterior cruciate ligament rupture. Proper management of lower quarter conditions should include assessment of balance and gait as increasing pain and chronicity may lead to altered gait patterns and falls. In addition, quantitative sensory testing may provide insight into pain mechanisms which affect management and prognosis of musculoskeletal conditions. Studies have demonstrated analgesic effects and modulation of spinal excitability with use of manual therapy techniques, with clinical outcomes of improved gait and functional ability. This paper will discuss the evidence which supports the use of manual therapy for lower quarter musculoskeletal dysfunction.

  14. Attenuation of postoperative adhesions using a modeled manual therapy.

    Directory of Open Access Journals (Sweden)

    Geoffrey M Bove

    Full Text Available Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

  15. Attenuation of postoperative adhesions using a modeled manual therapy.

    Science.gov (United States)

    Bove, Geoffrey M; Chapelle, Susan L; Hanlon, Katherine E; Diamond, Michael P; Mokler, David J

    2017-01-01

    Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

  16. The Use of Treatment Manuals in Cognitive Therapy: Experience and Issues.

    Science.gov (United States)

    Dobson, Keith S.; Shaw, Brian F.

    1988-01-01

    Traces historical developments in use of treatment manuals in psychotherapy research and reviews characteristics that have facilitated development of cognitive therapy manuals. Reviews arguments in favor of and opposed to further development of treatment manuals. Discusses relevant research and suggests three areas for future treatment manual…

  17. The Role of Descending Modulation in Manual Therapy and Its Analgesic Implications: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Andrew D. Vigotsky

    2015-01-01

    Full Text Available Manual therapy has long been a component of physical rehabilitation programs, especially to treat those in pain. The mechanisms of manual therapy, however, are not fully understood, and it has been suggested that its pain modulatory effects are of neurophysiological origin and may be mediated by the descending modulatory circuit. Therefore, the purpose of this review is to examine the neurophysiological response to different types of manual therapy, in order to better understand the neurophysiological mechanisms behind each therapy’s analgesic effects. It is concluded that different forms of manual therapy elicit analgesic effects via different mechanisms, and nearly all therapies appear to be at least partially mediated by descending modulation. Additionally, future avenues of mechanistic research pertaining to manual therapy are discussed.

  18. Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

    Science.gov (United States)

    Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

    2017-06-01

    The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

  19. Manual Therapy: The Historical, Current, and Future Role in the Treatment of Pain

    Directory of Open Access Journals (Sweden)

    A. Russell Smith

    2007-01-01

    Full Text Available Manual therapy has been an approach in the management of patients with various disorders dating back to ancient times and continues to play a significant role in current health care. The future role of manual therapy in health care is an important area of research. This paper reviews the history of manual therapy, examines the current literature related to the use of manual techniques (including manipulation, massage, and nerve manipulation, and discusses future research topics. The literature related to manual therapy has historically been anecdotal and theoretical, and current research tends to have a generic approach with broad definitions of manual therapy and inconsistencies in the classification of specific disorders. Systematic reviews of various types of manual therapy have differed on their conclusions regarding the effectiveness of this treatment modality. The current demand in health care for evidence-based practice necessitates a movement towards more specificity in the research of the effectiveness of manual therapy, with emphasis on specific patient signs and symptoms and specific manual techniques that result in effective care.

  20. Manual Therapy: The Historical, Current, and Future Role in the Treatment of Pain

    Science.gov (United States)

    Smith, A. Russell

    2007-01-01

    Manual therapy has been an approach in the management of patients with various disorders dating back to ancient times and continues to play a significant role in current health care. The future role of manual therapy in health care is an important area of research. This paper reviews the history of manual therapy, examines the current literature related to the use of manual techniques (including manipulation, massage, and nerve manipulation), and discusses future research topics. The literature related to manual therapy has historically been anecdotal and theoretical, and current research tends to have a generic approach with broad definitions of manual therapy and inconsistencies in the classification of specific disorders. Systematic reviews of various types of manual therapy have differed on their conclusions regarding the effectiveness of this treatment modality. The current demand in health care for evidence-based practice necessitates a movement towards more specificity in the research of the effectiveness of manual therapy, with emphasis on specific patient signs and symptoms and specific manual techniques that result in effective care. PMID:17334604

  1. Novel Targeted Therapies for Inflammatory Breast Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0461 TITLE: Novel Targeted Therapies for Inflammatory Breast Cancer PRINCIPAL INVESTIGATOR: Jose Silva CONTRACTING...CONTRACT NUMBER Novel Targeted Therapies for Inflammatory Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0461 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) l 5d...NOTES 14. ABSTRACT Inflammatory breast cancer (IBC, ~5% of all breast cancers ) is the most lethal form of breast cancer , presenting a 5- year

  2. Manual Physical Therapy Following Immobilization for Stable Ankle Fracture: A Case Series.

    Science.gov (United States)

    Painter, Elizabeth E; Deyle, Gail D; Allen, Christopher; Petersen, Evan J; Croy, Theodore; Rivera, Kenneth P

    2015-09-01

    Case series. Ankle fractures commonly result in persistent pain, stiffness, and functional impairments. There is insufficient evidence to favor any particular rehabilitation approach after ankle fracture. The purpose of this case series was to describe an impairment-based manual physical therapy approach to treating patients with conservatively managed ankle fractures. Patients with stable ankle fractures postimmobilization were treated with manual physical therapy and exercise targeted at associated impairments in the lower limb. The primary outcome measure was the Lower Extremity Functional Scale. Secondary outcome measures included the ankle lunge test, numeric pain-rating scale, and global rating of change. Outcome measures were collected at baseline (performed within 7 days of immobilization removal) and at 4 and 12 weeks postbaseline. Eleven patients (mean age, 39.6 years; range, 18-64 years; 2 male), after ankle fracture-related immobilization (mean duration, 48 days; range, 21-75 days), were treated for an average of 6.6 sessions (range, 3-10 sessions) over a mean of 46.1 days (range, 13-81 days). Compared to baseline, statistically significant and clinically meaningful improvements were observed in Lower Extremity Functional Scale score (P = .001; mean change, 21.9 points; 95% confidence interval: 10.4, 33.4) and in the ankle lunge test (P = .001; mean change, 7.8 cm; 95% confidence interval: 3.9, 11.7) at 4 weeks. These changes persisted at 12 weeks. Statistically significant and clinically meaningful improvements in self-reported function and ankle range of motion were observed at 4 and 12 weeks following treatment with impairment-based manual physical therapy. All patients tolerated treatment well. Results suggest that this approach may have efficacy in this population. Therapy, level 4.

  3. 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)

  4. Manual for target thickness measurement by alpha particle irradiation

    International Nuclear Information System (INIS)

    Dias, J.F.; Martins, M.N.

    1990-04-01

    A system is described for thin-target thickness measurement through the alpha particle energy loss when them traverse the target. It is also described the program used in the analysis of the target thickness. (L.C.) [pt

  5. Therapy response evaluation of malignant lymphoma in a multicenter study. Comparison of manual and semiautomatic measurements in CT

    International Nuclear Information System (INIS)

    Wessling, J.; Schuelke, C.; Koch, R.

    2014-01-01

    Purpose: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. Materials and Methods: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. Results: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. Conclusion: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. (orig.)

  6. Therapy response evaluation of malignant lymphoma in a multicenter study. Comparison of manual and semiautomatic measurements in CT

    Energy Technology Data Exchange (ETDEWEB)

    Wessling, J.; Schuelke, C. [Muenster Univ. (Germany). Dept. of Clinical Radiology; Koch, R. [Muenster Univ. (Germany). Dept. of Medical Informatics and Biomathematics; and others

    2014-08-15

    Purpose: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. Materials and Methods: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. Results: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. Conclusion: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. (orig.)

  7. PAEDIATRIC ASTHMA AND MANUAL THERAPY- A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Rahul Pandey

    2015-12-01

    Full Text Available Background: Asthma is an inflammatory clutter of the airways that causes wheezing, breathlessness, chest tightness, and coughing. In India, approximate calculation indicates a prevalence of between 10% and 15% in 5-11 year old children. Modern Western treatment focuses on controlling asthma with two classes of medication corticosteroids and bronchodilatorss. Another plan of action for reducing and potentially even throw out asthma manifestation affects manipulation of the craniosacral fascial system. This system is a unification of the craniosacral and fascial or connective tissue part. This idea can help in making clear the greatly high rate of achievement with manual therapy in pediatric asthma. Methods: In this case report first I have taken a brief history of the patient condition after the full assessment like brain cycle rhythm, chest and systemic. I have given cranio sacral therapy, Intercostal release, PNF for diaphragm release on child for seven sitting of about 45 minutes of each session. Results: After completion of treatment session of seven sitting his lungs to be bright of any wheezing or other impediment. Brain cycle was of 90 seconds. His peak flow meter readings were between 250 and 300 Liters/minute, which were in a satisfactory range for him. The physician suggested that at this point there was no requirement for any additional asthma medicines. Conclusion: It comes into sight that the loss to the respiratory system caused by fascial burden early in life may be fully reversible, if treated immediately. The latent grace of this interdependent approach is that it crop up to address the pathological origin of asthma.

  8. Targeted Therapies in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jurjees Hasan

    2010-02-01

    Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  9. Targeted Therapies in Epithelial Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

    2010-02-23

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  10. Regional interdependence and manual therapy directed at the thoracic spine.

    Science.gov (United States)

    McDevitt, Amy; Young, Jodi; Mintken, Paul; Cleland, Josh

    2015-07-01

    Thoracic spine manipulation is commonly used by physical therapists for the management of patients with upper quarter pain syndromes. The theoretical construct for using thoracic manipulation for upper quarter conditions is a mainstay of a regional interdependence (RI) approach. The RI concept is likely much more complex and is perhaps driven by a neurophysiological response including those related to peripheral, spinal cord and supraspinal mechanisms. Recent evidence suggests that thoracic spine manipulation results in neurophysiological changes, which may lead to improved pain and outcomes in individuals with musculoskeletal disorders. The intent of this narrative review is to describe the research supporting the RI concept and its application to the treatment of individuals with neck and/or shoulder pain. Treatment utilizing both thrust and non-thrust thoracic manipulation has been shown to result in improvements in pain, range of motion and disability in patients with upper quarter conditions. Research has yet to determine optimal dosage, techniques or patient populations to which the RI approach should be applied; however, emerging evidence supporting a neurophysiological effect for thoracic spine manipulation may negate the need to fully answer this question. Certainly, there is a need for further research examining both the clinical efficacy and effectiveness of manual therapy interventions utilized in the RI model as well as the neurophysiological effects resulting from this intervention.

  11. Metastasis Targeted Therapies in Renal Cell Cancer

    OpenAIRE

    K. Fehmi Narter; Bora Özveren

    2018-01-01

    Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

  12. Targeted Radiation Therapy for Cancer Initiative

    Science.gov (United States)

    2017-11-01

    AWARD NUMBER: W81XWH-08-2-0174 TITLE: Targeted Radiation Therapy for Cancer Initiative PRINCIPAL INVESTIGATOR: Dusten Macdonald, MD...for Cancer Initiative 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dusten Macdonald, MD 5d. PROJECT NUMBER...Cancer Initiative Final Report INTRODUCTION: The full potential of radiation therapy has not been realized due to the inability to locate and

  13. The working mechanism of manual therapy in participants with chronic tension-type headache.

    Science.gov (United States)

    Castien, René; Blankenstein, Annette; van der Windt, Daniëlle; Heymans, Martijn W; Dekker, Joost

    2013-10-01

    Prospective longitudinal study. To explore the working mechanism of manual therapy, we investigated whether 3 cervical spine variables were mediators of the effect of manual therapy on headache frequency. Background Manual therapy has been shown to reduce headache frequency in participants with chronic tension-type headache (CTTH). To what extent specific elements of treatment contribute to the effectiveness of manual therapy in CTTH is unknown. One hundred eighty-two participants with CTTH participated in a prospective longitudinal study: 142 underwent manual therapy and 40 participants received usual care by their general practitioner. Regression analysis was performed according to the steps described by Baron and Kenny, and the proportion of mediated effect was estimated for 3 potential mediators: (1) cervical range of motion, (2) neck flexor endurance, and (3) forward head posture. Outcome was defined as a 50% or greater reduction in headache days. Neck flexor endurance mediated 24.5% of the effect of manual therapy. Cervical range of motion and forward head posture showed no mediated effect. Increased neck flexor endurance appears to be a working mechanism of manual therapy. This finding supports isometric training of neck flexors in participants with CTTH. Trial registered with Netherlands Trial Register (TR 1074).

  14. Movement and manual therapy for adults with arthritis: 2012 National Health Interview Survey.

    Science.gov (United States)

    Pure, Elise; Terhorst, Lauren; Baker, Nancy

    2018-04-01

    The use of manual therapies (chiropractic manipulation, massage) and movement therapies (yoga, tai chi) by people with arthritis may relate to their personal characteristics, and the reported emotional and physical health outcomes may differ by type of therapy. To describe personal characteristics and predictors of manual and movement therapy use for people with arthritis, and to compare the use of manual versus movement therapy to improve physical and emotional health outcomes for people with arthritis. CAM respondents with arthritis were identified from the 2012 National Health Interview Survey (n = 8229). Data were analyzed to determine the overall percentages of CAM users, and to examine the associations between use/nonuse using multivariable linear regressions. White, well-educated, physically active females were more likely to use both types of therapy. Movement therapy users reported positive emotional health outcomes twice as much as manual therapy users and 10% more reported positive physical health outcomes. While both movement and manual therapies can have positive effects on people with arthritis, it appears that active therapies are more beneficial than passive therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Targeting Apoptosis Signaling Pathways for Anticancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fulda, Simone, E-mail: simone.fulda@kgu.de [Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt (Germany)

    2011-08-29

    Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

  16. Targeting Apoptosis Signaling Pathways for Anticancer Therapy

    International Nuclear Information System (INIS)

    Fulda, Simone

    2011-01-01

    Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

  17. Target marketing strategies for occupational therapy entrepreneurs.

    Science.gov (United States)

    Kautzmann, L N; Kautzmann, F N; Navarro, F H

    1989-01-01

    Understanding marketing techniques is one of the skills needed by successful entre renews. Target marketing is an effective method for occupational therapy entrepreneurs to use in determining when and where to enter the marketplace. The two components of target marketing, market segmentation and the development of marketing mix strategies for each identified market segment, are described. The Profife of Attitudes Toward Health Care (PATH) method of psychographic market segmentation of health care consumers is presented. Occupational therapy marketing mix strategies for each PATH consumer group are delineated and compatible groupings of market segments are suggested.

  18. Targeted alpha therapy: Applications and current status

    International Nuclear Information System (INIS)

    Bruchertseifer, Frank

    2017-01-01

    Full text: The field of targeted alpha therapy has been developed rapidly in the last decade. Besides 223 Ra, 211 At and 212 Pb/ 212 Bi the alpha emitters 225 Ac and 213 Bi are promising therapeutic radionuclides for application in targeted alpha therapy of cancer and infectious diseases. The presentation will give a short overview about the current clinical treatments with alpha emitting radionuclides and will place an emphasis on the most promising clinical testing of peptides and antibodies labelled with 225 Ac and 213 Bi for treatment of metastatic castration-resistant prostate cancer patients with glioma and glioblastoma multiform, PSMA-positive tumor phenotype and bladder carcinoma in situ. (author)

  19. Manual therapy with and without vestibular rehabilitation for cervicogenic dizziness: a systematic review

    Directory of Open Access Journals (Sweden)

    Lystad Reidar P

    2011-09-01

    Full Text Available Abstract Background Manual therapy is an intervention commonly advocated in the management of dizziness of a suspected cervical origin. Vestibular rehabilitation exercises have been shown to be effective in the treatment of unilateral peripheral vestibular disorders, and have also been suggested in the literature as an adjunct in the treatment of cervicogenic dizziness. The purpose of this systematic review is to evaluate the evidence for manual therapy, in conjunction with or without vestibular rehabilitation, in the management of cervicogenic dizziness. Methods A comprehensive search was conducted in the databases Scopus, Mantis, CINHAL and the Cochrane Library for terms related to manual therapy, vestibular rehabilitation and cervicogenic dizziness. Included studies were assessed using the Maastricht-Amsterdam criteria. Results A total of fifteen articles reporting findings from thirteen unique investigations, including five randomised controlled trials and eight prospective, non-controlled cohort studies were included in this review. The methodological quality of the included studies was generally poor to moderate. All but one study reported improvement in dizziness following either unimodal or multimodal manual therapy interventions. Some studies reported improvements in postural stability, joint positioning, range of motion, muscle tenderness, neck pain and vertebrobasilar artery blood flow velocity. Discussion Although it has been argued that manual therapy combined with vestibular rehabilitation may be superior in the treatment of cervicogenic dizziness, there are currently no observational and experimental studies demonstrating such effects. A rationale for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is presented. Conclusion There is moderate evidence to support the use of manual therapy, in particular spinal mobilisation and manipulation, for cervicogenic dizziness. The evidence

  20. Targeting Herpetic Keratitis by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Hossein Mostafa Elbadawy

    2012-01-01

    Full Text Available Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1 can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.

  1. Effectiveness of manual therapies: the UK evidence report.

    Science.gov (United States)

    Bronfort, Gert; Haas, Mitch; Evans, Roni; Leininger, Brent; Triano, Jay

    2010-02-25

    The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions. The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs), widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet included in the first three categories. The strength/quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs. By September 2009, 26 categories of conditions were located containing RCT evidence for the use of manual therapy: 13 musculoskeletal conditions, four types of chronic headache and nine non-musculoskeletal conditions. We identified 49 recent relevant systematic reviews and 16 evidence-based clinical guidelines plus an additional 46 RCTs not yet included in systematic reviews and guidelines.Additionally, brief references are made to other effective non-pharmacological, non-invasive physical treatments. Spinal manipulation/mobilization is effective in adults for: acute, subacute, and chronic low back pain; migraine and cervicogenic headache; cervicogenic dizziness; manipulation/mobilization is effective for several extremity joint conditions; and thoracic manipulation/mobilization is effective for acute/subacute neck pain. The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration, and for manipulation/mobilization for mid back pain, sciatica, tension-type headache, coccydynia, temporomandibular joint disorders, fibromyalgia, premenstrual syndrome, and pneumonia in older adults. Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation, or for Stage 1

  2. Effectiveness of manual therapies: the UK evidence report

    Directory of Open Access Journals (Sweden)

    Leininger Brent

    2010-02-01

    Full Text Available Abstract Background The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions. Methods The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs, widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet included in the first three categories. The strength/quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs. Results By September 2009, 26 categories of conditions were located containing RCT evidence for the use of manual therapy: 13 musculoskeletal conditions, four types of chronic headache and nine non-musculoskeletal conditions. We identified 49 recent relevant systematic reviews and 16 evidence-based clinical guidelines plus an additional 46 RCTs not yet included in systematic reviews and guidelines. Additionally, brief references are made to other effective non-pharmacological, non-invasive physical treatments. Conclusions Spinal manipulation/mobilization is effective in adults for: acute, subacute, and chronic low back pain; migraine and cervicogenic headache; cervicogenic dizziness; manipulation/mobilization is effective for several extremity joint conditions; and thoracic manipulation/mobilization is effective for acute/subacute neck pain. The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration, and for manipulation/mobilization for mid back pain, sciatica, tension-type headache, coccydynia, temporomandibular joint disorders, fibromyalgia, premenstrual syndrome, and pneumonia in older adults. Spinal manipulation is not effective for asthma and

  3. The Effect of Manual Therapy on the Adolescent Idiopathic Scoliosis in a 28 Years Old Woman

    OpenAIRE

    Marzieh Mohamadi; Farahnaz Ghaffari-Nejhad

    2013-01-01

    Idiopathic scoliosis (IS) is the most common type of scoliosis. Clinical signs and symptoms of scoliosis impair quality of life and daily function. Manual therapy is commonly used for treatment of scoliosis. This is a case report of scoliosis treatment with manual therapy in a 28 years old patient. A 28 years old woman complained of low back pain for 4 years. Spine x-ray, showed scoliosis with a 32 degrees Cobb angle. The patient received a manual therapy procedure of two visits per week for ...

  4. Research progess on treatment of cancer with targeted radionuclide therapy

    International Nuclear Information System (INIS)

    Luo Jiawen; Zhang Caixia

    2008-01-01

    The new development and situation of targeted radionuclide therapy in oncology is described, which include radioimmunotherapy, peptide receptor radionuclide therapy, gene therapy and radionuclide labled chemotherapeutics therapy. The application research on labled carrier of those therapy is emphasized. Meanwhile, the research progess of indomethacin and its combined with targeted radionuclide therapy is also described. (authors)

  5. Can Independent Judges Recognize Different Psychotherapies? An Experience with Manual-Guided Therapies.

    Science.gov (United States)

    Luborsky, Lester; And Others

    1982-01-01

    Tested whether independent judges could recognize three different manual-guided psychotherapies, drug counseling, supportive-expressive psychotherapy, and cognitive-behavioral using a special rating form containing scales for the characteristic aspects of each type. Results indicated that manual-guided therapies can be reliably recognized.…

  6. Analgesic effects of manual therapy in patients with musculoskeletal pain: a systematic review

    NARCIS (Netherlands)

    J. Nijs; Dr. L.P. Voogt; F. Struyf; M. Meeys; D. Meuffels; J. de Vries

    2015-01-01

    BACKGROUND: Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic

  7. The Effect of Manual Therapy on the Adolescent Idiopathic Scoliosis in a 28 Years Old Woman

    Directory of Open Access Journals (Sweden)

    Marzieh Mohamadi

    2013-04-01

    Full Text Available Idiopathic scoliosis (IS is the most common type of scoliosis. Clinical signs and symptoms of scoliosis impair quality of life and daily function. Manual therapy is commonly used for treatment of scoliosis. This is a case report of scoliosis treatment with manual therapy in a 28 years old patient. A 28 years old woman complained of low back pain for 4 years. Spine x-ray, showed scoliosis with a 32 degrees Cobb angle. The patient received a manual therapy procedure of two visits per week for 16 weeks including myofascial release technique, mobilization and manipulation. The Cobb angle was reduced 15.62% after 8 weeks and 21.87% after 16 weeks. In addition the pain was reduced by 50%. We can state that manual therapy was useful for this patient.

  8. Validation of an educative manual for patients with head and neck cancer submitted to radiation therapy.

    Science.gov (United States)

    Cruz, Flávia Oliveira de Almeida Marques da; Ferreira, Elaine Barros; Vasques, Christiane Inocêncio; Mata, Luciana Regina Ferreira da; Reis, Paula Elaine Diniz Dos

    2016-06-14

    develop the content and face validation of an educative manual for patients with head and neck cancer submitted to radiation therapy. descriptive methodological research. The Theory of Psychometrics was used for the validation process, developed by 15 experts in the theme area of the educative manual and by two language and publicity professionals. A minimum agreement level of 80% was considered to guarantee the validity of the material. the items addressed in the assessment tool of the educative manual were divided in three blocks: objectives, structure and format, and relevance. Only one item, related to the sociocultural level of the target public, obtained an agreement rate publicidade. Foi considerado o índice de concordância de, no mínimo, 80% para se garantir a validação do material. os itens abordados no instrumento de avaliação do manual educativo foram divididos em três blocos: objetivos, estrutura e apresentação, e relevância. Apenas um item, relacionado ao nível sociocultural do público-alvo, obteve índice de concordância publicidad. Fue considerado un índice de concordancia que fuese, por lo menos, de 80%, para garantizar la validación del material. los ítems abordados en el instrumento de evaluación del manual educativo fueron divididos en tres bloques: objetivos, estructura y presentación, y relevancia. Apenas un ítem, relacionado al nivel sociocultural del público-objetivo, obtuvo un índice de concordancia <80%, habiendo sido reformulado con base en las sugestiones de los participantes. Todos los otros ítems fueron considerados adecuados y/o totalmente adecuados en los tres bloques propuestos: objetivos (92,38%), estructura y presentación (89,74%), y relevancia (94,44%). el manual educativo propuesto fue considerado válido en lo que se refiere al contenido y a la apariencia. Se sugiere que puede contribuir para la comprensión del proceso terapéutico, al cual el paciente con cáncer de cabeza y cuello es sometido al

  9. Targeted Alpha Therapy: From Alpha to Omega

    International Nuclear Information System (INIS)

    Allen, Barry J; Clarke, Raymond; Huang Chenyu

    2013-01-01

    This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

  10. Targeted therapy using nanotechnology: focus on cancer.

    Science.gov (United States)

    Sanna, Vanna; Pala, Nicolino; Sechi, Mario

    2014-01-01

    Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

  11. Developing a Manualized Occupational Therapy Diabetes Management Intervention: Resilient, Empowered, Active Living With Diabetes.

    Science.gov (United States)

    Pyatak, Elizabeth A; Carandang, Kristine; Davis, Shain

    2015-07-01

    This article reports on the development of a manualized occupational therapy intervention for diabetes management. An initial theoretical framework and core content areas for a Stage I intervention manual were developed based on an in-depth needs assessment and review of existing literature. After evaluation by a panel of experts and completion of a feasibility study, the intervention was revised into a Stage 2 manual in preparation for a randomized study evaluating the intervention's efficacy. In developing the initial manual, we delineated core theoretical principles to allow for flexible application and tailoring of the intervention's content areas. Expert panel feedback and feasibility study results led to changes to the intervention structure and content as we developed the Stage 2 manual. Through describing this process, we illustrate the dynamic evolution of intervention manuals, which undergo revisions due to both theoretical and practical considerations at each stage of the research-to-clinical practice pipeline.

  12. Targeted alpha therapy: Applications and current status

    Energy Technology Data Exchange (ETDEWEB)

    Bruchertseifer, Frank, E-mail: frank.bruchertseifer@ec.europa.eu [European Commission, Joint Research Centre, Karlsruhe (Germany)

    2017-07-01

    Full text: The field of targeted alpha therapy has been developed rapidly in the last decade. Besides {sup 223}Ra, {sup 211}At and {sup 212}Pb/{sup 212}Bi the alpha emitters {sup 225}Ac and {sup 213}Bi are promising therapeutic radionuclides for application in targeted alpha therapy of cancer and infectious diseases. The presentation will give a short overview about the current clinical treatments with alpha emitting radionuclides and will place an emphasis on the most promising clinical testing of peptides and antibodies labelled with {sup 225}Ac and {sup 213}Bi for treatment of metastatic castration-resistant prostate cancer patients with glioma and glioblastoma multiform, PSMA-positive tumor phenotype and bladder carcinoma in situ. (author)

  13. Cardiotoxicity of novel HER2-targeted therapies.

    Science.gov (United States)

    Sendur, Mehmet A N; Aksoy, Sercan; Altundag, Kadri

    2013-08-01

    Trastuzumab, an anti-HER2 humanized monoclonal antibody, is the standard treatment for both early and metastatic HER2-positive breast cancer. In addition to other chemotherapeutic agents, trastuzumab significantly improves response rate and survival in HER2-positive early and metastatic breast cancer. Although it is well known that trastuzumab therapy is closely associated with both symptomatic and asymptomatic cardiotoxicity, less is known about novel HER2-targeted therapies. The aim of this review is to discuss the cardiac safety data from recent studies of novel anti-HER2 drugs other than trastuzumab. Novel HER2-targeted therapies showed favorable results in HER2 positive metastatic breast cancer patients. Pubmed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched until January 2013 using the following search keywords; 'trastuzumab, trastuzumab cardiotoxicity, HER-2 targeted therapies, lapatinib, pertuzumab, trastuzumab emtansine, afatinib and neratinib'; papers which were considered relevant for the aim of this review were selected by the authors. Lapatinib, pertuzumab, T-DM1, neratinib and afatinib molecules are evaluated in the study. In a comprehensive analysis, 3689 lapatinib treated patients enrolled in 49 trials; asymptomatic cardiac events were reported in 53 patients (1.4%) and symptomatic grade III and IV systolic dysfunction was observed only in 7 patients (0.2%) treated with lapatinib. In phase I-III trials of pertuzumab, cardiac dysfunction was seen in 4.5-14.5% of patients with pertuzumab treatment and cardiac dysfunction was usually grade I and II. Cardiotoxicity of pertuzumab was usually reported with the trastuzumab combination and no additive cardiotoxicity was reported with addition of pertuzumab to trastuzumab. T-DM1 had a better safety profile compared to trastuzumab, no significant cardiotoxicity was observed with T-DM1 in heavily pre-treated patients. In the EMILIA study, only in 1.7% of patients in the T

  14. Manual lateralization in macaques: handedness, target laterality and task complexity.

    Science.gov (United States)

    Regaiolli, Barbara; Spiezio, Caterina; Vallortigara, Giorgio

    2016-01-01

    Non-human primates represent models to understand the evolution of handedness in humans. Despite several researches have been investigating non-human primates handedness, few studies examined the relationship between target position, hand preference and task complexity. This study aimed at investigating macaque handedness in relation to target laterality and tastiness, as well as task complexity. Seven pig-tailed macaques (Macaca nemestrina) were involved in three different "two alternative choice" tests: one low-level task and two high-level tasks (HLTs). During the first and the third tests macaques could select a preferred food and a non-preferred food, whereas by modifying the design of the second test, macaques were presented with no-difference alternative per trial. Furthermore, a simple-reaching test was administered to assess hand preference in a social context. Macaques showed hand preference at individual level both in simple and complex tasks, but not in the simple-reaching test. Moreover, target position seemed to affect hand preference in retrieving an object in the low-level task, but not in the HLT. Additionally, individual hand preference seemed to be affected from the tastiness of the item to be retrieved. The results suggest that both target laterality and individual motivation might influence hand preference of macaques, especially in simple tasks.

  15. Introduction to radiobiology of targeted radionuclide therapy

    Directory of Open Access Journals (Sweden)

    Jean-Pierre ePOUGET

    2015-03-01

    Full Text Available During the last decades, new radionuclide-based targeted therapies have emerged as efficient tools for cancer treatment. Targeted radionuclide therapies (TRT are based on a multidisciplinary approach that involves the cooperation of specialists in several research fields. Among them, radiobiologists investigate the biological effects of ionizing radiation, specifically the molecular and cellular mechanisms involved in the radiation response. Most of the knowledge about radiation effects concerns external beam radiation therapy (EBRT and radiobiology has then strongly contributed to the development of this therapeutic approach. Similarly, radiobiology and dosimetry are also assumed to be ways for improving TRT, in particular in the therapy of solid tumors which are radioresistant. However, extrapolation of EBRT radiobiology to TRT is not straightforward. Indeed, the specific physical characteristics of TRT (heterogeneous and mixed irradiation, protracted exposure and low absorbed dose rate differ from those of conventional EBRT (homogeneous irradiation, short exposure and high absorbed dose rate, and consequently the response of irradiated tissues might be different. Therefore, specific TRT radiobiology needs to be explored. Determining dose-effect correlation is also a prerequisite for rigorous preclinical radiobiology studies because dosimetry provides the necessary referential to all TRT situations. It is required too for developing patient-tailored TRT in the clinic in order to estimate the best dose for tumor control, while protecting the healthy tissues, thereby improving therapeutic efficacy. Finally, it will allow to determine the relative contribution of targeted effects (assumed to be dose-related and non-targeted effects (assumed to be non-dose-related of ionizing radiation. However, conversely to EBRT where it is routinely used, dosimetry is still challenging in TRT. Therefore, it constitutes with radiobiology, one of the main

  16. Manualization of Occupational Therapy Interventions: Illustrations from the Pressure Ulcer Prevention Research Program

    Science.gov (United States)

    Blanche, Erna Imperatore; Fogelberg, Donald; Diaz, Jesus; Carlson, Mike; Clark, Florence

    2011-01-01

    The manualization of a complex occupational therapy intervention is a crucial step in ensuring treatment fidelity for both clinical application and research purposes. Towards this latter end, intervention manuals are essential for assuring trustworthiness and replicability of randomized controlled trials (RCT’s) that aim to provide evidence of the effectiveness of occupational therapy. In this paper, literature on the process of intervention manualization is reviewed. The prescribed steps are then illustrated through our experience in implementing the University of Southern California/Rancho Los Amigos National Rehabilitation Center’s collaborative Pressure Ulcer Prevention Project (PUPP). In this research program, qualitative research provided the initial foundation for manualization of a multifaceted occupational therapy intervention designed to reduce incidence of medically serious pressure ulcers in people with SCI. PMID:22214116

  17. Targeted Therapy in Nonmelanoma Skin Cancers

    Directory of Open Access Journals (Sweden)

    Giulia Spallone

    2011-05-01

    Full Text Available Nonmelanoma skin cancer (NMSC is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC, representing around 75% of NMSC and Squamous Cell Carcinomas (SCC. The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

  18. Targeted Therapy in Nonmelanoma Skin Cancers

    International Nuclear Information System (INIS)

    Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio

    2011-01-01

    Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC

  19. [Resistance to target-based therapy and its circumvention].

    Science.gov (United States)

    Nishio, Kazuto

    2004-07-01

    Intrinsic and acquired resistance to molecular target therapy critically limits the outcome of cancer treatments. Target levels including quantitative and gene alteration should be determinants for the resistance. Downstream of the target molecules, drug metabolism, and drug transport influences the tumor sensitivity to molecular target therapy. The mechanisms of resistance to antibody therapy have not been fully clarified. Correlative clinical studies using these biomarkers of resistance are extremely important for circumvention of clinical resistance to target based therapy.

  20. Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

    Science.gov (United States)

    Gravis, Gwenaelle; Faure, Marjorie; Rybikowski, Stanislas; Dermeche, Slimane; Tyran, Marguerite; Calderon, Benoit; Thomassin, Jeanne; Walz, Jochen; Salem, Naji

    2015-11-01

    Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.

  1. Manual therapy in osteoarthritis of the hip: outcome in specific subgroups of patients.

    NARCIS (Netherlands)

    Hoeksma, H.L.; Dekker, J.; Ronday, H.K.; Breedveld, F.C.; Ende, C.H.M. van den

    2005-01-01

    OBJECTIVE: To investigate whether manual therapy has particular benefit in subgroups of patients defined on the basis of hip function, range of joint motion, pain and radiological deterioration. METHODS: The study was performed in the out-patient clinic of physical therapy of a large hospital. Data

  2. Engineering liposomal nanoparticles for targeted gene therapy.

    Science.gov (United States)

    Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

    2017-08-01

    Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

  3. Radionuclide molecular target therapy for lung cancer

    International Nuclear Information System (INIS)

    Zhang Fuhai; Meng Zhaowei; Tan Jian

    2012-01-01

    Lung cancer harms people's health or even lives severely. Currently, the morbidity and mortality of lung cancer are ascending all over the world. Accounting for 38.08% of malignant tumor caused death in male and 16% in female in cities,ranking top in both sex. Especially, the therapy of non-small cell lung cancer has not been obviously improved for many years. Recently, sodium/iodide transporter gene transfection and the therapy of molecular target drugs mediated radionuclide are being taken into account and become the new research directions in treatment of advanced lung cancer patients with the development of technology and theory for medical molecular biology and the new knowledge of lung cancer's pathogenesis. (authors)

  4. MAIN MOLECULAR TARGETS FOR PROSTATE CANCER THERAPY

    Directory of Open Access Journals (Sweden)

    G. S. Krasnov

    2014-01-01

    Full Text Available Androgenic pathway plays a pivotal role in the development of benign and malignant prostate tumors. Most of the prostate neoplasms are hormone-dependent at the time of diagnosis. Therapeutic interventions aimed at reducing the level of testosterone in the blood allow to stop progression of the disease. But over time, the tumor almost inevitably starts to progress, moving in the castration-resistant state (CRPC, representing a serious problem of oncourology. In recent years, the possibility of CRRPC therapy increased significantly – there was developed a number of new drugs that effectively inhibit the development of castration-resistant tumors and significantly push back the start of chemotherapy. This review describes the major drug targets and mechanisms of action of abiraterone, enzalutamide, galeterone, VT-464 and other approved and promising CRPC therapies.

  5. Manualization of Occupational Therapy Using Ayres Sensory Integration® for Autism.

    Science.gov (United States)

    Hunt, Joanne; van Hooydonk, Elke; Faller, Patricia; Mailloux, Zoe; Schaaf, Roseann

    2017-07-01

    This article reports on the development of a Stage 3 manual (following pilot effectiveness study) for implementing occupational therapy using Ayres Sensory Integration® (OT/ASI) for children with autism spectrum disorders to enhance participation in daily occupations. Three stakeholder groups were surveyed to aid in translation of manual from research to practice (i.e., Stage 3 manual) and an expert consensus meeting was held to finalize recommendations. Data indicated that the manuals usability could be improved by including a section on frequently encountered problems and solutions, and by including video case examples. Also recommended were greater chapter uniformity, improved clarity of forms and charts, and inclusion of a glossary. Changes were made and subject to expert review and consensus using modified Delphi process. The Stage 3 manual has been rigorously vetted and is ready for practice and research replication.

  6. Manual therapy in the treatment of patients with hemophilia B and inhibitor.

    Science.gov (United States)

    Cuesta-Barriuso, Rubén; Trelles-Martínez, Roberto O

    2018-01-22

    The main clinical manifestations of hemophilia are muscle and joint bleeding. Recurrent bleeding leads to a degenerative process known as hemophilic arthropathy. The development of inhibitors (antibodies against FVIII/FIX concentrates) is the main complication in the treatment of hemophilia. The objective was to assess the safety and efficacy of manual therapy treatment in a patient with hemophilia and inhibitor. A 26-year-old patient with hemophilia B and inhibitor received physiotherapy treatment based on manual therapy for 3 months, with a frequency of 2 sessions per week. The joint status was evaluated using the Hemophilia Joint Health Score; pain was assessed with the Visual Analog Scale; and the range of movement was evaluated using a universal goniometer. The patient developed no joint bleeding in the knees or ankles as a result of the physiotherapy treatment. Following treatment, improvements were noted in the range of movement of knees and ankles, the perception of pain in both knees, and ankle functionality. Until now, manual therapy using joint traction was contraindicated in patients with hemophilia and inhibitor, as it was feared to cause possible joint bleeding. This is the first case study to address the safety and efficacy of manual therapy in a patient with hemophilia and an inhibitor. The results of this study may help to establish which manual therapy treatments are indicated in patients with hemophilic arthropathy and inhibitors. Thus, a physiotherapy program based on manual therapy may be safe in patients with hemophilia and inhibitor and such therapy may improve joint condition, pain, and joint range of motion in patients with hemophilia and inhibitor. Randomized clinical trials are needed to confirm the results of this case study.

  7. Effectiveness of manual therapies: the UK evidence report

    OpenAIRE

    Bronfort, Gert; Haas, Mitch; Evans, Roni; Leininger, Brent; Triano, Jay

    2010-01-01

    Abstract Background The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions. Methods The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs), widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet incl...

  8. Cancer gene therapy with targeted adenoviruses.

    Science.gov (United States)

    Bachtarzi, Houria; Stevenson, Mark; Fisher, Kerry

    2008-11-01

    Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. This manuscript aims to provide an overview of the techniques currently under development for improving adenovirus delivery to malignant cells in vivo. Primary research articles reporting improvements in adenoviral gene delivery are described. Strategies include genetic modification of viral coat proteins, non-genetic modifications including polymer encapsulation approaches and pharmacological interventions. Reprogramming adenovirus tropism in vitro has been convincingly demonstrated using a range of genetic and physical strategies. These studies have provided new insights into our understanding of virology and the field is progressing. However, there are still some limitations that need special consideration before adenovirus-targeted cancer gene therapy emerges as a routine treatment in the clinical setting.

  9. Oncolytic viral therapy: targeting cancer stem cells

    Directory of Open Access Journals (Sweden)

    Smith TT

    2014-02-01

    Full Text Available Tyrel T Smith,1 Justin C Roth,1 Gregory K Friedman,1 G Yancey Gillespie2 1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Cancer stem cells (CSCs are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression. Keywords: oncolytic virotherapy, cancer stem cell niche

  10. Targeting embryonic signaling pathways in cancer therapy.

    Science.gov (United States)

    Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

    2012-01-01

    The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

  11. Advances in the targeted therapy of liposarcoma

    Directory of Open Access Journals (Sweden)

    Guan Z

    2015-01-01

    Full Text Available Zhonghai Guan,1 Xiongfei Yu,1 Haohao Wang,1 Haiyong Wang,1 Jing Zhang,1 Guangliang Li,2 Jiang Cao,3 Lisong Teng1 1Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, 2Department of Medicine Oncology, Zhejiang Cancer Hospital, 3Clinical Research Center, The 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: Liposarcoma (LPS is the most common type of soft-tissue sarcoma. Complete surgical resection is the only curative means for localized disease; however, both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. An increasing number of trials with novel targeted therapy of LPS have provided encouraging data during recent years. This review will provide an overview of the advances in our understanding of LPS and summarize the results of recent trials with novel therapies targeting different genetic and molecular aberrations for different subtypes of LPS. Keywords: well-/dedifferentiated, myxoid/round cell, pleomorphic, soft-tissue sarcoma

  12. Effectiveness of exercise therapy and manual mobilisation in ankle sprain and functional instability: a systematic review.

    Science.gov (United States)

    van der Wees, Philip J; Lenssen, Anton F; Hendriks, Erik J M; Stomp, Derrick J; Dekker, Joost; de Bie, Rob A

    2006-01-01

    This study critically reviews the effectiveness of exercise therapy and manual mobilisation in acute ankle sprains and functional instability by conducting a systematic review of randomised controlled trials. Trials were searched electronically and manually from 1966 to March 2005. Randomised controlled trials that evaluated exercise therapy or manual mobilisation of the ankle joint with at least one clinically relevant outcome measure were included. Internal validity of the studies was independently assessed by two reviewers. When applicable, relative risk (RR) or standardised mean differences (SMD) were calculated for individual and pooled data. In total 17 studies were included. In thirteen studies the intervention included exercise therapy and in four studies the effects of manual mobilisation of the ankle joint was evaluated. Average internal validity score of the studies was 3.1 (range 1 to 7) on a 10-point scale. Exercise therapy was effective in reducing the risk of recurrent sprains after acute ankle sprain: RR 0.37 (95% CI 0.18 to 0.74), and with functional instability: RR 0.38 (95% CI 0.23 to 0.62). No effects of exercise therapy were found on postural sway in patients with functional instability: SMD: 0.38 (95% CI -0.15 to 0.91). Four studies demonstrated an initial positive effect of different modes of manual mobilisation on dorsiflexion range of motion. It is likely that exercise therapy, including the use of a wobble board, is effective in the prevention of recurrent ankle sprains. Manual mobilisation has an (initial) effect on dorsiflexion range of motion, but the clinical relevance of these findings for physiotherapy practice may be limited.

  13. Effectiveness of Manual Therapy and Stretching for Baseball Players With Shoulder Range of Motion Deficits.

    Science.gov (United States)

    Bailey, Lane B; Thigpen, Charles A; Hawkins, Richard J; Beattie, Paul F; Shanley, Ellen

    Baseball players displaying deficits in shoulder range of motion (ROM) are at increased risk of arm injury. Currently, there is a lack of consensus regarding the best available treatment options to restore shoulder ROM. Instrumented manual therapy with self-stretching will result in clinically significant deficit reductions when compared with self-stretching alone. Controlled laboratory study. Shoulder ROM and humeral torsion were assessed in 60 active baseball players (mean age, 19 ± 2 years) with ROM deficits (nondominant - dominant, ≥15°). Athletes were randomly assigned to receive a single treatment of instrumented manual therapy plus self-stretching (n = 30) or self-stretching only (n = 30). Deficits in internal rotation, horizontal adduction, and total arc of motion were compared between groups immediately before and after a single treatment session. Treatment effectiveness was determined by mean comparison data, and a number-needed-to-treat (NNT) analysis was used for assessing the presence of ROM risk factors. Prior to intervention, players displayed significant ( P < 0.001) dominant-sided deficits in internal rotation (-26°), total arc of motion (-18°), and horizontal adduction (-17°). After the intervention, both groups displayed significant improvements in ROM, with the instrumented manual therapy plus self-stretching group displaying greater increases in internal rotation (+5°, P = 0.010), total arc of motion (+6°, P = 0.010), and horizontal adduction (+7°, P = 0.004) compared with self-stretching alone. For horizontal adduction deficits, the added use of instrumented manual therapy with self-stretching decreased the NNT to 2.2 (95% CI, 2.1-2.4; P = 0.010). Instrumented manual therapy with self-stretching significantly reduces ROM risk factors in baseball players with motion deficits when compared with stretching alone. The added benefits of manual therapy may help to reduce ROM deficits in clinical scenarios where stretching alone is

  14. Management of Chronic Lateral Epicondylitis With Manual Therapy and Local Cryostimulation: A Pilot Study.

    Science.gov (United States)

    Richer, Nadia; Marchand, Andrée-Anne; Descarreaux, Martin

    2017-12-01

    The purpose of this pilot study was to evaluate the feasibility and efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. The control group (n = 19) was treated with manual therapy consisting of soft-tissue therapy and radial head mobilizations. The experimental group (n = 18) received cryostimulation in addition to manual therapy care similar to that for the control group. Both protocols consisted of 8 treatments over a 4-week period. Outcome measures included pain intensity (visual analog scale), pain-free grip strength (handheld dynamometer), and functional index (Patient-Rated Tennis Elbow Evaluation questionnaire). Assessments were performed at baseline, postintervention, and 3-month follow-up. Adherence and dropout rates were also considered. Both groups exhibited significant improvements in pain intensity and functional index at postintervention assessments, which were maintained at follow-up. All participants attended the prescribed number of treatments, but 27% were lost at follow-up. Minor adverse events were reported after cryostimulation in 4 cases. This study indicated that it is feasible to complete a clinical trial evaluating the efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. On the basis of these preliminary data, the combination of cryostimulation and manual therapy care did not provide any additional benefits in both the short term and the long term. Manual myofascial point treatment and mobilization techniques yielded positive outcomes in chronic lateral epicondylitis. Further studies should focus on the sole therapeutic effect of cryostimulation in both patients with acute and those with chronic conditions.

  15. Possible adverse events in children treated by manual therapy: a review

    Directory of Open Access Journals (Sweden)

    Humphreys B Kim

    2010-06-01

    Full Text Available Abstract Background Pediatric manual therapy is controversial within the medical community particularly with respect to adverse events. Pediatric manual therapy (Ped MT is commonly used by a number of professions such as chiropractors, osteopaths and naturopaths for a variety of treatments in children. Ped MT interventions range from advice, light touch, massage, through to mobilisation and high velocity spinal manipulation. However, current evidence related to adverse events associated with Ped MT is not well understood. Objective To update the clinical research literature from the 2007 report by Vohra, Johnston, Cramer and Humphreys on possible adverse events in children treated by spinal manipulation. Methods A review of the clinical research literature from June 2004 until January 2010 as reported in MEDLINE, PubMed and PubMed Central for adverse events specifically related to the treatment of pediatric cases by manual therapy. Results Only three new clinical studies, one systematic review with meta-analysis and one evidence report were identified. Two clinical studies reported on chiropractic care and one on osteopathic spinal manipulation in children. The systematic review investigated all studies of adverse events and manual therapy and was not specific for pediatric patients. The evidence review focused on effectiveness of spinal manipulation in a variety of musculoskeletal conditions. No serious or catastrophic adverse events were reported in the clinical studies or systematic review. However for adults, it has been estimated that between 0.003% and 0.13% of manual therapy treatments may result in a serious adverse event. Although mild to moderate adverse events are common in adults, an accurate estimate from high quality pediatric studies is currently not available. Conclusions There is currently insufficient research evidence related to adverse events and manual therapy. However, clinical studies and systematic reviews from adult

  16. 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

  17. Effectiveness of using ultrasound therapy and manual therapy in the conservative treatment of calcaneal spur – pilot study

    Directory of Open Access Journals (Sweden)

    Twarowska Natalia

    2016-06-01

    Full Text Available Introduction: Calcaneal spur is a pathology of the fibrocartilage enthesis of the Achilles tendon and plantar fascia or a pathology of the mixed enthesis of the flexor digitorum brevis muscle. Ultrasound therapy is commonly applied in the conservative treatment of a calcaneal spur. Foot muscle strengthening exercises, stretching exercises and soft tissue therapy are indicated as effective methods of conservative treatment. The aim of the study was to compare and assess the effects of ultrasound therapy and selected techniques of manual therapy on pain level and functional state in patients with calcaneal spur.

  18. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  19. Targeted Therapy for Biliary Tract Cancer

    International Nuclear Information System (INIS)

    Furuse, Junji; Okusaka, Takuji

    2011-01-01

    It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important

  20. Molecular targeted therapy for advanced gastric cancer.

    Science.gov (United States)

    Kim, Jong Gwang

    2013-03-01

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

  1. Targeted Therapy for Breast Cancer Prevention

    Science.gov (United States)

    den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

    2013-01-01

    With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

  2. Gene transfer technology and genetic radioisotope targeting therapy

    International Nuclear Information System (INIS)

    Wang Jiaqiong; Wang Zizheng

    2004-01-01

    With deeper cognition about mechanisms of disease at the cellular and molecular level, gene therapy has become one of the most important research fields in medical molecular biology at present. Gene transfer technology plays an important role during the course of gene therapy, and further improvement should be made about vectors carrying target gene sequences. Also, gene survey is needed during gene therapy, and gene imaging is the most effective method. The combination of gene therapy and targeted radiotherapy, that is, 'Genetic Radioisotope Targeting Therapy', will be a novel approach to tumor gene therapy

  3. TARGETED NANOPARTICLES FOR PEDIATRIC LEUKEMIA THERAPY

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    Riyaz eBasha

    2014-05-01

    Full Text Available The two major forms of leukemia, acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML account for about one third of the malignancies diagnosed in children. Despite the marked successes in ALL and AML treatment, concerns remain regarding the occurrence of resistant disease in subsets of patients the residual effects of therapy that often persist for decades beyond the cessation of treatment. Therefore, new approaches are needed to reduce or to avoid off target toxicities, associated with chemotherapy and their long term residual effects. Recently, nanotechnology has been employed to enhance cancer therapy, via improving the bioavailability and therapeutic efficacy of anti-cancer agents. While in the last several years, numerous review articles appeared detailing the size, composition, assembly and performance evaluation of different types of drug carrying nanoparticles, the description and evaluation of lipoprotein based drug carriers have been conspicuously absent from most of these major reviews. The current review focuses on such information regarding nanoparticles with an emphasis on high density lipoprotein (HDL-based drug delivery systems to examine their potential role(s in the enhanced treatment of children with leukemia.

  4. Changes in rat spinal cord gene expression after inflammatory hyperalgesia of the joint and manual therapy.

    Science.gov (United States)

    Ruhlen, Rachel L; Singh, Vineet K; Pazdernik, Vanessa K; Towns, Lex C; Snider, Eric J; Sargentini, Neil J; Degenhardt, Brian F

    2014-10-01

    Mobilization of a joint affects local tissue directly but may also have other effects that are mediated through the central nervous system. To identify differential gene expression in the spinal cords of rats with or without inflammatory joint injury after manual therapy or no treatment. Rats were randomly assigned to 1 of 4 treatment groups: no injury and no touch (NI/NT), injury and no touch (I/NT), no injury and manual therapy (NI/MT), and injury and manual therapy (I/MT). We induced acute inflammatory joint injury in the rats by injecting carrageenan into an ankle. Rats in the no-injury groups did not receive carrageenan injection. One day after injury, rats received manual therapy to the knee of the injured limb. Rats in the no-touch groups were anesthetized without receiving manual therapy. Spinal cords were harvested 30 minutes after therapy or no touch, and spinal cord gene expression was analyzed by microarray for 3 comparisons: NI/NT vs I/NT, I/MT vs I/NT, and NI/NT vs NI/MT. Three rats were assigned to each group. Of 38,875 expressed sequence tags, 755 were differentially expressed in the NI/NT vs I/NT comparison. For the other comparisons, no expressed sequence tags were differentially expressed. Cluster analysis revealed that the differentially expressed sequence tags were over-represented in several categories, including ion homeostasis (enrichment score, 2.29), transmembrane (enrichment score, 1.55), and disulfide bond (enrichment score, 2.04). An inflammatory injury to the ankle of rats caused differential expression of genes in the spinal cord. Consistent with other studies, genes involved in ion transport were among those affected. However, manual therapy to the knees of injured limbs or to rats without injury did not alter gene expression in the spinal cord. Thus, evidence for central nervous system mediation of manual therapy was not observed. © 2014 The American Osteopathic Association.

  5. Exercise therapy, manual therapy, or both, for osteoarthritis of the hip or knee: a factorial randomised controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Baxter G David

    2009-02-01

    Full Text Available Abstract Background Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether: 1. Exercise therapy versus no exercise therapy improves disability at 12 months; 2. Manual physiotherapy versus no manual therapy improves disability at 12 months; 3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months. Methods This is a 2 × 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a a supervised multi-modal exercise therapy programme; (b an individualised manual therapy programme; (c both exercise therapy and manual therapy; or, (d no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200. Discussion The MOA Trial will be the first to investigate the effectiveness and cost

  6. Online manual movement adjustments in response to target position changes and apparent target motion

    NARCIS (Netherlands)

    Oostwoud Wijdenes, L.; Brenner, E.; Smeets, J.B.J.

    2014-01-01

    This study set out to determine whether the fastest online hand movement corrections are only responses to changing judgments of the targets' position or whether they are also influenced by the apparent target motion. Introducing a gap between when a target disappears and when it reappears at a new

  7. Manual therapy in the management of a patient with a symptomatic Morton's Neuroma: A case report.

    Science.gov (United States)

    Sault, Josiah D; Morris, Matthew V; Jayaseelan, Dhinu J; Emerson-Kavchak, Alicia J

    2016-02-01

    Patients with Morton's neuroma are rarely referred to physical therapy. This case reports the resolution of pain, increase in local pressure pain thresholds, and improvement of scores on the Lower Extremity Functional Scale and Foot and Ankle Ability Measure following a course of joint based manual therapy for a patient who had failed standard conservative medical treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Therapies targeting inflammation after stent implantation.

    Science.gov (United States)

    Okura, Hiroyuki; Takagi, Tsutomu; Yoshida, Kiyoshi

    2013-07-01

    Since the introduction of coronary vessel scaffold by metallic stent, percutaneous coronary intervention has become widely performed all over the world. Although drug-eluting stent technology has further decrease the incidence of in-stent restenosis, there still remaining issues related to stent implantation. Vessel inflammation is one of the causes that may be related to stent restenosis as well as stent thrombosis. Therefore, systemic therapies targeting inflammation emerged as adjunctive pharmacological intervention to improve outcome. Statins, corticosteroids, antiplatelets, and immunosuppresive or anti-cancer drugs are reported to favorably impact outcome after bare-metal stent implantation. In type 2 diabetic patients, pioglitazone may be the most promising drug that can lower neointimal proliferation and, as a result, lower incidence of restenosis and target lesion revascularization. On the other hand, several new stent platforms that might decrease inflammatory response after drug-eluting stent implantation have been introduced. Because durable polymer used in the first generation drug-eluting stents are recognized to be responsible for unfavorable vessel response, biocompatible or bioabsorbable polymer has been introduce and already used clinically. Furthermore, polymer-free drug-eluting stent and bioresorbable scaffold are under investigation. Although vessel inflammation may be reduced by using these new drug-eluting stents or scaffold, long-term impact needs to be investigated further.

  9. RLIP76 Targeted Therapy for Kidney Cancer.

    Science.gov (United States)

    Singhal, Sharad S; Singhal, Jyotsana; Figarola, James; Horne, David; Awasthi, Sanjay

    2015-10-01

    Despite recent improvements in chemotherapeutic approaches to treating kidney cancer, this malignancy remains deadly if not found and removed at an early stage of the disease. Kidney cancer is highly drug-resistant, which may at least partially result from high expression of transporter proteins in the cell membranes of kidney cells. Although these transporter proteins can contribute to drug-resistance, targeting proteins from the ATP-binding cassette transporter family has not been effective in reversing drug-resistance in kidney cancer. Recent studies have identified RLIP76 as a key stress-defense protein that protects normal cells from damage caused by stress conditions, including heat, ultra-violet light, X-irradiation, and oxidant/electrophilic toxic chemicals, and is crucial for protecting cancer cells from apoptosis. RLIP76 is the predominant glutathione-electrophile-conjugate (GS-E) transporter in cells, and inhibiting it with antibodies or through siRNA or antisense causes apoptosis in many cancer cell types. To date, blocking of RLIP76, either alone or in combination with chemotherapeutic drugs, as a therapeutic strategy for kidney cancer has not yet been evaluated in human clinical trials, although there is considerable potential for RLIP76 to be developed as a therapeutic agent for kidney cancer. In the present review, we discuss the mechanisms underlying apoptosis caused by RLIP76 depletion, the role of RLIP76 in clathrin-dependent endocytosis deficiency, and the feasibility of RLIP76-targeted therapy for kidney cancer.

  10. The journal 'chiropractic & osteopathy' changes its title to 'chiropractic & manual therapies'. a new name, a new era

    NARCIS (Netherlands)

    Walker, Bruce F; French, Simon D; Cameron, Melanie; Perle, Stephen M; Lebouef-Yde, Charlotte; Rubinstein, Sidney M

    2011-01-01

    Chiropractic & Osteopathy changes its title to Chiropractic & Manual Therapies in January 2011. This change reflects the expanding base of submissions from clinical scientists interested in the discipline of manual therapy. It is also in accord with the findings of a review of the journal content

  11. Case Study: Manual Therapy in Patient of 18 Years with Youthful Scoliosis Idiopathic Summary

    Directory of Open Access Journals (Sweden)

    Claudia Yaneth Franco Monsalve

    2007-12-01

    Full Text Available Scoliosis is a lateral deviation of the spine from the mean line, characterized by a lateral curvature and a vertebral rotation. It is generallyof idiopathic character and appears mainly in adolescent females. Multiple techniques of conservative treatment for the scoliosis exist such as the manual therapy that complements the treatment for this pathology. This technique uses manipulation of soft tissue and bone, obtainingtherefore a more effective recovery, improving the quality of life of the patient. The objective of this study of case was to compareand to describe the changes in the conditionsof an eighteen years old patient, with left thoracolumbar scoliosis by the application of manual therapy; integral valuation was carried out by manual therapy, orthopedic, computerizedposition analysis, analyses the place of job, treatments with physical instruments, mobilizationsof the thoracic and lumbar joints (segmentsT5-T6, T6-T7, T7-T8, T8-T9, muscular energy techniques, exercises of global postural re-education, cervical and lumbar stabilization, exercises of fortification for weak musculature and stretching exercises to elongate retracted musculature. At the beginning of the treatment, the angle of Cobb was 24º ,verified through ax-ray, and after the sessions of manual therapy it was 18º, demonstrating significantly improved angle (6º. The effectiveness of the treatment was verified: diminution of the pain, increase of the muscular force, postural realignment, the satisfactionof the patient and significant recovery confirmed by the radiographic studies.

  12. Manual therapy in adults with tension-type headache: A systematic review.

    Science.gov (United States)

    Cumplido-Trasmonte, C; Fernández-González, P; Alguacil-Diego, I M; Molina-Rueda, F

    2018-03-07

    Tension-type headache is the most common primary headache, with a high prevalence and a considerable socioeconomic impact. Manual physical therapy techniques are widely used in the clinical field to treat the symptoms associated with tension-type headache. This systematic review aims to determine the effectiveness of manual and non-invasive therapies in the treatment of patients with tension-type headache. We conducted a systematic review of randomised controlled trials in the following databases: Brain, PubMed, Web of Science, PEDro, Scopus, CINAHL, and Science Direct. Ten randomised controlled trials were included for analysis. According to these studies, manual therapy improves symptoms, increasing patients' well-being and improving the outcome measures analysed. Manual therapy has positive effects on pain intensity, pain frequency, disability, overall impact, quality of life, and craniocervical range of motion in adults with tension-type headache. None of the techniques was found to be superior to the others; combining different techniques seems to be the most effective approach. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Therapist Adherence and Competence with Manualized Cognitive-Behavioral Therapy for PTSD Delivered via Videoconferencing Technology

    Science.gov (United States)

    Frueh, B. Christopher; Monnier, Jeannine; Grubaugh, Anouk L.; Elhai, Jon D.; Yim, Eunsil; Knapp, Rebecca

    2007-01-01

    Using secondary analyses from a randomized trial comparing the effectiveness of manualized cognitive-behavioral therapy for posttraumatic stress disorder, we compared ratings of therapist competency and adherence between two service delivery modes: telepsychiatry (TP) and same room (SR). Patients were 38 male treatment-seeking veterans recruited…

  14. Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy.

    Science.gov (United States)

    Barar, Jaleh; Omidi, Yadollah

    2013-01-01

    It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called "tumor microenvironment (TME)", in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF) functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

  15. Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy

    Directory of Open Access Journals (Sweden)

    Jaleh Barar

    2013-02-01

    Full Text Available It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called “tumor microenvironment (TME”, in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

  16. A clinical perspective on a pain neuroscience education approach to manual therapy.

    Science.gov (United States)

    Louw, Adriaan; Nijs, Jo; Puentedura, Emilio J

    2017-07-01

    In recent years, there has been an increased interest in pain neuroscience education (PNE) in physical therapy. There is growing evidence for the efficacy of PNE to decrease pain, disability, fear-avoidance, pain catastrophization, limited movement, and health care utilization in people struggling with pain. PNE teaches people in pain more about the biology and physiology of their pain experience including processes such as central sensitization, peripheral sensitization, allodynia, inhibition, facilitation, neuroplasticity and more. PNE's neurobiological model often finds itself at odds with traditional biomedical models used in physical therapy. Traditional biomedical models, focusing on anatomy, pathoanatomy, and biomechanics have been shown to have limited efficacy in helping people understand their pain, especially chronic pain, and may in fact even increase a person's pain experience by increasing fear-avoidance and pain catastrophization. An area of physical therapy where the biomedical model is used a lot is manual therapy. This contrast between PNE and manual therapy has seemingly polarized followers from each approach to see PNE as a 'hands-off' approach even having clinicians categorize patients as either in need of receiving PNE (with no hands-on), or hands-on with no PNE. In this paper, we explore the notion of PNE and manual therapy co-existing. PNE research has shown to have immediate effects of various clinical signs and symptoms associated with central sensitization. Using a model of sensitization (innocuous, noxious, and allodynia), we argue that PNE can be used in a manual therapy model, especially treating someone where the nervous system has become increasingly hypervigilant. Level of Evidence : VII.

  17. Manual therapy for unsettled, distressed and excessively crying infants: a systematic review and meta-analyses.

    Science.gov (United States)

    Carnes, Dawn; Plunkett, Austin; Ellwood, Julie; Miles, Clare

    2018-01-24

    To conduct a systematic review and meta-analyses to assess the effect of manual therapy interventions for healthy but unsettled, distressed and excessively crying infants and to provide information to help clinicians and parents inform decisions about care. We reviewed published peer-reviewed primary research articles in the last 26 years from nine databases (Medline Ovid, Embase, Web of Science, Physiotherapy Evidence Database, Osteopathic Medicine Digital Repository , Cochrane (all databases), Index of Chiropractic Literature, Open Access Theses and Dissertations and Cumulative Index to Nursing and Allied Health Literature). Our inclusion criteria were: manual therapy (by regulated or registered professionals) of unsettled, distressed and excessively crying infants who were otherwise healthy and treated in a primary care setting. Outcomes of interest were: crying, feeding, sleep, parent-child relations, parent experience/satisfaction and parent-reported global change. Nineteen studies were selected for full review: seven randomised controlled trials, seven case series, three cohort studies, one service evaluation study and one qualitative study.We found moderate strength evidence for the effectiveness of manual therapy on: reduction in crying time (favourable: -1.27 hours per day (95% CI -2.19 to -0.36)), sleep (inconclusive), parent-child relations (inconclusive) and global improvement (no effect). The risk of reported adverse events was low: seven non-serious events per 1000 infants exposed to manual therapy (n=1308) and 110 per 1000 in those not exposed. Some small benefits were found, but whether these are meaningful to parents remains unclear as does the mechanisms of action. Manual therapy appears relatively safe. CRD42016037353. © 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.

  18. Manual therapy and therapeutic exercise in the treatment of osteoarthritis of the hip: a systematic review

    Directory of Open Access Journals (Sweden)

    A. Romeo

    2013-05-01

    Full Text Available This systematic review aimed at investigating the role of therapeutic exercise and/or manual therapy in the treatment of hip osteoarthritis (OA. Two independent reviewers (AR, CV searched PubMed, Cinahl, Cochrane Library, PEDro and Scopus databases and a third one (SP was consulted in case of disagreement. The research criteria were publication period (from May 2007 to April 2012 and publication language (English or Italian. Ten randomized controlled trials matched inclusion criteria, eight of which concerning therapeutic exercise and two manual therapy. Few good quality studies were found. At mid- and long-term follow-up land-based exercises showed insufficient evidence of effectiveness with respect to pain and quality of life, but positive results were found for physical function. Water exercises significantly reduced fall risk when combined with functional exercises. Programs containing progressive and gradual exposure of difficult activities, education and exercises promoted better outcomes, higher adherence to home program and increased amount of physical activity, especially walking. Manual therapy seemed to reduce pain and decrease disability at short-term. Less use of nonsteroidal anti-inflammatory drugs was statistically significant at long-term follow-up in patients treated with manual therapy. The relationship between clinical results and radiological grade of OA was not investigated. Encouraging results were found in recent literature for manual therapy and functional training. Further research is needed to elucidate this issue through high-quality trials, especially addressing the aspects that have not been thoroughly explored yet, for instance type, amount and scheduling of conservative treatment.

  19. Manual Therapy in the Treatment of Idiopathic Scoliosis. Analysis of Current Knowledge.

    Science.gov (United States)

    Czaprowski, Dariusz

    2016-10-28

    Apart from the recommended specific physiotherapy, the treatment of idiopathic scoliosis (IS) also incorporates non-specific manual therapy (NMT). The aim of this paper is to assess the efficacy of NMT (manual therapy, chiropractic, osteopathy) used in the treatment of children and adolescents with IS. The study analysed systematic reviews (Analysis 1) and other recent scientific publications (Analysis 2). Analysis 1 encompassed papers on the use of NMT in patients with IS. Works concerning specific physiotherapy (SP) or bracing (B) and other types of scoliosis were excluded from the analysis. Inclusion criteria for Analysis 2 were: treatment with NMT; subjects aged 10-18 years with IS. The following types of papers were excluded: works analysing NMT combined with SP or B, reports concerning adult pa tients, analyses of single cases and publications included in Analysis 1. Analysis 1: six systematic reviews contained 6 papers on the efficacy of NMT in the treatment of IS. The results of these studies are contradictory, ranging from Cobb angle reduction to no treatment effects whatsoever. The papers analysed are characterised by poor methodological quality: small group sizes, incomplete descriptions of the study groups, no follow-up and no control groups. Analysis 2: in total, 217 papers were found. None of them met the criteria set for the analysis. 1. Few papers verifying the efficacy of manual therapy, chiropractic and osteopathy in the treatment of idiopathic scoliosis have been published to date. 2. The majority are experimental studies with poor methodology or observational case studies. 3. At present, the efficacy of non-specific manual therapy in the treatment of patients with idiopathic scoliosis cannot be reliably evaluated. 4. It is necessary to conduct further research based on appropriate methods (prospective, rando mi s ed, controlled studies) in order to reliably assess the usefulness of non-specific manual therapy in the treatment of idiopathic

  20. 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.

  1. Clinical targeting recombinant immunotoxins for cancer therapy

    Directory of Open Access Journals (Sweden)

    Li M

    2017-07-01

    Full Text Available Meng Li,1,* Zeng-Shan Liu,1,* Xi-Lin Liu,1,* Qi Hui,2,* Shi-Ying Lu,1 Lin-Lin Qu,1 Yan-Song Li,1 Yu Zhou,1 Hong-Lin Ren,1 Pan Hu1 1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, China-Japan Union Hospital, The First Hospital, Jilin University, Changchun, 2School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Recombinant immunotoxins (RITs are proteins that contain a toxin fused to an antibody or small molecules and are constructed by the genetic engineering technique. RITs can bind to and be internalized by cells and kill cancerous or non-cancerous cells by inhibiting protein synthesis. A wide variety of RITs have been tested against different cancers in cell culture, xenograft models, and human patients during the past several decades. RITs have shown activity in therapy of several kinds of cancers, but different levels of side effects, mainly related to vascular leak syndrome, were also observed in the treated patients. High immunogenicity of RITs limited their long-term or repeat applications in clinical cases. Recent advances in the design of immunotoxins, such as humanization of antibody fragment, PEGylation, and modification of human B- and T-cell epitopes, are overcoming the above mentioned problems, which predict the use of these immunotoxins as a potential therapeutic method to treat cancer patients. Keywords: targeted therapy, hematologic malignancies, solid tumors, vascular leak syndrome, immunogenicity 

  2. Utilization of manual therapy to the lumbar spine in conjunction with traditional conservative care for individuals with bilateral lower extremity complex regional pain syndrome: A case series.

    Science.gov (United States)

    Walston, Zachary; Hernandez, Luis; Yake, Dale

    2018-06-06

    Conservative therapies for complex regional pain syndrome (CRPS) have traditionally focused on exercise and desensitization techniques targeted at the involved extremity. The primary purpose of this case series is to report on the potential benefit of utilizing manual therapy to the lumbar spine in conjunction with traditional conservative care when treating patients with lower extremity CRPS. Two patients with the diagnosis of lower extremity CRPS were treated with manual therapy to the lumbar spine in conjunction with education, exercise, desensitization, and soft tissue techniques for the extremity. Patient 1 received 13 sessions over 6 weeks resulting in a 34-point improvement in oswestry disability index (ODI) and 35-point improvement in lower extremity functional scale (LEFS). Patient 2 received 21 sessions over 12 weeks resulting in a 28-point improvement in ODI and a 41-point improvement in LEFS. Both patients exhibited reductions in pain and clinically meaningful improvements in function. Manual therapies when applied to the lumbar spine in these patients as part of a comprehensive treatment plan resulted in improved spinal mobility, decreased pain, and reduction is distal referred symptoms. Although one cannot infer a cause and effect relationship from a case series, this report identifies meaningful clinical outcomes potentially associated with manual physical therapy to the lumbar spine for two patients with complex regional pain syndrome type 1.

  3. Comparative study between manual therapy and TENS Burst in patients with tension-type cephalalgia

    Directory of Open Access Journals (Sweden)

    Denise Vasconcelos Fernandes

    Full Text Available Introduction Cephalgia or cephalalgia is one of the most common symptoms in the general population. Objective To compare the efficacy of physical therapy modalities, through manual therapy and the effect of Transcutaneous Nerve Stimulation (TENS for tension-type cephalalgia. Materials and methods The study was compounded by 60 subjects, but only 40 of them completed it, due to the exclusion criteria. These were divided into control group and intervention group. The control group received treatment — manual therapy. The intervention group received TENS Burst. Patients underwent ten sessions of treatment, made at every two days on a week, lasting 30 minutes each session. Results The characteristics related to lifestyle, postural issues and range of motion are responsible for the main causes of tension-type cephalalgia. Discussion treatments showed effective results in all cases in relation to pain intensity, but the use of manual therapy techniques give the patient a better quality of life compared to the use of TENS. Final considerations The treatment of this condition deserves analysis and studies; however, there are only a few studying physical therapy techniques, especially regarding to the use of TENS.

  4. Manual therapy as a conservative treatment for adolescent idiopathic scoliosis: a systematic review

    Directory of Open Access Journals (Sweden)

    Negrini Stefano

    2008-01-01

    Full Text Available Abstract Background The treatment of adolescent idiopathic scoliosis is contingent upon many variables. Simple observation is enough for less serious curvatures, but for very serious cases surgical intervention could be proposed. Between these there is a wide range of different treatments. Manual therapy is commonly used: the aim of this paper is to verify the data existing in the literature on the efficacy of this approach. Methods A systematic review of the scientific literature published internationally has been performed. We have included in the term manual therapy all the manipulative and generally passive techniques performed by an external operator. In a more specific meaning, osteopathic, chiropractic and massage techniques have been considered as manipulative therapeutic methods. We performed our systematic research in Medline, Embase, Cinhal, Cochrane Library, Pedro with the following terms: idiopathic scoliosis combined with chiropractic; manipulation; mobilization; manual therapy; massage; osteopathy; and therapeutic manipulation. The criteria for inclusion were as follows: Any kind of research; diagnosis of adolescent idiopathic scoliosis; patients treated exclusively by one of the procedures established as a standard for this review (chiropractic manipulation, osteopathic techniques, massage; and outcome in Cobb degrees. Results We founded 145 texts, but only three papers were relevant to our study. However, no one of the three satisfied all the required inclusion criteria because they were characterized by a combination of manual techniques and other therapeutic approaches. Conclusion The lack of any kind of serious scientific data does not allow us to draw any conclusion on the efficacy of manual therapy as an efficacious technique for the treatment of Adolescent idiopathic scoliosis.

  5. Manual therapy as a conservative treatment for adolescent idiopathic scoliosis: a systematic review.

    Science.gov (United States)

    Romano, Michele; Negrini, Stefano

    2008-01-22

    The treatment of adolescent idiopathic scoliosis is contingent upon many variables. Simple observation is enough for less serious curvatures, but for very serious cases surgical intervention could be proposed. Between these there is a wide range of different treatments. Manual therapy is commonly used: the aim of this paper is to verify the data existing in the literature on the efficacy of this approach. A systematic review of the scientific literature published internationally has been performed. We have included in the term manual therapy all the manipulative and generally passive techniques performed by an external operator. In a more specific meaning, osteopathic, chiropractic and massage techniques have been considered as manipulative therapeutic methods. We performed our systematic research in Medline, Embase, Cinhal, Cochrane Library, Pedro with the following terms: idiopathic scoliosis combined with chiropractic; manipulation; mobilization; manual therapy; massage; osteopathy; and therapeutic manipulation. The criteria for inclusion were as follows: Any kind of research; diagnosis of adolescent idiopathic scoliosis; patients treated exclusively by one of the procedures established as a standard for this review (chiropractic manipulation, osteopathic techniques, massage); and outcome in Cobb degrees. We founded 145 texts, but only three papers were relevant to our study. However, no one of the three satisfied all the required inclusion criteria because they were characterized by a combination of manual techniques and other therapeutic approaches. The lack of any kind of serious scientific data does not allow us to draw any conclusion on the efficacy of manual therapy as an efficacious technique for the treatment of Adolescent idiopathic scoliosis.

  6. Efficacy of Manual Therapy versus Conventional Physical Therapy in Chronic Low Back Pain Due to Lumbar Spondylosis. A Pilot Study

    Directory of Open Access Journals (Sweden)

    Arti Sharma

    2015-06-01

    Full Text Available Objectives: The objective of this work was to compare the efficacy of Maitland mobilization and conventional physical therapy on pain response, range of motion (ROM and functional ability in patients with chronic low back pain due to lumbar spondylosis. Methods: A total sample of 30 subjects (40–70 years of age with complaints of slow insidious onset of low back pain (LBP, with or without radiation not less than three months duration and decrease ROM were randomly assigned to: group-I, Maitland mobilization and lumbar stabilization exercises; group-II conventional physical therapy (traction, strengthening, stretching exercises. and outcomes were assessed for dependent variables. Results: There is statically a significant difference between pre and post measurement readings with time (p = 0.00 and between groups (p < 0.05 with respect to pain and function, but, with respect to ROM readings, showed statistical significance with time (p = 0.00 and no significance between groups (p > 0.05, indicating manual therapy group-I is improving faster and better than conventional physical therapy group-II. Conclusion: Our results showed that manual therapy interventions are more effective in managing low back pain, and function and range of motion of the lumbar spine than conventional physical therapy treatment.

  7. Influence of manual therapy on functional mobility after joint injury in a rat model.

    Science.gov (United States)

    Ruhlen, Rachel L; Snider, Eric J; Sargentini, Neil J; Worthington, Bart D; Singh, Vineet K; Pazdernik, Vanessa K; Johnson, Jane C; Degenhardt, Brian F

    2013-10-01

    Animal models can be used to investigate manual therapy mechanisms, but testing manipulation in animal models is problematic because animals cannot directly report their pain. To develop a rat model of inflammatory joint injury to test the efficacy of manual therapy in reducing nociception and restoring function. The authors induced acute inflammatory joint injury in rats by injecting carrageenan into the ankle and then measured voluntary running wheel activity in treated and untreated rats. Treatments included manual therapy applied to the ankle and knee of the injured limb and several analgesic medications (eg, morphine, ketorolac, prednisone). Intra-articular injection of carrageenan to the ankle produced significant swelling (diameter of the ankle increased by 64% after injection; P=.004) and a robust reduction in voluntary running wheel activity (running distance reduced by 91% compared with controls; Pmanual therapy nor analgesic medications increased running wheel activity relative to untreated rats. Voluntary running wheel activity appears to be an appropriate functional measure to evaluate the impact of an acute inflammatory joint injury. However, efforts to treat the injury did not restore running relative to untreated rats.

  8. Development of iPad application "Postima" for quantitative analysis of the effects of manual therapy

    Science.gov (United States)

    Sugiyama, Naruhisa; Shirakawa, Tomohiro

    2017-07-01

    The technical difficulty of diagnosing joint misalignment and/or dysfunction by quantitative evaluation is commonly acknowledged among manual therapists. Usually, manual therapists make a diagnosis based on a combination of observing patient symptoms and performing physical examinations, both of which rely on subjective criteria and thus contain some uncertainty. We thus sought to investigate the correlations among posture, skeletal misalignment, and pain severity over the course of manual therapy treatment, and to explore the possibility of establishing objective criteria for diagnosis. For this purpose, we developed an iPad application that realizes the measurement of patients' postures and analyzes them quantitatively. We also discuss the results and effectiveness of the measurement and analysis.

  9. The journal 'chiropractic & osteopathy' changes its title to 'chiropractic & manual therapies'. a new name, a new era

    Directory of Open Access Journals (Sweden)

    Walker Bruce F

    2011-01-01

    Full Text Available Abstract Chiropractic & Osteopathy changes its title to Chiropractic & Manual Therapies in January 2011. This change reflects the expanding base of submissions from clinical scientists interested in the discipline of manual therapy. It is also in accord with the findings of a review of the journal content and a joint venture between the original parent organisation the Chiropractic and Osteopathic College of Australasia and a new partner the European Academy of Chiropractic, which is a subsidiary body of the European Chiropractors' Union. The title change should encourage submissions from all professionals interested in manual therapy including chiropractors, osteopaths, physiotherapists, medical doctors and scientists interested in this field.

  10. Ankle sprains: combination of manual therapy and supervised exercise leads to better recovery.

    Science.gov (United States)

    2013-01-01

    Ankle sprains often occur when running, walking on uneven ground, or jumping. Usually, people are told to rest, elevate the foot, apply ice, and use an elastic wrap to reduce swelling. This treatment is typically followed by exercises that can be performed at home. Although the pain and swelling usually improve quickly, more than 70% of people who sprain their ankles continue to have problems with them and up to 80% will sprain their ankles again. This suggests that it is important to better care for ankle sprains. One option is manual therapy, where the therapist moves the ankle and surrounding joints to help restore normal joint movement. A research report published in the July 2013 issue of JOSPT examines and compares the outcomes of a home exercise program with a more involved treatment program that includes manual therapy and supervised exercises.

  11. Understanding and working with the psychodynamics of practitioner-patient relationships in the manual therapies.

    Science.gov (United States)

    Sher, Danny; Sher, Mannie

    2016-04-01

    In this paper, we argue that practitioner-patient relationships in the manual therapies would be strengthened by a deeper understanding of the psychodynamics and emotions of those relationships. We suggest that in many cases, a purely bio-mechanical approach may neglect underlying psychological and emotional reasons of the patient's presenting condition, and consequently, lead to a less than adequate outcome for the patient. We offer easily adopted suggestions that could enhance the practice of practitioners of manual therapies as well as other professions that rely on the application of physical methods of diagnosis and treatment. These suggestions could lead to improved prognosis and increased professional satisfaction for practitioners. This paper describes five key dynamics that characterize practitioner-patient relationships: (i) pain as a form of communication; (ii) the 'heart-sink' patient; (iii) dependency; (iv) the erotic transference; (v) endings and loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Manual therapy is an effective treatment for frozen shoulder in diabetics: an observational study.

    Science.gov (United States)

    Düzgün, Irem; Baltaci, Gül; Atay, Ozgür Ahmet

    2012-01-01

    This study aims to compare the efficacy of manual therapy in the frozen shoulder patients with or without diabetes mellitus. Between May 2006 and January 2008, 50 patients (10 males, 40 females; mean age 52 ± 10 years; range 40 to 65 years) orthopedic surgeons referred to the Sports Physiotherapy Unit were included in the study. The patients were divided into two groups, including patients with primary frozen shoulder with type II diabetes mellitus (n=12) and non diabetics (n=38). All patients underwent a rehabilitation program including cold application, manual therapy and exercises twice a week. A total of 16 treatment sessions were performed. The most important part of the manual therapy included scapular mobilization and posterior capsule stretching. The range of motion was measured by goniometry. Functional activity status was assessed by Constant's score. The pain level was evaluated by visual analog scale, while muscle strength was evaluated by hand-held dynamometer. Student t-test was used to compare between the parameters of groups, while Paired sample t-test was used to compare pre- and post-treatment parameters of the patients. The range of motion, functional activity status and muscular strength were improved and the pain level was reduced after rehabilitation in all of the patients in both groups (p0.05). There were no differences in range of motion, functional activity status, pain level, and muscle strength before and after rehabilitation between the groups (p>0.05). Manual therapy approaches may be safely applied in diabetic patients with frozen shoulder.

  13. Remodelling of motor act and manual therapy application at humeroscapular periarthrosis

    Directory of Open Access Journals (Sweden)

    V.V. Gubanov

    2010-03-01

    Full Text Available The research objective is to develop methods for reducing terms and possible complications of humeroscapular periarthrosis treatment. 30 patients with various nosologic disease units were under observation. the comparison group consisted of 50 patients having the same age, sex and nosologic criteria (according to ambulatory card in comparison with the main group. the treatment was conducted by manual therapy and remodelling of motor act. this method proved to be effective at acute tendonitis and could be used as monotherapy

  14. Case Study: Manual Therapy in Patient of 18 Years with Youthful Scoliosis Idiopathic Summary

    OpenAIRE

    Claudia Yaneth Franco Monsalve; Zorika María Guerra Corena; María Patricia Otero Samudio

    2007-01-01

    Scoliosis is a lateral deviation of the spine from the mean line, characterized by a lateral curvature and a vertebral rotation. It is generallyof idiopathic character and appears mainly in adolescent females. Multiple techniques of conservative treatment for the scoliosis exist such as the manual therapy that complements the treatment for this pathology. This technique uses manipulation of soft tissue and bone, obtainingtherefore a more effective recovery, improving the quality of life of th...

  15. Manual therapy as a conservative treatment for adolescent idiopathic scoliosis: a systematic review

    OpenAIRE

    Romano, Michele; Negrini, Stefano

    2008-01-01

    Abstract Background The treatment of adolescent idiopathic scoliosis is contingent upon many variables. Simple observation is enough for less serious curvatures, but for very serious cases surgical intervention could be proposed. Between these there is a wide range of different treatments. Manual therapy is commonly used: the aim of this paper is to verify the data existing in the literature on the efficacy of this approach. Methods A systematic review of the scientific literature published i...

  16. Why Neck Pain Patients Are Not Referred to Manual Therapy: A Qualitative Study among Dutch Primary Care Stakeholders.

    Science.gov (United States)

    Dikkers, Marije F; Westerman, Marjan J; Rubinstein, Sidney M; van Tulder, Maurits W; Anema, Johannes R

    2016-01-01

    Treatment of neck pain with manual therapy demonstrated to be more effective and cost-effective than general practitioner (GP) care or physiotherapy in a high quality RCT in the Netherlands in 2002. However, referral to manual therapy for neck pain is still relatively low. This study aims to explore the barriers and facilitators affecting the implementation of manual therapy in neck pain management in primary care. An explorative study was conducted comprising semi-structured interviews with GPs (n = 13), physiotherapists (n = 10), manual therapists (n = 7) and their patients with neck pain (n = 27), and three focus groups with additional stakeholders (n = 10-12 per group). A thematic analysis approach was used. Different barriers and facilitators for referral were found for patients, GPs and physiotherapists on the individual level, but also in the interaction between stakeholders and their context. Individual perceptions such as knowledge and beliefs about manual therapy for neck pain either impeded or facilitated referral. Fear for complications associated with cervical manipulation was an important barrier for patients as well as GPs. For GPs and physiotherapists it was important whether they perceived it was part of their professional role to refer for manual therapy. Existing relations formed referral behavior, and the trust in a particular practitioner was a recurrent theme among GPs and physiotherapist as well as patients. The contextual factor availability of manual therapy played a role for all stakeholders. Barriers and facilitators were found especially in individual perceptions on manual therapy for neck pain (e.g. knowledge and beliefs), the interaction between stakeholders (e.g. collaboration and trust) and the organizational context. Implementation strategies that focus on these different aspects seem to be likely to optimize referral rates and the use of manual therapy in primary care management of neck pain.

  17. Why Neck Pain Patients Are Not Referred to Manual Therapy: A Qualitative Study among Dutch Primary Care Stakeholders.

    Directory of Open Access Journals (Sweden)

    Marije F Dikkers

    Full Text Available Treatment of neck pain with manual therapy demonstrated to be more effective and cost-effective than general practitioner (GP care or physiotherapy in a high quality RCT in the Netherlands in 2002. However, referral to manual therapy for neck pain is still relatively low. This study aims to explore the barriers and facilitators affecting the implementation of manual therapy in neck pain management in primary care.An explorative study was conducted comprising semi-structured interviews with GPs (n = 13, physiotherapists (n = 10, manual therapists (n = 7 and their patients with neck pain (n = 27, and three focus groups with additional stakeholders (n = 10-12 per group. A thematic analysis approach was used.Different barriers and facilitators for referral were found for patients, GPs and physiotherapists on the individual level, but also in the interaction between stakeholders and their context. Individual perceptions such as knowledge and beliefs about manual therapy for neck pain either impeded or facilitated referral. Fear for complications associated with cervical manipulation was an important barrier for patients as well as GPs. For GPs and physiotherapists it was important whether they perceived it was part of their professional role to refer for manual therapy. Existing relations formed referral behavior, and the trust in a particular practitioner was a recurrent theme among GPs and physiotherapist as well as patients. The contextual factor availability of manual therapy played a role for all stakeholders.Barriers and facilitators were found especially in individual perceptions on manual therapy for neck pain (e.g. knowledge and beliefs, the interaction between stakeholders (e.g. collaboration and trust and the organizational context. Implementation strategies that focus on these different aspects seem to be likely to optimize referral rates and the use of manual therapy in primary care management of neck pain.

  18. Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.

    Science.gov (United States)

    Lin, Chung-Wei Christine; Moseley, Anne M; Haas, Marion; Refshauge, Kathryn M; Herbert, Robert D

    2008-06-01

    The primary aim of this study was to determine the effectiveness and cost-effectiveness of adding manual therapy to a physiotherapy programme for ankle fracture. Assessor-blinded randomized controlled trial. Ninety-four adults were recruited within one week of cast removal for isolated ankle fracture. Inclusion criteria were: they were able to weight-bear as tolerated or partial weight-bear, were referred for physiotherapy, and experienced pain. Ninety-one participants completed the study. Participants were randomly allocated to receive manual therapy (anterior-posterior joint mobilization over the talus) plus a standard physiotherapy programme (experimental), or the standard physiotherapy programme only (control). They were assessed by a blinded assessor at baseline, and at 4, 12 and 24 weeks. The main outcomes were activity limitation and quality of life. Information on costs and healthcare utilization was collected every 4 weeks up to 24 weeks. There were no clinically worthwhile differences in activity limitation or quality of life between groups at any time-point. There was also no between-group difference in quality-adjusted life-years, but the experimental group incurred higher out-of-pocket costs (mean between-group difference = AU$200, 95% confidence interval 26-432). When provided in addition to a physiotherapy programme, manual therapy did not enhance outcome in adults after ankle fracture.

  19. The effectiveness of manual therapy in treating cervicogenic dizziness: a systematic review.

    Science.gov (United States)

    Yaseen, Khalid; Hendrick, Paul; Ismail, Ayah; Felemban, Mohannad; Alshehri, Mansour Abdullah

    2018-01-01

    [Purpose] This review provides an evaluation of the evidence for the effectiveness of using manual therapy to treat cervicogenic dizziness. [Subjects and Methods] The literature was systematically searched on the May 2, 2016 using the following online databases: Medline, EMBASE, CINAHL and PEDro. This review included randomised controlled trials and compared the efficacy of manual therapy for the treatment of cervicogenic dizziness, compared to other types of intervention. This study measured changes based on dizziness intensity and frequency. [Results] The primary search found 30 articles, but only four articles met the inclusion criteria. Assessment of methodological quality was performed by two researchers using the PEDro scale. The level of evidence was determined using a recognised grading scale. Three out of the four articles were deemed to have high methodological quality, while the fourth was rated as moderate quality. The attributed level of evidence was moderate (level 2). [Conclusion] Manual therapy is potentially effective for managing cervicogenic dizziness. However, due to the heterogeneity of the results and techniques and the low number of studies, further research is recommended to provide conclusive evidence.

  20. The functional manual therapy intervention in infants with nonsynostotic plagiocephaly: a pilot study.

    Science.gov (United States)

    Billi, Mariangela; Greco, Angelo; Colonneli, Paola; Volpi, Giordana; Valente, Donatella; Galeoto, Giovanni

    2017-10-25

    To document the evolution of cranial asymmetries in infants with signs of nonsynostotic occipital plagiocephaly (NSOP) who were undergo to many functional manual therapy treatments (in addition to the standard positioning recommendations) as well as to determine the feasibility of this methodology to conduct an outcome research investigating the impact of this intervention for infants with NSOP. Pilot clinical standardization project using pre-post design in which 10 infants participated. Nine infants presented an initial Oblique Diameter Difference Index (ODDI) over 104%, three an initial Ear Deviation Index (EDI) over 4%, and three a Cranial Proportional Index (CPI) over 90%. Infants received three functional manual therapy treatments for week during the first month of intervention and two ones for week during the second month. Plagiocephalometric measurememts were administered at the first assessment pre-intervention (T0), after 30 days (+/-5) (T1) and at a third time after 60 days (+/5) of treatment (T2). 9/10 participants showed a significant decrease in ODDI under 104% between T0 and T2 assessments. 5/10 infants showed an EDI under 4%, and 3/10 showed a value about 0%. 3/10 maintained their CPI over 90% with a considerable decrease. These clinical findings support the hypothesis that functional manual therapy treatments contribute to the improvement of cranial asymmetries in infants younger than 6.5 months old presenting with NSOP.

  1. Psychodynamic psychotherapy for social phobia: a treatment manual based on supportive-expressive therapy.

    Science.gov (United States)

    Leichsenring, Falk; Beutel, Manfred; Leibing, Eric

    2007-01-01

    Social phobia is a very frequent mental disorder characterized by an early onset, a chronic unremitting course, severe psychosocial impairments and high socioeconomic costs. To date, no manual for the psychodynamic treatment of social phobia exists. After a brief description of the disorder, a manual for a short-term psychodynamic treatment of social phobia is presented. The treatment is based on Luborsky s supportive-expressive (SE) therapy, which is complemented by treatment elements specific to social phobia. The treatment includes the characteristic elements of SE therapy, that is, setting goals, focus on the Core Conflictual Relationship Theme (CCRT) associated with the patient s symptoms, interpretive interventions to enhance insight into the CCRT, and supportive interventions, in particular fostering a helping alliance. In order to tailor the treatment more specifically to social phobia, treatment elements have been added, for example informing the patient about the disorder and the treatment, a specific focus on shame and on unrealistic demands, and encouraging the patient to confront anxiety-producing situations. More directive interventions are included as well, such as specific prescriptions to stop persisting self-devaluations. The treatment manual is presently being used in a large-scale randomized controlled multicenter study comparing short-term psychodynamic psychotherapy and cognitive-behavioral therapy in the treatment of social phobia.

  2. Adherence and competence in two manual-guided therapies for co-occurring substance use and posttraumatic stress disorders: clinician factors and patient outcomes.

    Science.gov (United States)

    Meier, Andrea; McGovern, Mark P; Lambert-Harris, Chantal; McLeman, Bethany; Franklin, Anna; Saunders, Elizabeth C; Xie, Haiyi

    2015-01-01

    The challenges of implementing and sustaining evidence-based therapies into routine practice have been well-documented. This study examines the relationship among clinician factors, quality of therapy delivery, and patient outcomes. Within a randomized controlled trial, 121 patients with current co-occurring substance use and posttraumatic stress disorders were allocated to receive either manualized Integrated Cognitive Behavioral Therapy (ICBT) or Individual Addiction Counseling (IAC). Twenty-two clinicians from seven addiction treatment programs were trained and supervised to deliver both therapies. Clinician characteristics were assessed at baseline; clinician adherence and competence were assessed over the course of delivering both therapies; and patient outcomes were measured at baseline and 6-month follow-up. Although ICBT was delivered at acceptable levels, clinicians were significantly more adherent to IAC (p drug problem severity. The differential impact of adherence and competence for both therapy types is consistent with their purported primary target: ICBT for PTSD and IAC for substance use. These findings also suggest the benefits of considering clinician factors when implementing manual-guided therapies. Future research should focus on diverse clinician samples, randomization of clinicians to therapy type, and prospective designs to evaluate models of supervision and quality monitoring.

  3. IS MANUAL THERAPY A RATIONAL APPROACH TO IMPROVING HEALTH-RELATED QUALITY OF LIFE IN PEOPLE WITH ARTHRITIS?

    Science.gov (United States)

    Cameron, Melainie

    2002-01-01

    Background: People with arthritic disease are advised to participate in gentle exercise on a regular basis, and pursue long-term medication regimes. Alternative therapies are also used by people with arthritis, and may sometimes be recommended by rheumatologists and other medical personnel. Alternative therapies may be divided into two types: active therapies, in which the patient takes a driving role, and passive therapies, in which the therapy cannot proceed unless driven by a therapist. Objective: To review the effectiveness of manual therapy in improving the health-related quality of life (HRQOL) of people with two common arthritis conditions: Osteoarthritis and rheumatoid arthritis. Discussion: Massage, and other passive (practitioner-driven) manual therapies, have been anecdotally reported to improve health-related quality of life (HRQOL) in people with arthritis. Many manual therapists consult with patients who have arthritic diseases, receive referrals from rheumatologists, and consider the arthritic diseases to be within their field of practise. Although there is empirical evidence that manual therapy with some types of arthritis is beneficial, the level of effectiveness however is under-researched. Medical authorities are reluctant to endorse manual therapies for arthritis due to a lack of scientific evidence demonstrating efficacy, safety, and cost effectiveness. PMID:17987169

  4. 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

  5. Manual therapy intervention in the treatment of patients with carpal tunnel syndrome: median nerve mobilization versus medical treatment

    Directory of Open Access Journals (Sweden)

    Faten I Mohamed

    2016-01-01

    Conclusion CTS improves after median nerve mobilization, which is better than conventional medical treatment. It provides support for the use of manual therapy in conservative management of CTS with satisfactory Results .

  6. Lumbar segmental instability: a criterion-related validity study of manual therapy assessment

    Directory of Open Access Journals (Sweden)

    Chapple Cathy

    2005-11-01

    Full Text Available Abstract Background Musculoskeletal physiotherapists routinely assess lumbar segmental motion during the clinical examination of a patient with low back pain. The validity of manual assessment of segmental motion has not, however, been adequately investigated. Methods In this prospective, multi-centre, pragmatic, diagnostic validity study, 138 consecutive patients with recurrent or chronic low back pain (R/CLBP were recruited. Physiotherapists with post-graduate training in manual therapy performed passive accessory intervertebral motion tests (PAIVMs and passive physiological intervertebral motion tests (PPIVMs. Consenting patients were referred for flexion-extension radiographs. Sagittal angular rotation and sagittal translation of each lumbar spinal motion segment was measured from these radiographs, and compared to a reference range derived from a study of 30 asymptomatic volunteers. Motion beyond two standard deviations from the reference mean was considered diagnostic of rotational lumbar segmental instability (LSI and translational LSI. Accuracy and validity of the clinical assessments were expressed using sensitivity, specificity, and likelihood ratio statistics with 95% confidence intervals (CI. Results Only translation LSI was found to be significantly associated with R/CLBP (p Conclusion This study provides the first evidence reporting the concurrent validity of manual tests for the detection of abnormal sagittal planar motion. PAIVMs and PPIVMs are highly specific, but not sensitive, for the detection of translation LSI. Likelihood ratios resulting from positive test results were only moderate. This research indicates that manual clinical examination procedures have moderate validity for detecting segmental motion abnormality.

  7. Manual hyperinflation and the role of physical therapy in intensive care and emergency units

    Directory of Open Access Journals (Sweden)

    Rafael Vinícius Santos Cruz

    Full Text Available Abstract Introduction: Although manual hyperinflation (MHI is a physical therapy technique commonly used in intensive care and emergency units, there is little consensus about its use. Objective: To investigate the knowledge of physical therapists working in intensive care and emergency units about manual hyperinflation. Methods: Data were collected through self-administered questionnaires on manual hyperinflation. Data collection took place between September 2014 and January 2015, in Itabuna and Ilhéus, Bahia, Brazil. Results: The study sample was composed of 32 physical therapists who had between 4 months and 10 years working experience. All respondents affirmed that they used the technique in their professional practice. However, only 34.4% reported it to be a routine practice. 90.6% stated that the most common patient position during manual hyperinflation is “supine”. Participants were almost unanimous (93.8% in citing secretion removal and cough stimulation as perceived benefits of MHI. High peak airway pressure was identified as being a precaution to treatment with MHI by 84.4% of participants, whilst 100% of the sample agreed that an undrained pneumothorax was a contraindication to MHI. Conclusion: The most common answers to the questionnaire were: supine position during MHI; secretion removal and cough stimulation as perceived benefits; high peak airway pressure as a precaution; and an undrained pneumothorax as a contraindication.

  8. Case report: manualized trauma-focused cognitive behavioral therapy with an unaccompanied refugee minor girl.

    Science.gov (United States)

    Unterhitzenberger, Johanna; Rosner, Rita

    2016-01-01

    There is uncertainty whether young traumatized refugees should be treated with culturally adapted psychotherapy or with an evidence-based western approach. As yet, empirical studies on culturally adapted treatments for unaccompanied young refugees in industrialized host countries are not available. Studies do, however, suggest that trauma-focused treatment is promising for this group. We describe the treatment of an unaccompanied refugee minor girl with posttraumatic stress disorder (PTSD) who underwent manualized trauma-focused cognitive behavioral therapy (TF-CBT; Cohen, Mannarino, & Deblinger, 2006). A 17-year-old girl from East Africa, who came to Germany without a caregiver, was treated for PTSD resulting from several traumatic experiences and losses in her home country and while fleeing. She lived in a group home for adolescents. Baseline, post, and follow-up data are reported. The girl participated in 12 sessions of manualized TF-CBT. Her caregiver from the youth services received another 12 sessions in line with the treatment manual. Symptoms decreased in a clinically significant manner; at the end of the treatment, the girl was deemed to have recovered from PTSD. Treatment success remained stable over 6 months. Manualized TF-CBT is feasible for young refugees without significant cultural adaptations. It can, however, be seen as culturally sensitive.

  9. Case report: manualized trauma-focused cognitive behavioral therapy with an unaccompanied refugee minor girl

    Directory of Open Access Journals (Sweden)

    Johanna Unterhitzenberger

    2016-01-01

    Full Text Available Background: There is uncertainty whether young traumatized refugees should be treated with culturally adapted psychotherapy or with an evidence-based western approach. As yet, empirical studies on culturally adapted treatments for unaccompanied young refugees in industrialized host countries are not available. Studies do, however, suggest that trauma-focused treatment is promising for this group. Objective: We describe the treatment of an unaccompanied refugee minor girl with posttraumatic stress disorder (PTSD who underwent manualized trauma-focused cognitive behavioral therapy (TF-CBT; Cohen, Mannarino, & Deblinger, 2006. Methods: A 17-year-old girl from East Africa, who came to Germany without a caregiver, was treated for PTSD resulting from several traumatic experiences and losses in her home country and while fleeing. She lived in a group home for adolescents. Baseline, post, and follow-up data are reported. Results: The girl participated in 12 sessions of manualized TF-CBT. Her caregiver from the youth services received another 12 sessions in line with the treatment manual. Symptoms decreased in a clinically significant manner; at the end of the treatment, the girl was deemed to have recovered from PTSD. Treatment success remained stable over 6 months. Conclusions: Manualized TF-CBT is feasible for young refugees without significant cultural adaptations. It can, however, be seen as culturally sensitive.

  10. Effects of Maitland manual therapy on the treatment of pain syndromes of the cervical spine

    Directory of Open Access Journals (Sweden)

    Ireneusz Dzierżek

    2017-03-01

    Full Text Available Introduction: The aim of this study was evaluate the effect of Maitland's manual therapy on selected motor function parameters in cervical spine pain syndromes. Material and Methods: 30 subjects were enrolled, in the age from 27 to 66, including 15 men and 15 women with chronic functional cervical spine syndrome who had a 10-day physiotherapy cycle that did not produce the expected results. The study included: pain assessment in the Dziak scale, measurements of mobility of the cervical spine and shoulder joints, functional evaluation by Hautanta, De`Klein, Jackson, and palpation of muscle irritation. Results: A comparison of average pain scores before and after therapy indicated that the pain level after treatment decreased (p 0.05. There has been a decrease in positive clinical trials and muscle irritation after therapy. Conclusions: Maitland manual therapy is effective in the treatment of cervical spine pain syndromes. The technique results in a significant increase in the mobility of the cervical spine as well as an improvement in the functional state of the cervical segment without affecting the mobility of the shoulder ridge. There was a decrease in palpate tenderness of the soft tissue studied.

  11. Efficacy of manual therapy in the treatment of tension-type headache. A systematic review from 2000-2013.

    Science.gov (United States)

    Lozano López, C; Mesa Jiménez, J; de la Hoz Aizpurúa, J L; Pareja Grande, J; Fernández de Las Peñas, C

    2016-01-01

    To study the efficacy of manual therapy in the treatment of tension-type headache (TTH) by assessing the quality of randomized control trials (RCTs) published from the year 2000 to April 2013. A search was performed in the following databases: MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO and OVID. An analysis was made of RCT including patients with TTH receiving any manual therapy, and assessing outcome measures including the intensity, and frequency or duration of the headache. Two independent referees reviewed the methodological quality of RCTs using the Jadad scale. Data from the studies were extracted by two different reviewers. A total of fourteen RCTs were selected. Twelve studies showed acceptable quality (Jadad scale ≥3), and the remaining 2 had low quality (Jadad=2). The studies showed positive results, including reduction in headache intensity and/or frequency, reduction of medication consumption, and improvement in quality of life. The effectiveness of manual therapy for TTH cannot be completely assessed due to the heterogeneity in study design, outcome measures, and different treatments. Nevertheless, the results suggest patients with TTH receiving manual therapies showed better progress than those receiving conventional treatment or placebo. Further studies of high quality using manual therapy protocols, and also including standardized outcome measures, are now needed to clarify the efficacy of manual therapy in the management of TTH. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Comparative study between the effects of isolated manual therapy techniques and those associated with low level laser therapy on pain in patients with temporomandibular dysfunction

    Directory of Open Access Journals (Sweden)

    Juliana Cristina Frare

    2008-01-01

    Full Text Available Objective: This study sought to evaluate the pain condition in patients with temporomandibular dysfunction after applying manual therapy techniques and those associated with this low level laser therapy. Methods: The study involved 20 patients with temporomandibular dysfunction, divided randomly into two groups: G1 (n = 10, formed by 7 women and 3 men, average age 28.2 years (± 7, treated with manual therapy techniques and G2 (n = 10, formed by 8 women and 2 men, with average age 24.01 (± 6.04, treated with the combination of manual therapy techniques and low level laser therapy. The patients were treated three times a week for four consecutive weeks. The memorandum of manual therapy techniques based on Chaintow,Makofsky and Bienfaint was used. For low level laser therapy GaAs laser (904 nm, 6 J/cm2, 0.38 mW/cm2 was used, applied at 4pre-auricular points. To analyze the pain level, the visual analog pain scale was used. For data analysis the Student’s-t and Wilcoxon tests were used, both with significance level of 5% (p <0.05.Results: There was significant reduction (p <0.05 in the level of pain in both groups treated, but in G2 the significance was higher.Conclusion: Manual therapy techniques, either alone or associated with low level laser therapy showed satisfactory results for pain control in patients with temporomandibular dysfunction.

  13. Inflammation as target in cancer therapy.

    Czech Academy of Sciences Publication Activity Database

    Marelli, G.; Sica, A.; Vannucci, Luca; Allavena, P.

    2017-01-01

    Roč. 35, August 2017 (2017), s. 57-65 ISSN 1471-4892 Institutional support: RVO:61388971 Keywords : cancer therapy * cancer-promoting inflammation * Tumour-Associated Macrophages Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 5.363, year: 2016

  14. Hitting the target with antithrombotic therapy.

    Science.gov (United States)

    Fritsma, Margaret G; Rodak, Bernadette F

    2007-05-01

    Thrombus treatment and prevention can be regulated by a number of intravenous or subcutaneous drugs, as well as oral warfarin. Many therapies require laboratory monitoring for efficacy and for detection of dangerous sequelae, such as bleeding, thrombosis, or heparin induced thrombocytopenia.

  15. Group cognitive-behavioral therapy for depression in Spanish: culture-sensitive manualized treatment in practice.

    Science.gov (United States)

    Aguilera, Adrian; Garza, Monica J; Muñoz, Ricardo F

    2010-08-01

    The authors applied cognitive-behavioral therapy (CBT) for depression using the Healthy Management of Reality treatment manual. This 16-week group treatment comprised four 4-week modules: thoughts (cognitive restructuring), activities (behavioral activation), people (interpersonal skills training), and health (addresses physical health and depression). They illustrated the use of the culture-sensitive treatment manuals by way of the member characteristics and clinical process of a Spanish-language CBT group for depression. They highlighted the challenges and satisfactions of working with a Spanish-speaking population in the public sector, and focused on how culture and socioeconomic status influence patients, and how to adapt treatment to these factors. Last, they demonstrated how technological advances integrate with culture-sensitive, evidence-based treatments to better serve this population and reduce disparities.

  16. Group Cognitive-Behavioral Therapy for Depression in Spanish: Culture-Sensitive Manualized Treatment in Practice

    Science.gov (United States)

    Aguilera, Adrian; Garza, Monica J.; Muñoz, Ricardo F.

    2014-01-01

    The authors applied cognitive-behavioral therapy (CBT) for depression using the Healthy Management of Reality treatment manual. This 16-week group treatment comprised four 4-week modules: thoughts (cognitive restructuring), activities (behavioral activation), people (interpersonal skills training), and health (addresses physical health and depression). They illustrated the use of the culture-sensitive treatment manuals by way of the member characteristics and clinical process of a Spanish-language CBT group for depression. They highlighted the challenges and satisfactions of working with a Spanish-speaking population in the public sector, and focused on how culture and socioeconomic status influence patients, and how to adapt treatment to these factors. Last, they demonstrated how technological advances integrate with culture-sensitive, evidence-based treatments to better serve this population and reduce disparities. PMID:20549680

  17. Emission of Biophotons and Adjustable Sounds by the Fascial System: Review and Reflections for Manual Therapy.

    Science.gov (United States)

    Bordoni, Bruno; Marelli, Fabiola; Morabito, Bruno; Sacconi, Beatrice

    2018-01-01

    Every body structure is wrapped in connective tissue or fascia, creating a structural continuity that gives form and function to every tissue and organ. The fascial tissue is uniformly distributed throughout the body, enveloping, interacting with and permeating blood vessels, nerves, viscera, meninges, bones and muscles, creating various layers at different depths and forming a tridimensional metabolic and mechanical matrix. This article reviews the literature on the emission of biophotons and adjustable sounds by the fascial system, because these biological changes could be a means of local and systemic cellular communication and become another assessment tool for manual (therapy) practitioners. This is the first article that discusses these topics in a single text, attempting to bring such information into an area of application that is beneficial to osteopaths, chiropractors, and manual therapists.

  18. MSCT follow-up in malignant lymphoma. Comparison of manual linear measurements with semi-automated lymph node analysis for therapy response classification

    International Nuclear Information System (INIS)

    Wessling, J.; Puesken, M.; Kohlhase, N.; Persigehl, T.; Mesters, R.; Heindel, W.; Buerke, B.; Koch, R.

    2012-01-01

    Purpose: Assignment of semi-automated lymph node analysis compared to manual measurements for therapy response classification of malignant lymphoma in MSCT. Materials and Methods: MSCT scans of 63 malignant lymphoma patients before and after 2 cycles of chemotherapy (307 target lymph nodes) were evaluated. The long axis diameter (LAD), short axis diameter (SAD) and bi-dimensional WHO were determined manually and semi-automatically. The time for manual and semi-automatic segmentation was evaluated. The ref. standard response was defined as the mean relative change across all manual and semi-automatic measurements (mean manual/semi-automatic LAD, SAD, semi-automatic volume). Statistical analysis encompassed t-test and McNemar's test for clustered data. Results: Response classification per lymph node revealed semi-automated volumetry and bi-dimensional WHO to be significantly more accurate than manual linear metric measurements. Response classification per patient based on RECIST revealed more patients to be correctly classified by semi-automatic measurements, e.g. 96.0 %/92.9 % (WHO bi-dimensional/volume) compared to 85.7/84.1 % for manual LAD and SAD, respectively (mean reduction in misclassified patients of 9.95 %). Considering the use of correction tools, the time expenditure for lymph node segmentation (29.7 ± 17.4 sec) was the same as with the manual approach (29.1 ± 14.5 sec). Conclusion: Semi-automatically derived 'lymph node volume' and 'bi-dimensional WHO' significantly reduce the number of misclassified patients in the CT follow-up of malignant lymphoma by at least 10 %. However, lymph node volumetry does not outperform bi-dimensional WHO. (orig.)

  19. MSCT follow-up in malignant lymphoma. Comparison of manual linear measurements with semi-automated lymph node analysis for therapy response classification

    Energy Technology Data Exchange (ETDEWEB)

    Wessling, J.; Puesken, M.; Kohlhase, N.; Persigehl, T.; Mesters, R.; Heindel, W.; Buerke, B. [Muenster Univ. (Germany). Dept. of Clinical Radiology; Koch, R. [Muenster Univ. (Germany). Inst. of Biostatistics and Clinical Research

    2012-09-15

    Purpose: Assignment of semi-automated lymph node analysis compared to manual measurements for therapy response classification of malignant lymphoma in MSCT. Materials and Methods: MSCT scans of 63 malignant lymphoma patients before and after 2 cycles of chemotherapy (307 target lymph nodes) were evaluated. The long axis diameter (LAD), short axis diameter (SAD) and bi-dimensional WHO were determined manually and semi-automatically. The time for manual and semi-automatic segmentation was evaluated. The ref. standard response was defined as the mean relative change across all manual and semi-automatic measurements (mean manual/semi-automatic LAD, SAD, semi-automatic volume). Statistical analysis encompassed t-test and McNemar's test for clustered data. Results: Response classification per lymph node revealed semi-automated volumetry and bi-dimensional WHO to be significantly more accurate than manual linear metric measurements. Response classification per patient based on RECIST revealed more patients to be correctly classified by semi-automatic measurements, e.g. 96.0 %/92.9 % (WHO bi-dimensional/volume) compared to 85.7/84.1 % for manual LAD and SAD, respectively (mean reduction in misclassified patients of 9.95 %). Considering the use of correction tools, the time expenditure for lymph node segmentation (29.7 {+-} 17.4 sec) was the same as with the manual approach (29.1 {+-} 14.5 sec). Conclusion: Semi-automatically derived 'lymph node volume' and 'bi-dimensional WHO' significantly reduce the number of misclassified patients in the CT follow-up of malignant lymphoma by at least 10 %. However, lymph node volumetry does not outperform bi-dimensional WHO. (orig.)

  20. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-12-01

    deprivation therapy (ADT) or androgen receptor (AR) pathway inhibition (ARPI) but eventually develops into lethal castration resistance prostate cancer ...AWARD NUMBER: W81XWH-14-1-0553 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Gleave...Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0553 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Martin Gleave 5d

  1. Targeting the Thioredoxin System for Cancer Therapy.

    Science.gov (United States)

    Zhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, Jianguo

    2017-09-01

    Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Does an online psychological intervention improve self-efficacy and disability in people also receiving Multimodal Manual Therapy for chronic low back pain compared to Multimodal Manual Therapy alone? Design of a randomized controlled trial

    NARCIS (Netherlands)

    Petrozzi, M.J.; Leaver, A.; Jones, M.K.; Ferreira, P.H.; Rubinstein, S.M.; Mackey, M.G.

    2015-01-01

    Background: Various interventions are available for the treatment of chronic low back pain (LBP), including Manual Therapy and Cognitive Behavioural Therapy (CBT). The purpose of this study is to evaluate whether the addition of an internet-based CBT program leads to better outcomes in patients who

  3. The effects of sustained manual pressure stimulation according to Vojta Therapy on heart rate variability.

    Science.gov (United States)

    Opavsky, Jaroslav; Slachtova, Martina; Kutin, Miroslav; Hok, Pavel; Uhlir, Petr; Opavska, Hana; Hlustik, Petr

    2018-05-23

    The physiotherapeutic technique of Vojta reflex locomotion is often accompanied by various autonomic activity changes and unpleasant sensations. It is unknown whether these effects are specific to Vojta Therapy. Therefore, the aim of this study was to compare changes in cardiac autonomic control after Vojta reflex locomotion stimulation and after an appropriate sham stimulation. A total of 28 young healthy adults (20.4 - 25.7 years) were enrolled in this single-blind randomized cross-over study. Participants underwent two modes of 20-minute sustained manual pressure stimulation on the surface of the foot on two separate visits. One mode used manual pressure on the lateral heel, i.e., in a zone employed in the Vojta Therapy (active stimulation). The other mode used pressure on the lateral ankle (control), in an area not included among the active zones used by Vojta Therapy and whose activation does not evoke manifestations of reflex locomotion. Autonomic nervous system activity was evaluated using spectral analysis of heart rate variability before and after the intervention. The active stimulation was perceived as more unpleasant than the control stimulation. Heart rate variability parameters demonstrated almost identical autonomic responses after both stimulation types, showing either modest increase in parasympathetic activity, or increased heart rate variability with similar contribution of parasympathetic and sympathetic activity. The results demonstrate changes of cardiac autonomic control in both active and control stimulation, without evidence for a significant difference between the two.

  4. Immunological targeting of cytomegalovirus for glioblastoma therapy

    OpenAIRE

    Nair, Smita K; Sampson, John H; Mitchell, Duane A

    2014-01-01

    Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are capable of recognizing and killing autologous GBM tumor cells. This data supports CMV antigen-directed immunotherapies against GBM.

  5. Bacterial proteases: targets for diagnostics and therapy

    NARCIS (Netherlands)

    Kaman, W.E.; Hays, J.P.; Endtz, H.P.; Bikker, F.J.

    2014-01-01

    Proteases are essential for the proliferation and growth of bacteria, and are also known to contribute to bacterial virulence. This makes them interesting candidates as diagnostic and therapeutic targets for infectious diseases. In this review, the authors discuss the most recent developments and

  6. An online community of practice to support evidence-based physiotherapy practice in manual therapy.

    Science.gov (United States)

    Evans, Cathy; Yeung, Euson; Markoulakis, Roula; Guilcher, Sara

    2014-01-01

    The purpose of this study was to explore how a community of practice promoted the creation and sharing of new knowledge in evidence-based manual therapy using Wenger's constructs of mutual engagement, joint enterprise, and shared repertoire as a theoretical framework. We used a qualitative approach to analyze the discussion board contributions of the 19 physiotherapists who participated in the 10-week online continuing education course in evidence-based practice (EBP) in manual therapy. The course was founded on community of practice, constructivism, social, and situated learning principles. The 1436 postings on 9 active discussion boards revealed that the community of practice was a social learning environment that supported strong participation and mutual engagement. Design features such as consistent facilitation, weekly guiding questions, and collaborative assignments promoted the creation and sharing of knowledge. Participants applied research evidence to the contexts in which they worked through reflective comparison of what they were reading to its applicability in their everyday practice. Participants' shared goals contributed to the common ground established in developing collective knowledge about different study designs, how to answer research questions, and the difficulties of conducting sound research. An online longitudinal community of practice utilized as a continuing education approach to deliver an online course based on constructivist and social learning principles allowed geographically dispersed physiotherapists to be mutually engaged in a joint enterprise in evidence-based manual therapy. Advantages included opportunity for reflection, modeling, and collaboration. Future studies should examine the impact of participation on clinical practice. © 2014 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on Continuing Medical Education, Association for Hospital

  7. Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome.

    Science.gov (United States)

    Weiss, J M

    2001-12-01

    The effectiveness of manual physical therapy was evaluated in patients with interstitial cystitis and the urethral syndrome, that is urgency-frequency with or without pelvic pain. The rationale was based on the hypothesis that pelvic floor myofascial trigger points are not only a source of pain and voiding symptoms, but also a trigger for neurogenic bladder inflammation via antidromic reflexes. From September 1995 to November 2000, 45 women and 7 men, including 10 with interstitial cystitis and 42 with the urgency-frequency syndrome, underwent manual physical therapy to the pelvic floor for 1 to 2 visits weekly for 8 to 12 weeks. Results were determined by patient completed symptom score sheets indicating the rate of improvement according to outcome parameters, including 25% to 50%-mild, 51% to 75%-moderate, 76% to 99%-marked and 100%-complete resolution. In 10 cases these subjective results were confirmed by measuring resting pelvic floor tension by electromyography before and after the treatment course. Of the 42 patients with the urgency-frequency syndrome with or without pain 35 (83%) had moderate to marked improvement or complete resolution, while 7 of the 10 (70%) with interstitial cystitis had moderate to marked improvement. The mean duration of symptoms before treatment in those with interstitial cystitis and the urgency-frequency syndrome was 14 (median 12) and 6 years (median 2.5), respectively. In patients with no symptoms or brief, low intensity flares mean followup was 1.5 years. In 10 patients who underwent electromyography mean resting pelvic floor tension decreased from 9.73 to 3.61 microV., which was a 65% improvement. Pelvic floor manual therapy for decreasing pelvic floor hypertonus effectively ameliorates the symptoms of the urgency/frequency syndrome and interstitial cystitis.

  8. Identification of the feedforward component in manual control with predictable target signals.

    Science.gov (United States)

    Drop, Frank M; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus M; Mulder, Max

    2013-12-01

    In the manual control of a dynamic system, the human controller (HC) often follows a visible and predictable reference path. Compared with a purely feedback control strategy, performance can be improved by making use of this knowledge of the reference. The operator could effectively introduce feedforward control in conjunction with a feedback path to compensate for errors, as hypothesized in literature. However, feedforward behavior has never been identified from experimental data, nor have the hypothesized models been validated. This paper investigates human control behavior in pursuit tracking of a predictable reference signal while being perturbed by a quasi-random multisine disturbance signal. An experiment was done in which the relative strength of the target and disturbance signals were systematically varied. The anticipated changes in control behavior were studied by means of an ARX model analysis and by fitting three parametric HC models: two different feedback models and a combined feedforward and feedback model. The ARX analysis shows that the experiment participants employed control action on both the error and the target signal. The control action on the target was similar to the inverse of the system dynamics. Model fits show that this behavior can be modeled best by the combined feedforward and feedback model.

  9. Energy costs of manual therapy: effects of plinth height and an assistive device.

    Science.gov (United States)

    O'Connell, D G; Holmes, C F; Santos, J L; Jordan, E; Acosta, F

    1994-01-01

    The purpose of this investigation was to examine the metabolic and cardiopulmonary responses of an experienced therapist (8 years experience) performing manual therapy at standard (S) plinth height (31 in), elevated (E) plinth height (38 in), and standard (SMTH) and elevated (EMTH) plinth height wearing a manual therapy harness (MTH). The MTH, developed by one of the investigators (J.L.S.), is a vestlike device worn by the therapist, which, when attached to the patient, can be used to distract articular surfaces. The MTH allows the therapist more freedom of hand movement and use of body weight to help provide joint distraction. Inferior glide (Grade 3-Maitland) was provided to the lift hip of 12 individuals at a rate of 20 oscillations per minute for 4 minutes, continuously, so that steady-rate metabolic conditions could be established. Mean body mass and height for the 12 individuals was 70±10.5 kg and 174.5±13 cm, respectively. The therapist's heart rate returned to resting levels between each of the randomly assigned treatments. One subject was treated daily. The therapist (age 32) was chosen because of his clinical experience, similar height (172 em) and weight (73 kg) to the average adult American male, and excellent intra- and interday (5%≤ METs, 5%≤ HR) reproducibility. Metabolic equivalents (METs), heart rate (HR), and rate of perceived exertion (RPE) were measured and averaged for the last 2 minutes of each treatment condition. The therapist was unaware of day-to-day test results except for RPE. Mean METs were 3. 7,3.2,2.6, and 2.4 for S, E, SMTH, and EMTH, respectively. Mean HRs were .117, 110, 104, and 93 beats/min for S, E, SMTH, and EMTH, respectively. RPE was 11. 0,8.7, 7.9, and 7.3jorS, E, SMTH, and EMTH, respectively. Repeated-measures analysis of variance (Scheffé F-test) revealed that SMTH and EMTH METs were similar, and significantly different (p≤0.05) from Sand E. METs for E were significantly different and lower than for S. HRs were

  10. Immediate Changes After Manual Therapy in Patients With Persistent, Nonspecific Back Pain: A Randomized Controlled Trial.

    Science.gov (United States)

    Espí-López, Gemma Victoria; Ruescas-Nicolau, Maria-Arantzazu; Sanchez-Sanchez, M Luz; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Marques-Sule, Elena

    2018-02-10

    Context • Thoracic manipulation decreases pain and disability. However, when such manipulation is contraindicated, the use of other manual techniques based on the regional interdependence of the thoracic spine, upper ribs, and shoulders is an alternative approach. Objective • The study intended to investigate the immediate changes resulting from 3 manual therapy treatments on spinal mobility, flexibility, comfort, and pain perception in patients with persistent, nonspecific back pain as well as changes in their sense of physical well-being and their perception of change after treatment. Design • The study was a randomized, double-blind, controlled trial. Setting • The study took place in the Department of Physiotherapy of the Faculty of Physiotherapy at the University of Valencia (Valencia, Spain). Participants • Participants were 112 individuals from the community-56.6% female, with a mean age of 21.8 ± 0.2 y-who had persistent, nonspecific back pain. Intervention • Participants were randomly assigned to 1 of 3 groups, receiving (1) neurolymphatic therapy (NL group), (2) articulatory spinal manual therapy (AS group), or (3) articulatory costal manual therapy (AC group). Outcome Measures • Cervical mobility, lumbar flexibility, comfort, pain perception, and physical well-being were assessed at baseline and immediately postintervention. Perception of change was evaluated postintervention. Results • Between baseline and postintervention, the AC group showed a significant increase in cervical flexion (P = .010), whereas the NL and AS groups improved in lumbar flexibility, P = .047 and P = .012, respectively. For that period, significant changes were found in lumbar comfort for the AS group (P < .001) and the NL group (P < .026) and in thoracic comfort (P < .001) for the AC group. All groups improved in physical well-being and pain perception (P < .05). Changes in thoracic comfort, lumbar comfort, and physical well-being differed among the groups, with

  11. Effectiveness of manual therapy versus surgery in pain processing due to carpal tunnel syndrome: A randomized clinical trial.

    Science.gov (United States)

    Fernández-de-Las-Peñas, C; Cleland, J; Palacios-Ceña, M; Fuensalida-Novo, S; Alonso-Blanco, C; Pareja, J A; Alburquerque-Sendín, F

    2017-08-01

    People with carpal tunnel syndrome (CTS) exhibit widespread pressure pain and thermal pain hypersensitivity as a manifestation of central sensitization. The aim of our study was to compare the effectiveness of manual therapy versus surgery for improving pain and nociceptive gain processing in people with CTS. The trial was conducted at a local regional Hospital in Madrid, Spain from August 2014 to February 2015. In this randomized parallel-group, blinded, clinical trial, 100 women with CTS were randomly allocated to either manual therapy (n = 50), who received three sessions (once/week) of manual therapies including desensitization manoeuvres of the central nervous system, or surgical intervention (n = 50) group. Outcomes including pressure pain thresholds (PPT), thermal pain thresholds (HPT or CPT), and pain intensity which were assessed at baseline, and 3, 6, 9 and 12 months after the intervention by an assessor unaware of group assignment. Analysis was by intention to treat with mixed ANCOVAs adjusted for baseline scores. At 12 months, 95 women completed the follow-up. Patients receiving manual therapy exhibited higher increases in PPT over the carpal tunnel at 3, 6 and 9 months (all, p < 0.01) and higher decrease of pain intensity at 3 month follow-up (p < 0.001) than those receiving surgery. No significant differences were observed between groups for the remaining outcomes. Manual therapy and surgery have similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with CTS. Neither manual therapy nor surgery resulted in changes in thermal pain sensitivity. The current study found that manual therapy and surgery exhibited similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with carpal tunnel syndrome at medium- and long-term follow-ups investigating changes in nociceptive gain processing after treatment in carpal tunnel syndrome. © 2017 European Pain Federation - EFIC®.

  12. Hepatocarcinoma: from pathogenic mechanisms to target therapy

    Directory of Open Access Journals (Sweden)

    Luigi Manzione

    2011-12-01

    Full Text Available Hepatocellular carcinoma (HCC is among the most prevalent and lethal cancers worldwide. It is currently estimated that there are 14,000–18,000 new cases of hepatocellular carcinoma in the United States each year. It is often difficult to identify individuals at risk for HCC. The main associated diseases are chronic hepatitis B and chronic hepatitis C viral infections. While a significant number of potential mutations have been generated including p53 and Insulin-like Growth Factor, our understanding of the molecular mechanisms driving the genesis and progression of HCC remain limited. HCC screening is recommended in high-risk patients. High-risk patients include virtually all patients with cirrhosis and some HBV-infected patients irrespective of cirrhosis (>40 years in men and >50 years in women. A diagnostic approach to HCC has been developed incorporating serology, cytohistology, and radiological characteristics. A precise staging of the disease may help decide on prognosis as well as choice of therapy with the greatest survival potential. Liver transplantation, in theory, is the optimal therapeutic option for HCC; it simultaneously removes the tumor and underlying cirrhosis thus minimizing the risk of HCC recurrence. When it is impossible for this to be performed, percutaneous ablation, chemoembolization, chemotherapy and the newer molecular therapies can be used. Sorafenib is the only drug registered today for the treatment of advanced HCC.

  13. 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

  14. Design of a cryogenic deuterium gas target for neutron therapy

    International Nuclear Information System (INIS)

    Kuchnir, F.T.; Waterman, F.M.; Forsthoff, H.; Skaggs, L.S.; Vander Arend, P.C.; Stoy, S.

    1976-01-01

    A cryogenic deuterium gas target operating at 80 0 K and 10 atm pressure has been designed for use with a small cyclotron; the D(d,n) reaction is used to produce a neutron beam suitable for radiation therapy. The target is cooled by circulation of the gas in a closed loop between the target and an external heat exchanger immersed in liquid nitrogen

  15. Targeted therapy in lung and breast cancer: a big deal

    OpenAIRE

    Caffarra, Cristina

    2015-01-01

    Great strides have been done in treating cancer. For decades, the hallmark of medical treatment for cancer has been intravenous cytotoxic chemotherapy which targets all dividing cells. In the last ten years the identification of different driver oncogenic mutations has allowed the development of targeted drugs. Targeted cancer therapies are based on the use of drugs that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. The ...

  16. Novel targeted therapies for cancer cachexia.

    Science.gov (United States)

    Argilés, Josep M; López-Soriano, Francisco Javier; Stemmler, Britta; Busquets, Sílvia

    2017-07-27

    Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations are involved in the development of cancer cachexia, a multi-organ syndrome. Nutritional approach strategies are not satisfactory in reversing the cachectic syndrome. The aim of the present review is to deal with the recent therapeutic targeted approaches that have been designed to fight and counteract wasting in cancer patients. Indeed, some promising targeted therapeutic approaches include ghrelin agonists, selective androgen receptor agonists, β-blockers and antimyostatin peptides. However, a multi-targeted approach seems absolutely essential to treat patients affected by cancer cachexia. This approach should not only involve combinations of drugs but also nutrition and an adequate program of physical exercise, factors that may lead to a synergy, essential to overcome the syndrome. This may efficiently reverse the metabolic changes described above and, at the same time, ameliorate the anorexia. Defining this therapeutic combination of drugs/nutrients/exercise is an exciting project that will stimulate many scientific efforts. Other aspects that will, no doubt, be very important for successful treatment of cancer wasting will be an optimized design of future clinical trials, together with a protocol for staging cancer patients in relation to their degree of cachexia. This will permit that nutritional/metabolic/pharmacological support can be started early in the course of the disease, before severe weight loss occurs. Indeed, timing is crucial and has to be taken very seriously when applying the therapeutic approach. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  17. Radiolabelled peptides: New radiopharmaceuticals for targeted therapy

    International Nuclear Information System (INIS)

    Chinol, M.

    2001-01-01

    Radiolabelled peptides have been the focus of an increasing interest by the nuclear medicine community within the last few years. This has mainly been due to successful development of one of these peptides, somatostatin, as a tool to visualise various pathologic conditions known to express a high number of somatostatin receptors. Somatostatin receptors have been identified in different tumours such as neuroendocrine tumours, tumours of the central nervous system, breast, lung and lymphatic tissue. These observations served as the biomolecular basis for the clinical use of radiolabelled somatostatin analogs, which are at present of great interest for diagnostic and therapeutic applications. A promising somatostatin analogue, DOTA-D-Phe 1 -Ty 3 -octreotide, named DOTATOC, has shown favourable biodistribution and high affinity binding to SSTR2 and SSTR5, high hydrophilicity and ease of labelling and stability with 111 In and 90 Y. A clinical trial aimed at evaluating the biodistribution and dosimetry of DOTATOC radiolabelled with 111 In, in anticipation of therapy trials with 90 Y-DOTATOC in patients was undertaken. 111 In-DOTATOC showed favourable pharmacokinetics (fast blood clearance and urinary excretion) and biodistribution, and high affinity to tumours expressing somatostatin receptors (thus, a high residence time in tumour). These results are promising for therapy trials with 90 Y-DOTAOC, for which radiation dosimetry appears acceptable for normal organs (including the red marrow). Moreover, labelling conditions of DOTATOC with 90 Y has been optimised in order to achieve labelling yields of more than 98% and specific activities of greater than 60 GBq (1.6 Ci)/μmol. (author)

  18. Molecular targeted therapies of aggressive thyroid cancer

    Directory of Open Access Journals (Sweden)

    Silvia Martina eFerrari

    2015-11-01

    Full Text Available Differentiated thyroid carcinomas (DTC that arise from follicular cells account > 90% of thyroid cancer (TC [papillary thyroid cancer (PTC 90%, follicular thyroid cancer (FTC 10%], while medullary thyroid cancer (MTC accounts < 5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts towards the development of new drugs.Several genetic alterations in different molecular pathways in TC have been shown in the last decades, associated with TC development and progression. Rearranged during transfection (RET/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the above-mentioned molecular pathways involved in growth, angiogenesis, local and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC and anaplastic thyroid cancer (ATC, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds, and to personalize

  19. Biomarkers and Targeted Therapy in Pancreatic Cancer

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    Fataneh Karandish

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  20. Biomarkers and Targeted Therapy in Pancreatic Cancer.

    Science.gov (United States)

    Karandish, Fataneh; Mallik, Sanku

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%-3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  1. Initial Sleep Time Predicts Success in Manual-Guided Cognitive Behavioral Therapy for Insomnia.

    Science.gov (United States)

    Bothelius, Kristoffer; Kyhle, Kicki; Broman, Jan-Erik; Gordh, Torsten; Fredrikson, Mats

    2016-01-01

    Cognitive behavioral therapy produces significant and long-lasting improvement for individuals with insomnia, but treatment resources are scarce. A "stepped care" approach has therefore been proposed, but knowledge is limited on how to best allocate patients to different treatment steps. In this study, 66 primary-care patients with insomnia attended a low-end treatment step: manual-guided cognitive behavioral therapy (CBT) for insomnia delivered by ordinary primary-care personnel. Based on clinically significant treatment effects, subjects were grouped into treatment responders or nonresponders. Baseline data were analyzed to identify predictors for treatment success. Long total sleep time at baseline assessment was the only statistically significant predictor for becoming a responder, and sleep time may thus be important to consider before enrolling patients in low-end treatments.

  2. Apoptosis and Molecular Targeting Therapy in Cancer

    Science.gov (United States)

    Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

  3. Targeted therapy for esophagogastric cancers: a review

    Directory of Open Access Journals (Sweden)

    Khattak MA

    2012-05-01

    Full Text Available Muhammad A Khattak,1 Hilary L Martin,2 Christos S Karapetis1,31Flinders Medical Centre, Adelaide, South Australia; 2Calvary Hospital, Adelaide, SA, Australia; 3Flinders University, Adelaide, SA, AustraliaAbstract: The incidence of esophagogastric cancers is increasing rapidly in the Western population. Despite better understanding of the biology and intense research in the treatment of these cancers, the long-term survival remains poor both in the locally advanced and metastatic settings. The addition of combined modality strategies has resulted in modest improvement in 5-year survival rates. A number of biologic agents targeting epidermal-derived growth factor receptor, vascular endothelial derived growth factor and its receptor, and mammalian target of rapamycin (mTOR are being currently evaluated in Phase II and III clinical trials. Some of these, like trastuzumab, cetuximab, and bevacizumab, have shown promising results. This review provides a brief overview of the recent developments in biologic agents for the treatment of esophagogastric cancers.Keywords: adenocarcinoma, squamous cell carcinoma, VEGF, trastuzumab, Her2- positive EGC

  4. Neoadjuvant targeted therapy in patients with renal cell carcinoma

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    B. Ya. Alekseev

    2015-01-01

    Full Text Available Cytoreductive nephrectomy as an independent option in patients with metastatic renal cell carcinoma (mRCC cannot be considered as the only effective method, with rare exception, of a few patients with solitary metastases. Cytoreductive nephrectomy is now part of a multimodal approach encompassing surgical treatment and systemic drug therapy. Many retrospective and two prospective studies have demonstrated that it is expedient to perform cytoreductive nephrectomy. Immunotherapy should not be used as preoperatively in the era of cytokine therapy for mRCC due to that fact that it has no impact on primary tumor. In the current targeted therapy era, many investigators have concentrated attentionon the role of neoadjuvant targeted therapy for the treatment of patients with both localized and locally advanced mRCC. The potential benefits of neoadjuvant therapy for localized and locally advanced RCC include to make surgery easier and to increase the possibility of organsparing treatment, by decreasing the stage of primary tumor and the size of tumors. The possible potential advantages of neoadjuvant targeted therapy in patients with mRCC include prompt initiation of necessary systemic therapy; identification of patients with primary refractory tumors; and a preoperative reduction in the stage of primary tumor. Numerous retrospective and some prospective phase II studies have shown that neoadjuvant targeted therapy in patients with localized and locally advanced RCC is possible and tolerable and surgical treatment after neoadjuvant targeted therapy is safe and executable with a low incidence of complications. If neoadjuvant therapy is to be performed, it should be done within 2–4 months before surgery. Sorafenib and sunitinib are now most tested and suitable for neoadjuvant targeted therapy. Sorafenib is a more preferred drug due to its shorter half-life and accordingly to the possibility of discontinuing the drug immediately prior to

  5. Manual therapy in the treatment of ankle hemophilic arthropathy. A randomized pilot study.

    Science.gov (United States)

    Cuesta-Barriuso, Rubén; Gómez-Conesa, Antonia; López-Pina, José-Antonio

    2014-11-01

    Although physiotherapy has demonstrated effectiveness in preventing ankle arthropathy compared to prophylaxis treatment from early ages, there have been no conclusive studies examining physiotherapy intervention once hemophilic arthropathy of the ankle has been established. The aim of this study was to evaluate the effectiveness of two physiotherapy interventions, in patients with hemophilic arthropathy of the ankle that had not been operated on previously. Nine patients with hemophilia (mean age of 35.7 SD 11.9 years) were randomized to a mobilization group (n = 5) and manual therapy group (n = 4). The two physiotherapy interventions were: (1) passive mobilization and stretching; and (2) manual orthopaedic therapy, both with proprioception training. The study lasted for six weeks, with two sessions a week. Ankle mobility and pain perception, lower limb proprioception and quality of life were the outcome measures. Both treatments improved all ankle movements (p ankle arthropathy. No haemarthrosis was recorded during treatment or during the follow-up period.

  6. PNF and manual therapy treatment results of patients with cervical spine osteoarthritis.

    Science.gov (United States)

    Maicki, Tomasz; Bilski, Jan; Szczygieł, Elżbieta; Trąbka, Rafał

    2017-09-22

    The aim of this study was to evaluate the effectiveness of PNF and manual therapy methods in the treatment of patients with cervical spine osteoarthritis, especially their efficacy in reducing pain and improving functionality in everyday life. Long-term results were also compared in order to determine which method of treatment is more effective. Eighty randomly selected females aged 45-65 were included in the study. They were randomly divided into two groups of 40 persons. One group received PNF treatment and the other received manual therapy (MAN.T). To evaluate functional capabilities, the Functional Rating Index was used. To evaluate changes in pain, a shortened version of the McGill Questionnaire was used. The PNF group achieved a greater reduction in pain than the MAN.T group. The PNF group showed a greater improvement in performing daily activities such as sleeping, personal care, travelling, work, recreation, lifting, walking and standing as well as decreased intensity and frequency of pain compared to the MAN.T group. The PNF method proved to be more effective in both short (after two weeks) and long (after three months) term.

  7. Treating Small Bowel Obstruction with a Manual Physical Therapy: A Prospective Efficacy Study

    Directory of Open Access Journals (Sweden)

    Amanda D. Rice

    2016-01-01

    Full Text Available Small bowel obstructions (SBOs caused by adhesions are a common, often life-threatening postsurgical complication with few treatment options available for patients. This study examines the efficacy of a manual physical therapy treatment regimen on the pain and quality of life of subjects with a history of bowel obstructions due to adhesions in a prospective, controlled survey based study. Changes in six domains of quality of life were measured via ratings reported before and after treatment using the validated Small Bowel Obstruction Questionnaire (SBO-Q. Improvements in the domains for pain (p=0.0087, overall quality of life (p=0.0016, and pain severity (p=0.0006 were significant when average scores before treatment were compared with scores after treatment. The gastrointestinal symptoms (p=0.0258 domain was marginally significant. There was no statistically significant improvement identified in the diet or medication domains in the SBO-Q for this population. Significant improvements in range of motion in the trunk (p≤0.001, often limited by adhesions, were also observed for all measures. This study demonstrates in a small number of subjects that this manual physical therapy protocol is an effective treatment option for patients with adhesive small bowel obstructions as measured by subject reported symptoms and quality of life.

  8. Shoulder functionality after manual therapy in subjects with shoulder impingement syndrome: a case series.

    Science.gov (United States)

    Heredia-Rizo, Alberto Marcos; López-Hervás, Antonia; Herrera-Monge, Patricia; Gutiérrez-Leonard, Ana; Piña-Pozo, Fernando

    2013-04-01

    The aim of the study was to identify the differences in functionality of the upper limb in subjects suffering from shoulder impingement syndrome after intervention by two manual therapy protocols. Randomized, single-blind study with a sample of 22 subjects (58 ± 10.86 years old) divided into two groups. The conventional-group (n = 11) received mobilizations of the shoulder and the experimental-group (n = 11) was treated with soft tissue techniques in the cervical and upper thoracic regions. These two groups received electrotherapy and postural advices. The treatment lasted three weeks (15 daily sessions of 1 h and 30 min). Both active and passive range of motion (ROM) and self-perceived functionality of the upper limb (DASH questionnaire) were measured. The experimental group showed a significant improvement in the DASH scores and both groups improved mobility in the intra-group comparison pre-intervention versus post-intervention (p .05). Our results suggest that a combined treatment with electrotherapy, postural hygiene and manual therapy, regardless of the protocol, improves shoulder mobility and functionality. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Work-related thumb disorders in South African physiotherapists treating musculoskeletal conditions using manual therapy techniques

    Directory of Open Access Journals (Sweden)

    Heather Jenkins

    2015-05-01

    Full Text Available Research question: What is the prevalence of and factors associated with work-related thumb problems (WRTP in South African physiotherapists treating musculoskeletal conditions using manual therapy techniques? Design: A cross-sectional, descriptive study design was used and data were collected using two Internet-based questionnaires. Participants: The sample size calculated for the study was 284 using 95% confidence levels and a 5% margin of error. There were 395 participants that were included in the study. Outcome measures: The variables measured included demographic, employment, educational and occupational factors. Results: The lifetime prevalence of WRTP in the physiotherapists was 65.3%. The manual techniques that were significantly associated with WRTP in the respondents who reported thumb problems were all grades of transverse glides applied to the spine as well as grade II–IV unilateral and central posterior-anterior pressures to the spine. The factors that remained significantly associated with WRTP in all 395 respondents after regression analysis were the cervical treatment of up to six patients a day and hyperextension > 30° of the non-dominant interphalangeal (IP joint of the thumb. Conclusion: This study confirms that a high percentage of physiotherapists using manual therapy techniques to treat musculoskeletal conditions are experiencing WRTP. Recommendations: The development of a valid and reliable WRTP screening tool is needed to aid in the identification of physiotherapists at risk and thus in the primary prevention of WRTP. A longitudinal study which follows newly qualified physiotherapists is recommended to investigate a possible cause-effect relationship and preventative strategies for WRTP in physiotherapists.

  10. A manual therapy and exercise approach to meralgia paresthetica in pregnancy: a case report

    Science.gov (United States)

    Skaggs, Clayton D.; Winchester, Brett A.; Vianin, Michael; Prather, Heidi

    2006-01-01

    Abstract Objective To present a case of a pregnant patient with meralgia paresthetica who improved using manual therapy and exercise procedures. Clinical Features A 22-year-old patient in the sixteenth week of pregnancy had low back pain, bilateral anterolateral thigh paresthesia and groin pain for a duration of 1 month. She had no motor deficits in either lower extremity and her reflexes were intact. As a standard clinic procedure, a battery of functional tests were performed including: active straight leg raise, long dorsal ligament test, and the pelvic pain provocation procedure. Based on her clinical history and physical responses to the aforementioned functional tests, the diagnosis of meralgia paresthetica was deduced. Intervention and Outcome Treatment was provided at 6 visits over a 6-week period where the patient underwent evaluation, manual intervention, and exercise prescription. Active Release Technique (ART) was performed to the restricted right sacroiliac (SIJ) complex and quadratus lumborum muscles. ART and post-isometric relaxation were applied to the illiopsoas muscles. The home exercise program consisted of pelvic/low back mobility, stabilization and relaxation exercises. After 6 treatments, the patient reported complete resolution of low back pain and left lower extremity symptoms and a 90% improvement in the right thigh symptoms. At her one-year follow-up, the patient reported no further complications and the absence of pain. Conclusions Manual therapy and exercises may serve as an effective treatment protocol for pregnant patients experiencing low back pain complicated by paresthesia. Because these conservative procedures offer a low-risk intervention, additional clinical studies are warranted to further study this treatment. PMID:19674679

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Inflammation as target in cancer therapy.

    Science.gov (United States)

    Marelli, Giulia; Sica, Antonio; Vannucci, Luca; Allavena, Paola

    2017-08-01

    Cells of the innate immunity infiltrating tumour tissues promote, rather than halt, cancer cell proliferation and distant spreading. Tumour-Associated Macrophages (TAMs) are abundantly present in the tumour milieu and here trigger and perpetrate a state of chronic inflammation which ultimately supports disease development and contributes to an immune-suppressive environment. Therapeutic strategies to limit inflammatory cells and their products have been successful in pre-clinical tumour models. Early clinical trials with specific cytokine and chemokine inhibitors, or with strategies designed to target TAMs, are on their way in different solid malignancies. Partial clinical responses and stabilization of diseases were observed in some patients, in the absence of significant toxicity. These encouraging results open new perspectives of combination treatments aimed at reducing cancer-promoting inflammation to maximize the anti-tumour efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Targeted therapy in the treatment of malignant gliomas

    Directory of Open Access Journals (Sweden)

    Rimas V Lukas

    2009-05-01

    Full Text Available Rimas V Lukas1, Adrienne Boire2, M Kelly Nicholas1,2 1Department of Neurology; 2Department of Medicine, University of Chicago, Chicago, IL, USAAbstract: Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In addition, we will discuss strategies that target the extracellular matrix in which these cells reside as well as angiogenesis, a process emerging as central to tumor development and growth. Finally, we will briefly touch on the role of neural stem cells as both potential targets as well as delivery vectors for other therapies. Interdependence between these varied pathways, both in maintaining health and in causing disease, is clear. Thus, attempts to easily classify some targeted therapies are problematic.Keywords: glioma, EGFR, mTOR, HDAC, Ras, angiogenesis

  15. Familial breast cancer - targeted therapy in secondary and tertiary prevention.

    Science.gov (United States)

    Kast, Karin; Rhiem, Kerstin

    2015-02-01

    The introduction of an increasing number of individualized molecular targeted therapies into clinical routine mirrors their importance in modern cancer prevention and treatment. Well-known examples for targeted agents are the monoclonal antibody trastuzumab and the selective estrogen receptor modulator tamoxifen. The identification of an unaltered gene in tumor tissue in colon cancer (KRAS) is a predictor for the patient's response to targeted therapy with a monoclonal antibody (cetuximab). Targeted therapy for hereditary breast and ovarian cancer has become a reality with the approval of olaparib for platin-sensitive late relapsed BRCA-associated ovarian cancer in December 2014. This manuscript reviews the status quo of poly-ADP-ribose polymerase inhibitors (PARPi) in the therapy of breast and ovarian cancer as well as the struggle for carboplatin as a potential standard of care for triple-negative and, in particular, BRCA-associated breast cancer. Details of the mechanism of action with information on tumor development are provided, and an outlook for further relevant research is given. The efficacy of agents against molecular targets together with the identification of an increasing number of cancer-associated genes will open the floodgates to a new era of treatment decision-making based on molecular tumor profiles. Current clinical trials involving patients with BRCA-associated cancer explore the efficacy of the molecular targeted therapeutics platinum and PARPi.

  16. Family Mode Deactivation Therapy as a Manualized Cognitive Behavioral Therapy Treatment

    Science.gov (United States)

    Apsche, Jack A.; Bass, Christopher K.; Houston, Marsha-Ann

    2008-01-01

    This article examines the effectiveness of Mode Deactivation Family Therapy (MDT) in an outpatient setting as compared to Treatment as Usual (TAU). MDT is an evidence-based psychotherapy and has been shown to be effective treating adolescents with a variety of problems involving emotional disorder, physical and sexual aggression, as well as…

  17. Recent advances in targeted drug therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    FAN Yongqiang

    2018-02-01

    Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

  18. The comparison of manual lymph drainage and ultrasound therapy on the leg swelling caused by wearing high heels.

    Science.gov (United States)

    Lee, Dong-Yeop; Han, Ji-Su; Jang, Eun-Ji; Seo, Dong-Kwon; Hong, Ji-Heon; Lee, Sang-Sook; Lee, Dong-Geol; Yu Lee, Jae-Ho

    2014-01-01

    One of the major symptoms when women are wearing high heels for a long time is leg swelling. The purpose of this study was to compare the effect of manual lymph drainage with ultrasound therapy. The forty-five healthy women of twenties were participated in this study and divided randomly into three groups; manual lymph drainage group (n=15), ultrasound therapy group (n=15) and control group (n=15). Swelling was measured before wearing the high heels (10 cm-height), after one-hour of wearing the high heels, wearing the high heels of one-hour after the intervention of 15 minutes. Also swelling was calculated by using a tape measure, volumeter and body composition analyzer. Statistical analysis of the comparison between the three groups was performed by one-way ANOVA. Also comparison to the mean value in swelling according to the time was performed by repeated measure ANOVA. As the result of this study, a significant changes have emerged within each of manual lymph drainage, ultrasound therapy and control group (p 0.05). But the mean value of manual lymph drainage group showed the tendency of fast recovering before causing swelling. Therefore, we consider that the clinical treatment of manual lymph drainage and ongoing studies will be made since manual lymph drainage is very effective in releasing the leg swelling caused by wearing high heels and standing for a long time at work.

  19. Target volumes in gastric cancer radiation therapy

    International Nuclear Information System (INIS)

    Caudry, M.; Maire, J.P.; Ratoanina, J.L.; Escarmant, P.

    2001-01-01

    The spread of gastric adenocarcinoma may follow three main patterns: hemato-genic, lymphatic and intraperitoneal. A GTV should be considered in preoperative or exclusive radiation therapy. After non-radical surgery, a 'residual GTV' will be defined with the help of the surgeon. The CTV encompasses three intricated volumes. a) A 'tumor bed' volume. After radical surgery, local recurrences appear as frequent as distant metastases. The risk depends upon the depth of parietal invasion and the nodal status. Parietal infiltration may extend beyond macroscopic limits of the tumor, especially in dinitis plastica. Therefore this volume will include: the tumor and the remaining stomach or their 'bed of resection', a part of the transverse colon, the duodenum, the pancreas and the troncus of the portal vein. In postoperative RT, this CTV also includes the jejuno-gastric or jejuno-esophageal anastomosis. b) A peritoneal volume. For practical purposes, two degrees of spread must be considered: (1) contiguous microscopic extension from deeply invasive T3 and T4 tumors, that remain amenable to local sterilization with doses of 45-50 Gy, delivered in a CTV including the peritoneal cavity at the level of the gastric bed, and under the parietal incision; (2) true 'peritoneal carcinomatosis', with widespread seeds, where chemotherapy (systemic or intraperitoneal) is more appropriate. c) A lymphatic volume including the lymph node groups 1 to 16 of the Japanese classification. This volume must encompass the hepatic pedicle and the splenic hilum. In proximal tumors, it is possible to restrict the lover part of the CTV to the lymphatic volume, and therefore to avoid irradiation of large intestinal and renal volumes. In distal and proximal tumors, involvement of resection margins is of poor prognosis -a radiation boost must be delivered at this level. The CTV in tumors of the cardia should encompass the lover part of the thoracic esophagus and the corresponding posterior mediastinum. In

  20. New perspectives on biological HDL-targeted therapies

    OpenAIRE

    Muthuramu, Ilayaraja; Amin, Md Ruhul; De Geest, Bart

    2017-01-01

    According to a modified high-density lipoprotein (HDL) hypothesis, improving HDL function will lead to a decrease of coronary events. The stringent requirement for proving or refuting this hypothesis is that the causal pathway between the therapeutic intervention and a clinically meaningful endpoint obligatory passes through HDL. Infusion therapy of reconstituted HDL particles and human apolipoprotein A-I gene transfer are biological HDL-targeted therapies that are distinguished by HDL specif...

  1. Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Hongguang Sun

    2014-01-01

    Full Text Available Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy.

  2. Increasing Orgasm and Decreasing Dyspareunia by a Manual Physical Therapy Technique

    Science.gov (United States)

    Wurn, Lawrence J; Wurn, Belinda F; Roscow, Amanda S; King, C Richard; Scharf, Eugenia S; Shuster, Jonathan J

    2004-01-01

    Context Female sexual pain and dysfunction Objective To evaluate the effectiveness of a new site-specific, manual soft-tissue therapy in increasing orgasm and reducing dyspareunia (painful intercourse) in women with histories indicating abdominopelvic adhesion formation. Design and Intervention A total of 29 new patients presenting with infertility or abdominopelvic pain-related problems, and also indicating sexual pain or dysfunction, received a series of treatments (mean, 19.5 hours) designed to address biomechanical dysfunction and restricted mobility due to adhesions affecting the reproductive organs and adjacent structures. Outcome Measures Primary outcome measures were post-test vs pretest scores on: (1) the Female Sexual Function Index (FSFI) full scale, orgasm domain, and pain domain; and (2) 3 supplemental 10-point rating scales of sexual pain levels. Secondary outcome measures were post-test vs pretest scores in the other 4 FSFI domains (desire, arousal, lubrication, and satisfaction). The Wilcoxon signed-rank test was used for all statistical analyses. Results For the 23 patients available for follow-up, the paired FSFI post-test vs pretest scores were significant (P ≤ .003) on all measures. Of the 17 patients who completed the 3 sexual pain scales, the paired post-test vs pretest scores were significant (P ≤ .002) Conclusions Many cases of inhibited orgasm, dyspareunia, and other aspects of sexual dysfunction seem to be treatable by a distinctive, noninvasive manual therapy with no risks and few, if any, adverse effects. The therapy should be considered a new adjunct to existing gynecologic and medical treatments. PMID:15775874

  3. Targeting therapy-resistant cancer stem cells by hyperthermia

    DEFF Research Database (Denmark)

    Oei, A L; Vriend, L E M; Krawczyk, P M

    2017-01-01

    Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

  4. Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy

    Directory of Open Access Journals (Sweden)

    Li Kuiyuan

    2009-04-01

    Full Text Available Abstract Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS status has emerged as a predictor of response to epidermal growth factor receptor (EGFR targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.

  5. Multimodal manual therapy vs. pharmacological care for management of tension type headache: A meta-analysis of randomized trials.

    Science.gov (United States)

    Mesa-Jiménez, Juan A; Lozano-López, Cristina; Angulo-Díaz-Parreño, Santiago; Rodríguez-Fernández, Ángel L; De-la-Hoz-Aizpurua, Jose L; Fernández-de-Las-Peñas, Cesar

    2015-12-01

    Manual therapies are generally requested by patients with tension type headache. To compare the efficacy of multimodal manual therapy vs. pharmacological care for the management of tension type headache pain by conducting a meta-analysis of randomized controlled trials. PubMed, MEDLINE, EMBASE, AMED, CINAHL, EBSCO, Cochrane Database of Systematic Reviews, Cochrane Collaboration Trials Register, PEDro and SCOPUS were searched from their inception until June 2014. All randomized controlled trials comparing any manual therapy vs. medication care for treating tension type headache adults were included. Data were extracted and methodological quality assessed independently by two reviewers. We pooled headache frequency as the main outcome and also intensity and duration. The weighted mean difference between manual therapy and pharmacological care was used to determine effect sizes. Five randomized controlled trials met our inclusion criteria and were included in the meta-analysis. Pooled analyses found that manual therapies were more effective than pharmacological care in reducing frequency (weighted mean difference -0.8036, 95% confidence interval -1.66 to -0.44; three trials), intensity (weighted mean difference -0.5974, 95% confidence interval -0.8875 to -0.3073; five trials) and duration (weighted mean difference -0.5558, 95% confidence interval -0.9124 to -0.1992; three trials) of the headache immediately after treatment. No differences were found at longer follow-up for headache intensity (weighted mean difference -0.3498, 95% confidence interval -1.106 to 0.407; three trials). Manual therapies were associated with moderate effectiveness at short term, but similar effectiveness at longer follow-up for reducing headache frequency, intensity and duration in tension type headache than pharmacological medical drug care. However, due to the heterogeneity of the interventions, these results should be considered with caution at this stage. © International Headache

  6. Palliative nephrectomy until targeted therapy of disseminated kidney cancer patients

    Directory of Open Access Journals (Sweden)

    A. V. Klimov

    2015-01-01

    Full Text Available Objective: to assess the role of palliative nephrectomy in disseminated kidney cancer patients planned to undergo targeted antiangiogenic treatment.Subjects and methods. The investigation included data on 83 patients with T1-4N0 / +M1 disseminated renal cell carcinoma (RCC who had received at least 2 targeted therapy cycles in 2009 to 2011. In 48 (57.8 % patients, the treatment was preceded by palliative nephrectomy that was not carried out in 35 (42.2 %. Before starting targeted therapy, all the cases were confirmed to be diagnosed with clear cell RCC, with a sarcomatoid component being in 7 (8.4 % patients. The median follow-up of all the patients was 21 (12–36 months.Results. The unremoved affected kidney in disseminated kidney cancer patients receiving targeted antiangiogenic therapy is an independent factor for the poor prognosis of progression-free (odds ratio (OR, 2.4; 95 % confidence interval (CI, 1.2–4.7 and overall (OR, 2.8; 95 % CI, 1.3–6.3 survival. Palliative nephrectomy does not improve the prognosis in patients with a low somatic status, the N+ category, and metastases into the bones and nonregional lymph nodes.Conclusion. Palliative nephrectomy in the selected patients with disseminated kidney cancer on targeted antiangiogenic therapy increases progression-free and overall survival.

  7. Metastatic gastric cancer – focus on targeted therapies

    Directory of Open Access Journals (Sweden)

    Meza-Junco J

    2012-06-01

    Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

  8. Heart failure—potential new targets for therapy

    Science.gov (United States)

    Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

    2016-01-01

    Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

  9. 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

  10. Targeted therapies for diarrhea-predominant irritable bowel syndrome

    OpenAIRE

    Olden, Kevin W

    2012-01-01

    Kevin W OldenDepartment of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ, USAAbstract: Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was t...

  11. Targeted Therapies for Myeloma and Metastatic Bone Cancers

    Science.gov (United States)

    2010-09-01

    Cancer J Clin 2003; 53:5. Kasugai S, Fujisawa R, Waki Y, Miyamoto K, Ohya K 2000 Selective drug delivery system to bone: small peptide (Asp)6...page. Bone targeted nanoparticles , bone cancer myeloma, mice studies, PLGA , Biodegradable materials. Targeted Therapies for Myeloma and Metastatic Bone...present results from this program at talk at the Particles 2006 –Medical/Biochemical Diagnostic , Pharmaceutical, and Drug Delivery . 3

  12. Examinations on Applications of Manual Calculation Programs on Lung Cancer Radiation Therapy Using Analytical Anisotropic Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Min; Kim, Dae Sup; Hong, Dong Ki; Back, Geum Mun; Kwak, Jung Won [Dept. of Radiation Oncology, , Seoul (Korea, Republic of)

    2012-03-15

    There was a problem with using MU verification programs for the reasons that there were errors of MU when using MU verification programs based on Pencil Beam Convolution (PBC) Algorithm with radiation treatment plans around lung using Analytical Anisotropic Algorithm (AAA). On this study, we studied the methods that can verify the calculated treatment plans using AAA. Using Eclipse treatment planning system (Version 8.9, Varian, USA), for each 57 fields of 7 cases of Lung Stereotactic Body Radiation Therapy (SBRT), we have calculated using PBC and AAA with dose calculation algorithm. By developing MU of established plans, we compared and analyzed with MU of manual calculation programs. We have analyzed relationship between errors and 4 variables such as field size, lung path distance of radiation, Tumor path distance of radiation, effective depth that can affect on errors created from PBC algorithm and AAA using commonly used programs. Errors of PBC algorithm have showned 0.2{+-}1.0% and errors of AAA have showned 3.5{+-}2.8%. Moreover, as a result of analyzing 4 variables that can affect on errors, relationship in errors between lung path distance and MU, connection coefficient 0.648 (P=0.000) has been increased and we could calculate MU correction factor that is A.E=L.P 0.00903+0.02048 and as a result of replying for manual calculation program, errors of 3.5{+-}2.8% before the application has been decreased within 0.4{+-}2.0%. On this study, we have learned that errors from manual calculation program have been increased as lung path distance of radiation increases and we could verified MU of AAA with a simple method that is called MU correction factor.

  13. Examinations on Applications of Manual Calculation Programs on Lung Cancer Radiation Therapy Using Analytical Anisotropic Algorithm

    International Nuclear Information System (INIS)

    Kim, Jung Min; Kim, Dae Sup; Hong, Dong Ki; Back, Geum Mun; Kwak, Jung Won

    2012-01-01

    There was a problem with using MU verification programs for the reasons that there were errors of MU when using MU verification programs based on Pencil Beam Convolution (PBC) Algorithm with radiation treatment plans around lung using Analytical Anisotropic Algorithm (AAA). On this study, we studied the methods that can verify the calculated treatment plans using AAA. Using Eclipse treatment planning system (Version 8.9, Varian, USA), for each 57 fields of 7 cases of Lung Stereotactic Body Radiation Therapy (SBRT), we have calculated using PBC and AAA with dose calculation algorithm. By developing MU of established plans, we compared and analyzed with MU of manual calculation programs. We have analyzed relationship between errors and 4 variables such as field size, lung path distance of radiation, Tumor path distance of radiation, effective depth that can affect on errors created from PBC algorithm and AAA using commonly used programs. Errors of PBC algorithm have showned 0.2±1.0% and errors of AAA have showned 3.5±2.8%. Moreover, as a result of analyzing 4 variables that can affect on errors, relationship in errors between lung path distance and MU, connection coefficient 0.648 (P=0.000) has been increased and we could calculate MU correction factor that is A.E=L.P 0.00903+0.02048 and as a result of replying for manual calculation program, errors of 3.5±2.8% before the application has been decreased within 0.4±2.0%. On this study, we have learned that errors from manual calculation program have been increased as lung path distance of radiation increases and we could verified MU of AAA with a simple method that is called MU correction factor.

  14. Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

    Science.gov (United States)

    Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

    2010-08-10

    The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the

  15. Manual therapy and eccentric exercise in the management of Achilles tendinopathy.

    Science.gov (United States)

    Jayaseelan, Dhinu J; Kecman, Michael; Alcorn, Daniel; Sault, Josiah D

    2017-05-01

    Chronic Achilles tendinopathy (AT) is an overuse condition seen among runners. Eccentric exercise can decrease pain and improve function for those with chronic degenerative tendon changes; however, some individuals have continued pain requiring additional intervention. While joint mobilization and manipulation has not been studied in the management in Achilles tendinopathy, other chronic tendon dysfunction, such as lateral epicondylalgia, has responded well to manual therapy (MT). Three runners were seen in physical therapy (PT) for chronic AT. They were prescribed eccentric loading exercises and calf stretching. Joint mobilization and manipulation was implemented to improve foot and ankle mobility, decrease pain, and improve function. Immediate within-session changes in pain, heel raise repetitions, and pressure pain thresholds (PPT) were noted following joint-directed MT in each patient. Each patient improved in self-reported function on the Achilles tendon specific Victorian Institute for Sport Assessment questionnaire (VISA-A), pain levels, PPT, joint mobility, ankle motion, and single-leg heel raises at discharge and 9-month follow-up. The addition of MT directed at local and remote sites may enhance the rehabilitation of patients with AT. Further research is necessary to determine the efficacy of adding joint mobilization to standard care for AT. Case series. Therapy, Level 4.

  16. Novel use of a manual therapy technique and management of a patient with peroneal tendinopathy: a case report.

    Science.gov (United States)

    Hensley, Craig P; Kavchak, Alicia J Emerson

    2012-02-01

    Peroneal tendinopathy is an uncommon but underappreciated source of lateral hindfoot pain and dysfunction. There is a paucity of literature describing optimal intervention for those suffering with pain secondary to peroneal tendinopathy. The purpose of this case report is to describe the evaluation and treatment incorporating manual therapy and therapeutic exercise for a patient diagnosed with peroneal tendinopathy. The patient was a 50 year-old female with a history of chronic lateral ankle pain and whose presentation was consistent with peroneal tendinopathy. Despite attempts to improve pain and function with over-the-counter orthotics, manual therapy to a hypomobile talocrural joint, and strengthening of the peroneal tendons, successful response was not reported until a lateral calcaneal glide was added. Improvement in impairments (pain, talocrural dorsiflexion, unilateral heel raises, and Star Excursion Balance Test) and function (Lower Extremity Functional Scale and Global Rating of Change), were observed over a course of eight visits. The patient was able to return to work and her recreational work out routine without limitations. In conclusion a successful physical therapy intervention for a patient with peroneal tendinopathy included a unique manual therapy technique, the lateral calcaneal glide, in conjunction with other manual therapy techniques and a structured home exercise program. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. New Molecular Targets of Anticancer Therapy - Current Status and Perspectives.

    Science.gov (United States)

    Zajac, Marianna; Muszalska, Izabela; Jelinska, Anna

    2016-01-01

    Molecularly targeted anticancer therapy involves the use of drugs or other substances affecting specific molecular targets that play a part in the development, progression and spread of a given neoplasm. By contrast, the majority of classical chemotherapeutics act on all rapidly proliferating cells, both healthy and cancerous ones. Target anticancer drugs are designed to achieve a particular aim and they usually act cytostatically, not cytotoxically like classical chemotherapeutics. At present, more than 300 biological molecular targets have been identified. The proteins involved in cellular metabolism include (among others) receptor proteins, signal transduction proteins, mRNA thread matrix synthesis proteins participating in neoplastic transformation, cell cycle control proteins, functional and structural proteins. The receptor proteins that are targeted by currently used anticancer drugs comprise the epithelial growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor(VEGFR). Target anticancer drugs may affect extracellular receptor domains (antibodies) or intracellular receptor domains (tyrosine kinase inhibitors). The blocking of the mRNA thread containing information about the structure of oncogenes (signal transduction proteins) is another molecular target of anticancer drugs. That type of treatment, referred to as antisense therapy, is in clinical trials. When the synthesis of genetic material is disturbed, in most cases the passage to the next cycle phase is blocked. The key proteins responsible for the blockage are cyclines and cycline- dependent kinases (CDK). Clinical trials are focused on natural and synthetic substances capable of blocking various CDKs. The paper discusses the molecular targets and chemical structure of target anticancer drugs that have been approved for and currently applied in antineoplastic therapy together with indications and contraindications for their

  18. The sterno-clavicular joint: anatomy, biomechanic, clinical features and aspects of manual therapy

    Directory of Open Access Journals (Sweden)

    M. Cutolo

    2011-09-01

    Full Text Available The sterno-clavicular joint covers one remarkable importance in the complex of the shoulder girdle. This review investigates the anatomy, biomechanics, main affections and involvement of this joint in the pathological processes of the shoulder girdle in its complex. Moreover, it focuses on the opportunities offered from the conservative treatment, using in particular the manual therapy. Active and passive, as well as against isometric resistance movements, are discussed. In particular, the passive mobilization is demonstrated effective in the restoration of joint mobility. The sterno- clavicular joint is not structured in order to complete great work loads and has the tendency to become hypermotile or unstable, if subordinate to overload works, becoming painful. In this case, the techniques of passive mobilization and of modulation of the pain turn out effective.

  19. Nanobody-photosensitizer conjugates for targeted photodynamic therapy

    NARCIS (Netherlands)

    Heukers, Raimond; van Bergen en Henegouwen, P; Oliveira, Sabrina

    2014-01-01

    Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an attempt

  20. Auger radiation targeted into DNA: a therapy perspective

    International Nuclear Information System (INIS)

    Buchegger, Franz; Perillo-Adamer, Florence; Bischof Delaloye, Angelika; Dupertuis, Yves M.

    2006-01-01

    Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of α particles. In contrast to α radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided α and β radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation. (orig.)

  1. Auger radiation targeted into DNA: a therapy perspective

    Energy Technology Data Exchange (ETDEWEB)

    Buchegger, Franz [University Hospital of Lausanne CHUV, Service of Nuclear Medicine, Lausanne (Switzerland); University Hospital of Lausanne, Service of Nuclear Medicine, Lausanne (Switzerland); Perillo-Adamer, Florence; Bischof Delaloye, Angelika [University Hospital of Lausanne CHUV, Service of Nuclear Medicine, Lausanne (Switzerland); Dupertuis, Yves M. [University Hospital of Geneva, Service of Nutrition, Geneva (Switzerland)

    2006-11-15

    Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of {alpha} particles. In contrast to {alpha} radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided {alpha} and {beta} radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation. (orig.)

  2. Targeted therapies in the treatment of urothelial cancers.

    Science.gov (United States)

    Aragon-Ching, Jeanny B; Trump, Donald L

    2017-07-01

    Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  4. Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

    Science.gov (United States)

    Durcan, Laura; Petri, Michelle

    2016-01-01

    Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

  5. Chromatin-regulating proteins as targets for cancer therapy

    International Nuclear Information System (INIS)

    Oike, Takahiro; Ogiwara, Hideaki; Kohno, Takashi; Amornwichet, Napapat; Nakano, Takashi

    2014-01-01

    Chromatin-regulating proteins represent a large class of novel targets for cancer therapy. In the context of radiotherapy, acetylation and deacetylation of histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) play important roles in the repair of DNA double-strand breaks generated by ionizing irradiation, and are therefore attractive targets for radiosensitization. Small-molecule inhibitors of HATs (garcinol, anacardic acid and curcumin) and HDACs (vorinostat, sodium butyrate and valproic acid) have been shown to sensitize cancer cells to ionizing irradiation in preclinical models, and some of these molecules are being tested in clinical trials, either alone or in combination with radiotherapy. Meanwhile, recent large-scale genome analyses have identified frequent mutations in genes encoding chromatin-regulating proteins, especially in those encoding subunits of the SWI/SNF chromatin-remodeling complex, in various human cancers. These observations have driven researchers toward development of targeted therapies against cancers carrying these mutations. DOT1L inhibition in MLL-rearranged leukemia, EZH2 inhibition in EZH2-mutant or MLL-rearranged hematologic malignancies and SNF5-deficient tumors, BRD4 inhibition in various hematologic malignancies, and BRM inhibition in BRG1-deficient tumors have demonstrated promising anti-tumor effects in preclinical models, and these strategies are currently awaiting clinical application. Overall, the data collected so far suggest that targeting chromatin-regulating proteins is a promising strategy for tomorrow's cancer therapy, including radiotherapy and molecularly targeted chemotherapy. (author)

  6. Strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilisation each reduce pain and disability in people with knee osteoarthritis: a systematic review.

    Science.gov (United States)

    Jansen, Mariette J; Viechtbauer, Wolfgang; Lenssen, Antoine F; Hendriks, Erik J M; de Bie, Rob A

    2011-01-01

    What are the effects of strength training alone, exercise therapy alone, and exercise with additional passive manual mobilisation on pain and function in people with knee osteoarthritis compared to control? What are the effects of these interventions relative to each other? A meta-analysis of randomised controlled trials. Adults with osteoarthritis of the knee. INTERVENTION TYPES: Strength training alone, exercise therapy alone (combination of strength training with active range of motion exercises and aerobic activity), or exercise with additional passive manual mobilisation, versus any non-exercise control. Comparisons between the three interventions were also sought. The primary outcome measures were pain and physical function. 12 trials compared one of the interventions against control. The effect size on pain was 0.38 (95% CI 0.23 to 0.54) for strength training, 0.34 (95% CI 0.19 to 0.49) for exercise, and 0.69 (95% CI 0.42 to 0.96) for exercise plus manual mobilisation. Each intervention also improved physical function significantly. No randomised comparisons of the three interventions were identified. However, meta-regression indicated that exercise plus manual mobilisations improved pain significantly more than exercise alone (p = 0.03). The remaining comparisons between the three interventions for pain and physical function were not significant. Exercise therapy plus manual mobilisation showed a moderate effect size on pain compared to the small effect sizes for strength training or exercise therapy alone. To achieve better pain relief in patients with knee osteoarthritis physiotherapists or manual therapists might consider adding manual mobilisation to optimise supervised active exercise programs. Copyright © 2011 Australian Physiotherapy Association. Published by .. All rights reserved.

  7. DNA repair in cancer: emerging targets for personalized therapy

    International Nuclear Information System (INIS)

    Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan

    2014-01-01

    Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer

  8. Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

    Science.gov (United States)

    Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

    2012-01-01

    Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

  9. Comparison between effectiveness of Mechanical and Manual Traction combined with mobilization and exercise therapy in Patients with Cervical Radiculopathy.

    Science.gov (United States)

    Bukhari, Syed Rehan Iftikhar; Shakil-Ur-Rehman, Syed; Ahmad, Shakeel; Naeem, Aamer

    2016-01-01

    Cervical radiculopathy is a common neuro-musculo-skeletal disorder causing pain and disability. Traction is part of the evidence based manual physical therapy management due to its mechanical nature, type of traction and parameters related to its applicability and are still to be explored more through research. Our objective was to determine the Effects of Mechanical versus Manual Traction in Manual Physical Therapy combined with segmental mobilization and exercise therapy in the physical therapy management of Patients with Cervical Radiculopathy. This randomized control trial was conducted at department of physical therapy and rehabilitation, Rathore Hospital Faisalabad, from February to July 2015. Inclusion criteria were both male and female patients with evident symptoms of cervical spine radiculopathy and age ranged between 20-70 years. The exclusion criteria were Patients with history of trauma, neck pain without radiculopathy, aged less than 20 and more than 70. A total of 72 patients with cervical radiculopathy were screened out as per the inclusion criteria, 42 patients were randomly selected and placed into two groups by toss and trial method, and only 36 patients completed the study, while 6 dropped out. The mechanical traction was applied in group A and manual traction in group B along with common intervention of segmental mobilization and exercise therapy in both groups for 6 weeks. The patient's outcomes were assessed by self reported NPRS and NDI at the baseline and after completion of 06 weeks exercise program at 3 days per week. The data was analyzed through SPSS version-21, and paired T test was applied at 95% level significance to determine the statistical deference between two groups. Clinically the group of patients treated with mechanical traction managed pain (mean pre 6.26, mean post 1.43), and disability (mean pre 24.43 and mean post 7.26) more effectively as compared with the group of patients treated with manual traction (Pain mean pre 6

  10. Becoming a Manual Occupation? The Construction of a Therapy Manual for Use with Language Impaired Children in Mainstream Primary Schools

    Science.gov (United States)

    McCartney, Elspeth; Boyle, James; Bannatyne, Susan; Jessiman, Emma; Campbell, Cathy; Kelsey, Cherry; Smith, Jennifer; O'Hare, Anne

    2003-01-01

    The construction of therapy protocols for a large-scale randomized controlled trial comparing speech and language therapists and assistants, and group and individual therapy approaches for children aged 6-11 in mainstream schools is outlined. The aim was to outline the decision-making processes that led to the construction of the research therapy…

  11. RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Stéphane Mathis

    2018-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS.

  12. RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Mathis, Stéphane; Le Masson, Gwendal

    2018-01-15

    Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS.

  13. Manual Therapy and Exercise to Improve Outcomes in Patients With Muscle Tension Dysphonia: A Case Series

    Science.gov (United States)

    Archer, Kristin R.

    2015-01-01

    Background and Purpose Muscle tension dysphonia (MTD), a common voice disorder that is not commonly referred for physical therapy intervention, is characterized by excessive muscle recruitment, resulting in incorrect vibratory patterns of vocal folds and an alteration in voice production. This case series was conducted to determine whether physical therapy including manual therapy, exercise, and stress management education would be beneficial to this population by reducing excess muscle tension. Case Description Nine patients with MTD completed a minimum of 9 sessions of the intervention. Patient-reported outcomes of pain, function, and quality of life were assessed at baseline and the conclusion of treatment. The outcome measures were the numeric rating scale (NRS), Patient-Specific Functional Scale (PSFS), and Voice Handicap Index (VHI). Cervical and jaw range of motion also were assessed at baseline and postintervention using standard goniometric measurements. Outcomes Eight of the patients had no pain after treatment. All 9 of the patients demonstrated an improvement in PSFS score, with 7 patients exceeding a clinically meaningful improvement at the conclusion of the intervention. Three of the patients also had a clinically meaningful change in VHI scores. All 9 of the patients demonstrated improvement in cervical flexion and lateral flexion and jaw opening, whereas 8 patients improved in cervical extension and rotation postintervention. Discussion The findings suggest that physical therapists can feasibly implement an intervention to improve outcomes in patients with MTD. However, a randomized clinical trial is needed to confirm the results of this case series and the efficacy of the intervention. A clinical implication is the expansion of physical therapy to include referrals from voice centers for the treatment of MTD. PMID:25256740

  14. Somato-Visceral Effects in the Treatment of Dysmenorrhea: Neuromuscular Manual Therapy and Standard Pharmacological Treatment.

    Science.gov (United States)

    Barassi, Giovanni; Bellomo, Rosa Grazia; Porreca, Annamaria; Di Felice, Piera Attilia; Prosperi, Loris; Saggini, Raoul

    2018-03-01

    This study aims to verify whether neuromuscular therapy (NMT) or pharmacology therapy (PT) is more effective for reducing symptoms in women affected by primary dysmenorrhea and the effects associated with each treatment. A controlled, randomized, single-blind clinical trial within the framework of the chair of physical medicine and rehabilitation of the University "G. d'Annunzio" of Chieti-Pescara. The study was conducted on a sample of 60 women suffering from primary dysmenorrhea. Subjects were randomly divided in two groups (A and B). Group A was treated with NMT and group B with PT. Group B was given ibuprofen or naproxen because they are considered the best painkillers for this condition. Group A was treated with 8 neuromuscular manual lumbosacral and abdominal therapy sessions twice per week for 4 weeks. Results were analyzed at the beginning (T0) and end (T1) of the study with a menstrual distress questionnaire, brief pain inventory, and visual analogue scale. Twenty patients from Group A were selected for evaluation of their maintenance of the eventual improvement that was detected in T1 at follow-up (T2). Both therapies had significant short-term effects in reducing the perception and duration of pain. However, NMT appears to give more improvements in the duration of pain. NMT had a long-term effect on perception of pain because patients conserved the positive effects of treatment after 4 weeks. NMT also had a long-term effect on duration of pain because patients conserved benefits of treatment, but this improvement started to decrease after 4 weeks. In the treatment of primary dysmenorrhea, NMT represents a valid therapeutic alternative method to PT. NMT is free from potential adverse effects of analgesics, is noninvasive, and is easy to perform.

  15. Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial

    NARCIS (Netherlands)

    Korthals-de Bos, Ingeborg B. C.; Hoving, Jan L.; van Tulder, Maurits W.; Rutten-van Mölken, Maureen P. M. H.; Adèr, Herman J.; de Vet, Henrica C. W.; Koes, Bart W.; Vondeling, Hindrik; Bouter, Lex M.

    2003-01-01

    OBJECTIVE: To evaluate the cost effectiveness of physiotherapy, manual therapy, and care by a general practitioner for patients with neck pain. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Primary care. PARTICIPANTS: 183 patients with neck pain for at least two weeks

  16. Orofacial manual therapy improves cervical movement impairment associated with headache and features of temporomandibular dysfunction: a randomized controlled trial.

    Science.gov (United States)

    von Piekartz, Harry; Hall, Toby

    2013-08-01

    There is evidence that temporomandibular disorder (TMD) may be a contributing factor to cervicogenic headache (CGH), in part because of the influence of dysfunction of the temporomandibular joint on the cervical spine. The purpose of this randomized controlled trial was to determine whether orofacial treatment in addition to cervical manual therapy, was more effective than cervical manual therapy alone on measures of cervical movement impairment in patients with features of CGH and signs of TMD. In this study, 43 patients (27 women) with headache for more than 3-months and with some features of CGH and signs of TMD were randomly assigned to receive either cervical manual therapy (usual care) or orofacial manual therapy to address TMD in addition to usual care. Subjects were assessed at baseline, after 6 treatment sessions (3-months), and at 6-months follow-up. 38 subjects (25 female) completed all analysis at 6-months follow-up. The outcome criteria were: cervical range of movement (including the C1-2 flexion-rotation test) and manual examination of the upper 3 cervical vertebra. The group that received orofacial treatment in addition to usual care showed significant reduction in all aspects of cervical impairment after the treatment period. These improvements persisted to the 6-month follow-up, but were not observed in the usual care group at any point. These observations together with previous reports indicate that manual therapists should look for features of TMD when examining patients with headache, particularly if treatment fails when directed to the cervical spine. Copyright © 2013. Published by Elsevier Ltd.

  17. Context effects on smooth pursuit and manual interception of a disappearing target.

    Science.gov (United States)

    Kreyenmeier, Philipp; Fooken, Jolande; Spering, Miriam

    2017-07-01

    In our natural environment, we interact with moving objects that are surrounded by richly textured, dynamic visual contexts. Yet most laboratory studies on vision and movement show visual objects in front of uniform gray backgrounds. Context effects on eye movements have been widely studied, but it is less well known how visual contexts affect hand movements. Here we ask whether eye and hand movements integrate motion signals from target and context similarly or differently, and whether context effects on eye and hand change over time. We developed a track-intercept task requiring participants to track the initial launch of a moving object ("ball") with smooth pursuit eye movements. The ball disappeared after a brief presentation, and participants had to intercept it in a designated "hit zone." In two experiments ( n = 18 human observers each), the ball was shown in front of a uniform or a textured background that either was stationary or moved along with the target. Eye and hand movement latencies and speeds were similarly affected by the visual context, but eye and hand interception (eye position at time of interception, and hand interception timing error) did not differ significantly between context conditions. Eye and hand interception timing errors were strongly correlated on a trial-by-trial basis across all context conditions, highlighting the close relation between these responses in manual interception tasks. Our results indicate that visual contexts similarly affect eye and hand movements but that these effects may be short-lasting, affecting movement trajectories more than movement end points. NEW & NOTEWORTHY In a novel track-intercept paradigm, human observers tracked a briefly shown object moving across a textured, dynamic context and intercepted it with their finger after it had disappeared. Context motion significantly affected eye and hand movement latency and speed, but not interception accuracy; eye and hand position at interception were

  18. Financial relationships in economic analyses of targeted therapies in oncology.

    Science.gov (United States)

    Valachis, Antonis; Polyzos, Nikolaos P; Nearchou, Andreas; Lind, Pehr; Mauri, Davide

    2012-04-20

    A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.

  19. Cancer gene therapy targeting angiogenesis: An updated Review

    Science.gov (United States)

    Liu, Ching-Chiu; Shen, Zan; Kung, Hsiang-Fu; Lin, Marie CM

    2006-01-01

    Since the relationship between angiogenesis and tumor growth was established by Folkman in 1971, scientists have made efforts exploring the possibilities in treating cancer by targeting angiogenesis. Inhibition of angiogenesis growth factors and administration of angiogenesis inhibitors are the basics of anti-angiogenesis therapy. Transfer of anti-angiogenesis genes has received attention recently not only because of the advancement of recombinant vectors, but also because of the localized and sustained expression of therapeutic gene product inside the tumor after gene transfer. This review provides the up-to-date information about the strategies and the vectors studied in the field of anti-angiogenesis cancer gene therapy. PMID:17109514

  20. Manual de Adiestramiento sobre Terapia de Rehidratacion Oral y Control de las Enfermedades Diarreicas (Oral Rehydration Therapy and the Control of Diarrheal Diseases). Training for Development. Peace Corps Information Collection & Exchange Training Manual No. T-53.

    Science.gov (United States)

    Clark, Mari; And Others

    This Spanish-language manual was developed to train Peace Corps volunteers and other community health workers in Spanish-speaking countries in oral rehydration therapy (ORT) and the control of diarrheal diseases. Using a competency-based format, the manual contains three training modules (organized in seven sessions) that focus on interrelated…

  1. Development of lithium target for accelerator based neutron capture therapy

    International Nuclear Information System (INIS)

    Taskaev, Sergey; Bayanov, Boris; Belov, Victor; Zhoorov, Eugene

    2006-01-01

    Pilot innovative accelerator based neutron source for neutron capture therapy of cancer is now of the threshold of its operation at the BINP, Russia. One of the main elements of the facility is lithium target producing neutrons via threshold 7 Li(p,n) 7 Be reaction at 25 kW proton beam with energies 1.915 MeV or 2.5 MeV. The main problems of lithium target were determined to be: 7 Be radioactive isotope activation keeping lithium layer solid, presence of photons due to proton inelastic scattering on lithium nuclei, and radiation blistering. The results of thermal test of target prototype were presented as previous NCT Congress. It becomes clear that water is preferable for cooling the target, and that lithium target 10 cm in diameter is able to run before melting. In the present report, the conception of optimal target is proposed: thin metal disk 10 cm in diameter easy for detaching, with evaporated thin layer of pure lithium from the side of proton beam exposure, its back being intensively cooled with turbulent water flow to maintain lithium layer solid. Design of the target for the neutron source constructed at BINP is shown. The results of investigation of radiation blistering and lithium layer are presented. Target unit of facility is under construction now, and obtaining neutrons is expected in nearest future. (author)

  2. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Allen, Barry J.; Abbas Rizvi, Syed M.; Qu, Chang F.; Smith, Ross C.

    2011-01-01

    Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213 Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro

  3. Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies.

    Science.gov (United States)

    Ransohoff, Julia D; Kwong, Bernice Y

    2017-12-01

    The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies. We systematically review according to drug-targeting pathway the cutaneous AE profiles of these drugs, and offer insight when possible into whether pharmacologic target versus immunologic modulation primarily underlie presentation. We include discussion of tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib), blinatumomab, ibrutinib, idelalisib, anti-B cell antibodies (rituximab, ibritumomab, obinutuzumab, ofatumumab, tositumomab), immune checkpoint inhibitors (nivolumab, pembrolizumab), alemtuzumab, brentuximab, and proteasome inhibitors (bortezomib, carfilzomib, ixazomib). We highlight skin reactions seen with antiliquid but not solid tumor agents, draw attention to serious cutaneous AEs that might require therapy modification or cessation, and offer management strategies to permit treatment tolerability. We emphasize the importance of early diagnosis and treatment to minimize disruptions to care, optimize prognosis and quality of life, and promptly address life-threatening skin or infectious events. This evolving partnership between oncologists and dermatologists in the iterative characterization and management of skin toxicities will contribute to a better understanding of these drugs' cutaneous targets and improved patient care. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Epithelioid Sarcoma: Opportunities for Biology-driven Targeted Therapy

    Directory of Open Access Journals (Sweden)

    Jonathan eNoujaim

    2015-08-01

    Full Text Available Epithelioid sarcoma is a soft tissue sarcoma of children and young adults for which the preferred treatment for localised disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review we will summarize clinically-relevant biomarkers (e.g., SMARCB1, CA125, dysadherin and others with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR and polykinase inhibitors (e.g., sunitinib in the management of local and disseminated disease. Towards building a consortium of pharmaceutical, academic and non-profit collaborators, we will discuss the state of resources for investigating epithelioid sarcoma with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed towards effective biology-driven therapies.

  5. Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy.

    Science.gov (United States)

    Noujaim, Jonathan; Thway, Khin; Bajwa, Zia; Bajwa, Ayeza; Maki, Robert G; Jones, Robin L; Keller, Charles

    2015-01-01

    Epithelioid sarcoma (ES) is a soft tissue sarcoma of children and young adults for which the preferred treatment for localized disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.

  6. Cancer Nanomedicine: From Targeted Delivery to Combination Therapy

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-01-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of a variety of diseases, including cancer. The unique properties of nanoparticles, such as large surface-to volume ratio, small size, the ability to encapsulate a variety of drugs, and tunable surface chemistry, gives them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make nanoparticles a mode of treatment potentially superior to conventional cancer therapies. This article highlights the most recent developments in cancer treatment using nanoparticles as drug-delivery vehicles, including promising opportunities in targeted and combination therapy. PMID:25656384

  7. Adoptive T cell therapy targeting CD1 and MR1

    Directory of Open Access Journals (Sweden)

    Tingxi eGuo

    2015-05-01

    Full Text Available Adoptive T cell immunotherapy has demonstrated clinically relevant efficacy in treating malignant and infectious diseases. However, much of these therapies have been focused on enhancing, or generating de novo, effector functions of conventional T cells recognizing HLA molecules. Given the heterogeneity of HLA alleles, mismatched patients are ineligible for current HLA-restricted adoptive T cell therapies. CD1 and MR1 are class I-like monomorphic molecules and their restricted T cells possess unique T cell receptor specificity against entirely different classes of antigens. CD1 and MR1 molecules present lipid and vitamin B metabolite antigens, respectively, and offer a new front of targets for T cell therapies. This review will cover the recent progress in the basic research of CD1, MR1, and their restricted T cells that possess translational potential.

  8. Targeted therapies for diarrhea-predominant irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Olden KW

    2012-05-01

    Full Text Available Kevin W OldenDepartment of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ, USAAbstract: Irritable bowel syndrome (IBS causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1 for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized

  9. Targeting Signaling to YAP for the Therapy of NF2

    Science.gov (United States)

    2015-10-01

    which encodes the FERM domain-containing protein Merlin. Children and young adults, who inherit an NF2 mutation, develop Schwannomas, usually of the...targeted therapy in the same way Chronic Myelogenous Leukemia is cured by Gleevec. The prospect of resistance is minimal, as Schwannoma cells do not seem to... treatment with Verteporfin, suggesting that this reporter system is not sensitive enough in physiopathologically relevant cell types. In parallel, it

  10. The effect of manual therapy and exercise in patients with chronic low back pain: Double blind randomized controlled trial.

    Science.gov (United States)

    Ulger, Ozlem; Demirel, Aynur; Oz, Müzeyyen; Tamer, Seval

    2017-11-06

    To determine the effects of spinal stabilization exercises (SSE) and manual therapy methods on pain, function and quality of life (QoL) levels in individuals with chronic low back pain (CLBP). A total of one-hundred thirteen patients diagnosed as CLBP were enrolled to the study. The patients allocated into Spinal Stabilization group (SG) and manual therapy group (MG), randomly. While SSE performed in SG, soft tissue mobilizations, muscle-energy techniques, joint mobilizations and manipulations were performed in MG. While the severity of pain was assessed with Visual Analog Scale (VAS), Oswestry Disability Index (ODI) and Short Form 36 (SF-36) assessments were performed to evaluate the functional status and QoL, respectively. All assessments were repeated before and after the treatment. Intragroup analyses both treatments were effective in terms of sub parameters of pain, function and life quality (p< 0.05). Inter group analyses, there was more reduction in pain and improvement in functional status in favor of MG (p< 0.05). This study showed that SSE and manual therapy methods have the same effects on QoL, while the manual treatment is more effective on the pain and functional parameters in particular.

  11. Targeted Therapy for Medullary Thyroid Cancer: A Review

    Directory of Open Access Journals (Sweden)

    S. R. Priya

    2017-10-01

    Full Text Available Medullary thyroid cancers (MTCs constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS. The management of residual, recurrent, or metastatic disease till a few years ago was re-surgery with local measures such as radiation. Chemotherapy was used with marginal benefit. The development of targeted therapy has brought in a major advantage in management of such patients. Two drugs—vandetanib and cabozantinib—have been approved for use in progressive or metastatic MTC. In addition, several drugs acting on other steps of the molecular pathway are being investigated with promising results. Targeted radionuclide therapy also provides an effective treatment option with good quality of life. This review covers the rationale of targeted therapy for MTC, present treatment options, drugs and methods under investigation, as well as an outline of the adverse effects and their management.

  12. Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Salvatore Giovanni Vitale

    2017-05-01

    Full Text Available Carcinosarcomas (CS in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%. Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”, “angiogenesis therapy”, “cancer stem cell therapy”, “prognostic biomarker”, and “novel antibody-drug”. Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2 open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

  13. New perspectives on targeted therapy in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Coward JIG

    2015-02-01

    Full Text Available Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation

  14. Immediate effect of manual therapy on respiratory functions and inspiratory muscle strength in patients with COPD

    Directory of Open Access Journals (Sweden)

    Yilmaz Yelvar GD

    2016-06-01

    Full Text Available Gul Deniz Yilmaz Yelvar,1 Yasemin Çirak,2 Yasemin Parlak Demir,3 Murat Dalkilinç,1 Bülent Bozkurt4 1Department of Musculoskeletal Physiotherapy, 2Department of Cardiopulmonary Physiotherapy, 3Department of Neurological Rehabilitation, School of Physiotherapy and Rehabilitation, 4Department of Respiratory Medicine, Faculty of Medicine, Turgut Özal University, Ankara, Turkey Objective: The objective of this study was to investigate the immediate effect of manual therapy (MT on respiratory functions and inspiratory muscle strength in patients with COPD.Participants and methods: Thirty patients with severe COPD (eight females and 22 males; mean age 62.4±6.8 years referred to pulmonary physiotherapy were included in this study. The patients participated in a single session of MT to measure the short-term effects. The lung function was measured using a portable spirometer. An electronic pressure transducer was used to measure respiratory muscle strength. Heart rate, breathing frequency, and oxygen saturation were measured with a pulse oximeter. For fatigue and dyspnea perception, the modified Borg rating of perceived exertion scale was used. All measurements were taken before and immediately after the first MT session. The ease-of-breathing visual analog scale was used for rating patients’ symptoms subjectively during the MT session.Results: There was a significant improvement in the forced expiratory volume in the first second, forced vital capacity, and vital capacity values (P<0.05. The maximal inspiratory pressure and maximal expiratory pressure values increased significantly after MT, compared to the pre-MT session (P<0.05. There was a significant decrease in heart rate, respiratory rate (P<0.05, and dyspnea and fatigue perception (P<0.05.Conclusion: A single MT session immediately improved pulmonary function, inspiratory muscle strength, and oxygen saturation and reduced dyspnea, fatigue, and heart and respiratory rates in patients with

  15. [50 years of hepatology - from therapeutic nihilism to targeted therapies].

    Science.gov (United States)

    Manns, Michael P

    2013-04-01

    Over the past 50 years significant progress has been made in the whole field of hepatology. Part of this is translation of basic research (biochemistry, immunology, virology, molecular biology and others) into clinical hepatology. This enabled us to understand more about the pathogenesis of liver diseases and led to the discovery of the five major hepatotropic viruses, the identification of hepatocellular autoantigens, and to the development of specific therapies for chronic hepatitis B, C and D. In addition, the molecular basis of most genetic liver diseases has been identified. Significant progress was made in the development of medical therapies for various liver diseases with different underlying etiologies. Surgery significantly contributed to the progress in the management of liver diseases; examples are laparoscopic cholecystectomy and the development of liver transplantation. A multimodal therapeutic algorithm has been established for the therapy of hepatocelluar carcinoma (HCC); with Sorafenib "targeted therapy" has entered the area of HCC. The progress made over the last 50 years not only led to an aetiological differentiation of acute and chronic liver diseases but also to specific therapies based on the identification and understanding of the underlying etiology. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Current Molecular Targeted Therapies for Bone and Soft Tissue Sarcomas

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    Kenji Nakano

    2018-03-01

    Full Text Available Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib’s approval as a treatment for gastrointestinal stromal tumors (GISTs has been a great achievement. Following imatinib, other tyrosine kinase inhibitors (TKIs have been approved for GISTs such as sunitinib and regorafenib, and pazopanib was approved for non-GIST soft tissue sarcomas. Olaratumab, the monoclonal antibody that targets platelet-derived growth factor receptor (PDGFR-α, was shown to extend the overall survival of soft tissue sarcoma patients and was approved in 2016 in the U.S. as a breakthrough therapy. For bone tumors, new drugs are limited to denosumab, a receptor activator of nuclear factor κB ligand (RANKL inhibitor, for treating giant cell tumors of bone. In this review, we explain and summarize the current molecular targeting therapies approved and in development for bone and soft tissue sarcomas.

  17. Folate-targeted nanoparticles for rheumatoid arthritis therapy.

    Science.gov (United States)

    Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

    2016-05-01

    Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Targeting SR-BI for cancer diagnostics, imaging and therapy

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    Maneesha Amrita Rajora

    2016-09-01

    Full Text Available Scavenger receptor class B type I (SR-BI plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumours and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents. This brief review highlights these key developments in SR-BI-targeted cancer therapies and imaging probes. Special attention is given to the exploration of high density lipoprotein nanomimetic platforms that take advantage of upregulated SR-BI expression to facilitate targeted drug-delivery and cancer diagnostics, and promising future directions in the development of these agents.

  19. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Science.gov (United States)

    Faltermeier, Claire; Busuttil, Ronald W.; Zarrinpar, Ali

    2015-01-01

    Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC. PMID:28943622

  20. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Claire Faltermeier

    2015-09-01

    Full Text Available Hepatocellular carcinoma (HCC, the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.

  1. TARGETED RADIOFREQUENCY THERAPY FOR TRAINING INDUCED MUSCLE FATIGUE EFFECTIVE OR NOT

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    Ondrej Prouza

    2016-12-01

    Full Text Available Background: Training induced muscle fatigue (hereinafter also referred as TIMF is leading to unwanted consequences among sportsmen and actively sporting people such as decreased muscle strength and additional painful discomfort and mobility issues. The knowledge about the mechanisms of influencing the fatigue induced processes in muscle tissue is not comprehensive. The conventional manual techniques, cold patches and conventional physiotherapy have some effect in improving these conditions, however, finding effective methods to influence these consequences appears beneficial in sports medicine. Such method could be Radiofrequency therapy up to 0.5 MHz, known as Targeted Radiofrequency Therapy (hereinafter also referred as TR-Therapy. Aim of this self-controlled study is to evaluate the effect of the TR-Therapy for over-exertion management including the effect on decreased muscle strength, limited range of motion and possible painful discomfort. Materials: 7 healthy and actively sporting participants underwent through 2 stages (Active stage – including overexertion of the forearm flexors and subsequent TR-Therapy session; and Control stage - including overexertion of the forearm flexors and subsequent resting period. Data for muscle strength in kg, active Range of Motion (ROM in (º and Pain and discomfort perception by 10 point Visual Analog Scale (VAS were obtained and evaluated. Results: 31% increase in the muscle strength during the active stage was observed and respectively 12% during the control stage, with level of significance p0.05. Conclusions: The results of this study suggest TR-Therapy as effective solution for muscle strength restoration after TIMF.

  2. Transcutaneous Electrical Nerve Stimulation (TENS) and Laryngeal Manual Therapy (LMT): Immediate Effects in Women With Dysphonia.

    Science.gov (United States)

    Conde, Mariana de Cásisa Macedo; Siqueira, Larissa Thaís Donalonso; Vendramini, José Eduardo; Brasolotto, Alcione Ghedini; Guirro, Rinaldo Roberto de Jesus; Silverio, Kelly Cristina Alves

    2018-05-01

    This study aimed to verify the immediate effect of low-frequency transcutaneous electrical nerve stimulation (TENS) and laryngeal manual therapy (LMT) in musculoskeletal pain, voice quality, and self-reported signs in women with dysphonia. Thirty women with behavioral dysphonia were randomly divided into the TENS group and the LMT group. All participants fulfilled the pain survey and had their voices recorded to posterior perceptual and acoustic analysis before and after intervention. The TENS group received a unique low-frequency TENS session (20 minutes). The LMT group received LMT (20 minutes) with soft and superficial massage in the sternocleidomastoid muscle, suprahyoid muscles, and larynx. Afterward, the volunteers reported their voice, larynx, breathing, and articulatory signs. Pre and post data were compared by parametric and nonparametric tests. After TENS, a decrease in pain intensity in the posterior or anterior region of the neck, shoulders, upper or lower back, and masseter was observed. After LMT, a decrease in pain intensity in the neck anterior region, shoulders, lower back, and temporal region was observed. Also, after TENS, there was an improvement in vowel /a/ instability; after LMT, there was a general improvement in voice quality, decrease in tension, and decrease in breathiness in speech. Positive voice and laryngeal signs were reported after TENS, and positive laryngeal signs and articulation were reported after LMT. TENS and LMT may be used in voice treatment of women with behavioral dysphonia, and both may be considered important therapy resources that reduce musculoskeletal pain and cause positive laryngeal signs. Both TENS and LMT are able to partially improve voice quality, but TENS presented better results. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  3. Using PubMed search strings for efficient retrieval of manual therapy research literature.

    Science.gov (United States)

    Pillastrini, Paolo; Vanti, Carla; Curti, Stefania; Mattioli, Stefano; Ferrari, Silvano; Violante, Francesco Saverio; Guccione, Andrew

    2015-02-01

    The aim of this study was to construct PubMed search strings that could efficiently retrieve studies on manual therapy (MT), especially for time-constrained clinicians. Our experts chose 11 Medical Subject Heading terms describing MT along with 84 additional potential terms. For each term that was able to retrieve more than 100 abstracts, we systematically extracted a sample of abstracts from which we estimated the proportion of studies potentially relevant to MT. We then constructed 2 search strings: 1 narrow (threshold of pertinent articles ≥40%) and 1 expanded (including all terms for which a proportion had been calculated). We tested these search strings against articles on 2 conditions relevant to MT (thoracic and temporomandibular pain). We calculated the number of abstracts needed to read (NNR) to identify 1 potentially pertinent article in the context of these conditions. Finally, we evaluated the efficiency of the proposed PubMed search strings to identify relevant articles included in a systematic review on spinal manipulative therapy for chronic low back pain. Fifty-five search terms were able to extract more than 100 citations. The NNR to find 1 potentially pertinent article using the narrow string was 1.2 for thoracic pain and 1.3 for temporomandibular pain, and the NNR for the expanded string was 1.9 and 1.6, respectively. The narrow search strategy retrieved all the randomized controlled trials included in the systematic review selected for comparison. The proposed PubMed search strings may help health care professionals locate potentially pertinent articles and review a large number of MT studies efficiently to better implement evidence-based practice. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  4. Adverse effects as a consequence of being the subject of orthopaedic manual therapy training, a worldwide retrospective survey.

    Science.gov (United States)

    Thoomes-de Graaf, M; Thoomes, E; Carlesso, L; Kerry, R; Rushton, A

    2017-06-01

    Physical therapists (PTs) use a range of manual therapy techniques developed to an advanced level through postgraduate orthopaedic manipulative physical therapy (OMPT) programmes. The aim of this study was to describe the adverse effects experienced by students after having techniques performed on them as part of their OMPT training. A descriptive online survey of current students and recent graduates (≤5 years)m of OMPT programmes across the 22 Member Organisations of the International Federation of Orthopaedic Manipulative Physical Therapists. The questionnaire was completed by 1640 respondents across 22 countries (1263 graduates, 377 students. Some 60% of respondents reported never having experienced adverse effects during their manual therapy training. Of the 40% who did, 66.4% reported neck pain, 50.9% headache and 32% low back pain. Most reports of neck pain started after a manipulation and/or mobilisation, of which 53.4% lasted ≤24 h, 38.1% > 24 h but <3 months and 13.7% still experienced neck pain to date. A small percentage of respondents (3.3%) reported knowing of a fellow student experiencing a major adverse effect. Mild to moderate adverse effects after practising manual therapy techniques are commonly reported, but usually resolve within 24 h. However, this survey has identified the reported occurrence of major adverse effects that warrant further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Recruitment and accrual of women in a placebo-controlled clinical pilot study on manual therapy.

    Science.gov (United States)

    Cambron, Jerrilyn A; Hawk, Cheryl; Evans, Roni; Long, Cynthia R

    2004-06-01

    To investigate the accrual rates and recruitment processes among 3 Midwestern sites during a pilot study on manual therapy for chronic pelvic pain. Multisite pilot study for a randomized, placebo-controlled clinical trial. Three chiropractic institutions in or near major metropolitan cities in the Midwestern United States. Thirty-nine women aged 18 to 45 with chronic pelvic pain of at least 6 months duration, diagnosed by a board certified gynecologist. The method of recruitment was collected for each individual who responded to an advertisement and completed an interviewer-administered telephone screen. Participants who were willing and eligible after 3 baseline visits were entered into a randomized clinical trial. The number of responses and accrual rates were determined for the overall study, each of the 3 treatment sites, and each of the 5 recruitment efforts. In this study, 355 women were screened over the telephone and 39 were randomized, making the rate of randomization approximately 10%. The most effective recruitment methods leading to randomization were direct mail (38%) and radio advertisements (34%). However, success of the recruitment process differed by site. Based on the accrual of this multisite pilot study, a full-scale trial would not be feasible using this study's parameters. However, useful information was gained on recruitment effectiveness, eligibility criteria, and screening protocols among the 3 metropolitan sites.

  6. The Development of a Postgraduate Orthopaedic Manual Therapy Residency Program in Nairobi, Kenya

    Directory of Open Access Journals (Sweden)

    Shala Cunningham

    2017-06-01

    Full Text Available IntroductionThere are very few opportunities for long-term, comprehensive postgraduate education in developing countries because of fiscal and human resource constraints. Therefore, physiotherapists have little opportunity following graduation to advance their skills through the improvement of clinical reasoning and treatment planning and application.BackgroundTo address the need for sustainable advanced instruction in physiotherapy within the country, a postgraduate Residency program was initiated in Nairobi, Kenya in 2012. The mission of the program is to graduate advanced orthopedic practitioners who can lead their communities and local profession in the advancement of clinical care and education. Since its inception, six cohorts have been initiated for a total of 90 resident participants. In addition, six program graduates are being trained to continue the Residency program and are serving as teaching assistants for the on campus modules. This training will result in a self-sustaining program by 2020.DiscussionThe manual therapy Residency education model allowed for advancement of the participating physiotherapists professional development utilizing evidence-based practice. This was done without altering the current education system within the country, or accessing expensive equipment.Concluding remarksThe Residency program was developed and established with the cooperation of a local education institution and a non-profit corporation in the United States. This collaboration has facilitated the advancement of orthopedic clinical standards in the country and will, hopefully, one day serve an as a template for future programs.

  7. The Development of a Postgraduate Orthopaedic Manual Therapy Residency Program in Nairobi, Kenya.

    Science.gov (United States)

    Cunningham, Shala; Jackson, Richard; Muli, Daniel Kangutu; McFelea, Joni

    2017-01-01

    There are very few opportunities for long-term, comprehensive postgraduate education in developing countries because of fiscal and human resource constraints. Therefore, physiotherapists have little opportunity following graduation to advance their skills through the improvement of clinical reasoning and treatment planning and application. To address the need for sustainable advanced instruction in physiotherapy within the country, a postgraduate Residency program was initiated in Nairobi, Kenya in 2012. The mission of the program is to graduate advanced orthopedic practitioners who can lead their communities and local profession in the advancement of clinical care and education. Since its inception, six cohorts have been initiated for a total of 90 resident participants. In addition, six program graduates are being trained to continue the Residency program and are serving as teaching assistants for the on campus modules. This training will result in a self-sustaining program by 2020. The manual therapy Residency education model allowed for advancement of the participating physiotherapists professional development utilizing evidence-based practice. This was done without altering the current education system within the country, or accessing expensive equipment. The Residency program was developed and established with the cooperation of a local education institution and a non-profit corporation in the United States. This collaboration has facilitated the advancement of orthopedic clinical standards in the country and will, hopefully, one day serve an as a template for future programs.

  8. The EdUReP approach plus manual therapy for the management of insertional Achilles tendinopathy.

    Science.gov (United States)

    Sartorio, Francesco; Zanetta, Anna; Ferriero, Giorgio; Bravini, Elisabetta; Vercelli, Stefano

    2018-05-01

    Insertional Achilles tendinopathy (IAT) is a challenging overuse disorder. The aim of this case report was to study the feasibility of a comprehensive rehabilitative approach according to the Education, Unloading, Reloading, and Prevention (EdUReP) framework combined with Instrument-Augmented Soft Tissue Mobilization (I-ASTM). An active 51-year-old man patient with chronic IAT was studied. Clinical assessment battery was composed by visual analogue scale for pain during the Achilles tendon palpation test, passive straight leg raise test, single leg hop test, Patient-Specific Functional Scale, and Foot and Ankle Ability Measure. The patient was treated over a 8 weeks period using the EdUReP guidelines plus 8 sessions of I-ASTM, applied with a solid instrument to the Achilles tendon and to the muscle fibrotic areas previously identified during evaluation. Clinically significant improvements were observed in all outcome measures, and a resume of patient's usual sports activities without pain or limitations was possible after treatment. Results lasted over a 6-month follow-up. To the best of our knowledge, this is the first study applying a comprehensive approach based on accurate physical assessment, and using the EdUReP theoretical model. The combination of the EdUReP model and manual therapy was effective in resolving the patient's symptoms and restore his usual sport activities. While these results cannot be generalized, the present findings could provide a valuable foundation for future researches.

  9. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    International Nuclear Information System (INIS)

    Hosseinkhani, Hossein; Chen Yiru; He Wenjie; Hong Poda; Yu, Dah-Shyong; Domb, Abraham J.

    2013-01-01

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe 2+ solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  10. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinkhani, Hossein, E-mail: hosseinkhani@yahoo.com [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Chen Yiru [National Yang-Ming University, Department of Biomedical Engineering (China); He Wenjie; Hong Poda [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [Institute of Drug Research, The Center for Nanoscience and Nanotechnology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem (Israel)

    2013-01-15

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe{sup 2+} solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  11. Targeted radionuclide therapy for solid tumors: An overview

    International Nuclear Information System (INIS)

    De Nardo, Sally J.; De Nardo, Gerald L.

    2006-01-01

    Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET])

  12. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  13. Radiotherapy in combination with vascular-targeted therapies

    International Nuclear Information System (INIS)

    Ciric, Eva; Sersa, Gregor

    2010-01-01

    Given the critical role of tumor vasculature in tumor development, considerable efforts have been spent on developing therapeutic strategies targeting the tumor vascular network. A variety of agents have been developed, with two general approaches being pursued. Antiangiogenic agents (AAs) aim to interfere with the process of angiogenesis, preventing new tumor blood vessel formation. Vascular-disrupting agents (VDAs) target existing tumor vessels causing tumor ischemia and necrosis. Despite their great therapeutic potential, it has become clear that their greatest clinical utility may lie in combination with conventional anticancer therapies. Radiotherapy is a widely used treatment modality for cancer with its distinct therapeutic challenges. Thus, combining the two approaches seems reasonable. Strong biological rationale exist for combining vascular-targeted therapies with radiation. AAs and VDAs were shown to alter the tumor microenvironment in such a way as to enhance responses to radiation. The results of preclinical and early clinical studies have confirmed the therapeutic potential of this new treatment strategy in the clinical setting. However, concerns about increased normal tissue toxicity, have been raised

  14. HER3 signaling and targeted therapy in cancer

    Directory of Open Access Journals (Sweden)

    Rosalin Mishra

    2018-05-01

    Full Text Available ERBB family members including epidermal growth factor receptor (EGFR also known as HER1, ERBB2/HER2/Neu, ERBB3/HER3 and ERBB4/HER4 are aberrantly activated in multiple cancers and hence serve as drug targets and biomarkers in modern precision therapy. The therapeutic potential of HER3 has long been underappreciated, due to impaired kinase activity and relatively low expression in tumors. However, HER3 has received attention in recent years as it is a crucial heterodimeric partner for other EGFR family members and has the potential to regulate EGFR/HER2-mediated resistance. Upregulation of HER3 is associated with several malignancies where it fosters tumor progression via interaction with different receptor tyrosine kinases (RTKs. Studies also implicate HER3 contributing significantly to treatment failure, mostly through the activation of PI3K/AKT, MAPK/ERK and JAK/STAT pathways. Moreover, activating mutations in HER3 have highlighted the role of HER3 as a direct therapeutic target. Therapeutic targeting of HER3 includes abrogating its dimerization partners’ kinase activity using small molecule inhibitors (lapatinib, erlotinib, gefitinib, afatinib, neratinib or direct targeting of its extracellular domain. In this review, we focus on HER3-mediated signaling, its role in drug resistance and discuss the latest advances to overcome resistance by targeting HER3 using mono- and bispecific antibodies and small molecule inhibitors.

  15. A descriptive study of a manual therapy intervention within a randomised controlled trial for hamstring and lower limb injury prevention

    Directory of Open Access Journals (Sweden)

    Hoskins Wayne

    2010-08-01

    Full Text Available Abstract Background There is little literature describing the use of manual therapy performed on athletes. It was our purpose to document the usage of a sports chiropractic manual therapy intervention within a RCT by identifying the type, amount, frequency, location and reason for treatment provided. This information is useful for the uptake of the intervention into clinical settings and to allow clinicians to better understand a role that sports chiropractors offer. Methods All treatment rendered to 29 semi-elite Australian Rules footballers in the sports chiropractic intervention group of an 8 month RCT investigating hamstring and lower-limb injury prevention was recorded. Treatment was pragmatically and individually determined and could consist of high-velocity, low-amplitude (HVLA manipulation, mobilization and/or supporting soft tissue therapies. Descriptive statistics recorded the treatment rendered for symptomatic or asymptomatic benefit, delivered to joint or soft tissue structures and categorized into body regions. For the joint therapy, it was recorded whether treatment consisted of HVLA manipulation, HVLA manipulation and mobilization, or mobilization only. Breakdown of the HVLA technique was performed. Results A total of 487 treatments were provided (mean 16.8 consultations/player with 64% of treatment for asymptomatic benefit (73% joint therapies, 57% soft tissue therapies. Treatment was delivered to approximately 4 soft tissue and 4 joint regions each consultation. The most common asymptomatic regions treated with joint therapies were thoracic (22%, knee (20%, hip (19%, sacroiliac joint (13% and lumbar (11%. For soft tissue therapies it was gluteal (22%, hip flexor (14%, knee (12% and lumbar (11%. The most common symptomatic regions treated with joint therapies were lumbar (25%, thoracic (15% and hip (14%. For soft tissue therapies it was gluteal (22%, lumbar (15% and posterior thigh (8%. Of the joint therapy, 56% was HVLA

  16. Targeted radionuclide therapy for neuroendocrine tumours: principles and application.

    Science.gov (United States)

    Druce, Maralyn R; Lewington, Val; Grossman, Ashley B

    2010-01-01

    Neuroendocrine tumours comprise a group of neoplasms with variable clinical behaviour. Their growth and spread is often very slow and initially asymptomatic, and thus they are often metastatic at the time of diagnosis and incurable by surgery. An exciting therapeutic strategy for cytoreduction, both for stabilisation of tumour growth and inhibition of hormone production, is the use of targeted radionuclide therapy. Evidence from large-scale, randomised, placebo-controlled trials is very difficult to obtain in these rare diseases, but current data appear promising. It is timely to review the principles underlying the use of these therapies, together with the clinical outcomes to date and potential directions for future research. Copyright 2009 S. Karger AG, Basel.

  17. Denosumab for bone diseases: translating bone biology into targeted therapy.

    Science.gov (United States)

    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  18. Terapia manual no tratamento da espondilólise e espondilolistese: revisão de literatura Manual therapy for treating spondylolysis and spondylolisthesis: a literature review

    Directory of Open Access Journals (Sweden)

    Fabrício José Jassi

    2010-12-01

    /listhesis, especially manual therapy, in order to guide practitioners for effective intervention. Results show that both manual therapy and conventional physiotherapy were effective in relieving low-back pain and beneficial for patient's functional outcome. Manual therapy involved spine manipulation, sacroiliac joint manipulation, muscle-energy techniques and stretching affected muscles. Stabilizing lombopelvic exercises, postural muscles strengthening, and hamstring and psoas stretching were also considered important in treating spondylolysis/listhesis. Each case's clinical and radiological features must be individually considered in order to determinate therapeutic strategy. Among non-surgical options, none has proved better than others and all may be included in symptomatic treatment of patients with spondylolysis/listhesis.

  19. Neutrophils, a candidate biomarker and target for radiation therapy?

    Science.gov (United States)

    Schernberg, Antoine; Blanchard, Pierre; Chargari, Cyrus; Deutsch, Eric

    2017-11-01

    Neutrophils are the most abundant blood-circulating white blood cells, continuously generated in the bone marrow. Growing evidence suggests they regulate the innate and adaptive immune system during tumor evolution. This review will first summarize the recent findings on neutrophils as a key player in cancer evolution, then as a potential biomarker, and finally as therapeutic targets, with respective focuses on the interplay with radiation therapy. A complex interplay: Neutrophils have been associated with tumor progression through multiple pathways. Ionizing radiation has cytotoxic effects on cancer cells, but the sensitivity to radiation therapy in vivo differ from isolated cancer cells in vitro, partially due to the tumor microenvironment. Different microenvironmental states, whether baseline or induced, can modulate or even attenuate the effects of radiation, with consequences for therapeutic efficacy. Inflammatory biomarkers: Inflammation-based scores have been widely studied as prognostic biomarkers in cancer patients. We have performed a large retrospective cohort of patients undergoing radiation therapy (1233 patients), with robust relationship between baseline blood neutrophil count and 3-year's patient's overall survival in patients with different cancer histologies. (Pearson's correlation test: p = .001, r = -.93). Therapeutic approaches: Neutrophil-targeting agents are being developed for the treatment of inflammatory and autoimmune diseases. Neutrophils either can exert antitumoral (N1 phenotype) or protumoral (N2 phenotype) activity, depending on the Tumor Micro Environment. Tumor associated N2 neutrophils are characterized by high expression of CXCR4, VEGF, and gelatinase B/MMP9. TGF-β within the tumor microenvironment induces a population of TAN with a protumor N2 phenotype. TGF-β blockade slows tumor growth through activation of CD8 + T cells, macrophages, and tumor associated neutrophils with an antitumor N1 phenotype. This supports

  20. Economic evaluation of manual therapy for musculoskeletal diseases: a protocol for a systematic review and narrative synthesis of evidence.

    Science.gov (United States)

    Kim, Chang-Gon; Mun, Su-Jeong; Kim, Ka-Na; Shin, Byung-Cheul; Kim, Nam-Kwen; Lee, Dong-Hyo; Lee, Jung-Han

    2016-05-13

    Manual therapy is the non-surgical conservative management of musculoskeletal disorders using the practitioner's hands on the patient's body for diagnosing and treating disease. The aim of this study is to systematically review trial-based economic evaluations of manual therapy relative to other interventions used for the management of musculoskeletal diseases. Randomised clinical trials (RCTs) on the economic evaluation of manual therapy for musculoskeletal diseases will be included in the review. The following databases will be searched from their inception: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Econlit, Mantis, Index to Chiropractic Literature, Science Citation Index, Social Science Citation Index, Allied and Complementary Medicine Database (AMED), Cochrane Database of Systematic Reviews (CDSR), National Health Service Database of Abstracts of Reviews of Effects (NHS DARE), National Health Service Health Technology Assessment Database (NHS HTA), National Health Service Economic Evaluation Database (NHS EED), CENTRAL, five Korean medical databases (Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Service System (RISS), DBPIA, Korean Traditional Knowledge Portal (KTKP) and KoreaMed) and three Chinese databases (China National Knowledge Infrastructure (CNKI), VIP and Wanfang). The evidence for the cost-effectiveness, cost-utility and cost-benefit of manual therapy for musculoskeletal diseases will be assessed as the primary outcome. Health-related quality of life and adverse effects will be assessed as secondary outcomes. We will critically appraise the included studies using the Cochrane risk of bias tool and the Drummond checklist. Results will be summarised using Slavin's qualitative best-evidence synthesis approach. The results of the study will be disseminated via a peer-reviewed journal and/or conference presentations

  1. Auto-segmentation of low-risk clinical target volume for head and neck radiation therapy.

    Science.gov (United States)

    Yang, Jinzhong; Beadle, Beth M; Garden, Adam S; Gunn, Brandon; Rosenthal, David; Ang, Kian; Frank, Steven; Williamson, Ryan; Balter, Peter; Court, Laurence; Dong, Lei

    2014-01-01

    To investigate atlas-based auto-segmentation methods to improve the quality of the delineation of low-risk clinical target volumes (CTVs) of unilateral tonsil cancers. Sixteen patients received intensity modulated radiation therapy for left tonsil tumors. These patients were treated by a total of 8 oncologists, who delineated all contours manually on the planning CT image. We chose 6 of the patients as atlas cases and used atlas-based auto-segmentation to map each the atlas CTV to the other 10 patients (test patients). For each test patient, the final contour was produced by combining the 6 individual segmentations from the atlases using the simultaneous truth and performance level estimation algorithm. In addition, for each test patient, we identified a single atlas that produced deformed contours best matching the physician's manual contours. The auto-segmented contours were compared with the physician's manual contours using the slice-wise Hausdorff distance (HD), the slice-wise Dice similarity coefficient (DSC), and a total volume overlap index. No single atlas consistently produced good results for all 10 test cases. The multiatlas segmentation achieved a good agreement between auto-segmented contours and manual contours, with a median slice-wise HD of 7.4 ± 1.0 mm, median slice-wise DSC of 80.2% ± 5.9%, and total volume overlap of 77.8% ± 3.3% over the 10 test cases. For radiation oncologists who contoured both the test case and one of the atlas cases, the best atlas for a test case had almost always been contoured by the oncologist who had contoured that test case, indicating that individual physician's practice dominated in target delineation and was an important factor in optimal atlas selection. Multiatlas segmentation may improve the quality of CTV delineation in clinical practice for unilateral tonsil cancers. We also showed that individual physician's practice was an important factor in selecting the optimal atlas for atlas-based auto

  2. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  3. Exercise, Manual Therapy, and Booster Sessions in Knee Osteoarthritis: Cost-Effectiveness Analysis From a Multicenter Randomized Controlled Trial.

    Science.gov (United States)

    Bove, Allyn M; Smith, Kenneth J; Bise, Christopher G; Fritz, Julie M; Childs, John; Brennan, Gerard P; Abbott, J Haxby; Fitzgerald, G Kelley

    2018-01-01

    Limited information exists regarding the cost-effectiveness of rehabilitation strategies for individuals with knee osteoarthritis (OA). The study objective was to compare the cost-effectiveness of 4 different combinations of exercise, manual therapy, and booster sessions for individuals with knee OA. This economic evaluation involved a cost-effectiveness analysis performed alongside a multicenter randomized controlled trial. The study took place in Pittsburgh, Pennsylvania; Salt Lake City, Utah; and San Antonio, Texas. The study participants were 300 individuals taking part in a randomized controlled trial investigating various physical therapy strategies for knee OA. Participants were randomized into 4 treatment groups: exercise only (EX), exercise plus booster sessions (EX+B), exercise plus manual therapy (EX+MT), and exercise plus manual therapy and booster sessions (EX+MT+B). For the 2-year base case scenario, a Markov model was constructed using the United States societal perspective and a 3% discount rate for costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated to compare differences in cost per QALY gained among the 4 treatment strategies. In the 2-year analysis, booster strategies (EX+MT+B and EX+B) dominated no-booster strategies, with both lower health care costs and greater effectiveness. EX+MT+B had the lowest total health care costs. EX+B cost ${\\$}$1061 more and gained 0.082 more QALYs than EX+MT+B, for an incremental cost-effectiveness ratio of ${\\$}$12,900/QALY gained. The small number of total knee arthroplasty surgeries received by individuals in this study made the assessment of whether any particular strategy was more successful at delaying or preventing surgery in individuals with knee OA difficult. Spacing exercise-based physical therapy sessions over 12 months using periodic booster sessions was less costly and more effective over 2 years than strategies not containing booster sessions for

  4. Target volumes in radiation therapy of childhood brain tumours

    International Nuclear Information System (INIS)

    Habrand, J.L.; Abdulkarim, B.; Beaudre, A.; El Khouri, M.; Kalifa, C.

    2001-01-01

    Pediatric tumors have enjoyed considerable improvements for the past 30 years. This is mainly due to the extensive use of combined therapeutical modalities in which chemotherapy plays a prominent role. In many children, local treatment including radiotherapy, can nowadays be adapted in terms of target volume and dose to the 'response' to an initial course of chemotherapy almost on a case by case basis. This makes precise recommendation on local therapy highly difficult in this age group. We will concentrate in this paper on brain tumors in which chemotherapy is of limited value and radiotherapy still plays a key-role. (authors)

  5. Interleukin-1 beta targeted therapy for type 2 diabetes

    DEFF Research Database (Denmark)

    Maedler, K.; Dharmadhikari, G.; Schumann, D.M.

    2009-01-01

    Since having been cloned in 1984, IL-1beta has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1beta is a regulator of the body's inflammatory response and is produced after infection, injury, and antigenic challenge. I....... We highlight recent clinical studies and experiments in animals and isolated islets using IL-1beta as a potential target for the therapy of type 2 diabetes Udgivelsesdato: 2009/9...

  6. Efficacy of complete decongestive therapy and manual lymphatic drainage on treatment-related lymphedema in breast cancer

    International Nuclear Information System (INIS)

    Koul, Rashmi; Dufan, Tarek; Russell, Catherine; Guenther, Wanda; Nugent, Zoan; Sun Xuyan; Cooke, Andrew L.

    2007-01-01

    Objective: To evaluate the results of combined decongestive therapy and manual lymphatic drainage in patients with breast cancer-related lymphedema. Methods and Materials: The data from 250 patients were reviewed. The pre- and posttreatment volumetric measurements were compared, and the correlation with age, body mass index, and type of surgery, chemotherapy, and radiotherapy was determined. The Spearman correlation coefficients and Wilcoxon two-sample test were used for statistical analysis. Results: Of the 250 patients, 138 were included in the final analysis. The mean age at presentation was 54.3 years. Patients were stratified on the basis of the treatment modality used for breast cancer management. Lymphedema was managed with combined decongestive therapy in 55%, manual lymphatic drainage alone in 32%, and the home program in 13%. The mean pretreatment volume of the affected and normal arms was 2929 and 2531 mL. At the end of 1 year, the posttreatment volume of the affected arm was 2741 mL. The absolute volume of the affected arm was reduced by a mean of 188 mL (p < 0.0001). The type of surgery (p = 0.0142), age (p = 0.0354), and body mass index (p < 0.0001) were related to the severity of lymphedema. Conclusion: Combined decongestive therapy and manual lymphatic drainage with exercises were associated with a significant reduction in the lymphedema volume

  7. Novel drugs targeting Toll-like receptors for antiviral therapy.

    Science.gov (United States)

    Patel, Mira C; Shirey, Kari Ann; Pletneva, Lioubov M; Boukhvalova, Marina S; Garzino-Demo, Alfredo; Vogel, Stefanie N; Blanco, Jorge Cg

    2014-09-01

    Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

  8. Histone lysine demethylases as targets for anticancer therapy

    DEFF Research Database (Denmark)

    Højfeldt, Jonas W; Agger, Karl; Helin, Kristian

    2013-01-01

    It has recently been demonstrated that the genes controlling the epigenetic programmes that are required for maintaining chromatin structure and cell identity include genes that drive human cancer. This observation has led to an increased awareness of chromatin-associated proteins as potentially...... interesting drug targets. The successful introduction of DNA methylation and histone deacetylase (HDAC) inhibitors for the treatment of specific subtypes of cancer has paved the way for the use of epigenetic therapy. Here, we highlight key biological findings demonstrating the roles of members of the histone...... lysine demethylase class of enzymes in the development of cancers, discuss the potential and challenges of therapeutically targeting them, and highlight emerging small-molecule inhibitors of these enzymes....

  9. Biomedical nanotechnology for molecular imaging, diagnostics, and targeted therapy.

    Science.gov (United States)

    Nie, Shuming

    2009-01-01

    Biomedical nanotechnology is a cross-disciplinary area of research in science, engineering and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The basic rationale is that nanometer-sized particles such as semiconductor quantum dots and iron oxide nanocrystals have optical, magnetic or structural properties that are not available from either molecules or bulk solids. When linked with biotargeting ligands such as monoclonal antibodies, peptides or small molecules, these nanoparticles can be used to target diseased cells and organs (such as malignant tumors and cardiovascular plaques) with high affinity and specificity. In the "mesoscopic" size range of 5-100 nm diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents.

  10. C595 antibody: A potential vector for targeted alpha therapy

    International Nuclear Information System (INIS)

    Perkins, A.C.; Allen, B.J.

    2005-01-01

    Full text: Mucins are high molecular-weight heavily glycosylated glycoproteins with many oligosaccharide side-chains, linked to a protein backbone called apomucin. A total of 19 different mucin genes (MUC1-MUC4, MUC5B, MUC5AC, MUC6-MUC18) have been identified to date. Mucins are present on the surface of most epithelial cells and play a role in their protection and lubrication. In cancer cells the mucin molecule becomes altered, thus representing an important target for diagnosis and therapy. Urinary epithelial mucin1 (MUC1) is found to be frequently up-regulated and abnormally glycosylated in a number of common malignancies, including breast, bladder, colon, ovarian and gastric cancer. The monoclonal antibody C595 is an IgG3 murine MAb raised against the protein core of human MUC1. Epitope mapping has shown that C595 recognizes a tetrapeptide motif (RPAP) within the protein core of MUC1 mucin that contains a large domain of multiples of a highly conserved 20-amino-acid-repeat sequence (PDTRPAPGSTAPPAHGVTSA). This antibody has previously been radiolabelled with 99m Tc and 111 In and used for imaging a range of tumour types including ovary, breast and bladder. The antibody has also been radiolabelled with 67 Cu and 188 Re for the therapy of superficial bladder cancer. More recently we have investigated the pre-clinical use of the C595 antibody for targeted alpha therapy using 213 Bi which emits alpha particles with high linear energy transfer (LET), short range (80 m) radiation and has a short physical half-life of 45.6 minutes. Alpha particles are some 7300 times heavier than beta particles and in theory, following binding of an alpha immunocongugates to the target, a large fraction of the alpha particle energy is delivered to cancer cells, with minimal concomitant radiation of normal tissues. 213 Bi was produced from the 225 Ac/ 213 Bi generator. For antibody conjugation the chelator, cyclic diethylenetriaminepentacetic acid anhydride (DTPA) was used. Initial

  11. Does manual therapy improve pain and function in patients with plantar fasciitis? A systematic review.

    Science.gov (United States)

    Fraser, John J; Corbett, Revay; Donner, Chris; Hertel, Jay

    2018-05-01

    To assess if manual therapy (MT) in the treatment of plantar fasciitis (PF) patients improves pain and function more effectively than other interventions. A systematic review of all randomized control trials (RCTs) investigating the effects of MT in the treatment of human patients with PF, plantar fasciosis, and heel pain published in English on PubMed, CINAHL, Cochrane, and Web of Science databases was conducted. Research quality was appraised utilizing the PEDro scale. Cohen's d effect sizes (ES) and associated 95% confidence intervals (CI) were calculated between treatment groups. Seven RCTs were selected that employed MT as a primary independent variable and pain and function as dependent variables. Inclusion of MT in treatment yielded greater improvement in function (6 of 7 studies, CI that did not cross zero in 14 of 25 variables, ES = 0.5-21.5) and algometry (3 of 3 studies, CI that did not cross zero in 9 of 10 variables, ES = 0.7-3.0) from 4 weeks to 6 months when compared to interventions such as stretching, strengthening, or modalities. Though pain improved with the inclusion of MT, ES calculations favored MT in only 2 of 6 studies (3 of 13 variables) and was otherwise equivalent in effectiveness to comparison interventions. MT is clearly associated with improved function and may be associated with pain reduction in PF patients. It is recommended that clinicians consider use of both joint and soft tissue mobilization techniques in conjunction with stretching and strengthening when treating patients with PF. Treatment, level 1a.

  12. Osteopathic manual therapy in heart failure patients: A randomized clinical trial.

    Science.gov (United States)

    Thomaz, Sergio R; Teixeira, Felipe A; de Lima, Alexandra C G B; Cipriano Júnior, Gerson; Formiga, Magno F; Cahalin, Lawrence Patrick

    2018-04-01

    Heart Failure (HF) patients usually present with increased arterial resistance and reduced blood pressure (BP) leading to an impaired functional capacity. Osteopathic Manual Therapy (OMT) focused on myofascial release techniques (MRT) and in the balancing of diaphragmatic tensions, has been shown to improve blood flow in individuals using the resistive index (RI). However, its effects in HF patients have not been examined. To evaluate the acute response of selected osteopathic techniques on RI, heart rate (HR), and BP in patients with HF. Randomized-controlled clinical trial of HF patients assigned to MRT (six different techniques with three aimed at the pelvis, two at the thorax, and one at the neck for 15 min) or Control group (subjects in supine position for 15 min without intervention). The RI of the femoral, brachial and carotid arteries was measured via doppler ultrasound while HR and BP were measured via sphygmomanometry before and after a single MRT or control intervention. Twenty-two HF patients equally distributed (50% male, mean age 53 years; range 32-69 years) (ejection fraction = 35.6%, VO 2peak : 12.9 mL/kg -1 min -1 ) were evaluated. We found no intra or inter group differences in RI of the carotid (Δ MRT : 0.07% vs Δ Control :11.8%), brachial (Δ MRT :0.17% vs Δ Control : 2.9%), or femoral arteries (Δ MRT :1.65% vs Δ Control : 0.97%) (P > 0.05) and no difference in HR or BP (Δ MRT :0.6% vs Δ Control : 3%), (P > 0.05). A single MRT session did not significantly change the RI, HR, or BP of HF patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Oral Rehydration Therapy and the Control of Diarrheal Diseases. Training for Development. Peace Corps Information Collection & Exchange Training Manual No. T-34.

    Science.gov (United States)

    Clark, Mari; And Others

    This manual was developed to train Peace Corps volunteers and other community health workers in oral rehydration therapy (ORT) and the control of diarrheal diseases. Using a competency-based format, the manual contains six training modules (organized in 22 sessions) that focus on interrelated health education and technical content areas. Each…

  14. Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

    Directory of Open Access Journals (Sweden)

    Ruqaya AL Darwish

    2015-01-01

    Full Text Available There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB, with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

  15. Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

    Directory of Open Access Journals (Sweden)

    Xiang-Hong Peng

    2008-10-01

    Full Text Available Xiang-Hong Peng1,4, Ximei Qian2,4, Hui Mao3,4, Andrew Y Wang5, Zhuo (Georgia Chen1,4, Shuming Nie2,4, Dong M Shin1,4*1Department of Medical Oncology/Hematology; 2Department of Biomedical Engineering; 3Department of Radiology; 4Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 5Ocean Nanotech, LLC, Fayetteville, AR, USAAbstract: Magnetic iron oxide (IO nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI, which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.Keywords: iron oxide nanoparticles, tumor imaging, MRI, therapy

  16. Active versus passive adverse event reporting after pediatric chiropractic manual therapy: study protocol for a cluster randomized controlled trial.

    Science.gov (United States)

    Pohlman, Katherine A; Carroll, Linda; Tsuyuki, Ross T; Hartling, Lisa; Vohra, Sunita

    2017-12-01

    Patient safety performance can be assessed with several systems, including passive and active surveillance. Passive surveillance systems provide opportunity for health care personnel to confidentially and voluntarily report incidents, including adverse events, occurring in their work environment. Active surveillance systems systematically monitor patient encounters to seek detailed information about adverse events that occur in work environments; unlike passive surveillance, active surveillance allows for collection of both numerator (number of adverse events) and denominator (number of patients seen) data. Chiropractic manual therapy is commonly used in both adults and children, yet few studies have been done to evaluate the safety of chiropractic manual therapy for children. In an attempt to evaluate this, this study will compare adverse event reporting in passive versus active surveillance systems after chiropractic manual therapy in the pediatric population. This cluster randomized controlled trial aims to enroll 70 physicians of chiropractic (unit of randomization) to either passive or active surveillance system to report adverse events that occur after treatment for 60 consecutive pediatric (13 years of age and younger) patient visits (unit of analysis). A modified enrollment process with a two-phase consent procedure will be implemented to maintain provider blinding and minimize dropouts. The first phase of consent is for the provider to confirm their interest in a trial investigating the safety of chiropractic manual therapy. The second phase ensures that they understand the specific requirements for the group to which they were randomized. Percentages, incidence estimates, and 95% confidence intervals will be used to describe the count of reported adverse events in each group. The primary outcome will be the number and quality of the adverse event reports in the active versus the passive surveillance group. With 80% power and 5% one-sided significance

  17. New Targets for End-Stage Chronic Kidney Disease Therapy

    Directory of Open Access Journals (Sweden)

    Prakoura Niki

    2015-05-01

    Full Text Available Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a not previously described in the kidney, b highly upregulated during progression and returning to the normal levels during reversal, and c producing proteins that are either circulating or membrane receptors.

  18. Update in Systemic and Targeted Therapies in Gastrointestinal Oncology

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2018-03-01

    Full Text Available Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented. The use of peri-operative chemotherapy comprised of 5-fluorouracil or capecitabine, leucovorin, oxaliplatin, and docetaxel (FLOT, and immunotherapy including pembrolizumab, nivolumab, and ipilimumab in gastroesophageal carcinoma are discussed. Data from clinical trials that investigated the targeted therapeutics including nivolumab, ramucirumab, lenvatinib, and BLU-554 are reported. The role of adjuvant capecitabine in resected biliary tract carcinoma (BTC and nab-paclitaxel in combination with gemcitabine and cisplatin in advanced BTC are presented. In colorectal carcinoma, the efficacy of nivolumab, adjuvant FOLFOX or CAPOX, irinotecan/cetuximab/vemurafenib, and trifluridine/tipiracil/bevacizumab, is examined. In summary, some of the above systemic therapies have become or are expected to become new standard of care, while the others demonstrate the potential of becoming new treatment options.

  19. Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

    Directory of Open Access Journals (Sweden)

    Mavroudi M

    2014-01-01

    Full Text Available Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The grim statistics speak for themselves with reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem guided gene therapy. Stem cells have the unique potential for self-renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we

  20. Novel epigenetic target therapy for prostate cancer: a preclinical study.

    Directory of Open Access Journals (Sweden)

    Ilaria Naldi

    Full Text Available Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine, hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap and hormone refractory (DU145 prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs drug delivery system (DDS carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

  1. Novel epigenetic target therapy for prostate cancer: a preclinical study.

    Science.gov (United States)

    Naldi, Ilaria; Taranta, Monia; Gherardini, Lisa; Pelosi, Gualtiero; Viglione, Federica; Grimaldi, Settimio; Pani, Luca; Cinti, Caterina

    2014-01-01

    Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap) and hormone refractory (DU145) prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs) drug delivery system (DDS) carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

  2. The Effectiveness of Manual Therapy for Relieving Pain, Stiffness, and Dysfunction in Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Xu, Qinguang; Chen, Bei; Wang, Yueyi; Wang, Xuezong; Han, Dapeng; Ding, Daofang; Zheng, Yuxin; Cao, Yuelong; Zhan, Hongsheng; Zhou, Yao

    2017-05-01

    Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Manual therapy is one widely used physical treatment for KOA. To evaluate the effectiveness and adverse events (AEs) of manual therapy compared to other treatments for relieving pain, stiffness, and physical dysfunction in patients with KOA. A systematic review and meta-analysis of manual therapy for KOA. We searched PubMed, EMBASE, the Cochrane Library, and Chinese databases for relevant randomized controlled trials (RCTs) of manual therapy for patients with KOA from the inception to October 2015 without language restrictions. RCTs compared manual therapy to the placebo or other interventional control with an appropriate description of randomization. Two reviewers independently conducted the search results identification, data extraction, and methodological quality assessment. The methodological quality was assessed by PEDro scale. Pooled data was expressed as standard mean difference (SMD), with 95% confident intervals (CIs) in a random effects model. The meta-analysis of manual therapy for KOA on pain, stiffness, and physical function were conducted. Fourteen studies involving 841 KOA participants compared to other treatments were included. The methodological quality of most included RCTs was poor. The mean PEDro scale score was 6.6. The meta-analyses results showed that manual therapy had statistically significant effects on relieving pain (standardized mean difference, SMD = -0.61, 95% CI -0.95 to -0.28, P = 76%), stiffness (SMD = -0.58, 95% CI -0.95 to -0.21, P = 81%), improving physical function (SMD = -0.49, 95% CI -0.76 to -0.22, P = 65%), and total score (SMD = -0.56, 95% CI -0.78 to -0.35, P = 50%). But in the subgroups, manual therapy did not show significant improvements on stiffness and physical function when treatment duration was less than 4 weeks. And the long-term information for manual therapy was

  3. Ultrasound-Guided Application of Percutaneous Electrolysis as an Adjunct to Exercise and Manual Therapy for Subacromial Pain Syndrome: a Randomized Clinical Trial.

    Science.gov (United States)

    de-Miguel-Valtierra, Lorena; Salom-Moreno, Jaime; Fernández-de-Las-Peñas, César; Cleland, Joshua A; Arias-Buría, José L

    2018-05-16

    This randomized clinical trial compared the effects of adding US-guided percutaneous electrolysis into a program consisting of manual therapy and exercise on pain, related-disability, function and pressure sensitivity in subacromial pain syndrome. Fifty patients with subacromial pain syndrome were randomized into manual therapy and exercise or percutaneous electrolysis group. All patients received the same manual therapy and exercise program, one session per week for 5 consecutive weeks. Patients assigned to the electrolysis group also received the application of percutaneous electrolysis at each session. The primary outcome was Disabilities of the Arm, Shoulder and Hand (DASH). Secondary outcomes included pain, function (Shoulder Pain and Disability Index-SPADI) pressure pain thresholds (PPTs) and Global Rating of Change (GROC). They were assessed at baseline, post-treatment, and 3, and 6 months after treatment. Both groups showed similar improvements in the primary outcome (DASH) at all follow-ups (P=0.051). Subjects receiving manual therapy, exercise, and percutaneous electrolysis showed significantly greater changes in shoulder pain (P0.91) for shoulder pain and function at 3 and 6 months in favour of the percutaneous electrolysis group. No between-groups differences in PPT were found. The current clinical trial found that the inclusion of US-guided percutaneous electrolysis in combination with manual therapy and exercise resulted in no significant differences for related-disability (DASH) than the application of manual therapy and exercise alone in patients with subacromial pain syndrome. Nevertheless, differences were reported for some secondary outcomes such as shoulder pain and function (SPADI). Whether or not these effects are reliable should be addressed in future studies Perspective This study found that the inclusion of US-guided percutaneous electrolysis into a manual therapy and exercise program resulted in no significant differences for disability

  4. Targeted therapies for diarrhea-predominant irritable bowel syndrome

    Science.gov (United States)

    Olden, Kevin W

    2012-01-01

    Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients’ daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder. PMID:22754282

  5. Efficacy of Manual Therapy Including Neurodynamic Techniques for the Treatment of Carpal Tunnel Syndrome: A Randomized Controlled Trial.

    Science.gov (United States)

    Wolny, Tomasz; Saulicz, Edward; Linek, Paweł; Shacklock, Michael; Myśliwiec, Andrzej

    2017-05-01

    The purpose of this randomized trial was to compare the efficacy of manual therapy, including the use of neurodynamic techniques, with electrophysical modalities on patients with mild and moderate carpal tunnel syndrome (CTS). The study included 140 CTS patients who were randomly assigned to the manual therapy (MT) group, which included the use of neurodynamic techniques, functional massage, and carpal bone mobilizations techniques, or to the electrophysical modalities (EM) group, which included laser and ultrasound therapy. Nerve conduction, pain severity, symptom severity, and functional status measured by the Boston Carpal Tunnel Questionnaire were assessed before and after treatment. Therapy was conducted twice weekly and both groups received 20 therapy sessions. A baseline assessment revealed group differences in sensory conduction of the median nerve (P < .01) but not in motor conduction (P = .82). Four weeks after the last treatment procedure, nerve conduction was examined again. In the MT group, median nerve sensory conduction velocity increased by 34% and motor conduction velocity by 6% (in both cases, P < .01). There was no change in median nerve sensory and motor conduction velocities in the EM. Distal motor latency was decreased (P < .01) in both groups. A baseline assessment revealed no group differences in pain severity, symptom severity, or functional status. Immediately after therapy, analysis of variance revealed group differences in pain severity (P < .01), with a reduction in pain in both groups (MT: 290%, P < .01; EM: 47%, P < .01). There were group differences in symptom severity (P < .01) and function (P < .01) on the Boston Carpal Tunnel Questionnaire. Both groups had an improvement in functional status (MT: 47%, P < .01; EM: 9%, P < .01) and a reduction in subjective CTS symptoms (MT: 67%, P < .01; EM: 15%, P < .01). Both therapies had a positive effect on nerve conduction, pain reduction, functional status, and subjective symptoms in

  6. Targeted Therapy Database (TTD: a model to match patient's molecular profile with current knowledge on cancer biology.

    Directory of Open Access Journals (Sweden)

    Simone Mocellin

    Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method

  7. Additional Effect of Static Ultrasound and Diadynamic Currents on Myofascial Trigger Points in a Manual Therapy Program for Patients With Chronic Neck Pain: A Randomized Clinical Trial.

    Science.gov (United States)

    Dibai-Filho, Almir Vieira; de Oliveira, Alessandra Kelly; Girasol, Carlos Eduardo; Dias, Fabiana Rodrigues Cancio; Guirro, Rinaldo Roberto de Jesus

    2017-04-01

    To assess the additional effect of static ultrasound and diadynamic currents on myofascial trigger points in a manual therapy program to treat individuals with chronic neck pain. A single-blind randomized trial was conducted. Both men and women, between ages 18 and 45, with chronic neck pain and active myofascial trigger points in the upper trapezius were included in the study. Subjects were assigned to 3 different groups: group 1 (n = 20) was treated with manual therapy; group 2 (n = 20) was treated with manual therapy and static ultrasound; group 3 (n = 20) was treated with manual therapy and diadynamic currents. Individuals were assessed before the first treatment session, 48 hours after the first treatment session, 48 hours after the tenth treatment session, and 4 weeks after the last session. There was no group-versus-time interaction for Numeric Rating Scale, Neck Disability Index, Pain-Related Self-Statement Scale, pressure pain threshold, cervical range of motion, and skin temperature (F-value range, 0.089-1.961; P-value range, 0.106-0.977). Moreover, we found no differences between groups regarding electromyographic activity (P > 0.05). The use of static ultrasound or diadynamic currents on myofascial trigger points in upper trapezius associated with a manual therapy program did not generate greater benefits than manual therapy alone.

  8. Effect of Adding Interferential Current in an Exercise and Manual Therapy Program for Patients With Unilateral Shoulder Impingement Syndrome: A Randomized Clinical Trial.

    Science.gov (United States)

    Gomes, Cid André Fidelis de Paula; Dibai-Filho, Almir Vieira; Moreira, William Arruda; Rivas, Shirley Quispe; Silva, Emanuela Dos Santos; Garrido, Ana Claudia Bogik

    The purpose of this study was to measure the additional effect of adding interferential current (IFC) to an exercise and manual therapy program for patients with unilateral shoulder impingement syndrome. Forty-five participants were randomly assigned to group 1 (exercise and manual therapy), group 2 (exercise and manual therapy + IFC), or group 3 (exercise and manual therapy + placebo ultrasound). Individuals participated in 16 treatment sessions, twice a week for 8 weeks. The primary outcome of the study was total score of the Shoulder Pain and Disability Index (SPADI). The secondary outcomes were the pain and disability subscales of SPADI, Numeric Rating Scale, and Pain-Related Self-Statement Scale. Adjusted between-group mean differences (MDs) and 95% confidence intervals (CIs) were calculated using linear mixed models. After 16 treatment sessions, statistically significant but not clinically important differences were identified in favor of the exercise and manual therapy program alone in the SPADI-total (group 1 vs group 2, MD 11.12 points, 95% CI 5.90-16.35; group 1 vs group 3, MD 13.43 points, 95% CI 8.21-18.65). Similar results were identified for secondary outcomes. The addition of IFC does not generate greater clinical effects in an exercise and manual therapy program for individuals with unilateral shoulder impingement syndrome. Copyright © 2018. Published by Elsevier Inc.

  9. The effectiveness of manual physical therapy interventions in pediatric patients with anterior hip pain: a retrospective study.

    Science.gov (United States)

    Galleher, Mindy; Crowe, Briana; Selhorst, Mitchell

    2017-12-01

    The purposes of this study were to: (1) assess the benefit of adding manual therapy (MT) to physical therapy care in pediatric patients with anterior hip pain; (2) assess the relative risk of adverse reactions when MT is used; and (3) report the types of MT used. This study was a retrospective chart review of patients treated in a hospital-based sports medicine clinic. The charts of 201 patients (mean age = 14.23 ± 2.15 years) met the inclusion criteria and were reviewed. Patients were grouped into those who received MT during their episode of care, and those who did not. Pain efficiency (change in pain/number of visits), number and type of adverse reactions, as well as frequency and type of manual therapy interventions used, were the outcomes of interest. The mean pain efficiency was significantly less if manual therapy was performed (MT = 0.60 [95% CI 0.47-0.72], no MT = 0.80 [95% CI 0.71-0.90] p  = 0.01). There was no significant difference between groups in risk of adverse reactions (MT = 5, no MT = 5). The number of visits was significantly different between groups (MT = 9.43 ± 3.9 sessions, and no MT = 7.6 ± 5.2 sessions). MT did not increase the risk of an adverse reaction in pediatric patients with anterior hip pain. While it appears to be a safe intervention, it did not improve pain efficiency or patient adherence. Future research should be performed to assess the effectiveness of MT, when performed by skilled therapists, in pediatric patients with hip pain in a controlled manner. Level of Evidence: 3b.

  10. Biologic Drugs: A New Target Therapy in COPD?

    Science.gov (United States)

    Yousuf, Ahmed; Brightling, Christopher E

    2018-04-23

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Current diagnostic criteria based on the presence of fixed airflow obstruction and symptoms do not integrate the complex pathological changes occurring within the lung and they do not define different airway inflammatory patterns. The current management of COPD is based on 'one size fits all' approach and does not take the importance of heterogeneity in COPD population into account. The available treatments aim to alleviate symptoms and reduce exacerbation frequency but do not alter the course of the disease. Recent advances in molecular biology have furthered our understanding of inflammatory pathways in pathogenesis of COPD and have led to development of targeted therapies (biologics and small molecules) based on predefined biomarkers. Herein we shall review the trials of biologics in COPD and potential future drug developments in the field.

  11. Physics at the biomolecular interface fundamentals for molecular targeted therapy

    CERN Document Server

    Fernández, Ariel

    2016-01-01

    This book focuses primarily on the role of interfacial forces in understanding biological phenomena at the molecular scale. By providing a suitable statistical mechanical apparatus to handle the biomolecular interface, the book becomes uniquely positioned to address core problems in molecular biophysics. It highlights the importance of interfacial tension in delineating a solution to the protein folding problem, in unravelling the physico-chemical basis of enzyme catalysis and protein associations, and in rationally designing molecular targeted therapies. Thus grounded in fundamental science, the book develops a powerful technological platform for drug discovery, while it is set to inspire scientists at any level in their careers determined to address the major challenges in molecular biophysics. The acknowledgment of how exquisitely the structure and dynamics of proteins and their aqueous environment are related attests to the overdue recognition that biomolecular phenomena cannot be effectively understood w...

  12. Vibrio cholerae infection, novel drug targets and phage therapy.

    Science.gov (United States)

    Fazil, Mobashar Hussain Urf Turabe; Singh, Durg V

    2011-10-01

    Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although antibiotic therapy shortens the duration of diarrhea, excessive use has contributed to the emergence of antibiotic resistance in V. cholerae. Mobile genetic elements have been shown to be largely responsible for the shift of drug resistance genes in bacteria, including some V. cholerae strains. Quorum sensing communication systems are used for interaction among bacteria and for sensing environmental signals. Sequence analysis of the ctxB gene of toxigenic V. cholerae strains demonstrated its presence in multiple cholera toxin genotypes. Moreover, bacteriophage that lyse the bacterium have been reported to modulate epidemics by decreasing the required infectious dose of the bacterium. In this article, we will briefly discuss the disease, its clinical manifestation, antimicrobial resistance and the novel approaches to locate drug targets to treat cholera.

  13. The nucleolus: an emerging target for cancer therapy.

    Science.gov (United States)

    Hein, Nadine; Hannan, Katherine M; George, Amee J; Sanij, Elaine; Hannan, Ross D

    2013-11-01

    For over 100 years, pathologists have utilised an increase in size and number of nucleoli, the subnuclear site of ribosome synthesis, as a marker of aggressive tumours. Despite this, the contribution of the nucleolus and ribosomal RNA synthesis to cancer has been largely overlooked. This concept has recently changed with the demonstration that the nucleolus indirectly controls numerous other cellular functions, in particular, the cellular activity of the critical tumour suppressor protein, p53. Moreover, selective inhibition of ribosomal gene transcription in the nucleolus has been shown to be an effective therapeutic strategy to promote cancer-specific activation of p53. This article reviews the largely untapped potential of the nucleolus and ribosomal gene transcription as exciting new targets for cancer therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Chemokine Signaling in Allergic Contact Dermatitis: Toward Targeted Therapies.

    Science.gov (United States)

    Smith, Jeffrey S; Rajagopal, Sudarshan; Atwater, Amber Reck

    2018-06-22

    Allergic contact dermatitis (ACD) is a common skin disease that results in significant cost and morbidity. Despite its high prevalence, therapeutic options are limited. Allergic contact dermatitis is regulated primarily by T cells within the adaptive immune system, but also by natural killer and innate lymphoid cells within the innate immune system. The chemokine receptor system, consisting of chemokine peptides and chemokine G protein-coupled receptors, is a critical regulator of inflammatory processes such as ACD. Specific chemokine signaling pathways are selectively up-regulated in ACD, most prominently CXCR3 and its endogenous chemokines CXCL9, CXCL10, and CXCL11. Recent research demonstrates that these 3 chemokines are not redundant and indeed activate distinct intracellular signaling profiles such as those activated by heterotrimeric G proteins and β-arrestin adapter proteins. Such differential signaling provides an attractive therapeutic target for novel ACD therapies and other inflammatory diseases.

  15. Structural and functional imaging for vascular targeted photodynamic therapy

    Science.gov (United States)

    Li, Buhong; Gu, Ying; Wilson, Brian C.

    2017-02-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

  16. Internal models of target motion: expected dynamics overrides measured kinematics in timing manual interceptions.

    Science.gov (United States)

    Zago, Myrka; Bosco, Gianfranco; Maffei, Vincenzo; Iosa, Marco; Ivanenko, Yuri P; Lacquaniti, Francesco

    2004-04-01

    Prevailing views on how we time the interception of a moving object assume that the visual inputs are informationally sufficient to estimate the time-to-contact from the object's kinematics. Here we present evidence in favor of a different view: the brain makes the best estimate about target motion based on measured kinematics and an a priori guess about the causes of motion. According to this theory, a predictive model is used to extrapolate time-to-contact from expected dynamics (kinetics). We projected a virtual target moving vertically downward on a wide screen with different randomized laws of motion. In the first series of experiments, subjects were asked to intercept this target by punching a real ball that fell hidden behind the screen and arrived in synchrony with the visual target. Subjects systematically timed their motor responses consistent with the assumption of gravity effects on an object's mass, even when the visual target did not accelerate. With training, the gravity model was not switched off but adapted to nonaccelerating targets by shifting the time of motor activation. In the second series of experiments, there was no real ball falling behind the screen. Instead the subjects were required to intercept the visual target by clicking a mousebutton. In this case, subjects timed their responses consistent with the assumption of uniform motion in the absence of forces, even when the target actually accelerated. Overall, the results are in accord with the theory that motor responses evoked by visual kinematics are modulated by a prior of the target dynamics. The prior appears surprisingly resistant to modifications based on performance errors.

  17. Osteosarcoma target therapy with stem cell transplant: A case review

    International Nuclear Information System (INIS)

    Fawzy, A.

    2005-01-01

    Full text: Radioisotopes with medium-energy beta emission and half life of a few days are attractive option for systemic delivery of targeted irradiation. Samarium-153 ethylene diamine tetra-ethylene phosphonale (153Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic osseous lesion. The usual dose of Sm-153 in metastatic disease is 1mCi/Kg (37MBq/Kg) and the dose limiting toxicity is thrombocytopenia. As local radiotherapy has only a limited therapeutic role in the treatment of osteosarcoma, and some types of the tumour portray an unpredictable response to chemotherapy. High dose Sm-153 (30mCi/Kg) was proposed for the target management of recurrent osteosarcoma, this was followed by stem cell transplant (peripheral-blood progenitor, PBPCs). A female child, 10 years old, with polyostotic osteosarcoma with local recurrence in the right hipbone was chosen for therapy. She had left knee prosthesis, right lower limb dis-articulation, and was given chemotherapy in multiple regions. She was subjected to MDP bone scan showing active uptake in an expanding bone lesion in the right hip bone, and was also subjected to MIBI scan, which showed negative uptake. She received 30mCi/Kg Sm-153 (660mCi in total dose), with no major events occurring in the post-injection period. After 10 days the patient went into pancytopenia, which necessitated haematological support. By day 14, there was minimal radiation in the whole body image and the child received her bone marrow transplant. There was marked improvement in the tumour size after 6 weeks of therapy, with improvement in the alkaline phosphatase level (from 1350Iu, before treatment to 350 post treatment). This was confirmed by serial MDP bone scan. High dose Sm-153 with stem cell transplant is considered view a promising method in the management of osteosarcoma. (author)

  18. HIV-derived vectors for gene therapy targeting dendritic cells.

    Science.gov (United States)

    Rossetti, Maura; Cavarelli, Mariangela; Gregori, Silvia; Scarlatti, Gabriella

    2013-01-01

    Human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LV) have the potential to mediate stable therapeutic gene transfer. However, similarly to other viral vectors, their benefit is compromised by the induction of an immune response toward transgene-expressing cells that closely mimics antiviral immunity. LV share with the parental HIV the ability to activate dendritic cells (DC), while lack the peculiar ability of subverting DC functions, which is responsible for HIV immune escape. Understanding the interaction between LV and DC, with plasmacytoid and myeloid DC playing fundamental and distinct roles, has paved the way to novel approaches aimed at regulating transgene-specific immune responses. Thanks to the ability to target either DC subsets LV might be a powerful tool to induce immunity (i.e., gene therapy of cancer), cell death (i.e., in HIV/AIDS infection), or tolerance (i.e., gene therapy strategies for monogenic diseases). In this chapter, similarities and differences between the LV-mediated and HIV-mediated induction of immune responses, with specific focus on their interactions with DC, are discussed.

  19. Effects of Mode of Target Task Selection on Learning about Plants in a Mobile Learning Environment: Effortful Manual Selection versus Effortless QR-Code Selection

    Science.gov (United States)

    Gao, Yuan; Liu, Tzu-Chien; Paas, Fred

    2016-01-01

    This study compared the effects of effortless selection of target plants using quick respond (QR) code technology to effortful manual search and selection of target plants on learning about plants in a mobile device supported learning environment. In addition, it was investigated whether the effectiveness of the 2 selection methods was…

  20. Dermatologic adverse events associated with chemotherapy and targeted anticancer therapy

    Directory of Open Access Journals (Sweden)

    Maria Kowalska

    2016-05-01

    Full Text Available Chemotherapeutic agents and drugs used for targeted tumor therapy often cause undesirable side effects of the skin which typically are toxic cutaneous reactions (toxicity grade 1 to 4. The first group of drugs that cause toxicities affecting the skin are inhibitors of epidermal growth factor receptor (EGFR. They cause a variety of skin changes (PRIDE syndrome, which are mainly manifested by papulopustular rash, also referred to as acneiform rash, occurring in 44–74% of patients. Another drug which causes cutaneous toxicities is inhibitor of CTLA4 (cytotoxic T lymphocyte-associated protein 4, which is represented by ipilimumab, used in the treatment of metastatic melanoma. The most common dermatological adverse event, observed in 40–64% of patients receiving ipilimumab, is generalized maculopapular rash with pruritus and dry skin, and in some cases vitiligo is also observed. BRAF and MEK inhibitors introduced for the treatment of advanced melanoma also cause skin rashes. BRAF inhibitors also affecting the proliferation of keratinocytes stimulate hypertrophic changes and cause the whole spectrum of lesions from benign and keratoacanthoma to squamous cell carcinoma. A hedgehog pathway inhibitor (vismodegib is used for the treatment of metastatic basal cell carcinoma. The most common adverse events it causes are reversible alopecia and dysgeusia, but it can also cause the development of keratoacanthoma and squamous cell carcinoma. Among the most common side effects of chemotherapy and targeted therapy are toxic changes within the hands and feet (hand-foot skin reaction – HFSR that early manifest as a neurological symptoms (numbness, paresthesia, and skin symptoms (erythematous swelling changes, blisters, hyperkeratosis occur later. Anti-cancer drugs can also cause serious skin diseases such as Stevens-Johnson syndrome (SJS, toxic epidermal necrolysis (TEN and DRESS (drug rash with eosinophilia and systemic symptoms, whose course and prognosis

  1. Theoretical and practical outline of the Copenhagen PACT narrative-based exercise counselling manual to promote physical activity in post-therapy cancer survivors.

    Science.gov (United States)

    Midtgaard, Julie

    2013-02-01

    Sedentary behaviour and reduced exercise capacity are potential persisting effects of anti-cancer therapy that may predispose to serious health conditions. It is well-established that physical exercise may prevent some of these problems. However, the extent to which cancer survivors are able to adopt long-term physical activity habits depends largely on their motivation. This theoretical paper aims to outline how researchers and practitioners can draw from Antonovsky's salutogenetic theory and White & Epston's Narrative Therapy to develop and implement intervention efforts centered on promotion of long-term physical activity behaviour, while at the same time increasing the individual cancer survivor's sense of meaning and personal health resources. The Copenhagen PACT (Physical Activity after Cancer Treatment) Study targeting adoption and maintenance of regular physical activity in post-therapy cancer survivors is briefly presented including a brief review of the theoretical rationale behind the psychological component of the intervention, i.e. a narrative-based exercise counselling programme. Subsequently, particular attention is given to the core principles, different components and structure of the counselling manual including sample questions and examples of written documents that have emanated from the individual counselling sessions. The discussion includes consideration of some methodological challenges that arise when attempting to evaluate narrative-based interventions in the context of physical activity promotion in cancer rehabilitation and survivorship care.

  2. Efficacy of manual therapy treatments for people with cervicogenic dizziness and pain: protocol of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Reid Susan A

    2012-10-01

    Full Text Available Abstract Background Cervicogenic dizziness is a disabling condition characterised by postural unsteadiness that is aggravated by cervical spine movements and associated with a painful and/or stiff neck. Two manual therapy treatments (Mulligan’s Sustained Natural Apophyseal Glides (SNAGs and Maitland’s passive joint mobilisations are used by physiotherapists to treat this condition but there is little evidence from randomised controlled trials to support their use. The aim of this study is to conduct a randomised controlled trial to compare these two forms of manual therapy (Mulligan glides and Maitland mobilisations to each other and to a placebo in reducing symptoms of cervicogenic dizziness in the longer term and to conduct an economic evaluation of the interventions. Methods Participants with symptoms of dizziness described as imbalance, together with a painful and/or stiff neck will be recruited via media releases, advertisements and mail-outs to medical practitioners in the Hunter region of NSW, Australia. Potential participants will be screened by a physiotherapist and a neurologist to rule out other causes of their dizziness. Once diagnosed with cervciogenic dizziness, 90 participants will be randomly allocated to one of three groups: Maitland mobilisations plus range-of-motion exercises, Mulligan SNAGs plus self-SNAG exercises or placebo. Participants will receive two to six treatments over six weeks. The trial will have unblinded treatment but blinded outcome assessments. Assessments will occur at baseline, post-treatment, six weeks, 12 weeks, six months and 12 months post treatment. The primary outcome will be intensity of dizziness. Other outcome measures will be frequency of dizziness, disability, intensity of cervical pain, cervical range of motion, balance, head repositioning, adverse effects and treatment satisfaction. Economic outcomes will also be collected. Discussion This paper describes the methods for a randomised

  3. The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized clinical trial.

    Science.gov (United States)

    Louw, Adriaan; Farrell, Kevin; Landers, Merrill; Barclay, Martin; Goodman, Elise; Gillund, Jordan; McCaffrey, Sara; Timmerman, Laura

    2017-12-01

    To determine if a neuroplasticity educational explanation for a manual therapy technique will produce a different outcome compared to a traditional mechanical explanation. Sixty-two patients with chronic low back pain (CLBP) were recruited for the study. Following consent, demographic data were obtained as well as pain ratings for low back pain (LBP) and leg pain (Numeric Pain Rating Scale), disability (Oswestry Disability Index), fear-avoidance (Fear-Avoidance-Beliefs Questionnaire), forward flexion (fingertips-to-floor), and straight leg raise (SLR) (inclinometer). Patients were then randomly allocated to receive one of two explanations (neuroplasticity or mechanical), a manual therapy technique to their lumbar spine, followed by post-intervention measurements of LBP, leg pain, forward flexion, and SLR. Sixty-two patients (female 35 [56.5%]), with a mean age of 60.1 years and mean duration of 9.26 years of CLBP participated in the study. There were no statistically significant interactions for LBP ( p  = .325), leg pain ( p  = .172), and trunk flexion ( p  = .818) between the groups, but SLR showed a significant difference in favor of the neuroplasticity explanation ( p  = .041). Additionally, the neuroplasticity group were 7.2 times (95% confidence interval = 1.8-28.6) more likely to improve beyond the MDC on the SLR than participants in the mechanical group. The results of this study show that a neuroplasticity explanation, compared to a traditional biomechanical explanation, resulted in a measureable difference in SLR in patients with CLBP when receiving manual therapy. Future studies need to explore if the increase in SLR correlated to changes in cortical maps of the low back.

  4. New Trends in Cancer Therapy: Targeting Ion Channels and Transporters

    Directory of Open Access Journals (Sweden)

    Annarosa Arcangeli

    2010-04-01

    Full Text Available The expression and activity of different channel types mark and regulate specific stages of cancer establishment and progression. Blocking channel activity impairs the growth of some tumors, both in vitro and in vivo, which opens a new field for pharmaceutical research. However, ion channel blockers may produce serious side effects, such as cardiac arrhythmias. For instance, Kv11.1 (hERG1 channels are aberrantly expressed in several human cancers, in which they control different aspects of the neoplastic cell behaviour. hERG1 blockers tend to inhibit cancer growth. However they also retard the cardiac repolarization, thus lengthening the electrocardiographic QT interval, which can lead to life-threatening ventricular arrhythmias. Several possibilities exist to produce less harmful compounds, such as developing specific drugs that bind hERG1 channels in the open state or disassemble the ion channel/integrin complex which appears to be crucial in certain stages of neoplastic progression. The potential approaches to improve the efficacy and safety of ion channel targeting in oncology include: (1 targeting specific conformational channel states; (2 finding ever more specific inhibitors, including peptide toxins, for channel subtypes mainly expressed in well-identified tumors; (3 using specific ligands to convey traceable or cytotoxic compounds; (4 developing channel blocking antibodies; (5 designing new molecular tools to decrease channel expression in selected cancer types. Similar concepts apply to ion transporters such as the Na+/K+ pump and the Na+/H+ exchanger. Pharmacological targeting of these transporters is also currently being considered in anti-neoplastic therapy.

  5. Triple-negative breast cancer: new perspectives for targeted therapies

    Directory of Open Access Journals (Sweden)

    Tomao F

    2015-01-01

    Full Text Available Federica Tomao,1 Anselmo Papa,2 Eleonora Zaccarelli,2 Luigi Rossi,2 Davide Caruso,2 Marina Minozzi,2 Patrizia Vici,3 Luigi Frati,4 Silverio Tomao21Department of Gynecology and Obstetrics, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, 2Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, 3Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy; 4Department of Molecular Medicine, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, ItalyAbstract: Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.Keywords: basal-like breast cancer, estrogen–progesterone receptors, gene-expression microarray, human epidermal growth factor receptor 2, chemotherapy, target therapy

  6. Individualized targeted therapy for glioblastoma: fact or fiction?

    Science.gov (United States)

    Weller, Michael; Stupp, Roger; Hegi, Monika; Wick, Wolfgang

    2012-01-01

    This review will address the current state of individualized cancer therapy for glioblastoma. Glioblastomas are highly malignant primary brain tumors presumably originating from neuroglial progenitor cells. Median survival is less than 1 year. Recent developments in the morphologic, clinical, and molecular classification of glioblastoma were reviewed, and their impact on clinical decision making was analyzed. Glioblastomas can be classified by morphology, clinical characteristics, complex molecular signatures, single biomarkers, or imaging parameters. Some of these characteristics, including age and Karnofsky Performance Scale score, provide important prognostic information. In contrast, few markers help to choose between various treatment options. Promoter methylation of the O-methylguanine methyltransferase gene seems to predict benefit from alkylating agent chemotherapy. Hence, it is used as an entry criterion for alkylator-free experimental combination therapy with radiotherapy. Screening for a specific type of epidermal growth factor receptor mutation is currently being explored as a biomarker for selecting patients for vaccination. Positron emission tomography for the detection of ανβ3/5 integrins could be used to select patients for treatment with anti-integrin antiangiogenic approaches. Despite extensive efforts at defining biological markers as a basis for selecting therapies, most treatment decisions for glioblastoma patients are still based on age and performance status. However, several ongoing clinical trials may enrich the repertoire of criteria for clinical decision making in the very near future. The concept of individualized or personalized targeted cancer therapy has gained significant attention throughout oncology. Yet, data in support of such an approach to glioblastoma, the most malignant subtype of glioma, are limited, and personalized medicine plays a minor role in current clinical neuro-oncology practice. In essence, this concept proposes

  7. Evaluation of a treatment manual and workshops for disseminating, parent-child interaction therapy.

    Science.gov (United States)

    Herschell, Amy D; McNeil, Cheryl B; Urquiza, Anthony J; McGrath, Jean M; Zebell, Nancy M; Timmer, Susan G; Porter, Alissa

    2009-01-01

    This study's main purposes were to: (a) evaluate a treatment manual as a dissemination strategy, (b) compare two workshop formats for evidence-based treatment (EBT) training, and (c) provide preliminary data on therapist characteristics potentially associated with successful EBT adoption. Forty-two community-based clinicians were assigned to one of two training groups (didactic or experiential). Behavior observation and self-report data were collected at four time points. Results suggest that reading a treatment manual is useful, but not sufficient. Experiential and didactic training were equally effective in increasing knowledge, skill, and satisfaction; however, after a 2-day training, few participants demonstrated mastery of skills.

  8. Effects of exercise and manual therapy on pain associated with hip osteoarthritis: a systematic review and meta-analysis.

    Science.gov (United States)

    Beumer, Lucy; Wong, Jennie; Warden, Stuart J; Kemp, Joanne L; Foster, Paul; Crossley, Kay M

    2016-04-01

    To explore the effects of exercise (water-based or land-based) and/or manual therapies on pain in adults with clinically and/or radiographically diagnosed hip osteoarthritis (OA). A systematic review and meta-analysis was performed, with patient reported pain assessed using a visual analogue scale (VAS) or the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Data were grouped by follow-up time (0-3 months=short term; 4-12 months=medium term and; >12 months=long term), and standardised mean differences (SMD) with 95% CIs were used to establish intervention effect sizes. Study quality was assessed using modified PEDro scores. 19 trials were included. Four studies showed short-term benefits favouring water-based exercise over minimal control using the WOMAC pain subscale (SMD -0.53, 95% CI -0.96 to -0.10). Six studies supported a short-term benefit of land-based exercise compared to minimal control on VAS assessed pain (SMD -0.49, 95% CI -0.70 to -0.29). There were no medium (SMD -0.23, 95% CI -0.48 to 0.03) or long (SMD -0.22, 95% CI -0.51 to 0.06) term benefits of exercise therapy, or benefit of combining exercise therapy with manual therapy (SMD -0.38, 95% CI -0.88 to 0.13) when compared to minimal control. Best available evidence indicates that exercise therapy (whether land-based or water-based) is more effective than minimal control in managing pain associated with hip OA in the short term. Larger high-quality RCTs are needed to establish the effectiveness of exercise and manual therapies in the medium and long term. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Cost-effectiveness of manual therapy for the management of musculoskeletal conditions: a systematic review and narrative synthesis of evidence from randomized controlled trials.

    Science.gov (United States)

    Tsertsvadze, Alexander; Clar, Christine; Court, Rachel; Clarke, Aileen; Mistry, Hema; Sutcliffe, Paul

    2014-01-01

    The purpose of this study was to systematically review trial-based economic evaluations of manual therapy relative to other alternative interventions used for the management of musculoskeletal conditions. A comprehensive literature search was undertaken in major medical, health-related, science and health economic electronic databases. Twenty-five publications were included (11 trial-based economic evaluations). The studies compared cost-effectiveness and/or cost-utility of manual therapy interventions to other treatment alternatives in reducing pain (spinal, shoulder, ankle). Manual therapy techniques (e.g., osteopathic spinal manipulation, physiotherapy manipulation and mobilization techniques, and chiropractic manipulation with or without other treatments) were more cost-effective than usual general practitioner (GP) care alone or with exercise, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. Chiropractic manipulation was found to be less costly and more effective than alternative treatment compared with either physiotherapy or GP care in improving neck pain. Preliminary evidence from this review shows some economic advantage of manual therapy relative to other interventions used for the management of musculoskeletal conditions, indicating that some manual therapy techniques may be more cost-effective than usual GP care, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. However, at present, there is a paucity of evidence on the cost-effectiveness and/or cost-utility evaluations for manual therapy interventions. Further improvements in the methodological conduct and reporting quality of economic evaluations of manual therapy are warranted in order to facilitate adequate evidence-based decisions among policy makers, health care practitioners, and patients. Copyright © 2014 National University

  10. Colorectal cancer heterogeneity and targeted therapy: a case for molecular disease subtypes

    NARCIS (Netherlands)

    Linnekamp, Janneke F.; Wang, Xin; Medema, Jan Paul; Vermeulen, Louis

    2015-01-01

    Personalized cancer medicine is becoming increasingly important in colorectal cancer treatment. Especially for targeted therapies, large variations between individual treatment responses exist. Predicting therapy response is of utmost significance, as it prevents overtreatment and adverse effects in

  11. Third prize : A blinded randomized clinical trial of manual therapy and physiotherapy for chronic back and neck complaints: Physical outcome measures

    NARCIS (Netherlands)

    Koes, B. W.; Bouter, L. M.; Van Mameren, H.; Essers, A. H M; Verstegen, G. M J R; Hofhuizen, D. M.; Houben, J. P.; Knipschild, P. G.

    1992-01-01

    In a blinded randomized clinical trial, we compared the effectiveness of manual therapy, physiotherapy, (continued) treatment by the general practitioner (GP), and a placebo therapy (detuned ultrasound and detuned short wave diathermy) for patients (n = 256) with chronic nonspecific back and neck

  12. The effectiveness of manual therapy, physiotherapy, and treatment by the general practitioner for nonspecific back and neck complaints : A randomized clinical trial

    NARCIS (Netherlands)

    Koes, B. W.; Bouter, L. M.; Van Mameren, H.; Essers, A. H.; Verstegen, G. M.; Hofhuizen, D. M.; Houben, J. P.; Knipschild, P. G.

    1992-01-01

    In a randomized trial, the effectiveness of manual therapy, physiotherapy, continued treatment by the general practitioner, and placebo therapy (detuned ultrasound and detuned short-wave diathermy) were compared for patients (n = 256) with nonspecific back and neck complaints lasting for at least 6

  13. Pilot study: whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with lipedema.

    Science.gov (United States)

    Herbst, Karen L; Ussery, Christopher; Eekema, Alyna

    2017-09-20

    Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

  14. Emergency Victim Care. A Training Manual for Emergency Medical Technicians. Module 5. CPR, Oxygen Therapy. Revised.

    Science.gov (United States)

    Ohio State Dept. of Education, Columbus. Div. of Vocational Education.

    This student manual, the fifth in a set of 14 modules, is designed to train emergency medical technicians (EMTs) in Ohio. The module contains two sections covering the following course content; cardiopulmonary resuscitation (CPR) (including artificial ventilation, foreign body obstructions, adjunctive equipment and special techniques, artificial…

  15. Articulatory Changes in Muscle Tension Dysphonia: Evidence of Vowel Space Expansion Following Manual Circumlaryngeal Therapy

    Science.gov (United States)

    Roy, Nelson; Nissen, Shawn L.; Dromey, Christopher; Sapir, Shimon

    2009-01-01

    In a preliminary study, we documented significant changes in formant transitions associated with successful manual circumlaryngeal treatment (MCT) of muscle tension dysphonia (MTD), suggesting improvement in speech articulation. The present study explores further the effects of MTD on vowel articulation by means of additional vowel acoustic…

  16. EMMPRIN as a novel target for pancreatic cancer therapy

    Science.gov (United States)

    Kim, Hyunki; Zhai, Guihua; Liu, Zhiyong; Samuel, Sharon; Shah, Nemil; Helman, Emily E.; Knowles, Joseph A.; Stockard, Cecil R.; Fineberg, Naomi S.; Grizzle, William E.; Zhou, Tong; Zinn, Kurt R.; Rosenthal, Eben L.

    2013-01-01

    The objective of this study was to evaluate extracelluar matrix metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic-cancer murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1 and 3-7, while MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2. Dosing with anti-EMMPRIN antibody started immediately after implantation for groups 1-3 (residual tumor model) and at 21 days after cell implantation for groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti-EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, while the other groups served as the control. In residual tumor model, tumor growth of anti-EMMPRIN treated group was successfully arrested for 21 days (15±4 mm3), significantly lower than that of EMMPRIN knockdown group (80±15 mm3; p=0.001) or control group (240±41 mm3; pEMMPRIN therapy lowered tumor-volume increase about 40% compared with control regardless of dose amount. Ki67-expressed cell densities of group 5 was 939±150 mm−2, significantly lower than that of group 4 (1709±145 mm−2; p=0.006). Microvessel density of group 5 (30±6 mm−2) was also significantly lower than that of group 4 (53±5 mm−2; p=0.014), while the microvessel size of group 5 (191±22 μm2) was significantly larger than that of group 4 (113±26 μm2; p=0.049). These data show the high potential of anti-EMMPRIN therapy for pancreatic cancer, and support its clinical translation. PMID:21730821

  17. Tuning flux: autophagy as a target of heart disease therapy

    Science.gov (United States)

    Xie, Min; Morales, Cyndi R.; Lavandero, Sergio; Hill, Joseph A.

    2013-01-01

    Purpose of review Despite maximum medical and mechanical support therapy, heart failure remains a relentlessly progressive disorder with substantial morbidity and mortality. Autophagy, an evolutionarily conserved process of cellular cannibalization, has been implicated in virtually all forms of cardiovascular disease. Indeed, its role is context dependent, antagonizing or promoting disease depending on the circumstance. Here, we review current understanding of the role of autophagy in the pathogenesis of heart failure and explore this pathway as a target of therapeutic intervention. Recent findings In preclinical models of heart disease, cardiomyocyte autophagic flux is activated; indeed, its role in disease pathogenesis is the subject of intense investigation to define mechanism. Similarly, in failing human heart of a variety of etiologies, cardiomyocyte autophagic activity is upregulated, and therapy, such as with mechanical support systems, elicits declines in autophagy activity. However, when suppression of autophagy is complete, rapid and catastrophic cell death occurs, consistent with a model in which basal autophagic flux is required for proteostasis. Thus, a narrow zone of ‘optimal’ autophagy seems to exist. The challenge moving forward is to tune the stress-triggered autophagic response within that ‘sweet spot’ range for therapeutic benefit. Summary Whereas we have known for some years of the participation of lysosomal mechanisms in heart disease, it is only recently that upstream mechanisms (autophagy) are being explored. The challenge for the future is to dissect the underlying circuitry and titrate the response into an optimal, proteostasis-promoting range in hopes of mitigating the ever-expanding epidemic of heart failure. PMID:21415729

  18. The immediate effect of soft tissue manual therapy intervention on lung function in severe chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Cruz-Montecinos C

    2017-02-01

    Full Text Available Carlos Cruz-Montecinos,1–3 Diego Godoy-Olave,4 Felipe A Contreras-Briceño,5 Paulina Gutiérrez,4 Rodrigo Torres-Castro,2 Leandro Miret-Venegas,3 Roger M Engel6 1Laboratory of Biomechanics and Kinesiology, San José Hospital, Santiago, Chile; 2Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile; 3Unit of Kinesiology and Physical Therapy, San José Hospital, Santiago, Chile; 4Departamento de Kinesiología, Universidad Metropolitana de Ciencias de la Educación, Santiago, Chile; 5Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; 6Department of Chiropractic, Macquarie University, Sydney, Australia Background and objective: In chronic obstructive pulmonary disease (COPD, accessory respiratory muscles are recruited as a compensatory adaptation to changes in respiratory mechanics. This results in shortening and overactivation of these and other muscles. Manual therapy is increasingly being investigated as a way to alleviate these changes. The aim of this study was to measure the immediate effect on lung function of a soft tissue manual therapy protocol (STMTP designed to address changes in the accessory respiratory muscles and their associated structures in patients with severe COPD.Methods: Twelve medically stable patients (n=12 with an existing diagnosis of severe COPD (ten: GOLD Stage III and two: GOLD Stage IV were included. Residual volume, inspiratory capacity and oxygen saturation (SpO2 were recorded immediately before and after administration of the STMTP. A Student’s t-test was used to determine the effect of the manual therapy intervention (P<0.05.Results: The mean age of the patients was 62.4 years (range 46–77. Nine were male. Residual volume decreased from 4.5 to 3.9 L (P=0.002, inspiratory capacity increased from 2.0 to 2.1 L (P=0.039 and SpO2 increased from 93% to 96% (P=0.001.Conclusion: A single application of an STMTP appears to have the potential to produce

  19. Accuracy of computer-calculated and manual QRS duration assessments: Clinical implications to select candidates for cardiac resynchronization therapy.

    Science.gov (United States)

    De Pooter, Jan; El Haddad, Milad; Stroobandt, Roland; De Buyzere, Marc; Timmermans, Frank

    2017-06-01

    QRS duration (QRSD) plays a key role in the field of cardiac resynchronization therapy (CRT). Computer-calculated QRSD assessments are widely used, however inter-manufacturer differences have not been investigated in CRT candidates. QRSD was assessed in 377 digitally stored ECGs: 139 narrow QRS, 140 LBBB and 98 ventricular paced ECGs. Manual QRSD was measured as global QRSD, using digital calipers, by two independent observers. Computer-calculated QRSD was assessed by Marquette 12SL (GE Healthcare, Waukesha, WI, USA) and SEMA3 (Schiller, Baar, Switzerland). Inter-manufacturer differences of computer-calculated QRSD assessments vary among different QRS morphologies: narrow QRSD: 4 [2-9] ms (median [IQR]), p=0.010; LBBB QRSD: 7 [2-10] ms, p=0.003 and paced QRSD: 13 [6-18] ms, p=0.007. Interobserver differences of manual QRSD assessments measured: narrow QRSD: 4 [2-6] ms, p=non-significant; LBBB QRSD: 6 [3-12] ms, p=0.006; paced QRSD: 8 [4-18] ms, p=0.001. In LBBB ECGs, intraclass correlation coefficients (ICCs) were comparable for inter-manufacturer and interobserver agreement (ICC 0.830 versus 0.837). When assessing paced QRSD, manual measurements showed higher ICC compared to inter-manufacturer agreement (ICC 0.902 versus 0.776). Using guideline cutoffs of 130ms, up to 15% of the LBBB ECGs would be misclassified as <130ms or ≥130ms by at least one method. Using a cutoff of 150ms, this number increases to 33% of ECGs being misclassified. However, by combining LBBB-morphology and QRSD, the number of misclassified ECGs can be decreased by half. Inter-manufacturer differences in computer-calculated QRSD assessments are significant and may compromise adequate selection of individual CRT candidates when using QRSD as sole parameter. Paced QRSD should preferentially be assessed by manual QRSD measurements. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Common Manual Therapy Practices in the Netherlands for Infants With Upper Cervical Dysfunction: A Prospective Cohort Study.

    Science.gov (United States)

    Saedt, Eric R I C; Driehuis, Femke; Hoogeboom, Thomas J; van der Woude, Bé H; de Bie, Rob A; Nijhuis-van der Sanden, Maria W G

    2018-01-01

    The purpose of this study was to describe common clinical practices of manual therapists (MTs) in the Netherlands for infants with indications of upper cervical dysfunction (UCD). A prospective observational cohort study was conducted to gain insight into characteristics, reasons for seeking care, and common clinical practice for infants (<27 weeks) with indications of UCD, referred to MTs. Pre- and posttreatment self-reported questionnaires were used to collect data from parents and MTs. Parents reported on infant characteristics and perceived effect of treatment. Manual therapists reported on diagnostics, therapeutic procedures, and outcomes. Between 2006 and 2007, data regarding 307 referred infants (mean age: 11.2 weeks) were collected by parents and 42 MTs. The most frequent reasons for seeking care were positional preference, restlessness, and/or abnormal head position. Manual therapists observed active, spontaneous, and provoked mobility and passive upper cervical mobility. Of the 307 infants, 295 were diagnosed with UCD based on positive outcomes on the flexion-rotation test and/or lateral flexion test. After treatment with mobilization techniques, positive outcomes on the flexion-rotation test decreased from 78.8% to 6.8%. For the lateral flexion test, the positive outcomes decreased from 91.5% to 6.2%. All parents perceived positive treatment effects. No serious adverse events were reported during this study. This is the first study to describe common clinical practice for infants referred for manual therapy. Infants with UCD were treated mainly with upper cervical mobilization techniques, and the greatest perceived effect was observed after approximately 2 treatment sessions. Copyright © 2018. Published by Elsevier Inc.

  1. Manual Physical Therapy for Non-Surgical Treatment of Adhesion-Related Small Bowel Obstructions: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Amanda D. Rice

    2013-02-01

    Full Text Available Background: Adhesion formation is a widely acknowledged risk following abdominal or pelvic surgery. Adhesions in the abdomen or pelvis can cause or contribute to partial or total small bowel obstruction (SBO. These adhesions deter or prevent the passage of nutrients through the digestive tract, and may bind the bowel to the peritoneum, or other organs. Small bowel obstructions can quickly become life-threatening, requiring immediate surgery to resect the bowel, or lyse any adhesions the surgeon can safely access. Bowel repair is an invasive surgery, with risks including bowel rupture, infection, and peritonitis. An additional risk includes the formation of new adhesions during the healing process, creating the potential for subsequent adhesiolysis or SBO surgeries. Objective: Report the use of manual soft tissue physical therapy for the reversal of adhesion-related partial SBOs, and create an initial inquiry into the possibility of nonsurgical lysis of adhesions. Case Reports: Two patients presenting with SBO symptoms due to abdominal adhesions secondary to abdominal and pelvic surgery were treated with manual soft tissue physical therapy focused on decreasing adhesions. Conclusions: Successful treatment with resolution of symptom presentation of partial SBO and sustained results were observed in both patients treated.

  2. Does early change predict long-term (6 months) improvements in subjects who receive manual therapy for low back pain?

    Science.gov (United States)

    Cook, Chad; Petersen, Shannon; Donaldson, Megan; Wilhelm, Mark; Learman, Ken

    2017-09-01

    Early change is commonly assessed for manual therapy interventions and has been used to determine treatment appropriateness. However, current studies have only explored the relationship of between or within-session changes and short-/medium-term outcomes. The goal of this study was to determine whether pain changes after two weeks of pragmatic manual therapy could predict those participants with chronic low back pain who demonstrate continued improvements at 6-month follow-up. This study was a retrospective observational design. Univariate logistic regression analyses were performed using a 33% and a 50% pain change to predict improvement. Those who experienced a ≥33% pain reduction by 2 weeks had 6.98 (95% CI = 1.29, 37.53) times higher odds of 50% improvement on the GRoC and 4.74 (95% CI = 1.31, 17.17) times higher odds of 50% improvement on the ODI (at 6 months). Subjects who reported a ≥50% pain reduction at 2 weeks had 5.98 (95% CI = 1.56, 22.88) times higher odds of a 50% improvement in the GRoC and 3.99 (95% CI = 1.23, 12.88) times higher odds of a 50% improvement in the ODI (at 6 months). Future studies may investigate whether a change in plan of care is beneficial for patients who are not showing early improvement predictive of a good long-term outcome.

  3. Effect of manual therapy techniques on headache disability in patients with tension-type headache. Randomized controlled trial.

    Science.gov (United States)

    Espí-López, G V; Rodríguez-Blanco, C; Oliva-Pascual-Vaca, A; Benítez-Martínez, J C; Lluch, E; Falla, D

    2014-12-01

    Tension-type headache (TTH) is the most common type of primary headache however there is no clear evidence as to which specific treatment is most effective or whether combined treatment is more effective than individual treatments. To assess the effectiveness of manual therapy techniques, applied to the suboccipital region, on aspects of disability in a sample of patients with tension-type headache. Randomized Controlled Trial. Specialized centre for headache treatment. Seventy-six (62 women) patients (age: 39.9 ± 10.9 years) with episodic chronic TTH. Patients were randomly divided into four treatment groups: 1) suboccipital soft tissue inhibition; 2) occiput-atlas-axis manipulation; 3) combined treatment of both techniques; 4) control. Four sessions were applied over 4 weeks and disability was assessed before and after treatment using the Headache Disability Inventory (HDI). Headache frequency, severity and the functional and emotional subscales of the questionnaire were assessed. Photophobia, phonophobia and pericranial tenderness were also monitored. Headache frequency was significantly reduced with the manipulative and combined treatment (Ptreatment groups (Ptreatment also reduced the score on the emotional subscale of the HDI (Ptreatments were combined, effectiveness was noted for all aspects of disability and other symptoms including photophobia, phonophobia and pericranial tenderness. Although individual manual therapy treatments showed a positive change in headache features, measures of photophobia, photophobia and pericranial tenderness only improved in the group that received the combined treatment suggesting that combined treatment is the most appropriate for symptomatic relief of TTH.

  4. [Critical care nurse learning of continuous renal replacement therapy: the efficacy of a self-learning manual].

    Science.gov (United States)

    Huang, Yi-Chen; Hsu, Li-Ling

    2011-02-01

    Many nurses have difficulty learning to use the complex, non-traditional, and regularly-updated critical care equipment. Failure to use such equipment properly can seriously compromise treatment and endanger patient health and lives. New self-learning materials for novice nurses are necessary to provide essential and effective guidance as a part of formal nursing training. Such materials can enhance the capabilities of critical care nurses and, thus, improve the general quality of critical care. The purpose of this research was to develop a continuous renal replacement therapy (CRRT)-themed self-learning manual that would provide easily absorbed and understood knowledge in an easy-to-carry format for ICU nursing staff. This study also investigated CCRT skill learning efficacy. This study adopted a quasi-experimental design with pretests and posttests. Purposive sampling generated a sample of 66 critical care nurses currently working at one hospital in Taipei City. Participants submitted a completed self-assessment survey that rated their command of continuous renal replacement therapy before and after the self-learning manual intervention. Survey data were analyzed using SPSS Version 17.0 for Windows. The two major findings derived from the study included: (1) The mean response score from the self-assessment survey filled out after the intervention was 91.06 and 79.75 (SD = 9.49 and 11.65), respectively, for experimental and control groups. Such demonstrated significant difference. (2) The mean posttest score after the intervention for the experimental group was 91.06 ± 9.49. This represents a significant increase of 10.35 ± 10.35 over their mean pretest score (80.71 ± 11.82). The experimental group showed other significant differences in terms of the CRRT self-assessment survey posttest. Self-learning manuals may be introduced in nursing education as useful aids and catalysts to achieve more effective and satisfying learning experiences.

  5. The Effectiveness and Safety of Manual Therapy on Pain and Disability in Older Persons With Chronic Low Back Pain: A Systematic Review.

    Science.gov (United States)

    de Luca, Katie E; Fang, Sheng Hung; Ong, Justin; Shin, Ki-Soo; Woods, Samuel; Tuchin, Peter J

    2017-09-01

    The aim of this study was to perform a systematic review of the literature of the effectiveness and safety of manual therapy interventions on pain and disability in older persons with chronic low back pain (LBP). A literature search of 4 electronic databases was performed (PubMed, EMBASE, OVID, and CINAHL). Inclusion criteria included randomized controlled trials of manual therapy interventions on older persons who had chronic LBP. Effectiveness was determined by extracting and examining outcomes for pain and disability, with safety determined by the report of adverse events. The PEDro scale was used for quality assessment of eligible studies. The search identified 405 articles, and 38 full-text articles were assessed. Four studies met the inclusion criteria. All trials were of good methodologic quality and had a low risk of bias. The included studies provided moderate evidence supporting the use of manual therapy to reduce pain levels and alleviate disability. A limited number of studies have investigated the effectiveness and safety of manual therapy in the management of older people with chronic LBP. The current evidence to make firm clinical recommendations is limited. Research with appropriately designed trials to investigate the effectiveness and safety of manual therapy interventions in older persons with chronic LBP is required. Copyright © 2017. Published by Elsevier Inc.

  6. Production of 177Lu for targeted radionuclide therapy: Available options

    International Nuclear Information System (INIS)

    Dah, Ashutosh; Pillai, Maroor Raghavan Ambikalmajan; Knapp, Furn F. Jr.

    2015-01-01

    This review provides a comprehensive summary of the production of 177 Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of 177 Lu having the required quality for preparation of a variety of 177 Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of 177 Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. While both “direct” and “indirect” reactor production routes offer the possibility for sustainable 177 Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. A broad understanding and discussion of the issues associated with 177 Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of 177 Lu-labeled radiopharmaceuticals, but also help future developments

  7. In vitro and preclinical targeted alpha therapy for cancer

    International Nuclear Information System (INIS)

    Allen, B.J.; Rizvi, S.; Li, Y.; Tian, Z.; University of Wollongong, NSW; Ranson, M.; Russell, P.J.

    2000-01-01

    Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotope Bi-213 is produced by generator and chelated to a cancer affined monoclonal antibody or protein to form the alpha-conjugate (AC) against melanoma, leukaemia, colorectal, bladder, breast and prostate cancers. These ACs are tested for stability, specificity and cytotoxicity. Subcutaneous inoculation of 1.5 million cells into the flanks of nude mice causes tumours to grow in all mice. The tumour growth is compared between untreated controls, nonspecific RIC and specific RIC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Results: Stable alpha-ACs can be produced which are highly specific and cytotoxic in vitro. Local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Local TAT can also completely regress (11/12) sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts. These results point to the potential application of local TAT and systemic TAT in the management of these cancers. A phase 1 and 2 clinical trial is planned for local TAT of sc recurrent melanoma. Copyright (2000) Australasian College of Physical Scientists and Engineers in Medicine

  8. Aptamer-Targeted Plasmonic Photothermal Therapy of Cancer

    Directory of Open Access Journals (Sweden)

    Olga S. Kolovskaya

    2017-12-01

    Full Text Available Novel nanoscale bioconjugates combining unique plasmonic photothermal properties of gold nanoparticles (AuNPs with targeted delivery using cell-specific DNA aptamers have a tremendous potential for medical diagnostics and therapy of many cell-based diseases. In this study, we demonstrate the high anti-cancer activity of aptamer-conjugated, 37-nm spherical gold nanoparticles toward Ehrlich carcinoma in tumor-bearing mice after photothermal treatment. The synthetic anti-tumor aptamers bring the nanoparticles precisely to the desired cells and selectively eliminate cancer cells after the subsequent laser treatment. To prove tumor eradication, we used positron emission tomography (PET utilizing radioactive glucose and computer tomography, followed by histological analysis of cancer tissue. Three injections of aptamer-conjugated AuNPs and 5 min of laser irradiations are enough to make the tumor undetectable by PET. Histological analysis proves PET results and shows lower damage of healthy tissue in addition to a higher treatment efficiency and selectivity of the gold nanoparticles functionalized with aptamers in comparison to control experiments using free unconjugated nanoparticles.

  9. Targeting sarcoma tumor-initiating cells through differentiation therapy

    Directory of Open Access Journals (Sweden)

    Dan Han

    2017-05-01

    Full Text Available Human leukocyte antigen class I (HLA-I down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.

  10. A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Deng L

    2012-09-01

    Full Text Available Li Deng,1,# Xingfa Ke,4,# Zhiying He,3,# Daoqiu Yang,5 Hai Gong,6 Yingying Zhang,1 Xiaolong Jing,4 Jianzhong Yao,2 Jianming Chen11Department of Pharmaceutics, 2Department of Medicinal Chemistry, School of Pharmacy, 3Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People's Republic of China; 5Department of Dermatology, 107th Hospital of PLA, Yantai, People's Republic of China; 6Department of Radiation Oncology, General Hospital of Jinan Military Region, Jinan, People’s Republic of China#These authors contributed equally to this workAbstract: Pancreatic cancer is a highly lethal disease with a 5-year survival rate less than 5% due to the lack of an early diagnosis method and effective therapy. To provide a novel early diagnostic method and targeted therapy for pancreatic cancer, a multifunctional nanoimmunoliposome with high loading of ultrasmall superparamagnetic iron oxides (USPIOs and doxorubicin (DOX was prepared by transient binding and reverse-phase evaporation method, and was conjugated with anti-mesothelin monoclonal antibody by post-insertion method to target anti-mesothelin-overexpressed pancreatic cancer cells. The in vitro and in vivo properties of this anti-mesothelin antibody-conjugated PEGlyated liposomal DOX and USPIOs (M-PLDU; and PEGlyated nanoimmunoliposome without antibody conjugation [PLDU] were evaluated both in human pancreatic cancer cell line Panc-1 cell and in a pancreatic cancer xenograft animal model. Results showed that M-PLDUs were spherical and uniform with a diameter about ~180 nm, with a zeta potential of about −28~−30 mV, and had good efficacy encapsulating DOX and USPIOs. The in vitro study demonstrated that M-PLDUs possessed good magnetic resonance imaging (MRI capability with a transverse relaxivity (r2 of about 58.5 mM–1 • s–1. Confocal microscopy showed more

  11. MRI definition of target volumes using fuzzy logic method for three-dimensional conformal radiation therapy

    International Nuclear Information System (INIS)

    Caudrelier, Jean-Michel; Vial, Stephane; Gibon, David; Kulik, Carine; Fournier, Charles; Castelain, Bernard; Coche-Dequeant, Bernard; Rousseau, Jean

    2003-01-01

    Purpose: Three-dimensional (3D) volume determination is one of the most important problems in conformal radiation therapy. Techniques of volume determination from tomographic medical imaging are usually based on two-dimensional (2D) contour definition with the result dependent on the segmentation method used, as well as on the user's manual procedure. The goal of this work is to describe and evaluate a new method that reduces the inaccuracies generally observed in the 2D contour definition and 3D volume reconstruction process. Methods and Materials: This new method has been developed by integrating the fuzziness in the 3D volume definition. It first defines semiautomatically a minimal 2D contour on each slice that definitely contains the volume and a maximal 2D contour that definitely does not contain the volume. The fuzziness region in between is processed using possibility functions in possibility theory. A volume of voxels, including the membership degree to the target volume, is then created on each slice axis, taking into account the slice position and slice profile. A resulting fuzzy volume is obtained after data fusion between multiorientation slices. Different studies have been designed to evaluate and compare this new method of target volume reconstruction and a classical reconstruction method. First, target definition accuracy and robustness were studied on phantom targets. Second, intra- and interobserver variations were studied on radiosurgery clinical cases. Results: The absolute volume errors are less than or equal to 1.5% for phantom volumes calculated by the fuzzy logic method, whereas the values obtained with the classical method are much larger than the actual volumes (absolute volume errors up to 72%). With increasing MRI slice thickness (1 mm to 8 mm), the phantom volumes calculated by the classical method are increasing exponentially with a maximum absolute error up to 300%. In contrast, the absolute volume errors are less than 12% for phantom

  12. A study to evaluate the effect of manual therapy and exercise on the levator plate in women with pelvic organ prolapse.

    OpenAIRE

    Whelan, Maeve

    2013-01-01

    Introduction Pelvic organ prolapse (POP) symptoms, severity and pelvic floor muscle (PFM) strength have been shown to improve significantly with pelvic floor muscle training (PFMT). In this study, a new approach to conservative treatment of POP was investigated by the addition of manual physiotherapy to conventional PFMT. Aim & Objectives The aim of this study was to investigate the effect of internal manual therapy and PFMT on the levator plate angle (LPA) in women with stage I or I...

  13. 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/.

  14. Opportunity of interventional radiology: advantages and application of interventional technique in biological target therapy

    International Nuclear Information System (INIS)

    Teng Gaojun; Lu Qin

    2007-01-01

    Interventional techniques not only provide opportunity of treatment for many diseases, but also alter the traditional therapeutic pattern. With the new century of wide application of biological therapies, interventional technique also shows extensive roles. The current biological therapy, including gene therapy, cell transplantation therapy, immunobiologic molecule therapy containing cell factors, tumor antibody or vaccine, recombined proteins, radioactive-particles and targeting materials therapy, can be locally administrated by interventional techniques. The combination of targeting biological therapies and high-targeted interventional technique holds advantages of minimal invasion, accurate delivery, vigorous local effect, and less systemic adverse reactions. Authors believe that the biological therapy may arise a great opportunity for interventional radiology, therefore interventional colleagues should grasp firmly and promptly for the development and extension in this field. (authors)

  15. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong

    2005-01-01

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  16. Emerging targeted therapies for plaque psoriasis – impact of ixekizumab

    Directory of Open Access Journals (Sweden)

    Kazemi T

    2017-04-01

    Full Text Available Tiana Kazemi,1 Benjamin Farahnik,2 John Koo,3 Kourosh Beroukhim1 1University of California – Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 2University of Vermont College of Medicine, Burlington, VT, 3University of California – San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center, San Francisco, CA, USA Background: Recent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17 in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis. Methods: We reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis. Additionally, we compared these results to phase II and phase III trials for other biologic psoriasis medications including the anti-IL-23 agents tildrakizumab and guselkumab, the combined anti-IL-12 and anti-IL-23 agent ustekinumab, and the anti-IL-17 agents brodalumab and secukinumab. Results: Pooled results from individual studies demonstrate that among the most efficacious dosing regimens of these anti-interleukin therapies, ixekizumab achieves higher Psoriasis Area and Severity Index 75 rates and similar or higher static Physician Global Assessment 0-1 rates than the other anti-IL-17 and anti-IL-23 agents. The safety profile of ixekizumab is similar to these agents, with nasopharyngitis, upper respiratory infection, headache, arthralgia, and injection-site erythema as the most commonly reported adverse events. Conclusion: Ixekizumab is a highly efficacious, newly FDA-approved treatment for moderate-to-severe plaque psoriasis that demonstrates a robust clinical response, significant improvement in patient quality of

  17. Targeted alpha therapy for melanoma : from bench to bedside

    International Nuclear Information System (INIS)

    Allen, B.J.; Rizvi, S.M.A.; Li, Y.; Tsui, W.; Douglas, S.; Raja, C.; Graham, P.; Smart, R.; Butler, P.; Kearsley, J.; Thompson, J.

    2001-01-01

    Full text: The control of metastatic melanoma remains an elusive objective. Targeted alpha therapy (TAT) offers a new approach to the control of micrometastases and regression of tumours. The alpha emitting immunoconjugate (AIC) against malignant melanoma has been prepared by chelating Bi-213 to the anti-melanoma antibody 9.2.27, and injected locally at 2 d post-inoculation of 1.5 million melanoma cells, or intralesionally into skin tumours. Human subjects receive 50μCi intralesional dose, escalating to 1 mCi. The clearances from the tumour, kidneys and bladder are monitored by a NaI detector that detects the 440 keV gamma ray. Blood samples and tumour photographs are taken at O. 2 and 4 weeks; tumours are excised at 4 weeks. Isolated cancer cells and preangiogenic cell clusters in mice can be eliminated with 25 μCi local AIC injection, and intra-lesional injections of 100 μCi are sufficient to completely regress melanomas with volumes up to 300 mm 3 without side-effects. Systemic TAT with a single administration is less effective with 100% growth delay of tumours observed, and ∼20% complete inhibition. The clinical TAT trial for recurrent subcutaneous melanoma has been approved by the NSW Radiation Advisory Committee and the SES Human Ethics Committee. In a world first phase 1 study, the first 5 subjects have been treated by intralesional injection, 3 at 50 μCi, and 2 at 150 μCi. All subjects having unchanged blood profiles at 2 and 4 weeks post-therapy. Tumour volumes appear little changed. However, histology of a 3 cm melanoma shows that almost complete cell kill occurred at 150 μCi, with only a few small cell clusters surviving. Local TAT inhibits tumourogenesis and intralesional TAT completely regresses melanoma in mice. Intralesional TAT for melanoma in human subjects is non-toxic so far and appears to be a promising modality. The ultimate objective is to apply systemic TAT for the control of melanoma micrometastases. Copyright (2001) Australasian

  18. Changes in co-contraction during stair descent after manual therapy protocol in knee osteoarthritis: A pilot, single-blind, randomized study.

    Science.gov (United States)

    Cruz-Montecinos, Carlos; Flores-Cartes, Rodrigo; Montt-Rodriguez, Agustín; Pozo, Esteban; Besoaín-Saldaña, Alvaro; Horment-Lara, Giselle

    2016-10-01

    Manual therapy has shown clinical results in patients with knee osteoarthritis. However, the biomechanical aspects during functional tasks have not been explored in depth. Through surface electromyography, the medial and lateral co-contractions of the knee were measured while descending stairs, prior and posterior to applying a manual therapy protocol in the knee, with emphasis on techniques of joint mobilization and soft-tissue management. Sixteen females with slight or moderate knee osteoarthritis were recruited (eight experimental, eight control). It was observed that the lateral co-contraction index of the experimental group, posterior to intervention, increased by 11.7% (p = 0.014). The application of a manual therapy protocol with emphasis on techniques of joint mobilization and soft-tissue management modified lateral co-contraction, which would have a protective effect on the joint. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Efficacy of manual and manipulative therapy in the perception of pain and cervical motion in patients with tension-type headache: a randomized, controlled clinical trial.

    Science.gov (United States)

    Espí-López, Gemma V; Gómez-Conesa, Antonia

    2014-03-01

    The purpose of this study was to evaluate the efficacy of manipulative and manual therapy treatments with regard to pain perception and neck mobility in patients with tension-type headache. A randomized clinical trial was conducted on 84 adults diagnosed with tension-type headache. Eighty-four subjects were enrolled in this study: 68 women and 16 men. Mean age was 39.76 years, ranging from 18 to 65 years. A total of 57.1% were diagnosed with chronic tension-type headache and 42.9% with tension-type headache. Participants were divided into 3 treatment groups (manual therapy, manipulative therapy, a combination of manual and manipulative therapy) and a control group. Four treatment sessions were administered during 4 weeks, with posttreatment assessment and follow-up at 1 month. Cervical ranges of motion pain perception, and frequency and intensity of headaches were assessed. All 3 treatment groups showed significant improvements in the different dimensions of pain perception. Manual therapy and manipulative treatment improved some cervical ranges of motion. Headache frequency was reduced with manipulative treatment (P treatment reported improvement after the treatment (P treatment and at follow-up with manipulative therapy (P treatment (P treatments, administered both separately and combined together, showed efficacy for patients with tension-type headache with regard to pain perception. As for cervical ranges of motion, treatments produced greater effect when separately administered.

  20. Vascular-targeted therapies for Duchenne muscular dystrophy

    Science.gov (United States)

    2013-01-01

    -receptor type 1 (VEGFR-1 or Flt-1). The pro-angiogenic approaches also seem to be pro-myogenic and could resolve the age-related decline in satellite cell (SC) quantity seen in mdx models through expansion of the SC juxtavascular niche. Here we review these four vascular targeted treatment strategies for DMD and discuss mechanisms, proof of concept, and the potential for clinical relevance associated with each therapy. PMID:23618411

  1. New strategy of cancer therapy by targeting the hypoxic circumstances

    International Nuclear Information System (INIS)

    Yasui, Hironobu; Yamamori, Tohru; Meike, Shunsuke; Eitaki, Masato; Kuwabara, Mikinori; Inanami, Osamu; Iizuka, Daisuke

    2010-01-01

    Described are studies on the sensitization of tumor cells in hypoxic circumstances (known as radio-resistant cells) by authors' recent molecular targeting to adaptive response as well as by the usual agents like nitro-imidazole compounds, and on the intermittent hypoxia, a new topic in this field. The hypoxia-inducible factor-1 (HIF-1) is a transcriptional factor and has been known to activate its many downstream genes to cause adoptive response of hypoxic cells. Authors have studied the anti-tumor and radiation sensitizing effects of ethynyl-cytidine (EC) which is found to suppress RNA synthesis through cytidine kinase (CK) inhibition, and the compound is of specificity to tumor cells as they have 5-10 times higher CK activity than normal cells. Authors have also found that EC is of the sensitizing efficacy to normoxic and hypoxic cells by enhancing the radiation-induced apoptosis essentially through inhibition of HIF-1 expression. Intermittent hypoxia in the tumor which has characteristic abnormal vascular morphology and function, occurs by the transient reduction of blood flow and occlusion of vessels in the tissue within minute to hour time cycles. Little is known about the regional hypoxic region and its distribution in the tumor due to difficulty of their detection and quantification. For this, authors have measured the temporal changes of oxygen levels in the mouse tumor with triaryl methyl radical, an oxygen-sensitive contrast compound continuously injected, by microwave-pulsed electron spin resonance imaging (EPRI). By superimposing the EPRI and T2-weighted MRI, the oxymetric imaging is possible in the tumor, which reveals the difference of oxygen level variation depending on the cell type and tissue size. Findings in the field are expected to give important information for more effective cancer therapy and its prognostic prediction in future. (T.T.)

  2. Tunneling nanotubes: A versatile target for cancer therapy.

    Science.gov (United States)

    Sahoo, Pragyaparamita; Jena, Soumya Ranjan; Samanta, Luna

    2017-11-29

    Currently Cancer is the leading cause of death worldwide. Malignancy or cancer is a class of diseases characterized by uncontrolled cell growth that eventually invade other tissues and dvelop secondary malignant growth at other sites by metastasis. Intercellular communication plays a major in cancer, particularly in the process of cell proliferation and coordination which in turn leads to tumor invasion, metastasis and development of resistance to therapy. Cells communicate among themselves in a variety of ways, namely, i) via gap junctions with adjacent cells, ii) via exosomes with nearby cells and iii) via chemical messengers with distant cells. Besides, cell - cell connection by tunneling nanotubes (TnTs) is recently gaining importance where intercellular components are transferred between cells. In general cell organelles like Golgi vesicle and mitochondria; and biomolecules like nucleic acids and proteins are transferred through these TnTs. These TnTs are long cytoplasmic extensions made up of actin that function as intercellular bridge and connect a wide verity of cell types. Malignant cells form TnTs with either another malignant cells or cells of the surrounding tumor matrix. These TnTs help in the process of initiation of tumor formation, its organization and propagation. The current review focuses on the role of TnTs mediated cell – cell signaling in cancer micro-environment. Drugs that inhibit TnT-formation such as metformin and everolimus can be targeted towards TnTs in the management of cancer growth, proliferation, tumor invasion and metastasis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical Insights and Practical Considerations

    NARCIS (Netherlands)

    Bex, A.; Fournier, L.; Lassau, N.; Mulders, P.F.A.; Nathan, P.; Oyen, W.J.G.; Powles, T.

    2014-01-01

    CONTEXT: The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to

  4. Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate Cancer...Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate

  5. Case Study: Manual Therapy in Patient of 18 Years with Youthful Scoliosis Idiopathic Summary

    OpenAIRE

    Franco Monsalve, Claudia Yaneth; Guerra Corena, Zorika María; Otero Samudio, María Patricia

    2010-01-01

    La escoliosis es una desviación lateral de la columna vertebral desde la línea media, caracterizada por una curvatura lateral y por una rotación vertebral. Generalmente, es de carácter idiopático y se presenta, principalmente, en niñas adolescentes. Existen múltiples técnicas de tratamiento conservador para la escoliosis, entre las cuales se encuentran la terapia manual, que complementa el tratamiento para dicha patología. Esta terapia utiliza menos medios físicos, más manipulación de tejidos...

  6. The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes

    Science.gov (United States)

    Leclerc, Julie B.; O’Connor, Kieron P.; J.-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E.

    2016-01-01

    Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8–12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive–behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12–14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically. PMID:27563292

  7. The effect of a new therapy for children with tics targeting underlying cognitive, behavioral and physiological processes

    Directory of Open Access Journals (Sweden)

    Julie B. Leclerc

    2016-08-01

    Full Text Available Tourette disorder (TD is characterized by motor and vocal tics and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder Facotik to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult Cognitive and Psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90-minute session contained 20 minutes of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population and seven cases completed therapy and post-treatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem post treatment. The results confirm the conclusion of a previous pilot study which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches which target tics specifically.

  8. The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes.

    Science.gov (United States)

    Leclerc, Julie B; O'Connor, Kieron P; J-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E

    2016-01-01

    Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically.

  9. Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

    Energy Technology Data Exchange (ETDEWEB)

    Aslian, Hossein [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Sadeghi, Mahdi [Agricultural, Medical and Industrial Research School, Karaj (Iran, Islamic Republic of); Mahdavi, Seied Rabie [Department of Medical Physics, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Babapour Mofrad, Farshid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Astarakee, Mahdi, E-mail: M-Astarakee@Engineer.com [Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khaledi, Navid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Fadavi, Pedram [Department of Radiation Oncology, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-09-01

    Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer.

  10. Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

    International Nuclear Information System (INIS)

    Aslian, Hossein; Sadeghi, Mahdi; Mahdavi, Seied Rabie; Babapour Mofrad, Farshid; Astarakee, Mahdi; Khaledi, Navid; Fadavi, Pedram

    2013-01-01

    Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer

  11. Current Status and Future Directions of Targeted Peptide Radionuclide Therapy

    International Nuclear Information System (INIS)

    Valkema, R.

    2009-01-01

    Current status: Peptide receptor radionuclide therapy (PRRT) is currently almost exclusively targeted at the somatostatin receptor (sst). Of the 5 receptor subtypes, sst2 is frequently very highly expressed at the cell surface of neuroendocrine tumors (NET). Octreotide is a small and stable derivative of native somatostatin, which can be very well labeled with therapeutic radionuclides such as the beta-emitters ''9''0Y, ''1''7''7Lu or the Auger emitter ''1''1''1In, chelated in DTPA or DOTA, linked to the peptide. All current therapeutic octreotide derivatives are agonists that are internalized in the cell. The affinity for the sst2 receptor is better for [DOTA,Tyr''3]octreotate than for [DOTA,Tyr''3]octreotide or [DTPA]octreotide. ''9''0Y is a pure beta-emitter, with a half-life of 2.7 days, a high energy of 2.270 MeV, and a maximum penetration in tissue of 12mm. ''1''7''7Lu with a half-life of 6.7 days emits a low abundance of gamma photons as well as beta particles of 497 keV, with a maximum tissue penetration of 2 mm. ''1''7''7Lu-[DOTA,Tyr''3]octreotate (Lu-DOTATE), ''9''0Y-[DOTA,Tyr''3]octreotate (Y-DOTATATE) and ''9''0Y-[DOTA,Tyr''3]octreotide (Y-DOTATOC) are today the most frequently used therapeutic radiopeptides. Main inclusion criteria: inoperable and/or metastatic NET, receptor-positivity in all known lesions demonstrated by sufficient uptake on ''1''1''1In-octreotide scintigraphy (intensity > liver parenchyma), life expectancy at least 3-6 months, sufficient bone marrow reserve (hemoglobin (HGB) ≥ 5 mmol/L, white blood cells (WBC) ≥ 2*10 9 /L, platelets (PLT) ≥ 75*10 12 /L), sufficient renal function (serum creatinine 40 mL/min), sufficient hepatic and cardiac reserve. Karnofski score ≥50. Efficacy: several groups have reported objective response rates (RECIST or WHO/SWOG; CT or MRI based). Complete remission (CR) is rarely seen, partial remission (PR; >50% shrinkage SWOG) in 7% - 37%, minor remission (MR, 25% - 50% shrinkage) in 13% - 17

  12. A manual-based phenomenological art therapy for individuals diagnosed with moderate to severe depression (PATd): A randomized controlled study.

    Science.gov (United States)

    Blomdahl, Christina; Guregård, Suzanne; Rusner, Marie; Wijk, Helle

    2018-05-14

    This study investigated the effects of manual-based Phenomenological Art Therapy for individuals living with depression in addition to treatment as usual (PATd/TAU) compared with only treatment as usual (TAU) for individuals diagnosed with moderate to severe depression. 79 adults (men = 29.1%) were included in this randomized-controlled-trial (RCT), multicenter study in Sweden with an intention-to-treat design. Participants were randomized into either the PATd/TAU-group (n = 43) or TAU-group (n = 36). Data were collected at baseline and at end of treatment. The main outcomes were depression levels and self-esteem. Secondary outcomes were suicide ideation and sickness absence. The PATd/TAU-group showed a significant decrease of depression levels. The PATd/TAU-group returned to work to a higher degree than the TAU-group. Self-esteem significantly improved in both groups. Suicide ideation was unaffected. Manual-based PATd works as expected, being an effective treatment, and contributes to recovery for individuals with moderate to severe depression. This outcome needs to be confirmed and its long-term effects examined in further studies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  13. Manual Intracardiac Electrogram Method Is Accurate Alternative to Echocardiography for Atrioventricular and Interventricular Optimization in Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Pezo Nikolić, Borka; Lovrić, Daniel; Ljubas Maček, Jana; Rešković Lukšić, Vlatka; Matasić, Richard; Šeparović Hanževački, Jadranka

    2017-12-01

    Some manufacturers do not provide automated intracardiac electrogram method (IEGM) systems for atrioventricular (AV) and interventricular (VV) delay optimization in cardiac resynchronization therapy (CRT). We aimed to evaluate the accuracy of manual IEGM method in 48 patients previously implanted with Medtronic Syncra CRT. All patients underwent standard device interrogation followed by CRT optimization by IEGM method and by echocardiography one month after implantation. The patient mean age was 60.7±11.8 years and there were 33 (68.8%) males. After CRT implantation, the left ventricular ejection fraction increased from 28.0±7.9% to 39.1±11.0% (p<0.001). Optimal aortic flow Velocity Time Integral (aVTI) was obtained when VV was set to 20-50 ms left ventricular pre-activation. There was a strong correlation between VV values determined by echocardiography and IEGM (R=0.823, p<0.001). We found no significant difference in AV, VV and aVTI values between echocardiography and IEGM method. However, IEGM was significantly less time-consuming than echocardiography [20 (10-28) vs. 40 (35-60) minutes, p<0.001]. Manual IEGM method may be good alternative to echocardiography and automated IEGM method. It also emphasizes the need for implementation of automated IEGM systems in as many CRT devices as possible.

  14. Risky business: target choice in adoptive cell therapy.

    Science.gov (United States)

    Morgan, Richard A

    2013-11-14

    In this issue of Blood, Casucci et al present an elegant study that describes a potential new target for adoptive cell transfer (ACT), in this case CD44 splice variant 6 (CD44v6), and detail why it may be a good target for ACT and how to manage expected off-tumor/on-target toxicities.

  15. Specifically targeted gene therapy for small-cell lung cancer

    DEFF Research Database (Denmark)

    Christensen, C.L.; Zandi, R.; Gjetting, T.

    2009-01-01

    Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous...

  16. Therapist adherence to manualized cognitive-behavioral therapy for anger management delivered to veterans with PTSD via videoconferencing.

    Science.gov (United States)

    Morland, Leslie A; Greene, Carolyn J; Grubbs, Kathleen; Kloezeman, Karen; Mackintosh, Margaret-Anne; Rosen, Craig; Frueh, B Christopher

    2011-06-01

    Therapist adherence to a manualized cognitive-behavioral anger management group treatment (AMT) was compared between therapy delivered via videoconference (VC) and the traditional in-person modality, using data from a large, randomized controlled trial comparing the effectiveness of AMT for veterans with combat-related posttraumatic stress disorder. Therapist adherence was rated for the presence or absence of process and content treatment elements. Secondary analyses were conducted using a repeated measures ANOVA. Overall adherence to the protocol was excellent (M = 96%, SD = 1%). Findings indicate that therapist adherence to AMT is similar across delivery modalities and VC is a viable service delivery strategy that does not compromise a therapist's ability to effectively structure sessions and manage patient care. © 2011 Wiley Periodicals, Inc.

  17. Combination of vascular targeting agents with thermal or radiation therapy

    International Nuclear Information System (INIS)

    Horsman, Michael R.; Murata, Rumi

    2002-01-01

    Purpose: The most likely clinical application of vascular targeting agents (VTAs) is in combination with more conventional therapies. In this study, we report on preclinical studies in which VTAs were combined with hyperthermia and/or radiation. Methods and Materials: A C3H mammary carcinoma grown in the right rear foot of female CDF1 mice was treated when at 200 mm 3 in size. The VTAs were combretastatin A-4 disodium phosphate (CA4DP, 25 mg/kg), flavone acetic acid (FAA, 150 mg/kg), and 5,6-dimethylxanthenone-4-acetic acid (DMXAA, 20 mg/kg), and were all injected i.p. Hyperthermia and radiation were locally administered to tumors of restrained, nonanesthetized mice, and response was assessed using either a tumor growth or tumor control assay. Results: Heating tumors at 41.5 degree sign C gave rise to a linear relationship between the heating time and tumor growth with a slope of 0.02. This slope was increased to 0.06, 0.09, and 0.08, respectively, by injecting the VTAs either 30 min (CA4DP), 3 h (FAA), or 6 h (DMXAA) before heating. The radiation dose (±95% confidence interval) that controls 50% of treated tumors (the TCD 50 value) was estimated to be 53 Gy (51-55 Gy) for radiation alone. This was decreased to 48 Gy (46-51 Gy), 45 Gy (41-49 Gy), and 42 Gy (39-45 Gy), respectively, by injecting CA4DP, DMXAA, or FAA 30-60 min after irradiating. These values were further decreased to around 28-33 Gy if the tumors of VTA-treated mice were also heated to 41.5 degree sign C for 1 h, starting 4 h after irradiation, and this effect was much larger than the enhancement seen with either 41.5 degree sign C or even 43 degree sign C alone. Conclusions: Our preclinical studies and those of others clearly demonstrate that VTAs can enhance tumor response to hyperthermia and/or radiation and support the concept that such combination studies should be undertaken clinically for the full potential of VTAs to be realized

  18. Acute electromyographic responses of deep thoracic paraspinal muscles to spinal manual therapy interventions. An experimental, randomized cross-over study.

    Science.gov (United States)

    Fryer, Gary; Bird, Michael; Robbins, Barry; Johnson, Jane C

    2017-07-01

    This single group, randomized, cross-over study explored whether manual therapy alters motor tone of deep thoracic back muscles by examining resting electromyographic activity (EMG) after 2 types of manual therapy and a sham control intervention. Twenty-two participants with thoracic spinal pain (15 females, 7 males, mean age 28.1 ± 6.4 years) had dual fine-wire, intramuscular electrodes inserted into deep transversospinalis muscles at a thoracic level where tissues appeared abnormal to palpation (AbP) and at 2 sites above and below normal and non-tender to palpation (NT). A surface electrode was on the contralateral paraspinal mass at the level of AbP. EMG signals were recorded for resting prone, two 3-s free neck extension efforts, two 3-s resisted maximal voluntary isometric contractions (MVIC), and resting prone before the intervention. Randomized spinal manipulation, counterstrain, or sham manipulation was delivered and EMG re-measured. Participants returned 1 and 2 weeks later for the remaining 2 treatments. Reductions in resting EMG followed counterstrain in AbP (median decrease 3.3%, P = 0.01) and NT sites (median decrease 1.0%, P = 0.05) and for the surface electrode site (median decrease 2.0%, P = 0.009). Reduction in EMG following counterstrain during free neck extension was found for the surface electrode site (median decrease 2.7%, P < 0.01). Spinal manipulation produced no change in EMG, whereas counterstrain technique produced small significant reductions in paraspinal muscle activity during prone resting and free neck extension conditions. The clinical relevance of these changes is unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Treatment outcome of radiation therapy and concurrent targeted molecular therapy in spinal metastasis from renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Joon; Kim, Kyung Hwan; Rhee, Woo Joong; Lee, Jeong Shin; Cho, Yeo Na; Koom, Woong Sub [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    To evaluate the clinical outcomes of patients who underwent radiation therapy with or without targeted molecular therapy for the treatment of spinal metastasis from renal cell carcinoma (RCC). A total of 28 spinal metastatic lesions from RCC patients treated with radiotherapy between June 2009 and June 2015 were retrospectively reviewed. Thirteen lesions were treated concurrently with targeted molecular therapy (concurrent group) and 15 lesions were not (nonconcurrent group). Local control was defined as lack of radiographically evident local progression and neurological deterioration. At a median follow-up of 11 months (range, 2 to 58 months), the 1-year local progression-free rate (LPFR) was 67.0%. The patients with concurrent targeted molecular therapy showed significantly higher LPFR than those without (p = 0.019). After multivariate analysis, use of concurrent targeted molecular therapy showed a tendency towards improved LPFR (hazard ratio, 0.13; 95% confidence interval, 0.01 to 1.16). There was no difference in the incidence of systemic progression between concurrent and nonconcurrent groups. No grade ≥2 toxicities were observed during or after radiotherapy. Our study suggests the possibility that concurrent use of targeted molecular therapy during radiotherapy may improve LPFR. Further study with a large population is required to confirm these results.

  20. Treatment outcome of radiation therapy and concurrent targeted molecular therapy in spinal metastasis from renal cell carcinoma

    International Nuclear Information System (INIS)

    Park, Sang Joon; Kim, Kyung Hwan; Rhee, Woo Joong; Lee, Jeong Shin; Cho, Yeo Na; Koom, Woong Sub

    2016-01-01

    To evaluate the clinical outcomes of patients who underwent radiation therapy with or without targeted molecular therapy for the treatment of spinal metastasis from renal cell carcinoma (RCC). A total of 28 spinal metastatic lesions from RCC patients treated with radiotherapy between June 2009 and June 2015 were retrospectively reviewed. Thirteen lesions were treated concurrently with targeted molecular therapy (concurrent group) and 15 lesions were not (nonconcurrent group). Local control was defined as lack of radiographically evident local progression and neurological deterioration. At a median follow-up of 11 months (range, 2 to 58 months), the 1-year local progression-free rate (LPFR) was 67.0%. The patients with concurrent targeted molecular therapy showed significantly higher LPFR than those without (p = 0.019). After multivariate analysis, use of concurrent targeted molecular therapy showed a tendency towards improved LPFR (hazard ratio, 0.13; 95% confidence interval, 0.01 to 1.16). There was no difference in the incidence of systemic progression between concurrent and nonconcurrent groups. No grade ≥2 toxicities were observed during or after radiotherapy. Our study suggests the possibility that concurrent use of targeted molecular therapy during radiotherapy may improve LPFR. Further study with a large population is required to confirm these results

  1. Targeted Therapies in Hematology and Their Impact on Patient Care: Chronic and Acute Myeloid Leukemia

    Science.gov (United States)

    Cortes, Elias Jabbour Jorge; Ravandi, Farhad; O’Brien, Susan; Kantarjian, Hagop

    2014-01-01

    Advances in the genetic and molecular characterizations of leukemias have enhanced our capabilities to develop targeted therapies. The most dramatic examples of targeted therapy in cancer to date are the use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) which has revolutionized the treatment of chronic myeloid leukemia (CML). Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. In contrast, acute myeloid leukemia (AML) is an extremely heterogeneous disease with outcomes that vary widely according to subtype of the disease. Targeted therapy with monoclonal antibodies and small molecule kinase inhibitors are promising strategies to help improve the cure rates in AML. In this review, we will highlight the results of recent clinical trials in which outcomes of CML and AML have been influenced significantly. Also, novel approaches to sequencing and combining available therapies will be covered. PMID:24246694

  2. Targeted Therapies for Myeloma and Metastatic Bone Cancers

    National Research Council Canada - National Science Library

    Vail, Neal

    2008-01-01

    ... done. Quantified functional groups available for ligand conjugation using S35-labeled ligands. Developed alternative assay to confirm affinity of bone-targeting nanoparticles to hydroxyapatite substrates...

  3. Patient education with or without manual therapy compared to a control group in patients with osteoarthritis of the hip. A proof-of-principle three-arm parallel group randomized clinical trial

    DEFF Research Database (Denmark)

    Poulsen, E; Hartvigsen, J; Christensen, H W

    2013-01-01

    To investigate the effectiveness of a patient education (PE) program with or without the added effect of manual therapy (MT) compared to a minimal control intervention (MCI).......To investigate the effectiveness of a patient education (PE) program with or without the added effect of manual therapy (MT) compared to a minimal control intervention (MCI)....

  4. A randomized clinical trial of manual therapy and physiotherapy for persistent back and neck complaints : Subgroup analysis and relationship between outcome measures

    NARCIS (Netherlands)

    Koes, B. W.; Bouter, L. M.; Van Mameren, H.; Essers, A. H M; Verstegen, G. J M G; Hofhuizen, D. M.; Houben, J. P.; Knipschild, P. G.

    1993-01-01

    Objective: To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints. The second objective was to determine the correlation between three important outcome measures used in this trial. Design: Randomized clinical trial (subgroup

  5. IGF-IR targeted therapy: Past, present and future

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); A.J. Varewijck (Aimee)

    2014-01-01

    textabstractThe IGF-I receptor (IGF-IR) has been studied as an anti-cancer target. However, monotherapy trials with IGF-IR targeted antibodies or with IGF-IR specific tyrosine kinase inhibitors have, overall, been very disappointing in the clinical setting. This review discusses potential reasons

  6. Unravelling functional neurology: a scoping review of theories and clinical applications in a context of chiropractic manual therapy.

    Science.gov (United States)

    Meyer, Anne-Laure; Meyer, Amanda; Etherington, Sarah; Leboeuf-Yde, Charlotte

    2017-01-01

    Functional Neurology (FN), a seemingly attractive treatment approach used by some chiropractors, proposes to have an effect on a multitude of conditions but some of its concepts are controversial. A scoping review was performed to describe, in the context of chiropractic manual therapy, 1) the FN theories, and 2) its clinical applications (i.e. its indications, examination procedures, treatment modalities, treatment plans, and clinical outcomes) using four sources: i) one key textbook, ii) the scientific peer-reviewed literature, iii) websites from chiropractors using FN, and iv) semi-structured interviews of chiropractors using FN. The scientific literature was searched in PubMed, PsycINFO, and SPORTDiscus, completed by a hand search in the journal Functional Neurology, Rehabilitation and Ergonomics (November 2016 and March 2017, respectively). The only textbook on the topic we found was included and articles were chosen if they had an element of manual therapy. There was no restriction for study design but discussion papers were excluded. Websites were found in Google using the search term "Functional Neurology". Chiropractors, known to use FN, were invited based on their geographical location. Theories were mainly uncovered in the textbook as were all aspects of the clinical applications except treatment plans. The other three sources were used for the five aspects of clinical applications. Results were summarized and reported extensively in tables. Eleven articles were included, five websites scrutinized, and four semi-structured interviews performed. FN is based on the belief that reversible lesions in the nervous system are the cause of a multitude of conditions and that specific clusters of neurons can be positively affected by manipulative therapy, but also by many other stimuli. Diagnostic procedures include both conventional and unusual tests, with an interpretation specific to FN. Initial treatment is intense and clinical outcomes reported as positive

  7. 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

    Directory of Open Access Journals (Sweden)

    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

  8. Manual therapy and neurodynamic mobilization in a patient with peroneal nerve paralysis: a case report.

    Science.gov (United States)

    Villafañe, Jorge Hugo; Pillastrini, Paolo; Borboni, Alberto

    2013-09-01

    The purpose of this case report is to describe a therapeutic intervention for peroneal nerve paralysis involving the sciatic nerve. A 24-year-old man presented with peroneal nerve paralysis with decreased sensation, severe pain in the popliteal fossa, and steppage gait, which occurred 3 days prior to the consultation. Magnetic resonance imaging and electromyography confirmed lumbar disk herniation with sciatic common peroneal nerve entrapment in the popliteal fossa. A combined treatment protocol of spinal and fibular head manipulation and neurodynamic mobilization including soft tissue work of the psoas and hamstring muscles was performed. Outcome measures were assessed at pretreatment, 1 week posttreatment, and 3-month follow-up and included numeric pain rating scale, range of motion, pressure pain threshold, and manual muscle testing. Treatment interventions were applied for 3 sessions over a period of 1 week. Results showed reduction of the patient's subjective pain and considerable improvement in range of motion, strength, and sensation in his left foot, which was restored to full function. A combined program of spinal and fibular head manipulation and neurodynamic mobilization reduced pain, increased range of motion and strength, and restored full function to the left leg in this patient who had severe functional impairment related to a compressed left common peroneal nerve.

  9. Assessment of Robotic Patient Simulators for Training in Manual Physical Therapy Examination Techniques

    Science.gov (United States)

    Ishikawa, Shun; Okamoto, Shogo; Isogai, Kaoru; Akiyama, Yasuhiro; Yanagihara, Naomi; Yamada, Yoji

    2015-01-01

    Robots that simulate patients suffering from joint resistance caused by biomechanical and neural impairments are used to aid the training of physical therapists in manual examination techniques. However, there are few methods for assessing such robots. This article proposes two types of assessment measures based on typical judgments of clinicians. One of the measures involves the evaluation of how well the simulator presents different severities of a specified disease. Experienced clinicians were requested to rate the simulated symptoms in terms of severity, and the consistency of their ratings was used as a performance measure. The other measure involves the evaluation of how well the simulator presents different types of symptoms. In this case, the clinicians were requested to classify the simulated resistances in terms of symptom type, and the average ratios of their answers were used as performance measures. For both types of assessment measures, a higher index implied higher agreement among the experienced clinicians that subjectively assessed the symptoms based on typical symptom features. We applied these two assessment methods to a patient knee robot and achieved positive appraisals. The assessment measures have potential for use in comparing several patient simulators for training physical therapists, rather than as absolute indices for developing a standard. PMID:25923719

  10. Assessment of robotic patient simulators for training in manual physical therapy examination techniques.

    Directory of Open Access Journals (Sweden)

    Shun Ishikawa

    Full Text Available Robots that simulate patients suffering from joint resistance caused by biomechanical and neural impairments are used to aid the training of physical therapists in manual examination techniques. However, there are few methods for assessing such robots. This article proposes two types of assessment measures based on typical judgments of clinicians. One of the measures involves the evaluation of how well the simulator presents different severities of a specified disease. Experienced clinicians were requested to rate the simulated symptoms in terms of severity, and the consistency of their ratings was used as a performance measure. The other measure involves the evaluation of how well the simulator presents different types of symptoms. In this case, the clinicians were requested to classify the simulated resistances in terms of symptom type, and the average ratios of their answers were used as performance measures. For both types of assessment measures, a higher index implied higher agreement among the experienced clinicians that subjectively assessed the symptoms based on typical symptom features. We applied these two assessment methods to a patient knee robot and achieved positive appraisals. The assessment measures have potential for use in comparing several patient simulators for training physical therapists, rather than as absolute indices for developing a standard.

  11. Assessment of robotic patient simulators for training in manual physical therapy examination techniques.

    Science.gov (United States)

    Ishikawa, Shun; Okamoto, Shogo; Isogai, Kaoru; Akiyama, Yasuhiro; Yanagihara, Naomi; Yamada, Yoji

    2015-01-01

    Robots that simulate patients suffering from joint resistance caused by biomechanical and neural impairments are used to aid the training of physical therapists in manual examination techniques. However, there are few methods for assessing such robots. This article proposes two types of assessment measures based on typical judgments of clinicians. One of the measures involves the evaluation of how well the simulator presents different severities of a specified disease. Experienced clinicians were requested to rate the simulated symptoms in terms of severity, and the consistency of their ratings was used as a performance measure. The other measure involves the evaluation of how well the simulator presents different types of symptoms. In this case, the clinicians were requested to classify the simulated resistances in terms of symptom type, and the average ratios of their answers were used as performance measures. For both types of assessment measures, a higher index implied higher agreement among the experienced clinicians that subjectively assessed the symptoms based on typical symptom features. We applied these two assessment methods to a patient knee robot and achieved positive appraisals. The assessment measures have potential for use in comparing several patient simulators for training physical therapists, rather than as absolute indices for developing a standard.

  12. IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

    Science.gov (United States)

    Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

    2017-11-01

    The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Manual therapy, exercise therapy or combined treatment in the management of adult neck pain - A systematic review and meta-analysis.

    Science.gov (United States)

    Fredin, Ken; Lorås, Håvard

    2017-10-01

    Neck pain is a common and often disabling musculoskeletal condition. Two therapies frequently prescribed for its management are manual therapy (MT) and exercise therapy (ET), and combining these treatment approaches are common. To assess whether or not combined treatment consisting of MT and ET is more effective than either therapy alone in relieving pain and improving function in adult patients with grade I-II neck pain. Systematic review with meta-analysis. A systematic search on EMBASE, MEDLINE, AMED, CENTRAL and PEDro were performed until June 2017. Randomized controlled trials with adult grade I-II neck pain patients were included if they investigated the combined effect of MT and ET to the same ET or MT alone, and reported pain intensity or disability on numerical scales. Quality of life was assessed as a secondary outcome. Quality of the included trials was assessed with the PEDro scale, and the quality of evidence was assessed with GRADE. 1169 articles were screened, and 7 studies were included, all of which investigated the addition of ET to MT. Only very small and non-significant between group differences was found on pain intensity at rest, neck disability, and quality of life at immediate post-treatment, 6 months, and 12 months follow-up. The quality of evidence was moderate for pain-at-rest outcomes and moderate too low for neck disability and quality of life outcomes. Combined treatment consisting of MT and ET does not seem to be more effective in reducing neck pain intensity at rest, neck disability or improving quality of life in adult patients with grade I-II neck pain, than ET alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2017-10-01

    prostate cancer . Cancer Res 70: 7992-8002, 2010 8. Nelson PS: Molecular states underlying an- drogen receptor activation: A framework for thera- peutics...targeting androgen signaling in prostate cancer . J Clin Oncol 30:644-646, 2012 9. Thadani-Mulero M, Nanus DM, Giannakakou P: Androgen receptor on the... prostate cancer . Clin Cancer Res 21:795-807, 2015 17. van Soest RJ, de Morrée ES, Kweldam CF, et al: Targeting the androgen receptor confers in vivo

  15. The role and position of passive intervertebral motion assessment within clinical reasoning and decision-making in manual physical therapy: a qualitative interview study.

    Science.gov (United States)

    van Trijffel, Emiel; Plochg, Thomas; van Hartingsveld, Frank; Lucas, Cees; Oostendorp, Rob A B

    2010-06-01

    Passive intervertebral motion (PIVM) assessment is a characterizing skill of manual physical therapists (MPTs) and is important for judgments about impairments in spinal joint function. It is unknown as to why and how MPTs use this mobility testing of spinal motion segments within their clinical reasoning and decision-making. This qualitative study aimed to explore and understand the role and position of PIVM assessment within the manual diagnostic process. Eight semistructured individual interviews with expert MPTs and three subsequent group interviews using manual physical therapy consultation platforms were conducted. Line-by-line coding was performed on the transcribed data, and final main themes were identified from subcategories. Three researchers were involved in the analysis process. Four themes emerged from the data: contextuality, consistency, impairment orientedness, and subjectivity. These themes were interrelated and linked to concepts of professionalism and clinical reasoning. MPTs used PIVM assessment within a multidimensional, biopsychosocial framework incorporating clinical data relating to mechanical dysfunction as well as to personal factors while applying various clinical reasoning strategies. Interpretation of PIVM assessment and subsequent decisions on manipulative treatment were strongly rooted within practitioners' practical knowledge. This study has identified the specific role and position of PIVM assessment as related to other clinical findings within clinical reasoning and decision-making in manual physical therapy in The Netherlands. We recommend future research in manual diagnostics to account for the multivariable character of physical examination of the spine.

  16. 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

  17. RANKL-Targeted Therapies: The Next Frontier in the Treatment of Male Osteoporosis

    Directory of Open Access Journals (Sweden)

    Alicia K. Morgans

    2011-01-01

    Full Text Available Male osteoporosis is an increasingly recognized problem in aging men. A common cause of male osteoporosis is hypogonadism. Thousands of men with prostate cancer are treated with androgen deprivation therapy, a treatment that dramatically reduces serum testosterone and causes severe hypogonadism. Men treated with androgen deprivation therapy experience a decline in bone mineral density and have an increased rate of fracture. This paper describes prostate cancer survivors as a model of hypogonadal osteoporosis and discusses the use of RANKL-targeted therapies in osteoporosis. Denosumab, the only RANKL-targeted therapy currently available, increases bone mineral density and decreases fracture rate in men with prostate cancer. Denosumab is also associated with delayed time to first skeletal-related event and an increase in bone metastasis-free survival in these men. It is reasonable to investigate the use of RANKL-targeted therapy in male osteoporosis in the general population.

  18. Systematic Clinical Reasoning in Physical Therapy (SCRIPT): Tool for the Purposeful Practice of Clinical Reasoning in Orthopedic Manual Physical Therapy.

    Science.gov (United States)

    Baker, Sarah E; Painter, Elizabeth E; Morgan, Brandon C; Kaus, Anna L; Petersen, Evan J; Allen, Christopher S; Deyle, Gail D; Jensen, Gail M

    2017-01-01

    Clinical reasoning is essential to physical therapist practice. Solid clinical reasoning processes may lead to greater understanding of the patient condition, early diagnostic hypothesis development, and well-tolerated examination and intervention strategies, as well as mitigate the risk of diagnostic error. However, the complex and often subconscious nature of clinical reasoning can impede the development of this skill. Protracted tools have been published to help guide self-reflection on clinical reasoning but might not be feasible in typical clinical settings. This case illustrates how the Systematic Clinical Reasoning in Physical Therapy (SCRIPT) tool can be used to guide the clinical reasoning process and prompt a physical therapist to search the literature to answer a clinical question and facilitate formal mentorship sessions in postprofessional physical therapist training programs. The SCRIPT tool enabled the mentee to generate appropriate hypotheses, plan the examination, query the literature to answer a clinical question, establish a physical therapist diagnosis, and design an effective treatment plan. The SCRIPT tool also facilitated the mentee's clinical reasoning and provided the mentor insight into the mentee's clinical reasoning. The reliability and validity of the SCRIPT tool have not been formally studied. Clinical mentorship is a cornerstone of postprofessional training programs and intended to develop advanced clinical reasoning skills. However, clinical reasoning is often subconscious and, therefore, a challenging skill to develop. The use of a tool such as the SCRIPT may facilitate developing clinical reasoning skills by providing a systematic approach to data gathering and making clinical judgments to bring clinical reasoning to the conscious level, facilitate self-reflection, and make a mentored physical therapist's thought processes explicit to his or her clinical mentor. © 2017 American Physical Therapy Association

  19. Apoptosis and cancer stem cells : Implications for apoptosis targeted therapy

    NARCIS (Netherlands)

    Kruyt, Frank A. E.; Schuringa, Jan Jacob

    2010-01-01

    Evidence is accumulating showing that cancer stem cells or tumor-initiating cells are key drivers of tumor formation and progression. Successful therapy must therefore eliminate these cells, which is hampered by their high resistance to commonly used treatment modalities. Thus far, only a limited

  20. Stimuli-responsive biodegradable polymeric micelles for targeted cancer therapy

    NARCIS (Netherlands)

    Talelli, M.A.

    2011-01-01

    Thermosensitive and biodegradable polymeric micelles based on mPEG-b-pHPMAmLacn have shown very promising results during the past years. The results presented in this thesis illustrate the high potential of these micelles for anticancer therapy and imaging and fully justify further pharmaceutical

  1. Anger Management for Substance Abuse and Mental Health Clients: A Cognitive Behavioral Therapy Manual [and] Participant Workbook.

    Science.gov (United States)

    Reilly, Patrick M.; Shopshire, Michael S.; Durazzo, Timothy C.; Campbell, Torri A.

    This manual and workbook set focuses on anger management. The manual was designed for use by qualified substance abuse and mental health clinicians who work with substance abuse and mental health clients with concurrent anger programs. The manual describes a 12-week cognitive behavioral anger management group treatment. Each of the 12 90-minute…

  2. Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

    Energy Technology Data Exchange (ETDEWEB)

    Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.; Buchpiguel, C. A. [Cancer Institute of São Paulo State (ICESP), Clinical Hospital, School of Medicine, University of São Paulo, São Paulo 01246-000 (Brazil); Nuclear Medicine Service, Department of Radiology, School of Medicine, University of São Paulo, Sao Paulo 01246-000 (Brazil); Watanabe, T. [Nuclear Medicine Service, Department of Radiology, School of Medicine, University of São Paulo, São Paulo 01246-000 (Brazil); Traino, A. C. [Unit of Medical Physics, Azienda Ospedaliero-Universitaria Pisana, Pisa 56126 (Italy)

    2014-01-15

    {sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.

  3. Development of a Novel Targeted RNAi Delivery Technology inTherapies for Metabolic Diseases

    Science.gov (United States)

    2017-10-01

    report Impact on other disciplines: Nothing to report Impact on technology transfer: Nothing to report Impact on society : Nothing to report 5. CHANGES...AWARD NUMBER: W81XWH-15-1-0569 TITLE: Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases PRINCIPAL...COVERED 30Sep2016 - 29Sep2017 4. TITLE AND SUBTITLE Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases 5a

  4. Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0419 TITLE: Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease...COVERED 1 Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal...inappropriate cell growth, fluid secretion, and dysregulation of cellular energy metabolism. The enzyme AMPK regulates a number of cellular pathways, including

  5. Effectiveness of Targeted Musical Therapy on Sleep Quality and Overcoming Insomnia in Seniors

    Directory of Open Access Journals (Sweden)

    Reza Mottaghi

    2016-07-01

    Conclusion: The present study showed that targeted music therapy can lead to the improvement in the overall sleep quality, daily functioning, and subjective sleep quality thereby resulting in a sharp decline in the number of sleep drugs in seniors with primary insomnia disorder. Therefore, it is highly recommended by the music therapy and mental health experts for overcoming the sleep problems in older adults.

  6. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly & Cushing Disease Paradigms

    Directory of Open Access Journals (Sweden)

    Michael Anthony Mooney

    2016-07-01

    Full Text Available The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  7. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    Science.gov (United States)

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  8. Companion diagnostics for the targeted therapy of gastric cancer.

    Science.gov (United States)

    Yoo, Changhoon; Park, Young Soo

    2015-10-21

    Gastric cancer is the fourth most common type of cancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer.

  9. The Influence of an Orthopedic, Manual Therapy Residency Program on Improved Knowledge, Psychomotor Skills, and Clinical Reasoning in Nairobi, Kenya.

    Science.gov (United States)

    Cunningham, Shala; McFelea, Joni

    2017-01-01

    The purpose of this study was to describe the influence of a post-graduate orthopedic manual therapy residency program in Kenya on the development of physical therapists' (PTs) knowledge and clinical reasoning related to the performance of a musculoskeletal examination and evaluation as compared to an experience-matched control group of PTs waiting to enter the program. A cross-sectional design was utilized in which 12 graduating residents and 10 PTs entering the residency program completed a live-patient practical examination to assess the knowledge, clinical reasoning, and psychomotor skills related to the examination and evaluation of musculoskeletal conditions. The assessment utilized was based on the tasks, procedures, and knowledge areas identified as important to advanced clinicians in the US as outlined by the Orthopaedic Description of Specialty Practice. Inclusion criteria included participation in or acceptance to the residency program, practice as a PT between 3 and 25 years, and 50% of workday being involved in direct patient care. Overall pass rates were analyzed using the Pearson chi-square and Fisher's exact tests to determine if the graduating residents achieved significantly higher scores than experience-matched controls consisting of PTs entering the residency program. PTs completing a post-graduate orthopedic manual therapy residency in Nairobi, Kenya, achieved higher scores and passing rates compared to their colleagues who had not completed a residency program as determined by a live-patient practical examination. Graduating residents demonstrated statistically significant higher scores in the categories of examination, evaluation, and diagnosis. The average live-patient practical examination score for PTs without residency training was 38.2%, and their pass rate was 0.0%. The average live-patient practical examination score for residency-trained PTs was 83.4%, and their pass rate was 92.3%. These findings are statistically significant ( p

  10. Cannabinoid Receptors: A Novel Target for Therapy of Prostate Cancer

    Science.gov (United States)

    2007-02-01

    study could be to develop nonhabit-forming cannabi - noid agonist (s) for the management of prostate cancer . REFERENCES 1. Jemal, A., Siegel, R.W...for Therapy of Prostate Cancer PRINCIPAL INVESTIGATOR: Prof. Hasan Mukhtar, Ph.D (PI) Dr. Farrukh Afaq, Ph.D (Co-Investigator...REPORT DATE: February 2007 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command

  11. Targeting dendritic cells in vivo for cancer therapy

    Directory of Open Access Journals (Sweden)

    Irina eCaminschi

    2012-02-01

    Full Text Available Monoclonal antibodies that recognise cell surface molecules have been used deliver antigenic cargo to dendritic cells (DC for induction of immune responses. The encouraging anti-tumour immunity elicited using this immunisation strategy suggests its suitability for clinical trials. This review discusses the complex network of DC, the functional specialisation of DC-subsets, the immunological outcomes of targeting different DC-subsets and their cell surface receptors, and the requirements for the induction of effective anti-tumour immunity. Finally, we review preclinical experiments and the progress towards targeting human DC in vivo.

  12. Targeting post-translational modifications of histones for cancer therapy.

    Science.gov (United States)

    Hsu, Y-C; Hsieh, Y-H; Liao, C-C; Chong, L-W; Lee, C-Y; Yu, Y-L; Chou, R-H

    2015-10-30

    Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

  13. Mexican Sobadores in North Carolina: Manual Therapy in a New Settlement Context.

    Science.gov (United States)

    Quandt, Sara A; Sandberg, Joanne C; Graham, Alan; Mora, Dana C; Stub, Trine; Arcury, Thomas A

    2017-10-01

    Latino immigrants to the New Settlement area of the southeastern United States face structural and cultural obstacles to accessing the conventional health care system, and come from areas with long traditions of medical treatments from healers without professional training or licensure. Little is known about the use of such healers in New Settlement areas. This study focuses on sobadores, healers who use manipulative therapy. Goals were to describe sobadores practicing in North Carolina, including their background, conditions treated, and their understanding of the pathophysiology of their patients' conditions and how their treatments work. The paper also describes who sobadores treat and sobadores' understanding of where their treatment fits into patients' pursuit of relief from symptoms. This focused ethnography draws from in-depth, semi-structured interviews conducted with six sobadores from Mexico practicing in North Carolina. These sobadores appear to meet both structural and cultural needs for healthcare in the immigrant Latino population.

  14. Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

    Science.gov (United States)

    Peng, Le; Zhang, Chao; Zhou, Lan; Zuo, Hong-Xia; He, Xiao-Kuo; Niu, Yu-Ming

    2018-04-01

    To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I 2  = 71%, P = 0.0005). Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

  15. Targeted gene therapy and cell reprogramming in Fanconi anemia

    Science.gov (United States)

    Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

    2014-01-01

    Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. PMID:24859981

  16. Sphingolipid metabolism enzymes as targets for anticancer therapy

    NARCIS (Netherlands)

    Kok, JW; Sietsma, H

    Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumour cells. Unfortunately, tumour cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics.

  17. Targeted gene therapy and cell reprogramming in Fanconi anemia.

    Science.gov (United States)

    Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

    2014-06-01

    Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  18. Small molecules and targeted therapies in distant metastatic disease

    DEFF Research Database (Denmark)

    Hersey, P; Bastholt, L; Chiarion-Sileni, V

    2009-01-01

    with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib...

  19. Reimbursement of targeted cancer therapies within 3 different European health care systems

    NARCIS (Netherlands)

    Mihajlović, Jovan; Dolk, Christiaan; Tolley, Keith; Simoens, Steven; Postma, Maarten J.

    2015-01-01

    PURPOSE: Targeted cancer therapies (TCTs) are drugs that specifically act on molecular targets within the cancer cell, causing its regression and/or destruction. Although TCTs offer clinically important gains in survival in one of the most challenging therapeutic areas, these gains are followed by

  20. mTOR in squamous cell carcinoma of the oesophagus: a potential target for molecular therapy?

    NARCIS (Netherlands)

    Boone, J.; ten Kate, F. J. W.; Offerhaus, G. J. A.; van Diest, P. J.; Borel Rinkes, I. H. M.; van Hillegersberg, R.

    2008-01-01

    AIMS: The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been

  1. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  2. Gene therapy of cancer and development of therapeutic target gene

    International Nuclear Information System (INIS)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

  3. Chuna (or Tuina Manual Therapy for Musculoskeletal Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Nam-Woo Lee

    2017-01-01

    Full Text Available Objective. To review the literature and systematically evaluate the effectiveness of Chuna (or Tuina manual therapy (C[T]MT on pain and function for musculoskeletal disorders. Methods. We searched 15 English, Chinese, Japanese, and Korean databases using relevant keywords. All randomized controlled trials (RCTs of C(TMT for musculoskeletal disorders were considered, and we limited analyses to studies with a low-risk bias for randomization and/or allocation concealment. Results. Sixty-six RCTs with 6,170 participants were included. One sham-controlled RCT showed that C(TMT relieved pain more effectively than a sham control (SMD -3.09 [-3.59, -2.59]. For active-controlled RCTs, pooled meta-analysis showed that C(TMT had statistically significant effects on pain reduction, especially compared to traction (P<0.00001, drugs (P=0.04, and physical therapies (P<0.0001. For functional improvement, combined effects of C(TMT with drugs (P=0.04 and traction (P=0.05 also showed similar positive effects. Conclusions. This systematic review suggests that C(TMT is safe and effective for pain reduction and functional improvement for musculoskeletal diseases; however, the evidence for functional improvement was not as strong as for pain reduction. For future studies, high-quality RCTs such as sham-controlled studies with standardized interventions are needed to provide sufficient evidence on the effects of C(TMT for musculoskeletal diseases. Protocol registration number is CRD42016038307 04/07/2016.

  4. Molecular targets in cancer therapy: the Ron approach

    Directory of Open Access Journals (Sweden)

    Serena Germano

    2011-12-01

    Full Text Available The receptor tyrosine kinase Ron and its ligand, Macrophage Stimulating Protein (MSP, mediate multiple processes involved in the control of cell proliferation, migration and protection from apoptosis. Dysregulated signaling of Ron, due to hyperactivation or loss of negative regulation, is involved in tumor progression and metastasis. Growing evidence indicates that Ron is abnormally expressed and activated in certain types of primary epithelial cancers (i.e. breast, colon, lung, pancreas, bladder and thyroid, where it critically contributes to the maintenance of tumorigenic and invasive phenotype. Furthermore, a positive association between aberrant Ron expression and aggressive biological indicators as well as a worse clinical outcome have been reported in breast, bladder and thyroid carcinomas. Different approaches have proved effective in targeting receptor activation/expression both in vitro and in animal models, leading to reversion of the tumorigenic phenotype. Altogether these results show that Ron is an attractive molecular target for clinical intervention.

  5. Molecular targeting of angiogenesis for imaging and therapy

    International Nuclear Information System (INIS)

    Brack, Simon S.; Neri, Dario; Dinkelborg, Ludger M.

    2004-01-01

    Angiogenesis, i.e. the proliferation of new blood vessels from pre-existing ones, is an underlying process in many human diseases, including cancer, blinding ocular disorders and rheumatoid arthritis. The ability to selectively target and interfere with neovascularisation would potentially be useful in the diagnosis and treatment of angiogenesis-related diseases. This review presents the authors' views on some of the most relevant markers of angiogenesis described to date, as well as on specific ligands which have been characterised in pre-clinical animal models and/or clinical studies. Furthermore, we present an overview on technologies which are likely to have an impact on the way molecular targeting of angiogenesis is performed in the future. (orig.)

  6. Improving superficial target delineation in radiation therapy with endoscopic tracking and registration

    Energy Technology Data Exchange (ETDEWEB)

    Weersink, R. A.; Qiu, J.; Hope, A. J.; Daly, M. J.; Cho, B. C. J.; DaCosta, R. S.; Sharpe, M. B.; Breen, S. L.; Chan, H.; Jaffray, D. A. [Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada) and Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada and Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada) and Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada)

    2011-12-15

    Purpose: Target delineation within volumetric imaging is a critical step in the planning process of intensity modulated radiation therapy. In endoluminal cancers, endoscopy often reveals superficial areas of visible disease beyond what is seen on volumetric imaging. Quantitatively relating these findings to the volumetric imaging is prone to human error during the recall and contouring of the target. We have developed a method to improve target delineation in the radiation therapy planning process by quantitatively registering endoscopic findings contours traced on endoscopic images to volumetric imaging. Methods: Using electromagnetic sensors embedded in an endoscope, 2D endoscopic images were registered to computed tomography (CT) volumetric images by tracking the position and orientation of the endoscope relative to a CT image set. Regions-of-interest (ROI) in the 2D endoscopic view were delineated. A mesh created within the boundary of the ROI was projected onto the 3D image data, registering the ROI with the volumetric image. This 3D ROI was exported to clinical radiation treatment planning software. The precision and accuracy of the procedure was tested on two solid phantoms with superficial markings visible on both endoscopy and CT images. The first phantom was T-shaped tube with X-marks etched on the interior. The second phantom was an anatomically correct skull phantom with a phantom superficial lesion placed on the pharyngeal surface. Markings were contoured on the endoscope images and compared with contours delineated in the treatment planning system based on the CT images. Clinical feasibility was tested on three patients with early stage glottic cancer. Image-based rendering using manually identified landmarks was used to improve the registration. Results: Using the T-shaped phantom with X-markings, the 2D to 3D registration accuracy was 1.5-3.5 mm, depending on the endoscope position relative to the markings. Intraobserver standard variation was 0

  7. Adverse Renal Effects of Novel Molecular Oncologic Targeted Therapies: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Kenar D. Jhaveri

    2017-01-01

    Full Text Available Novel targeted anti-cancer therapies have resulted in improvement in patient survival compared to standard chemotherapy. Renal toxicities of targeted agents are increasingly being recognized. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here we review the adverse renal effects associated with a selection of currently approved targeted cancer therapies, directed to EGFR, HER2, BRAF, MEK, ALK, PD1/PDL1, CTLA-4, and novel agents targeted to VEGF/R and TKIs. In summary, electrolyte disorders, renal impairment and hypertension are the most commonly reported events. Of the novel targeted agents, ipilumumab and cetuximab have the most nephrotoxic events reported. The early diagnosis and prompt recognition of these renal adverse events are essential for the general nephrologist taking care of these patients.

  8. A manual physical therapy intervention for symptoms of knee osteoarthritis and associated fall risk: A case series of four patients.

    Science.gov (United States)

    Allen, Chris; Sheehan, Riley; Deyle, Gail; Wilken, Jason; Gill, Norman

    2018-02-26

    Patients with knee osteoarthritis (OA) are at an increased risk of falling. Further, the symptoms associated with knee OA are correlated with fall risk. A manual physical therapy (MPT) approach consisting of mobilizing techniques and reinforcing exercise improves the symptoms and functional limitations associated with knee OA. The purpose of this case series is to evaluate an MPT intervention of mobilization techniques and exercise for knee OA on improving symptoms and quantify the secondary benefit of improving stumble recovery. Four patients with symptomatic knee OA and four matched controls completed a fall risk assessment. Following 4 weeks of intervention, patients were reevaluated. Initial Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores indicated notable symptoms and functional limitations in all patients. In addition, all patients displayed elevated fall risk and/or impaired stumble responses. Following 4 weeks of intervention, all patients reported meaningful reductions in all three WOMAC subscales and demonstrated improvements in at least two of the three fall risk measures. We identified potential connections between symptom relief in patients with knee OA, stumble response, and ultimately fall risk. The results suggest that MPT intervention designed to improve the signs and symptoms of knee OA may lead to a secondary benefit of improved gait stability and stumble response.

  9. A randomized controlled trial of manual therapy and pneumatic compression for recovery from prolonged running - an extended study.

    Science.gov (United States)

    Heapy, Amanda M; Hoffman, Martin D; Verhagen, Heidie H; Thompson, Samuel W; Dhamija, Pavitra; Sandford, Fiona J; Cooper, Mary C

    2018-03-07

    Manual therapy (MT) and intermittent pneumatic compression (IPC) are recovery methods used by endurance athletes with little evidence supporting effectiveness. This randomized controlled trial evaluated effectiveness of four daily post-race treatments of a specific MT protocol and IPC compared with supine rest on recovery following an ultramarathon among 56 ultramarathoners. Groups were comparable across all characteristics examined, including post-race plasma creatine kinase concentration. Subject completed timed 400 m runs before the race and on days three, five, seven and 14 post- race, and also provided muscle pain and soreness ratings and fatigue scores immediately before and after treatments, and during the 14 days post- race. Daily subjective measures and 400 m run times were not improved by either treatment, but both treatments reduced (p < .05) muscular fatigue scores acutely after treatment following the race and on post-race day 1, and MT improved (p < .05) muscle pain and soreness acutely following the race.

  10. Hypoalgesic effects of three different manual therapy techniques on cervical spine and psychological interaction: A randomized clinical trial.

    Science.gov (United States)

    Alonso-Perez, Jose Luis; Lopez-Lopez, Almudena; La Touche, Roy; Lerma-Lara, Sergio; Suarez, Emilio; Rojas, Javier; Bishop, Mark D; Villafañe, Jorge Hugo; Fernández-Carnero, Josué

    2017-10-01

    The purpose of this study was to evaluate the extent to which psychological factors interact with a particular manual therapy (MT) technique to induce hypoalgesia in healthy subjects. Seventy-five healthy volunteers (36 female, 39 males), were recruited in this double-blind, controlled and parallel study. Subjects were randomly assigned to receive: High velocity low amplitude technique (HVLA), joint mobilization, or Cervical Lateral glide mobilization (CLGM). Pressure pain threshold (PPT) over C7 unilaterally, trapezius muscle and lateral epicondyle bilaterally, were measured prior to single technique MT was applied and immediately after to applied MT. Pain catastrophizing, depression, anxiety and kinesiophobia were evaluated before treatment. The results indicate that hypoalgesia was observed in all groups after treatment in the neck and elbow region (P < 0.05), but mobilization induces more hypoalgesic effects. Catastrophizing interacted with change over time in PPT, for changes in C7 and in manipulation group. All the MT techniques studied produced local and segmental hypoalgesic effects, supporting the results of previous studies studying the individual interventions. Interaction between catastrophizing and HVLA technique suggest that whether catastrophizing level is low or medium, the chance of success is high, but high levels of catastrophizing may result in poor outcome after HVLA intervention. ClinicalTrials.gov Registration Number: NCT02782585. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Laryngeal manual therapy palpatory evaluation scale: A preliminary study to examine its usefulness in diagnosis of occupational dysphonia

    Directory of Open Access Journals (Sweden)

    Ewelina Woźnicka

    2017-04-01

    Full Text Available Background: The aim of this study has been to assess the larynx and soft tissue around the vocal tract in a group of people with healthy voice, and in a group of patients with occupational dysphonia using the new laryngeal manual therapy palpatory evaluation scale (LMTPE. Material and Methods: The examinations were performed in a study (dysphonic group of professional voice users who had developed voice disorders (N = 51 and in the control group of normophonic subjects (N = 50. All the participants underwent perceptual voice assessment and examination by means of the LMTPE scale. Additionally, phoniatric examination including VHI (Voice Handicap Index questionnaire, GRBAS (the Grade of hoarseness, Roughness, Breathiness, Asthenic, Strained perceptual evaluation, maximum phonation time (MPT measurement and videostroboscopy was performed in the study group. Results: The comparison of the LMTPE total score showed that the results of the study group were significantly poorer than those of controls (p < 0.001. In the study group, correlations were found between the LMTPE results and the VHI scores (p < 0.05, perceptual evaluation by the GRBAS (p < 0.05 and the objective parameter MPT (p < 0.05. Conclusions: The study has proven that the LMTPE scale is characterized by the high score of Cronbach’s α ratio estimating the reliability of the test. The results have confirmed that the LMTPE scale seems to be a valuable tool, useful in diagnostics of occupational dysphonia, particularly of hyperfunction origin. Med Pr 2017;68(2:179–188

  12. Treatment effectiveness and fidelity of manual therapy to the knee: A systematic review and meta-analysis.

    Science.gov (United States)

    Salamh, Paul; Cook, Chad; Reiman, Michael P; Sheets, Charles

    2017-09-01

    Manual therapy (MT) is a commonly used treatment for knee osteoarthritis (OA) but to date only one systematic review has explored its effectiveness. The purpos e of the present study was to perform a systematic review and meta-analysis of the literature, to determine the effectiveness and fidelity of studies using MT techniques in individuals with knee OA. Relevant studies were assessed for inclusion. Effectiveness was measured using effect sizes, and methodological bias and treatment fidelity were both explored. Effect sizes were calculated using standardized mean differences (SMD) based on pooled data depending on statistical and clinical heterogeneity, as well as risk of bias. The search captured 2,969 studies; after screening, 12 were included. Four had a low risk of bias and high treatment fidelity. For self-reported function, comparing MT with no treatment resulted in a large effect size (standardized mean difference [SMD] 0.84), as did adding MT to a comparator treatment (SMD 0.78). A significant difference was found for pain when adding MT to a comparator treatment (SMD 0.73). The findings in the present meta-analytical review support the use of MT versus a number of different comparators for improvement in self-reported knee function. Lesser support is present for pain reduction, and no endorsement of functional performance can be made at this time. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Clinical variables associated with recovery in patients with chronic tension-type headache after treatment with manual therapy.

    Science.gov (United States)

    Castien, René F; van der Windt, Daniëlle A W M; Blankenstein, Annette H; Heymans, Martijn W; Dekker, Joost

    2012-04-01

    The aims of this study were to describe the course of chronic tension-type headache (CTTH) in participants receiving manual therapy (MT), and to develop a prognostic model for predicting recovery in participants receiving MT. Outcomes in 145 adults with CTTH who received MT as participants in a previously published randomised clinical trial (n=41) or in a prospective cohort study (n=104) were evaluated. Assessments were made at baseline and at 8 and 26 weeks of follow-up. Recovery was defined as a 50% reduction in headache days in combination with a score of 'much improved' or 'very much improved' for global perceived improvement. Potential prognostic factors were analyzed by univariable and multivariable regression analysis. After 8 weeks 78% of the participants reported recovery after MT, and after 26 weeks the frequency of recovered participants was 73%. Prognostic factors related to recovery were co-existing migraine, absence of multiple-site pain, greater cervical range of motion and higher headache intensity. In participants classified as being likely to be recovered, the posterior probability for recovery at 8 weeks was 92%, whereas for those being classified at low probability of recovery this posterior probability was 61%. It is concluded that the course of CTTH is favourable in primary care patients receiving MT. The prognostic models provide additional information to improve prediction of outcome. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  14. User's manual of a supporting system for treatment planning in boron neutron capture therapy. JAERI computational dosimetry system

    International Nuclear Information System (INIS)

    Kumada, Hiroaki; Torii, Yoshiya

    2002-09-01

    A boron neutron capture therapy (BNCT) with epithermal neutron beam is expected to treat effectively for malignant tumor that is located deeply in the brain. It is indispensable to estimate preliminarily the irradiation dose in the brain of a patient in order to perform the epithermal neutron beam BNCT. Thus, the JAERI Computational Dosimetry System (JCDS), which can calculate the dose distributions in the brain, has been developed. JCDS is a software that creates a 3-dimensional head model of a patient by using CT and MRI images and that generates a input data file automatically for calculation neutron flux and gamma-ray dose distribution in the brain by the Monte Carlo code: MCNP, and that displays the dose distribution on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By treating CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is able to be made easily. The three-dimensional head image is editable to simulate the state of a head after its surgical processes such as skin flap opening and bone removal for the BNCT with craniotomy that are being performed in Japan. JCDS can provide information for the Patient Setting System to set the patient in an actual irradiation position swiftly and accurately. This report describes basic design and procedure of dosimetry, operation manual, data and library structure for JCDS (ver.1.0). (author)

  15. Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: design of a randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Dekker Joost

    2009-02-01

    Full Text Available Abstract Background Patients with Chronic Tension Type Headache (CTTH report functional and emotional impairments (loss of workdays, sleep disturbances, emotional well-being and are at risk for overuse of medication. Manual therapy may improve symptoms through mobilisation of the spine, correction of posture, and training of cervical muscles. We present the design of a randomised clinical trial (RCT evaluating the effectiveness of manual therapy (MT compared to usual care by the general practitioner (GP in patients with CTTH. Methods and design Patients are eligible for participation if they present in general practice with CTTH according to the classification of the International Headache Society (IHS. Participants are randomised to either usual GP care according to the national Dutch general practice guidelines for headache, or manual therapy, consisting of mobilisations (high- and low velocity techniques, exercise therapy for the cervical and thoracic spine and postural correction. The primary outcome measures are the number of headache days and use of medication. Secondary outcome measures are severity of headache, functional status, sickness absence, use of other healthcare resources, active cervical range of motion, algometry, endurance of the neckflexor muscles and head posture. Follow-up assessments are conducted after 8 and 26 weeks. Discussion This is a pragmatic trial in which interventions are offered as they are carried out in everyday practice. This increases generalisability of results, but blinding of patients, GPs and therapists is not possible. The results of this trial will contribute to clinical decision making of the GP regarding referral to manual therapy in patients with chronic tension headache.

  16. Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

    LENUS (Irish Health Repository)

    Gasch, Claudia

    2017-01-01

    It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.

  17. Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

    Science.gov (United States)

    Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-11-21

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  18. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  19. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options

    Directory of Open Access Journals (Sweden)

    Milic S

    2015-08-01

    Full Text Available Sandra Milic,1 Ivana Mikolasevic,1,2 Irena Krznaric-Zrnic,1 Marija Stanic,3 Goran Poropat,1 Davor Stimac,1 Vera Vlahovic-Palcevski,4 Lidija Orlic2 1Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia; 2Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia; 3Department of Hematology, UHC Rijeka, Rijeka, Croatia; 4Department for Clinical Pharmacology, University of Rijeka Medical School, UHC Rijeka, Rijeka, Croatia Abstract: Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD. NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only

  20. Complement, a target for therapy in inflammatory and degenerative diseases.

    Science.gov (United States)

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

  1. GPNMB expression in uveal melanoma: a potential for targeted therapy.

    Science.gov (United States)

    Williams, Michelle D; Esmaeli, Bita; Soheili, Aydin; Simantov, Ronit; Gombos, Dan S; Bedikian, Agop Y; Hwu, Patrick

    2010-06-01

    Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in >or=50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma.

  2. Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy

    International Nuclear Information System (INIS)

    Brown, Lindsay C.; Diehn, Felix E.; Boughey, Judy C.; Childs, Stephanie K.; Park, Sean S.; Yan, Elizabeth S.; Petersen, Ivy A.; Mutter, Robert W.

    2015-01-01

    Purpose: To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. Methods and Materials: Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Results: Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastases were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. Conclusions: For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted

  3. Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Lindsay C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Diehn, Felix E. [Department of Radiology, Mayo Clinic, Rochester, Minnesota (United States); Boughey, Judy C. [Department of Surgery, Mayo Clinic, Rochester, Minnesota (United States); Childs, Stephanie K.; Park, Sean S.; Yan, Elizabeth S.; Petersen, Ivy A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Mutter, Robert W., E-mail: mutter.robert@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2015-07-01

    Purpose: To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. Methods and Materials: Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Results: Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastases were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. Conclusions: For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted.

  4. Manualized cognitive therapy versus cognitive-behavioral treatment-as-usual for social anxiety disorder in routine practice: A cluster-randomized controlled trial.

    Science.gov (United States)

    Hoyer, Jürgen; Čolić, Jasmin; Pittig, Andre; Crawcour, Stephen; Moeser, Manuela; Ginzburg, Denise; Lin, Jihong; Wiltink, Joerg; Leibing, Eric; Stangier, Ulrich

    2017-08-01

    This study examined the effectiveness of manualized cognitive therapy (mCT) following the Clark-Wells approach versus non-manualized cognitive-behavioral treatment-as-usual (CBTAU) for social anxiety disorder (SAD) in routine practice. Forty-eight private practitioners were recruited within a multi-center trial and either received training in manualized CT for SAD or no such training. Practitioners treated 162 patients with SAD in routine practice (N = 107 completers, n = 57 for mCT, n = 50 for CBTAU). Social anxiety symptoms (Liebowitz Social Anxiety Scale; LSAS) and secondary measures were assessed before treatment, at treatment-hour 8, 15, and 25, at end of treatment, as well as 6 and 12 months after treatment. Patients in both groups showed significant reductions of SAD severity after treatment (d = 1.91 [mCT] and d = 1.80 [CBTAU], within-group effect sizes, intent-to-treat analyses, LSAS observer ratings), which remained stable at follow-up. There were no differences between groups in terms of symptom reduction and treatment duration. The present trial confirms the high effectiveness of CBTAU and mCT for SAD when practitioners conduct the treatments in routine practice. Additional training in the CT manual did not result in significant between-group effects on therapy outcome. Explanations for this unexpected result are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. SU-E-T-357: Semi-Automated Knowledge-Based Radiation Therapy (KBRT) Planning for Head-And-Neck Cancer (HNC): Can KBRT Plans Achieve Better Results Than Manual Planning?

    International Nuclear Information System (INIS)

    Lutzky, C; Grzetic, S; Lo, J; Das, S

    2014-01-01

    Purpose: Knowledge Based Radiation Therapy Treatment (KBRT) planning can be used to semi-automatically generate IMRT plans for new patients using constraints derived from previously manually-planned, geometrically similar patients. We investigate whether KBRT plans can achieve greater dose sparing than manual plans using optimized, organspecific constraint weighting factors. Methods: KBRT planning of HNC radiotherapy cases geometrically matched each new (query) case to one of the 105 clinically approved plans in our database. The dose distribution of the planned match was morphed to fit the querys geometry. Dose-volume constraints extracted from the morphed dose distribution were used to run the IMRT optimization with no user input. In the first version, all constraints were multiplied by a weighting factor of 0.7. The weighting factors were then systematically optimized (in order of OARs with increasing separation from the target) to maximize sparing to each OAR without compromising other OARs. The optimized, second version plans were compared against the first version plans and the clinically approved plans for 45 unilateral/bilateral target cases using the dose metrics: mean, median and maximum (brainstem and cord) doses. Results: Compared to the first version, the second version significantly reduced mean/median contralateral parotid doses (>2Gy) for bilateral cases. Other changes between the two versions were not clinically meaningful. Compared to the original clinical plans, both bilateral and unilateral plans in the second version had lower average dose metrics for 5 of the 6 OARs. Compared to the original plans, the second version achieved dose sparing that was at least as good for all OARs and better for the ipsilateral parotid (bilateral) and oral cavity (bilateral/unilateral). Differences in planning target volume coverage metrics were not clinically significant. Conclusion: HNC-KBRT planning generated IMRT plans with at least equivalent dose sparing to

  6. SU-E-T-357: Semi-Automated Knowledge-Based Radiation Therapy (KBRT) Planning for Head-And-Neck Cancer (HNC): Can KBRT Plans Achieve Better Results Than Manual Planning?

    Energy Technology Data Exchange (ETDEWEB)

    Lutzky, C; Grzetic, S; Lo, J; Das, S [Duke University Medical Center, Durham, NC (United States)

    2014-06-01

    Purpose: Knowledge Based Radiation Therapy Treatment (KBRT) planning can be used to semi-automatically generate IMRT plans for new patients using constraints derived from previously manually-planned, geometrically similar patients. We investigate whether KBRT plans can achieve greater dose sparing than manual plans using optimized, organspecific constraint weighting factors. Methods: KBRT planning of HNC radiotherapy cases geometrically matched each new (query) case to one of the 105 clinically approved plans in our database. The dose distribution of the planned match was morphed to fit the querys geometry. Dose-volume constraints extracted from the morphed dose distribution were used to run the IMRT optimization with no user input. In the first version, all constraints were multiplied by a weighting factor of 0.7. The weighting factors were then systematically optimized (in order of OARs with increasing separation from the target) to maximize sparing to each OAR without compromising other OARs. The optimized, second version plans were compared against the first version plans and the clinically approved plans for 45 unilateral/bilateral target cases using the dose metrics: mean, median and maximum (brainstem and cord) doses. Results: Compared to the first version, the second version significantly reduced mean/median contralateral parotid doses (>2Gy) for bilateral cases. Other changes between the two versions were not clinically meaningful. Compared to the original clinical plans, both bilateral and unilateral plans in the second version had lower average dose metrics for 5 of the 6 OARs. Compared to the original plans, the second version achieved dose sparing that was at least as good for all OARs and better for the ipsilateral parotid (bilateral) and oral cavity (bilateral/unilateral). Differences in planning target volume coverage metrics were not clinically significant. Conclusion: HNC-KBRT planning generated IMRT plans with at least equivalent dose sparing to

  7. Adult soft tissue sarcomas: conventional therapies and molecularly targeted approaches.

    Science.gov (United States)

    Mocellin, Simone; Rossi, Carlo R; Brandes, Alba; Nitti, Donato

    2006-02-01

    The therapeutic approach to soft tissue sarcomas (STS) has evolved over the past two decades based on the results from randomized controlled trials, which are guiding physicians in the treatment decision-making process. Despite significant improvements in the control of local disease, a significant number of patients ultimately die of recurrent/metastatic disease following radical surgery due to a lack of effective adjuvant treatments. In addition, the characteristic chemoresistance of STS has compromised the therapeutic value of conventional antineoplastic agents in cases of unresectable advanced/metastatic disease. Therefore, novel therapeutic strategies are urgently needed to improve the prognosis of patients with STS. Recent advances in STS biology are paving the way to the development of molecularly targeted therapeutic strategies, the efficacy of which relies not only on the knowledge of the molecular mechanisms underlying cancer development/progression but also on the personalization of the therapeutic regimen according to the molecular features of individual tumours. In this work, we review the state-of-the-art of conventional treatments for STS and summarize the most promising findings in the development of molecularly targeted therapeutic approaches.

  8. Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Wiebke Sihver

    2014-03-01

    Full Text Available The epidermal growth factor receptor (EGFR has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment.

  9. Multidisciplinary approach to non-surgical management of inguinal disruption in a professional hockey player treated with platelet-rich plasma, manual therapy and exercise: a case report.

    Science.gov (United States)

    St-Onge, Eric; MacIntyre, Ian G; Galea, Anthony M

    2015-12-01

    To present the clinical management of inguinal disruption in a professional hockey player and highlight the importance of a multidisciplinary approach to diagnosis and management. A professional hockey player with recurrent groin pain presented to the clinic after an acute exacerbation of pain while playing hockey. The patient received a clinical diagnosis of inguinal disruption. Imaging revealed a tear in the rectus abdominis. Management included two platelet-rich plasma (PRP) injections to the injured tissue, and subsequent manual therapy and exercise. The patient returned to his prior level of performance in 3.5 weeks. This case demonstrated the importance of a multidisciplinary team and the need for advanced imaging in athletes with groin pain. Research quality concerning the non-surgical management of inguinal disruption remains low. This case adds evidence that PRP, with the addition of manual therapy and exercise may serve as a relatively quick and effective non-surgical management strategy.

  10. Predicting Manual Therapy Treatment Success in Patients With Chronic Ankle Instability: Improving Self-Reported Function.

    Science.gov (United States)

    Wikstrom, Erik A; McKeon, Patrick O

    2017-04-01

      Therapeutic modalities that stimulate sensory receptors around the foot-ankle complex improve chronic ankle instability (CAI)-associated impairments. However, not all patients have equal responses to these modalities. Identifying predictors of treatment success could improve clinician efficiency when treating patients with CAI.   To conduct a response analysis on existing data to identify predictors of improved self-reported function in patients with CAI.   Secondary analysis of a randomized controlled clinical trial.   Sports medicine research laboratories.   Fifty-nine patients with CAI, which was defined in accordance with the International Ankle Consortium recommendations.   Participants were randomized into 3 treatment groups (plantar massage [PM], ankle-joint mobilization [AJM], or calf stretching [CS]) that received six 5-minute treatments over 2 weeks.   Treatment success, defined as a patient exceeding the minimally clinically important difference of the Foot and Ankle Ability Measure-Sport (FAAM-S).   Patients with ≤5 recurrent sprains and ≤82.73% on the Foot and Ankle Ability Measure had a 98% probability of having a meaningful FAAM-S improvement after AJM. As well, ≥5 balance errors demonstrated 98% probability of meaningful FAAM-S improvements from AJM. Patients <22 years old and with ≤9.9 cm of dorsiflexion had a 99% probability of a meaningful FAAM-S improvement after PM. Also, those who made ≥2 single-limb-stance errors had a 98% probability of a meaningful FAAM-S improvement from PM. Patients with ≤53.1% on the FAAM-S had an 83% probability of a meaningful FAAM-S improvement after CS.   Each sensory-targeted ankle-rehabilitation strategy resulted in a unique combination of predictors of success for patients with CAI. Specific indicators of success with AJM were deficits in self-reported function, single-limb balance, and <5 previous sprains. Age, weight-bearing-dorsiflexion restrictions, and single-limb balance

  11. SKIN TOXICITY OF TARGETED THERAPY: VEMURAFENIB, FIRST EXPERIENCES FROM MONTENEGRO

    Directory of Open Access Journals (Sweden)

    Todorović Vladimir

    2015-07-01

    Full Text Available Introduction: Data on melanoma incidence and mortality in Montenegro is only partially complete. GLOBOCAN and EUCAN reports estimate melanoma incidence in Montenegro to be between 4.6-7.3 cases/100 000. At least 50% of all metastatic melanoma cell lines carry an activating mutation in the BRAF oncogene. The treatment of advanced melanoma with the selective BRAF inhibitors, such as vemurafenib demonstrated improvement in progression free interval and overall survival when compared to conventional chemotherapy treatment. Up to 95% of patients treated with vemurafenib experience skin toxicity. Material and methods: Five patients with metastatic melanoma have been treated with vemurafenib at the Clinic for Oncology and Radiotherapy Podgorica, Montenegro, during the period 2013-2014. They were treated with standard dose (960 mg twice a day, per os. Data about the occurrence and management of skin side-effects in these patients were retrospectively collected from medical charts. Severity of side-effects was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Results: In 2013, 41 new cases of melanoma were registered in Montenegro, 20 (48.7% male and 21 (51.3% female. In 2014, 49 new cases of melanoma were registered, 27 (55.1% male and 22 (44.9% female. Two out of five (40% vemurafenib treated patients experienced photosensitivity, three (60% had rash eruptions, four (80% developed alopecia, and two (40% had dry skin problems. Alteration in nevus color and size occurred in one (20% patient, and two (40% patients developed new pigmented lesions. Conclusion: Skin side effects associated with vemurafenib are plentiful, but generally manageable with supportive care measures. In our experience, majority of described side-effects were of grade 1 or 2, and none required dose modifications, or discontinuation of the therapy. Our experience suggests that patients taking BRAF inhibitors should have regular

  12. Dose Dependent Survival Response in Chronic Myeloid Leukemia under Continuous and Pulsed Targeted Therapy

    International Nuclear Information System (INIS)

    Pizzolato, N.; Valenti, D.; Spagnolo, B.; Persano Adorno, D.

    2010-01-01

    A simulative study of cancer growth dynamics in patients affected by Chronic Myeloid Leukemia (CML), under the effect of a targeted dose dependent continuous or pulsed therapy, is presented. We have developed a model for the dynamics of CML in which the stochastic evolution of white blood cell populations are simulated by adopting a Monte Carlo approach. Several scenarios in the evolutionary dynamics of white blood cells, as a consequence of the efficacy of the different modelled therapies, pulsed or continuous, are described. The best results, in terms of a permanent disappearance of the leukemic phenotype, are achieved with a continuous therapy and higher dosage. However, our findings demonstrate that an intermittent therapy could represent a valid choice in patients with high risk of toxicity, when a long-term therapy is considered. A suitably tuned pulsed therapy can enhance the treatment efficacy and reduce the percentage of patients developing resistance. (authors)

  13. Targeting HIF-2α as therapy for advanced cancers.

    Science.gov (United States)

    Murugesan, Thanabal; Rajajeyabalachandran, Gurukumari; Kumar, Swetha; Nagaraju, Shruthi; Kumar, Sooriya

    2018-05-14

    Hypoxia-inducible factors (HIF-1α, -2α -3α, and -β) are key factors that control hypoxia-induced carcinogenic pathways. HIF-1α is predominantly involved in the early stages of cancer, whereas HIF-2α is actively involved in the later stages; in addition, chronic (prolonged) rather than acute (short) hypoxia is a feature of metastasis and chemoresistance that occur during the later stages of cancer. Oncometabolites, onco-miRNAs, glucose deprivation, pseudohypoxia, cytokine/chemokine secretion, and some unique upstream proteins are involved in the signaling switch from HIF-1α to HIF-2α; thus, understanding this signaling switch is critical for the treatment of advanced cancer. In this review, we highlight data relating to HIF-2α rather than HIF-1α signaling in cancer pathways and discuss prospective drugs that target this important factor. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Muscarinic receptors as targets for anti-inflammatory therapy.

    Science.gov (United States)

    Sales, María Elena

    2010-11-01

    ACh, the main neurotransmitter in the neuronal cholinergic system, is synthesized by pre-ganglionic fibers of the sympathetic and parasympathetic autonomic nervous system and by post-ganglionic parasympathetic fibers. There is increasing experimental evidence that ACh is widely expressed in prokaryotic and eukaryotic non-neuronal cells. The neuronal and non-neuronal cholinergic systems comprise ACh, choline acetyltransferase and cholinesterase, enzymes that synthesize and catabolize ACh, and the nicotinic and muscarinic ACh receptors (nAChRs and mAChRs, respectively), which are the targets for ACh action. This review analyzes the participation of the cholinergic system, particularly through mAChRs, in inflammation, and discusses the role of the different mAChR antagonists that have been used to treat skin inflammatory disorders, asthma and COPD, as well as intestinal inflammation and systemic inflammatory diseases, to assess the potential application of these compounds as therapeutic tools.

  15. Therapeutic responses in systematic targeted alpha therapy trial for melanoma

    International Nuclear Information System (INIS)

    Raja, C.; Rizvi, S.M.A.; Song, E.Y.; Graham, P.; Kearsley, J.H.; Goldsmith, H.; Bosserhoff, A.; Morgenstern, A.; Apostolidis, C.; Reisfeld, R.

    2006-01-01

    Full text: The therapeutic response of melanoma patients after systemic alpha therapy has been investigated in an open-labeled Phase 1 dose escalation study to establish the effective dose of alpha-immunoconjugate 2l3 Bi-cDTPA-9.2.27 mAb (AIC). The tools used to investigate the effects were physical examination; the images of the tumours, pathology comparisons over 12 weeks; CT comparisons and changes in tumour marker over 8 weeks. The physical examination indicated varied tumour responses. One patient showed complete response at 12 weeks post-TAT, with 20 of 21 tumours completely regressing, the last reduced by 80%. The tumour beds were biopsied for staining; S l OO was negative and no viable cells were observed. Most patients showed stable disease at 2 weeks. In one patient the CT comparison of 8 weeks with baseline showed marked reduction in three lung lesions. At least 4/21 patients showed partial response at 4 to 8 weeks and the same number showed stable disease. The disease progressed in 7 patients. The tumour marker melanoma inhibitory activity protein (MIA) showed reductions over 8 weeks, and was consistent with observations in most patients. Complete and partial responses were observed in systemic TAT for stage IV melanoma, but there was no dose-response relationship

  16. Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

    Science.gov (United States)

    Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

    2016-01-01

    Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

  17. Beyond typing and grading: target analysis in individualized therapy as a new challenge for tumour pathology.

    Science.gov (United States)

    Kreipe, Hans H; von Wasielewski, Reinhard

    2007-01-01

    In order to bring about its beneficial effects in oncology, targeted therapy depends on accurate target analysis. Whether cells of a tumour will be sensitive to a specific treatment is predicted by the detection of appropriate targets in cancer tissue by immunohistochemistry or molecular methods. In most instances this is performed by histopathologists. Reliability and reproducibility of tissue-based target analysis in histopathology require novel measures of quality assurance by internal and external controls. As a model for external quality assurance in targeted therapy an annual inter-laboratory trial has been set up in Germany applying tissue arrays with up to 60 mammary cancer samples which are tested by participants for expression of HER2/neu and steroid hormone receptors.

  18. A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

    Science.gov (United States)

    Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

    2014-04-01

    The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

  19. A comparison of two manual physical therapy approaches and electrotherapy modalities for patients with knee osteoarthritis: A randomized three arm clinical trial.

    Science.gov (United States)

    Kaya Mutlu, Ebru; Ercin, Ersin; Razak Ozdıncler, Arzu; Ones, Nadir

    2018-08-01

    A broad spectrum of physical therapy exercise programs provides symptom relief and functional benefit for patients with knee OA. Manual physical therapy, including tailored exercise programs provide relatively higher level benefit that persists to one year. It is currently unknown if there are important differences in the effects of different manual physical therapy techniques for patients with knee OA and there are virtually no studies comparing manual physical therapy and electro