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Sample records for clinical radionuclide therapy

  1. Radionuclide therapy revisited

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. (Nederlands Kanker Inst., Amsterdam (Netherlands). Dept. of Nuclear Medicine)

    1991-06-01

    Apart from its use in endocrinology and rheumatology, therapeutic nuclear medicine is developing rapidly as an additional treatment modality in oncology. Many different specific tumour-seeking radiopharmaceuticals are being applied both for diagnostic scintigraphy and treatment, using multiple routes and mechanisms to target radionuclides at tumours. After a brief introduction of some basic principles of radionuclide targeting, the therapeutic radiopharmaceuticals available are reviewed according to the accumulation site in relation to the cell nucleus; the results of their current clinical use for therapy are also reviewed. The response observed to a number of these applications, the non-invasiveness of the procedure and the relative lack of toxicity and late effects in comparison with chemotherapy and external beam radiotherapy make radionuclide therapy an attractive and realistic alternative in the management of malignant disease, as well as in the treatment of a few benign disorders. (orig.).

  2. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  3. 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.

  4. Targeted Radionuclide Therapy of Melanoma.

    Science.gov (United States)

    Norain, Abdullah; Dadachova, Ekaterina

    2016-05-01

    An estimated 60,000 individuals in the United States and 132,000 worldwide are yearly diagnosed with melanoma. Until recently, treatment options for patients with stages III-IV metastatic disease were limited and offered marginal, if any, improvement in overall survival. The situation changed with the introduction of B-RAF inhibitors and anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death protein 1 immunotherapies into the clinical practice. With only some patients responding well to the immune therapies and with very serious side effects and high costs of immunotherapy, there is still room for other approaches for the treatment of metastatic melanoma. Targeted radionuclide therapy of melanoma could be divided into the domains of radioimmunotherapy (RIT), radiolabeled peptides, and radiolabeled small molecules. RIT of melanoma is currently experiencing a renaissance with the clinical trials of alpha-emitter (213)Bi-labeled and beta-emitter (188)Rhenium-labeled monoclonal antibodies in patients with metastatic melanoma producing encouraging results. The investigation of the mechanism of efficacy of melanoma RIT points at killing of melanoma stem cells by RIT and involvement of immune system such as complement-dependent cytotoxicity. The domain of radiolabeled peptides for targeted melanoma therapy has been preclinical so far, with work concentrated on radiolabeled peptide analogues of melanocyte-stimulating hormone receptor and on melanin-binding peptides. The field of radiolabeled small molecule produced radioiodinated benzamides that cross the cellular membrane and bind to the intracellular melanin. The recent clinical trial demonstrated measurable antitumor effects and no acute or midterm toxicities. We are hopeful that the targeted radionuclide therapy of metastatic melanoma would become a clinical reality as a stand-alone therapy or in combination with the immunotherapies such as anti-PD1 programmed cell death protein 1 monoclonal antibodies

  5. PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status.

    Science.gov (United States)

    Lütje, Susanne; Heskamp, Sandra; Cornelissen, Alexander S; Poeppel, Thorsten D; van den Broek, Sebastiaan A M W; Rosenbaum-Krumme, Sandra; Bockisch, Andreas; Gotthardt, Martin; Rijpkema, Mark; Boerman, Otto C

    2015-01-01

    Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided.

  6. Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review.

    Science.gov (United States)

    Chalkia, M T; Stefanoyiannis, A P; Chatziioannou, S N; Round, W H; Efstathopoulos, E P; Nikiforidis, G C

    2015-03-01

    Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs' somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides (111)In-[DTPA(0),D-Phe(1)]-octreotide ((111)In-DTPA-octreotide), (90)Y-[DOTA(0),Tyr(3)]-octreotide ((90)Y-DOTATOC) and (177)Lu-[DOTA(0),Tyr(3),Thr(8)]-octreotide ((177)Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

  7. Peptide receptor radionuclide therapy (PRRT): clinical significance of re-treatment?

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    Virgolini, Irene [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Collaboration: The Innsbruck Team

    2015-12-15

    PRRT appears to be the most effective therapeutic option in the management of inoperable or metastasized NET patients with limited side effects if dose limits are respected. In patients with relapse after a first treatment period with {sup 90}Y-DOTATOC, multiple re-treatment cycles with {sup 177}Lu-DOTATATE are feasible, safe and efficacious. Quantitative imaging by dosimetry adds to formulate personalized and evidence-based treatment protocols. However, despite the large body of evidence regarding efficacy and safety of PRRT, the absence of prospective randomized controlled trials questions the utility of PRRT in the community. Furthermore, the growing number of pharmacological or liver-directed therapeutic options competes with the confusion based on the variety of somatostatin analogues to determine the optimal choice and sequencing of PRRT in the individual patient. However, the efficacy of PRRT should not be questioned rather than it should be explored as to when PRRT might be optimally applied in the sequence of available therapy modalities. The results of the present study by the Italian group [5] emphasizes that radiopharmaceuticals are still underused. Despite the huge potential of PRRT the non-availability of PRRT in many countries still limits its widespread use. After acquiring the exclusive rights for {sup 177}Lu-DOTATATE with granted orphan designation, the company Advanced Accelerator Applications (AAA) is currently running a phase III study comparing treatment with {sup 177}Lu-DOTATATE to Octreotide LAR in patients with inoperable, progressive, somatostatin receptor-positive, midgut carcinoid tumours with the aim of registering the radiopharmaceutical under the commercial name of Lutathera. Together with orphan designation also to other somatostatin-based radiopharmaceuticals, such as {sup 90}Y-DOTATOC, {sup 177}Lu-DOTATOC and the {sup 68}Ga-labelled somatostatin antagonist OPS202, these developments promote the advancement of PRRT and PET imaging

  8. Peptide receptor radionuclide therapy of neuroendocrine tumours.

    Science.gov (United States)

    Brabander, Tessa; Teunissen, Jaap J M; Van Eijck, Casper H J; Franssen, Gaston J H; Feelders, Richard A; de Herder, Wouter W; Kwekkeboom, Dik J

    2016-01-01

    In the past decades, the number of neuroendocrine tumours that are detected is increasing. A relative new and promising therapy for patients with metastasised or inoperable disease is peptide receptor radionuclide therapy (PRRT). This therapy involves an infusion of somatostatin analogues linked to radionuclides like Yttrium-90 or Lutetium-177. Objective response rates are reported in 15-35%. Response rates may vary between type of tumour and radionuclide. Besides the objective response rate, overall survival and progression free survival increase significantly. Also, the quality of life improves as well. Serious side-affects are rare. PRRT is usually well tolerated, also in patients with extensive metastasised disease. Recent studies combined PRRT with other types of therapies. Unfortunately no randomised trials comparing these strategies are available. In the future, more research is needed to evaluate the best therapy combinations or sequence of therapies.

  9. 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

  10. Development of medical application methods using radiation. Radionuclide therapy

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    Choi, Chang Woon; Lim, S. M.; Kim, E.H.; Woo, K. S.; Chung, W. S.; Lim, S. J.; Choi, T. H.; Hong, S. W.; Chung, H. Y.; No, W. C. [Korea Atomic Energy Research Institute. Korea Cancer Center Hospital, Seoul, (Korea, Republic of); Oh, B. H. [Seoul National University. Hospital, Seoul (Korea, Republic of); Hong, H. J. [Antibody Engineering Research Unit, Taejon (Korea, Republic of)

    1999-04-01

    In this project, we studied following subjects: 1. development of monoclonal antibodies and radiopharmaceuticals 2. clinical applications of radionuclide therapy 3. radioimmunoguided surgery 4. prevention of restenosis with intracoronary radiation. The results can be applied for the following objectives: (1) radionuclide therapy will be applied in clinical practice to treat the cancer patients or other diseases in multi-center trial. (2) The newly developed monoclonal antibodies and biomolecules can be used in biology, chemistry or other basic life science research. (3) The new methods for the analysis of therapeutic effects, such as dosimetry, and quantitative analysis methods of radioactivity, can be applied in basic research, such as radiation oncology and radiation biology.

  11. Radionuclide tumor therapy with ultrasound contrast microbubbles

    NARCIS (Netherlands)

    Wamel, van Annemieke; Bouakaz, Ayache; Bernard, Bert; Cate, ten Folkert; Jong, de Nico

    2004-01-01

    Radionuclides have shown to be effective in tumour therapy. However, the side effects determine the maximum deliverable dose. Recently, it has been demonstrated that cells can be permeabilised through sonoporation using ultrasound and contrast microbubbles. The use of sonoporation in treatment of tu

  12. 21 CFR 892.5750 - Radionuclide radiation therapy system.

    Science.gov (United States)

    2010-04-01

    ... operator to administer gamma radiation therapy, with the radiation source located at a distance from the... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radionuclide radiation therapy system. 892.5750... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5750 Radionuclide radiation...

  13. Prospects in folate receptor-targeted radionuclide therapy

    Directory of Open Access Journals (Sweden)

    Cristina eMüller

    2013-09-01

    Full Text Available Targeted radionuclide therapy is based on systemic application of particle-emitting radiopharmaceuticals which are directed towards a specific tumor-associated target. Accumulation of the radiopharmaceutical in targeted cancer cells results in high doses of absorbed radiation energy whereas toxicity to non-targeted healthy tissue is limited. This strategy has found widespread application in the palliative treatment of neuroendocrine tumors using somatostatin-based radiopeptides. The folate receptor (FR has been identified as a target associated with a variety of frequent tumor types (e.g. ovarian, lung, brain, renal and colorectal cancer. In healthy organs and tissue FR-expression is restricted to only a few sites such as for instance the kidneys. This demonstrates why FR-targeting is an attractive strategy for the development of new therapy concepts. Due to its high FR-binding affinity (KD < 10-9 M the vitamin folic acid has emerged as an almost ideal targeting agent. Therefore, a variety of folic acid radioconjugates for nuclear imaging have been developed. However, in spite of the large number of cancer patients who could benefit of a folate-based radionuclide therapy, a therapeutic concept with folate radioconjugates has not yet been envisaged for clinical application. The reason is the generally high accumulation of folate radioconjugates in the kidneys where emission of particle-radiation may result in damage to the renal tissue. Therefore, the design of more sophisticated folate radioconjugates providing improved tissue distribution profiles are needed.This review article summarizes recent developments with regard to a therapeutic application of folate radioconjugates. A new construct of a folate radioconjugate and an application protocol which makes use of a pharmacological interaction allowed the first preclinical therapy experiments with radiofolates. These results raise hope for future application of such new concepts also in the

  14. Advances in SPECT imaging with respect to radionuclide therapy.

    Science.gov (United States)

    D'Asseler, Y

    2009-06-01

    Radionuclide therapy is gradually becoming more important as a therapy option in various diseases. Nuclear medicine imaging plays an important role in this, before, during and after the therapy. Single photon emission computed tomography (SPECT) imaging can be used to predict therapy response, calculate doses delivered to the tumour and the surrounding organ, check radiopharmaceutical distribution and follow-up this distribution in time. On a technological level, radionuclide imaging in a therapy setting shows some particularities and issues to be resolved. Accurate quantification is important but is hampered by attenuation, scatter from different energy peaks and from bremsstrahlung photons, septal penetration, partial volume effects etc. Some of these issues are discussed in this paper. A technique specific for therapy imaging is bremsstrahlung imaging, which can be used if the therapeutical agent is a pure beta emitter. Quantitative bremsstrahlung imaging is particularly challenging due to the complicated nature of the energy spectrum of these photons. Some work towards quantitative bremsstrahlung imaging is discussed here. Finally, some recent technical advances relevant to this field are pointed out. On the software side, Monte Carlo simulations seem to have a great potential for accurate quantitative SPECT reconstruction and subsequent patient specific image based dose calculations. Concerning hardware, the availability of SPECT-CT technology may have a large impact in imaging in radionuclide therapy. Novel detector technologies such as solid-state detectors may also prove to have significant advantages in this field.

  15. Patient-Specific Dosimetry and Radiobiological Modeling of Targeted Radionuclide Therapy Grant - final report

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    George Sgouros, Ph.D.

    2007-03-20

    The broad, long-term objectives of this application are to 1. develop easily implementable tools for radionuclide dosimetry that can be used to predict normal organ toxicity and tumor response in targeted radionuclide therapy; and 2. to apply these tools to the analysis of clinical trial data in order to demonstrate dose-response relationships for radionuclide therapy treatment planning. The work is founded on the hypothesis that robust dose-response relationships have not been observed in targeted radionuclide therapy studies because currently available internal dosimetry methodologies are inadequate, failing to adequately account for individual variations in patient anatomy, radionuclide activity distribution/kinetics, absorbed dose-distribution, and absorbed dose-rate. To reduce development time the previously available software package, 3D-ID, one of the first dosimetry software packages to incorporate 3-D radionuclide distribution with individual patient anatomy; and the first to be applied for the comprehensive analysis of patient data, will be used as a platform to build the functionality listed above. The following specific aims are proposed to satisfy the long-term objectives stated above: 1. develop a comprehensive and validated methodology for converting one or more SPECT images of the radionuclide distribution to a 3-D representation of the cumulated activity distribution; 2. account for differences in tissue density and atomic number by incorporating an easily implementable Monte Carlo methodology for the 3-D dosimetry calculations; 3. incorporate the biologically equivalent dose (BED) and equivalent uniform dose (EUD) models to convert the spatial distribution of absorbed dose and dose-rate into equivalent single values that account for differences in dose uniformity and rate and that may be correlated with tumor response and normal organ toxicity; 4. test the hypothesis stated above by applying the resulting package to patient trials of targeted

  16. The necessity of nuclear reactors for targeted radionuclide therapies.

    Science.gov (United States)

    Krijger, Gerard C; Ponsard, Bernard; Harfensteller, Mark; Wolterbeek, Hubert T; Nijsen, Johannes W F

    2013-07-01

    Nuclear medicine has been contributing towards personalized therapies. Nuclear reactors are required for the working horses of both diagnosis and treatment, i.e., Tc-99m and I-131. In fact, reactors will remain necessary to fulfill the demand for a variety of radionuclides and are essential in the expanding field of targeted radionuclide therapies for cancer. However, the main reactors involved in the global supply are ageing and expected to shut down before 2025. Therefore, the fields of (nuclear) medicine, nuclear industry and politics share a global responsibility, faced with the task to secure future access to suitable nuclear reactors. At the same time, alternative production routes should be industrialized. For this, a coordinating entity should be put into place.

  17. Radionuclide therapy of endocrine-related cancer; Nuklearmedizinische Therapie endokriner Tumoren

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    Kratochwil, C.; Giesel, F.L. [Universitaetsklinikum Heidelberg, Abteilung Nuklearmedizin, Heidelberg (Germany)

    2014-10-15

    This article gives an overview of the established radionuclide therapies for endocrine-related cancer that already have market authorization or are currently under evaluation in clinical trials. Radioiodine therapy is still the gold standard for differentiated iodine-avid thyroid cancer. In patients with bone and lung metastases (near) total remission is seen in approximately 50 % and the 15-year survival rate for these patients is approximately 90 %. In contrast to the USA, meta-iodobenzylguanidine (MIBG) therapy has market approval in Europe. According to the current literature, in the setting of advanced stage neuroblastoma and malignant pheochromocytoma or paraganglioma, radiological remission can be achieved in > 30 % and symptom control in almost 80 % of the treated patients. Somatostatin receptor targeted radionuclide therapies (e.g. with DOTATATE or DOTATOC) demonstrated promising results in phase 2 trials, reporting progression-free survival in the range of 24-36 months. A first phase 3 pivotal trial for intestinal carcinoids is currently recruiting and another trial for pancreatic neuroendocrine tumors is planned. Radiopharmaceuticals based on glucagon-like peptide 1 (GLP1) or minigastrins are in the early evaluation stage for application in the treatment of insulinomas and medullary thyroid cancer. In general, radiopharmaceutical therapy belongs to the group of so-called theranostics which means that therapy is tailored for individual patients based on molecular imaging diagnostics to stratify target positive or target negative tumor phenotypes. (orig.) [German] Dieser Artikel gibt einen Ueberblick ueber die etablierten sowie weitere vielversprechende, aktuell im Rahmen von Studien eingesetzte nuklearmedizinische Therapiemoeglichkeiten diverser endokrinologischer Neoplasien. Die Radiojodtherapie ist unveraendert die Therapie der Wahl beim differenzierten, jodspeichernden Schilddruesenkarzinom. Im metastasierten Stadium sind in ca. 50 % der Faelle noch

  18. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  19. What is the role of the bystander response in radionuclide therapies?

    Directory of Open Access Journals (Sweden)

    Darren eBrady

    2013-08-01

    Full Text Available Radionuclide therapy for cancer is undergoing a renaissance, with a wide range of radionuclide and clinical delivery systems currently under investigation. Dosimetry at the cellular and subcellular level is complex with inhomogeneity and incomplete targeting of all cells such that some tumour cells will receive little or no direct radiation energy. There is now sufficient preclinical evidence of a bystander response which can modulate the biology of these unirradiated cells with current research demonstrating both protective and inhibitory responses. Dependence upon fraction of irradiated cells has also been found has and the presence of functional gap junctions appears to be import for several bystander responses. The selection of either high or low LET radionuclides may be critical. While low LET radionuclides appear to have a bystander response proportional to dose, the dose-response from high LET radionuclides are more complex. In media transfer experiments a U shaped response curve has been demonstrated for high LET treatments. However this U shaped response has not been seen with co-culture experiments and its relevance remains uncertain. For high LET treatments there is a suggestion that dose rate effects may also be important with inhibitory effects noted with 125I labelling study and a stimulatory seen with 123I labelling in one study.

  20. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  1. Peptide Receptor Radionuclide Therapy with (90)Y-DOTATOC and (177)Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  2. In Vivo Radionuclide Generators for Diagnostics and Therapy

    DEFF Research Database (Denmark)

    Edem, Patricia E.; Fonslet, Jesper; Kjær, Andreas;

    2016-01-01

    In vivo radionuclide generators make complex combinations of physical and chemical properties available for medical diagnostics and therapy. Perhaps the best-known in vivo generator is 212Pb/212Bi, which takes advantage of the extended half-life of 212Pb to execute a targeted delivery of the ther...... reviews some common and not-so-common in vivo generators with the purpose of understanding their value in medicine and medical research.This is currently relevant in light of a recent push for alpha emitters in targeted therapies, which often come with extended decay chains....... of the therapeutic short-lived 훼-emitter 212Bi. Often, as in the case of 81Rb/81Kr, chemical changes resulting from the transmutation of the parent are relied upon for diagnostic value. In other instances such as with extended alpha decay chains, chemical changes may lead to unwanted consequences.This article...

  3. MIRD Pamphlet No. 22 (Unabridged): Radiobiology and Dosimetry of alpha-Particle Emitters for Targeted Radionuclide Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sgouros, George; Roeske, John C.; McDevitt, Michael S.; Palm, Stig; Allen, Barry J.; Fisher, Darrell R.; Brill, Bertrand A.; Song, Hong; Howell, R. W.; Akabani, Gamal

    2010-02-28

    The potential of alpha-particle emitters to treat cancer has been recognized since the early 1900s. Advances in the targeted delivery of radionuclides, in radionuclide conjugation chemistry, and in the increased availability of alpha-emitters appropriate for clinical use have recently led to patient trials of alpha-particle-emitter labeled radiopharmaceuticals. Although alpha-emitters have been studied for many decades, their current use in humans for targeted therapy is an important milestone. The objective of this work is to review those aspects of the field that are pertinent to targeted alpha-particle-emitter therapy and to provide guidance and recommendations for human alpha-particle-emitter dosimetry.

  4. Peptide receptor radionuclide therapy: focus on bronchial neuroendocrine tumors.

    Science.gov (United States)

    Lo Russo, Giuseppe; Pusceddu, Sara; Prinzi, Natalie; Imbimbo, Martina; Proto, Claudia; Signorelli, Diego; Vitali, Milena; Ganzinelli, Monica; Maccauro, Marco; Buzzoni, Roberto; Seregni, Ettore; de Braud, Filippo; Garassino, Marina Chiara

    2016-10-01

    Well-differentiated bronchial neuroendocrine tumors (B-NETs) are rare. They represent 1-5 % of all lung cancers. The incidence of these neoplasms has risen over the past 30 years and, especially for advanced or metastatic disease, management is complex and requires a multidisciplinary approach. Treatment with somatostatin analogs (SSAs) is the most important first-line therapy, in particular in well-differentiated NETs with high somatostatin type receptor (SSTR) expression. In these tumors, the role of mammalian target of rapamycin (m-TOR) inhibitors and the potential utility of other target therapies remain unclear while chemotherapy represents the gold standard treatment only for aggressive forms with low SSTR expression. Peptide receptor radionuclide therapy (PRRT) is an emerging treatment modality for advanced NETs. There are many cumulative evidences about the effectiveness and tolerability of this therapeutic approach, especially in gastro-entero-pancreatic (GEP)-NETs. For B-NETs, scientific research is moving more slowly. Here, we performed a review in order to evaluate the efficacy and toxicity of PRRT with a focus on patients with inoperable or metastatic well-differentiated B-NETs.

  5. Clinical applications of newer radionuclide therapies.

    NARCIS (Netherlands)

    Brans, B.; Linden, O.; Giammarile, F.; Tennvall, J.; Punt, C.J.A.

    2006-01-01

    When radio-iodine was first used in the treatment of metastasized thyroid carcinoma in 1943, its success in terms of tumour response, quality of life improvement and survival was considered a 'miracle', as in those days metastatic cancer was generally fatal. Inspired by this, many efforts have been

  6. Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

    CERN Document Server

    Reber, Josefine Astrid

    The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

  7. Monte Carlo investigation of single cell beta dosimetry for intraperitoneal radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Syme, A M [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta, T6G 2J1 (Canada); Kirkby, C [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta, T6G 2J1 (Canada); Riauka, T A [Department of Medical Physics, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2 (Canada); Fallone, B G [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta, T6G 2J1 (Canada); McQuarrie, S A [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 3118 Dentistry/Pharmacy Centre, Edmonton, Alberta, T6G 2N8 (Canada)

    2004-05-21

    Single event spectra for five beta-emitting radionuclides (Lu-177, Cu-67, Re-186, Re-188, Y-90) were calculated for single cells from two source geometries. The first was a surface-bound isotropically emitting point source and the second was a bath of free radioactivity in which the cell was submerged. Together these represent a targeted intraperitoneal radionuclide therapy. Monoenergetic single event spectra were calculated over an energy range of 11 keV to 2500 keV using the EGSnrc Monte Carlo system. Radionuclide single event spectra were constructed by weighting monoenergetic single event spectra according to radionuclide spectra appropriate for each source geometry. In the case of surface-bound radioactivity, these were radionuclide beta decay spectra. For the free radioactivity, a continuous slowing down approximation spectrum was used that was calculated based on the radionuclide decay spectra. The frequency mean specific energy per event increased as the energy of the beta emitter decreased. This is because, at these energies, the stopping power of the electrons decreases with increasing energy. The free radioactivity produced a higher frequency mean specific energy per event than the corresponding surface-bound value. This was primarily due to the longer mean path length through the target for this geometry. This information differentiates the radionuclides in terms of the physical process of energy deposition and could be of use in the radionuclide selection procedure for this type of therapy.

  8. Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy.

    NARCIS (Netherlands)

    Melis, M.; Swart, J.; Visser, M. de; Berndsen, S.C.; Koelewijn, S.; Valkema, R.; Boerman, O.C.; Krenning, E.P.; Jong, M. de

    2010-01-01

    High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with beta-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal

  9. Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

    Energy Technology Data Exchange (ETDEWEB)

    Hrycushko, Brian A.; Li Shihong; Goins, Beth; Otto, Randal A.; Bao, Ande [Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 (United States); Department of Otolaryngology-Head and Neck Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 (United States); Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 and Department of Otolaryngology-Head and Neck Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 (United States)

    2011-03-15

    radionuclides with higher energy beta emissions, dose escalation through increased specific activity, and increasing the number of direct tumor infusion sites improve tumor control. For larger tumors, the use of multiple infusion locations was modeled to be much more efficient, in terms of activity usage, at improving EUD and TCP to achieve a tumoricidal effect. Conclusions: Direct intratumoral infusion of beta-emitting radionuclide encapsulated liposomes shows promise for cancer therapy by achieving large focally delivered tumor doses. However, the results of this work also indicate that average tumor dose may underestimate tumoricidal effect due to substantial heterogeneity in intratumoral liposomal radionuclide distributions. The resulting intratumoral distribution of liposomes following infusion should be taken into account in treatment planning and evaluation in a clinical setting for an optimal cancer therapy.

  10. Renal toxicity of radiolabeled peptides and antibody fragments: mechanisms, impact on radionuclide therapy, and strategies for prevention.

    NARCIS (Netherlands)

    Vegt, E. de; Jong, M. de; Wetzels, J.F.M.; Masereeuw, R.; Melis, M.; Oyen, W.J.G.; Gotthardt, M.; Boerman, O.C.

    2010-01-01

    Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody fragments are under investigation. Most of these compounds are cleared through the kidneys and reabso

  11. Renal toxicity of radiolabeled peptides and antibody fragments: Mechanisms, impact on radionuclide therapy, and strategies for prevention

    NARCIS (Netherlands)

    E. Vegt (Erik); M. de Jong (Marion); J.F.M. Wetzels (Jack); R. Masereeuw (Rosalinde); M.L. Melis (Marleen); W.J. Oyen (Wim); M. Gotthardt (Martin); O.C. Boerman (Otto)

    2010-01-01

    textabstractPeptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody fragments are under investigation. Most of these compounds are cleared through the kidney

  12. Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Baechler, Sebastien; Hobbs, Robert F.; Boubaker, Ariane; Buchegger, Franz; He Bin; Frey, Eric C.; Sgouros, George [Institute of Radiation Physics, Lausanne University Hospital, 1007 Lausanne (Switzerland); Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21231 (United States); Department of Nuclear Medicine, Lausanne University Hospital, 1011 Lausanne (Switzerland); Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21231 (United States)

    2012-10-15

    Purpose: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. Methods: Planar and SPECT data were available for a patient examined with {sup 111}In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., {sup 111}In, {sup 90}Y and {sup 177}Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. Results: Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for {sup 90}Y and {sup 177}Lu. Nevertheless, for {sup 111}In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated

  13. A Critical Review of Alpha Radionuclide Therapy: How to Deal with Recoiling Daughters?

    NARCIS (Netherlands)

    De Kruijff, R.M.; Wolterbeek, H.T.; Denkova, A.G.

    2015-01-01

    This review presents an overview of the successes and challenges currently faced in alpha radionuclide therapy. Alpha particles have an advantage in killing tumour cells as compared to beta or gamma radiation due to their short penetration depth and high linear energy transfer (LET). Touching briefl

  14. Peptide receptor radionuclide therapy with {sup 90}Y-DOTATOC in recurrent meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Bartolomei, Mirco; Bodei, Lisa; De Cicco, Concetta; Grana, Chiara Maria; Baio, Silvia Melania; Arico, Demetrio; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Botteri, Edoardo [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Radiometabolic Medicine Division, Meldola (Italy)

    2009-09-15

    Meningiomas are generally benign and in most cases surgery is curative. However, for high-grade histotypes or partially resected tumours, recurrence is fairly common. External beam radiation therapy (EBRT) is usually given in such cases but is not always effective. We assessed peptide receptor radionuclide therapy (PRRT) using {sup 90}Y-DOTATOC in a group of patients with meningioma recurring after standard treatments in all of whom somatostatin receptors were strongly expressed on meningioma cell surfaces. Twenty-nine patients with scintigraphically proven somatostatin subtype 2 receptor-positive meningiomas were enrolled: 14 had benign (grade I), 9 had atypical (grade II) and 6 had malignant (grade III) disease. Patients received intravenous {sup 90}Y-DOTATOC for 2-6 cycles for a cumulative dose in the range of 5-15 GBq. Clinical and neuroradiological evaluations were performed at baseline, during and after PRRT. The treatment was well tolerated in all patients. MRI 3 months after treatment completion showed disease stabilization in 19 of 29 patients (66%) and progressive disease in the remaining 10 (34%). Better results were obtained in patients with grade I meningioma than in those with grade II-III, with median time to progression (from beginning PRRT) of 61 months in the low-grade group and 13 months in the high-grade group. PRRT with {sup 90}Y-DOTATOC can interfere with the growth of meningiomas. The adjuvant role of this treatment, soon after surgery, especially in atypical and malignant histotypes, deserves further investigation. (orig.)

  15. Comprehensive evaluation of a somatostatin-based radiolabelled antagonist for diagnostic imaging and radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xuejuan; Fani, Melpomeni [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Schulz, Stefan [Jena University Hospital - Friedrich Schiller University Jena, Department of Pharmacology and Toxicology, Jena (Germany); Rivier, Jean [The Salk Institute for Biological Studies, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA (United States); Reubi, Jean Claude [University of Bern, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, Bern (Switzerland); Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-12-15

    Targeting of tumours positive for somatostatin receptors (sst) with radiolabelled peptides is of interest for tumour localization, staging, therapy follow-up and targeted radionuclide therapy. The peptides used clinically are exclusively agonists, but recently we have shown that the radiolabelled somatostatin-based antagonist {sup 111}In-DOTA-sst2-ANT may be preferable to agonists. However, a comprehensive study of this radiolabelled antagonist to determine its significance was lacking. The present report describes the evaluation of this novel antagonist labelled with {sup 111}In and {sup 177}Lu in three different tumour models. Radiopeptide binding, internalization and dissociation studies were performed using cells expressing HEK293-rsst{sub 2}. Biodistribution studies were performed in HEK293-rsst{sub 2}, HEK293-hsst{sub 2} and HEK293-rsst{sub 3} xenografted mice. Saturation binding analysis confirmed earlier IC{sub 50} data for {sup 111/nat}In-DOTA-sst2-ANT and showed similar affinity of {sup 177/nat}Lu-DOTA-sst2-ANT for the sst{sub 2}. Only low internalization was found in cell culture (6.68 {+-} 0.06 % at 4 h), which was not unexpected for an antagonist, and this could be further reduced by the addition of sucrose. No internalization was observed in HEK293 cells not expressing sst. Both results indicate that the internalization was specific. {sup 111}In-DOTA-sst2-ANT and {sup 177}Lu-DOTA-sst2-ANT were shown to target tumour xenografts expressing the rat and the human sst{sub 2} receptor with no differences in their uptake or pharmacokinetics. The uptake in rsst{sub 2} and hsst{sub 2} was high (about 30 %IA/g 4 h after injection) and surprisingly long-lasting (about 20-23 %IA/g 24 h after injection). Kidney uptake was blocked by approximately 50 % by lysine or Gelofusine. These results indicate that radiolabelled somatostatin-based antagonists may be superior to corresponding agonists. The long tumour retention time of {sup 177}Lu-DOTA-sst2-ANT indicates that

  16. Neuroendocrine Tumours : From Radiomolecular Imaging to Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    GEORGIOS eLIMOURIS

    2012-02-01

    Full Text Available Transhepatic radionuclide infusion (THRI has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan. Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabelled somatostatin analogues, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3±0.3 GBq (~ 160-180 mCi of In-111-DTPA-Phe1- Pentetreotide, 10-12 fold in total, administered monthly or of 4.1± 0.2 GBq (~105-116 mCi of Y-90 DOTA TOC, 3 fold in total or of 7.0 ± 0.4 GBq (~178-200 mCi of Lu-177 DOTA TATE, 4-6 fold in total (the choice of which being based on the tumor size, assessed by CT or MRI . Follow-up at monthly intervals has to be performed by means of ultrasonography (US. Treat- ment response has to be assessed according to the WHO criteria (RECIST or SWOG.

  17. The impact of PET and SPECT on dosimetry for targeted radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Flux, G. [Dept. of Physics, Royal Marsden Hospital, London (United Kingdom); Bardies, M. [INSERM UMR 601, Nantes (France); Monsieurs, M. [Dept. Anatomy, Embryology, Histology and Medical Physics, Ghent Univ. (Belgium); Savolainen, S. [HUS, Medical Imaging Centre and Dept. of Physical Sciences, Univ. of Helsinki (Finland); Strand, S.E. [Medical Radiation Physics, Dept. of Clinical Sciences, Lund Univ (Sweden); Lassmann, M. [Klinik und Poliklinik fuer Nuklearmedizin der Univ. Wuerzburg (Germany)

    2006-07-01

    Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for a range of cancers. To date, few treatments have involved the use of dosimetry either to plan treatment or to retrospectively ascertain the absorbed dose delivered during treatment. Also the correlation between absorbed dose and biological effect has been difficult to establish. Tomographic methods permit the determination of the activity volume on a macroscopic scale at different time points. Proper attenuation correction in tomographic imaging requires a patient-specific attenuation map. This can be obtained from scintillation-camera transmission scanning, CT, or by using segmented scatter-emission images. Attenuation corrections can be performed either on the projection images, on the reconstructed images, or as part of an iterative reconstruction method. The problem of image quantification for therapy radionuclides, particularly for I-131, is exacerbated by the fact that most cameras are optimised for diagnostic imaging with Tc-99m. In addition, problems may arise when high activities are to be measured due to count losses and mis-positioned events, because of insufficient pile-up and dead time correction methods. Sufficient image quantification, however, is only possible if all effects that degrade the quantitative content of the image have been corrected for. Monte Carlo simulations are an appealing tool that can help to model interactions occurring in the patient or in the detector system. This is helpful to develop and test correction techniques, or to help to define detectors better suited to quantitative imaging. PET is probably the most accurate imaging method for the determination of activity concentrations in tissue. PET imaging can be considered for pre-therapeutic treatment planning but ideally requires the use of a radioisotope from the same element as that used for treatment (e.g. I-124 for I-131; Y-86 for Y-90). Problems, however, are that - some of the positron

  18. Survival prediction in patients undergoing radionuclide therapy based on intratumoral somatostatin-receptor heterogeneity

    Science.gov (United States)

    Ilhan, Harun; Higuchi, Takahiro; Buck, Andreas K.; Lehner, Sebastian; Bartenstein, Peter; Bengel, Frank; Schatka, Imke; Muegge, Dirk O.; Papp, László; Zsótér, Norbert; Große-Ophoff, Tobias; Essler, Markus; Bundschuh, Ralph A.

    2017-01-01

    The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management. PMID:27705948

  19. Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies

    NARCIS (Netherlands)

    S. Bison (Sander); J.C. Haeck (Joost); K. Bol (Karin); S. Koelewijn (Stuart); H.C. Groen (Harald); M.L. Melis (Marleen); J.F. Veenland (Jifke); M.R. Bernsen (Monique); M. de Jong (Marion)

    2015-01-01

    textabstractBackground: Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate (177Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozo

  20. Cyclotron Produced Radionuclides for Diagnosis and Therapy of Human Neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Steven Larson MD

    2009-09-21

    This project funded since 1986 serves as a core project for cancer research throughout MSKCC, producing key radiotracers as well as basic knowledge about thel physics of radiation decay and imaging, for nuclear medicine applications to cancer diagnosis and therapy. In recent years this research application has broadened to include experiments intended to lead to an improved understanding of cancer biology and into the discovery and testing of new cancer drugs. Advances in immune based radiotargeting form the basis for this project. Both antibody and cellular based immune targeting methods have been explored. The multi-step targeting methodologies (MST) developed by NeoRex (Seattle,Washington), have been adapted for use with positron emitting isotopes and PET allowing the quantification and optimization of targeted delivery. In addition, novel methods for radiolabeling immune T-cells with PET tracers have advanced our ability to track these cells of prolonged period of time.

  1. Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Jonas Ahlstedt

    2015-12-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

  2. Clinical databases in physical therapy.

    NARCIS (Netherlands)

    Swinkels, I.C.; Ende, C.H.M. van den; Bakker, D. de; Wees, P.J. van der; Hart, D.L.; Deutscher, D.; Bosch, W.J.H.M. van den; Dekker, J.

    2007-01-01

    Clinical databases in physical therapy provide increasing opportunities for research into physical therapy theory and practice. At present, information on the characteristics of existing databases is lacking. The purpose of this study was to identify clinical databases in which physical therapists r

  3. Nuclisome: a novel concept for radionuclide therapy using targeting liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Fondell, Amelie; Carlsson, Joergen [Uppsala University, Department of Oncology, Radiology, and Clinical Immunology, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Edwards, Katarina; Ickenstein, Ludger M. [Uppsala University, Department of Physical and Analytical Chemistry, Box 579, Uppsala (Sweden); Sjoeberg, Stefan [Uppsala University, Department of Biochemistry and Organic Chemistry, Box 599, Uppsala (Sweden); Gedda, Lars [Uppsala University, Department of Oncology, Radiology, and Clinical Immunology, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2010-01-15

    For the treatment of cancer, the therapeutic potential of short-range, low-energy Auger-electron emitters, such as {sup 125}I, is getting progressively wider recognition. The potency of Auger-electron emitters is strongly dependent on their location in close vicinity to DNA. We have developed a new two-step targeting strategy to transport {sup 125}I into cancer-cell nuclei using PEG-stabilized tumour-cell targeting liposomes named ''Nuclisome-particles''. In the present study, epidermal growth factor (EGF) was used as a tumour-cell-specific agent to target the EGF-receptor (EGFR) and the liposomes were loaded with {sup 125}I-Comp1, a recently synthesized daunorubicin derivative. As analysed with cryo-TEM, the derivative precipitates inside liposomes at a drug-to-lipid molar ratio of 0.05:1. Receptor-specific uptake in cultured U-343MGaCl2:6 tumour cells of EGFR-targeting liposomes increased with time while non-specific and receptor-blocked uptake remained low. Nuclisome-particles were able to target single U-343MGaCl2:6 cells circulating in human blood during 4 h, with low uptake in white blood cells, as demonstrated in an ex vivo system using a Chandler loop. Autoradiography of targeted cells indicates that the grains from the radiolabelled drug are mainly co-localized with the cell nuclei. The successful targeting of the nucleus is shown to provide high-potency cell killing of cultured U-343MGaCl2:6 cells. At the concentration used, Nuclisome-particles were up to five orders of magnitude more effective in cell killing than EGFR-targeting liposomes loaded with doxorubicin. The results thus provide encouraging evidence that our two-step targeting strategy for tumour cell DNA has the potential to become an effective therapy against metastasizing cancer cells in the bloodstream. (orig.)

  4. Radionuclide investigations in clinical cardiology - 10 years of cooperation in Frankfurt/FRG

    Energy Technology Data Exchange (ETDEWEB)

    Klepzig, H. Jr.; Kaltenbach, M.

    1989-02-01

    Radionuclide investigations today are an important tool in cardiology. They close the diagnostic gap in cases where non-invasive procedures of cardiological diagnosis such as ecg, exercise-ecg, echocardiography and chest-x-ray remains unrevealing. Further, they are helpful when an exact quantitation of the disease or a precise follow-up is required. Radionuclide techniques are very useful to detect myocardial ischemia in patients with coronary heart disease and to judge myocardial function in patients with aortic or mitral regurgitation. Follow-up investigations after therapy (aortocoronary bypass, PTCA, valve replacement) permit conclusions regarding the benefit of these measures. Results of radionuclide investigations should consider the Bayes' theorem in order to keep false-negative and false-positive reports as low as possible.

  5. 术中125I粒子植入治疗肿瘤的临床应用%The clinical application of 125I radionuclide implantation in tumor therapy

    Institute of Scientific and Technical Information of China (English)

    孙启和; 孙彬; 杨永青

    2010-01-01

    Objective To investigate the safety and clinical efficacy of permanent implantation of125I radioactive particle in the urgery of malignancies such as brain tumors,liver cancer,cholangiocarcinoma,lung cancer,prostate cancer and malignant teratoma.Methods Thirty eight patients proved by puncture biopsy,his-tology or cytology were retrospectively analyzed.Three-D images of the tumor were reconstructed using treat-ment planning system (TPS),the number and the dose rate distribution of 125I seeds were calculated.The matched eripheral dose of 125I seeds implantation was 60~120Gy,the number of 125I seeds implanted ranged from 6~40 per lesion,and the median amount of implanted 125I seeds were 23.Results Twelve months followup after the therapy showed 9 cases of complete relief,24 cases of partial relief and 5 cases of no change.The overall effective rate(complete relief+partial relief) of 12 months was 86.8%.Conclusion Permanent implantation of 125I radioactive particle in the surgery of malignancies treatment is a safe,effective treatment for tumors.%目的 探讨在手术中永久性植入125I粒子治疗脑瘤、肝癌、胆管癌、肺癌、直肠癌、前列腺癌及恶性畸胎瘤临床应用的安全性及疗效.方法 回顾性分析38例经穿刺活检、组织学或细胞学检查确诊的肿瘤患者,采用治疗计划系统(TPS)重建肿瘤的三维图像,计算出粒子植入的数量和剂量分布曲线,125I粒子治疗肿瘤处方剂量为60~120 Gy,每例植入粒子6~40颗,中位粒子数为23颗.结果 随访12个月,肿瘤完全缓解9例,部分缓解24例,无变化5例.12个月总有效率为86.8%.结论 术中植入125I粒子治疗肿瘤是一种安全、有效的方法.

  6. Proton therapy in clinical practice

    Institute of Scientific and Technical Information of China (English)

    Hui Liu; Joe Y. Chang

    2011-01-01

    Radiation dose escalation and acceleration improves local control but also increases toxicity. Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients. Compared with photon therapy, proton therapy spares more critical structures due to its unique physics. The physical properties of a proton beam make it ideal for clinical applications. By modulating the Bragg peak of protons in energy and time, a conformal radiation dose with or without intensity modulation can be delivered to the target while sparing the surrounding normal tissues. Thus, proton therapy is ideal when organ preservation is a priority. However, protons are more sensitive to organ motion and anatomy changes compared with photons. In this article, we review practical issues of proton therapy, describe its image-guided treatment planning and delivery, discuss clinical outcome for cancer patients, and suggest challenges and the future development of proton therapy.

  7. Accelerator based Production of Auger-Electron-emitting Isotopes for Radionuclide Therapy

    DEFF Research Database (Denmark)

    Thisgaard, Helge

    Sb from the enriched 119Sn target material with high radionuclidic- and chemical purity. A method that also allows efficient recovery of the 119Sn for recycling. To demonstrate the ability of producing therapeutic quantities of 119Sb and other radioisotopes for therapy with a low-energy cyclotron...... isotopes (e.g. 119Sb or 64Cu) using the PETtrace cyclotron commonly found at the larger PET-centers in the hospitals. Finally, research in a new method to measure the radiotoxicity of Auger-emitters invitro using cellular microinjection has been carried out. The purpose of this method is to be able...

  8. Baculovirus vector-mediated transfer of NIS gene into colon tumor cells for radionuclide therapy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the feasibility of radionuclide therapy of colon tumor cells by baculovirus vector-mediated transfer of the sodium/iodide symporter(NIS) gene.METHODS:A recombinant baculovirus plasmid carrying the NIS gene was constructed,and the viruses(BacNIS) were prepared using the Bac-to-Bac system.The infection efficiency in the colon cancer cell line SW1116 of a green fluorescent protein(GFP) expressing baculovirus(Bac-GFP) at different multiplicities of infection(MOI) with various concentrations o...

  9. Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor

    Institute of Scientific and Technical Information of China (English)

    Daniel Kaemmerer; Vikas Prasad; Wolfgang Daffner; Dieter H(o)rsch; Günter Kl(o)ppel; Merten Hommann; Richard P Baum

    2009-01-01

    Pancreatic endocrine tumors are rare but are among the most common neuroendocrine neoplasms of the abdomen. At diagnosis many of them are already advanced and difficult to treat. We report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman, who received neoadjuvant peptide receptor radionuclide therapy (PRRT) as first-line treatment. This resulted in a significant downstaging of the tumor and allowed its subsequent complete surgical removal. Follow-up for eighteen months revealed a complete remission. This is the first report on neoadjuvant PRRT in a neuroendocrine neoplasm with subsequent successful complete resection.

  10. Development of modern approach to absorbed dose assessment in radionuclide therapy, based on Monte Carlo method simulation of patient scintigraphy

    Science.gov (United States)

    Lysak, Y. V.; Klimanov, V. A.; Narkevich, B. Ya

    2017-01-01

    One of the most difficult problems of modern radionuclide therapy (RNT) is control of the absorbed dose in pathological volume. This research presents new approach based on estimation of radiopharmaceutical (RP) accumulated activity value in tumor volume, based on planar scintigraphic images of the patient and calculated radiation transport using Monte Carlo method, including absorption and scattering in biological tissues of the patient, and elements of gamma camera itself. In our research, to obtain the data, we performed modeling scintigraphy of the vial with administered to the patient activity of RP in gamma camera, the vial was placed at the certain distance from the collimator, and the similar study was performed in identical geometry, with the same values of activity of radiopharmaceuticals in the pathological target in the body of the patient. For correct calculation results, adapted Fisher-Snyder human phantom was simulated in MCNP program. In the context of our technique, calculations were performed for different sizes of pathological targets and various tumors deeps inside patient’s body, using radiopharmaceuticals based on a mixed β-γ-radiating (131I, 177Lu), and clear β- emitting (89Sr, 90Y) therapeutic radionuclides. Presented method can be used for adequate implementing in clinical practice estimation of absorbed doses in the regions of interest on the basis of planar scintigraphy of the patient with sufficient accuracy.

  11. Activity determination of radionuclides for diagnostic and therapy; Aktivitaetsbestimmung von Radionukliden fuer Diagnostik und Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Kossert, Karsten [Physikalisch-Technische Bundesanstalt (PTB), Braunschweig (Germany). Arbeitsgruppe ' Aktivitaetseinheit'

    2013-06-15

    The application of radionuclides plays in medicine an important role and requires reliable activity determination. The PTB provides for this activity normals and determines the activity of the presented sources. The article describes, how activity determinations in the PTB occur, and by which ways this can be used for nuclear medicine. Research and development works in the PTB are just so illuminated as the determination of nuclide data of some isotopes relevant for medicine.

  12. VIDA: a voxel-based dosimetry method for targeted radionuclide therapy using Geant4.

    Science.gov (United States)

    Kost, Susan D; Dewaraja, Yuni K; Abramson, Richard G; Stabin, Michael G

    2015-02-01

    We have developed the Voxel-Based Internal Dosimetry Application (VIDA) to provide patient-specific dosimetry in targeted radionuclide therapy performing Monte Carlo simulations of radiation transport with the Geant4 toolkit. The code generates voxel-level dose rate maps using anatomical and physiological data taken from individual patients. Voxel level dose rate curves are then fit and integrated to yield a spatial map of radiation absorbed dose. In this article, we present validation studies using established dosimetry results, including self-dose factors (DFs) from the OLINDA/EXM program for uniform activity in unit density spheres and organ self- and cross-organ DFs in the Radiation Dose Assessment Resource (RADAR) reference adult phantom. The comparison with reference data demonstrated agreement within 5% for self-DFs to spheres and reference phantom source organs for four common radionuclides used in targeted therapy ((131)I, (90)Y, (111)In, (177)Lu). Agreement within 9% was achieved for cross-organ DFs. We also present dose estimates to normal tissues and tumors from studies of two non-Hodgkin Lymphoma patients treated by (131)I radioimmunotherapy, with comparison to results generated independently with another dosimetry code. A relative difference of 12% or less was found between methods for mean absorbed tumor doses accounting for tumor regression.

  13. Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy

    Science.gov (United States)

    Viallard, Claire; Chezal, Jean-Michel; Mishellany, Florence; Ranchon-Cole, Isabelle; Pereira, Bruno; Herbette, Aurélie; Besse, Sophie; Boudhraa, Zied; Jacquemot, Nathalie; Cayre, Anne; Miot-Noirault, Elisabeth; Sun, Jian-Sheng; Dutreix, Marie; Degoul, Françoise

    2016-01-01

    Radiolabelled melanin ligands offer an interesting strategy for the treatment of disseminated pigmented melanoma. One of these molecules, ICF01012 labelled with iodine 131, induced a significant slowing of melanoma growth. Here, we have explored the combination of [131I]ICF01012 with coDbait, a DNA repair inhibitor, to overcome melanoma radioresistance and increase targeted radionuclide therapy (TRT) efficacy. In human SK-Mel 3 melanoma xenograft, the addition of coDbait had a synergistic effect on tumor growth and median survival. The anti-tumor effect was additive in murine syngeneic B16Bl6 model whereas coDbait combination with [131I]ICF01012 did not increase TRT side effects in secondary pigmented tissues (e.g. hair follicles, eyes). Our results confirm that DNA lesions induced by TRT were not enhanced with coDbait association but, the presence of micronuclei and cell cycle blockade in tumor shows that coDbait acts by interrupting or delaying DNA repair. In this study, we demonstrate for the first time, the usefulness of DNA repair traps in the context of targeted radionuclide therapy. PMID:26887045

  14. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Wu, Yin; Pfeifer, Andreas Klaus; Myschetzky, Rebecca;

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising...... clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following...

  15. Photodynamic therapy in clinical practice

    OpenAIRE

    E. V. Filonenko; L. G. Serova

    2016-01-01

    The review is on opportunities and possibilities of application of photodynamic therapy in clinical practice. The advantages of this method are the targeting of effect on tumor foci and high efficiency along with low systemic toxicity. The results of the set of recent Russian and foreign clinical trials are represented in the review. The method is successfully used in clinical practice with both radical (for early vulvar, cervical cancer and pre-cancer, central early lung cancer, esophageal a...

  16. Photodynamic therapy in clinical practice

    Directory of Open Access Journals (Sweden)

    E. V. Filonenko

    2016-01-01

    Full Text Available The review is on opportunities and possibilities of application of photodynamic therapy in clinical practice. The advantages of this method are the targeting of effect on tumor foci and high efficiency along with low systemic toxicity. The results of the set of recent Russian and foreign clinical trials are represented in the review. The method is successfully used in clinical practice with both radical (for early vulvar, cervical cancer and pre-cancer, central early lung cancer, esophageal and gastric cancer, bladder cancer and other types of malignant tumors, and palliative care (including tumor pleuritis, gastrointestinal tumors and others. Photodynamic therapy delivers results which are not available for other methods of cancer therapy. Thus, photodynamic therapy allows to avoid gross scars (that is very important, for example, in gynecology for treatment of patients of reproductive age with cervical and vulvar cancer, delivers good cosmetic effect for skin tumors, allows minimal trauma for intact tissue surrounding tumor. Photodynamic therapy is also used in other fields of medicine, such as otorhinolaryngology, dermatology, ophthalmology, orthopaedics, for treatment of papilloma virus infection and purulent wounds as antibacterial therapy.

  17. DNA damage in blood lymphocytes in patients after {sup 177}Lu peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eberlein, Uta; Bluemel, Christina; Buck, Andreas Konrad; Werner, Rudolf Alexander; Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nowak, Carina; Scherthan, Harry [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany)

    2015-10-15

    The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with {sup 177}Lu-labelled DOTATATE/DOTATOC. The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time-activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with {sup 131}I and {sup 177}Lu. The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. Measurements of RIF and the absorbed dose to the blood after systemic administration of {sup 177}Lu may be used to obtain data on the individual dose-response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. (orig.)

  18. Focused interventional cancer radiation therapy using lipid nanoparticle-carried radionuclides

    Science.gov (United States)

    Hrycushko, Brian Andrew

    2011-07-01

    The overall goal in cancer therapy is to achieve complete tumor eradication while causing minimal damage to healthy organs and tissue. Based on the broadly accepted theory of tumor control being a probabilistic event, every fraction of radiation treatment kills a portion of cancer cells and higher radiation dose should result in improved tumor control. Ultimately, radiation oncologists must balance the delivery of high enough radiation to tumors for achieving tumor control while not delivering so much radiation as to cause unacceptable normal tissue risk. This project centers on the locoregional delivery of lipid (liposome) nanoparticle-carried therapeutic radionuclides (186Re/ 188Re) to apply a focal and ablative radiation dose to target regions while greatly decreasing normal tissue toxicity of surrounding tissues. Specific Aim 1 includes the development of dosimetric and radiobiological models to assess small animal / patient specific radionuclide therapy at a voxel level. This will be used for a proof of concept study to characterize a novel technique to treat the post-lumpectomy wall for residual early stage breast cancer while simultaneously treating draining lymph nodes. Specific Aim 2 will look at methods of improving therapeutic ratio by evaluating in vivo characteristics of different liposome formulations and tumor vasculature modification chemicals following direct intratumoral infusion of 99m Tc-liposomes within a human head and neck squamous cell carcinoma xenograft (HNSCC) model in nude rats. Specific Aim 3 will evaluate the therapy potential for direct intratumoral injection of 186Re-liposomes within a human HNSCC xenograft model in nude rats using the dosimetric and radiobiological models of Aim 1 with improved treatment modifications from Aim 2.

  19. Radiation exposure to caregivers from patients undergoing common radionuclide therapies: a review.

    Science.gov (United States)

    Stefanoyiannis, A P; Ioannidou, S P; Round, W H; Carinou, E; Mavros, M N; Liotsou, T; Geronikola-Trapali, X; Armeniakos, I; Chatziioannou, S N

    2015-12-01

    The contribution of radionuclide therapies (RNTs) to effective patient treatment is widely appreciated. The administration of high doses has necessitated investigating the potential radiation hazard to caregivers from patients undergoing RNTs. This work aimed to review the literature regarding measured effective doses to caregivers from such patients. The main selection criterion was the presence of real radiation exposure measurements. The results were categorised according to the treatment protocol and dose parameters. Analysis of the collected data demonstrated that the measured effective dose values were within the dose constraints defined by the International Commission on Radiological Protection, provided that the radiation protection instructions were followed by both patients and caregivers. In conclusion, the radiation risk for caregivers was almost negligible. In this context, treatments could be administered more often on an outpatient basis, once cost-effectiveness criteria were established and radiation protection training and procedures were appropriately applied.

  20. Complete Remission of Metastatic Neuroendocrine Paragastric Carcinoma After "Neoadjuvant" Peptide Receptor Radionuclide Therapy and Surgery.

    Science.gov (United States)

    Schmidt, Matthias C; Uhrhan, Klara; Fischer, Thomas; Schmitz, Stephan; Markiefka, Birgid; Drzezga, Alexander; Stippel, Dirk

    2015-08-01

    A 48-year-old man presenting with upper abdominal pain was diagnosed with neuroendocrine tumor after biopsy of a paragastric mass with multiple liver metastases. (68)Ga-DOTATATE PET/CT showed intense uptake in the paragastric tumor and in multiple liver metastases not allowing primary surgery. Two cycles with cumulative 14.6 GBq (177)Lu-DOTATATE were given resulting in a considerable improvement. Subsequent surgery resulted in a complete remission as demonstrated by (68)Ga-DOTATATE PET/CT. Usually, peptide receptor radionuclide (PRRT) therapy is considered a palliative treatment. Few patients demonstrate a very favorable response allowing resection of the primary tumor after downstaging metastatic disease burden.

  1. Monte Carlo modeling of the Yttrium-90 nanospheres application in the liver radionuclide therapy and organs doses calculation

    Directory of Open Access Journals (Sweden)

    Ghavami Seyed Mostafa

    2016-01-01

    Full Text Available Using the nano-scaled radionuclides in the radionuclide therapy significantly reduces the particles trapping in the organs vessels and avoids thrombosis formations. Additionally, uniform distribution in the target organ may be another benefit of the nanoradionuclides in the radionuclide therapy. Monte Carlo simulation was conducted to model a mathematical humanoid phantom and the liver cells of the simulated phantom were filled with the 90Y nanospheres. Healthy organs doses, fatal and nonfatal risks of the surrounding organs were estimated. The estimations and calculations were made in four different distribution patterns of the radionuclide seeds. Maximum doses and risks estimated for the surrounding organs were obtained in the high edge concentrated distribution model of the liver including the nanoradionuclides. For the dose equivalent, effective dose, fatal and non-fatal risks, the values obtained as 7.51E-03 Sv/Bq, 3.01E-01 Sv/Bq, and 9.16E-01 cases/104 persons for the bladder, colon, and kidney of the modeled phantom, respectively. The mentioned values were the maximum values among the studied modeled distributions. Maximum values of Normal Tissue Complication Probability for the healthy organs calculated as 5.9-8.9 %. Result of using nanoparticles of the 90Y provides promising dosimetric properties in MC simulation results considering non-toxicity reports for the radionuclide.

  2. Dose rate in intravascular radionuclide therapy using Re-188 coated balloon

    Energy Technology Data Exchange (ETDEWEB)

    Baek, M. Y.; Kim, J. K. [Hanyang Univ., Seoul (Korea, Republic of)

    2001-05-01

    Restenosis is the major drawback problem after percutaneous transluminal coronary angioplasty (PTCA). In order to reduce the restenosis, radionuclide therapy has been used, and these day balloon coating method with radionuclide is investigating to effective therapy. We intend to calculate the activity by Monte Carlo method, which is needed in the investigation of coated balloon using Re-188. We used EGSnrc code system to calculate this activity. Balloons were assumed be a length of 20 mm or 30 mm and to have a central catheter of diameter 0.5 mm. The surface of balloon is coated with 0.01 mm depth Re-188 using poly urethan. We calculated dose distribution as radial distance from the surface of balloon. And we calculate how much activities are needed to irradiate 18Gy at the 0.5 mm, 1.0 mm distance from balloon surface during 3 minutes. As results it is needed 19.3 mCi and 33.6 mCi relatively for each 0.5 mm and 1.0 mm in the 20 mm balloon. It is need 27.8 mCi and 48.3 mCi in the 30 mm balloon. Recent report for Ho-166 using EGS4 suggests 13.04 mCi at 0.5 mm distance in the 20 mm balloon. This value is lower than our result for Re-188 for the same size balloon. It is considered to be a systemic difference between two simulation codes ({approx}10%)

  3. Rhenium-188 Production in Hospitals, by W-188/Re-188 Generator, for Easy Use in Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Maria Argyrou

    2013-01-01

    Full Text Available Rhenium-188 (Re-188 is a high energy -emitting radioisotope obtained from the tungsten-188/rhenium-188 (W-188/Re-188 generator, which has shown utility for a variety of therapeutic applications in nuclear medicine, oncology, and interventional radiology/cardiology. Re-188 decay is accompanied by a 155 keV predominant energy -emission, which could be detected by -cameras, for imaging, biodistribution, or absorbed radiation dose studies. Its attractive physical properties and its potential low cost associated with a long-lived parent make it an interesting option for clinical use. The setup and daily use of W-188/Re-188 generator in hospital nuclear medicine departments are discussed in detail. The clinical efficacy, for several therapeutic applications, of a variety of Re-188-labeled agents is demonstrated. The high energy of the -emission of Re-188 is particularly well suited for effective penetration in solid tumours. Its total radiation dose delivered to tissues is comparable to other radionuclides used in therapy. Furthermore, radiation safety and shielding requirements are an important subject of matter. In the case of bone metastases treatment, therapeutic ratios are presented in order to describe the efficacy of Re-188 usage.

  4. 3D dosimetry in patients with early breast cancer undergoing Intraoperative Avidination for Radionuclide Therapy (IART {sup registered}) combined with external beam radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, Mahila E.; Cremonesi, Marta; Di Dia, Amalia; Botta, Francesca; Pedroli, Guido [European Institute of Oncology, Division of Medical Physics, Milan (Italy); De Cicco, Concetta; Calabrese, Michele; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Sarnelli, Anna [IRCCS Istituto Romagnolo per lo Studio e la Cura dei Tumori, Medical Physics Unit, Meldola, FC (Italy); Pedicini, Piernicola [Centro Regionale Oncologico Basilicata (IRCCS-CROB), Department of Radiation Oncology, Rionero in Vulture, PZ (Italy); Orecchia, Roberto [European Institute of Oncology, Division of Radiotherapy, Milan (Italy)

    2012-11-15

    Intraoperative Avidination for Radionuclide Therapy (IART {sup registered}) is a novel targeted radionuclide therapy recently used in patients with early breast cancer. It is a radionuclide approach with {sup 90}Y-biotin combined with external beam radiotherapy (EBRT) to release a boost of radiation in the tumour bed. Two previous clinical trials using dosimetry based on the calculation of mean absorbed dose values with the hypothesis of uniform activity distribution (MIRD 16 method) assessed the feasibility and safety of IART {sup registered}. In the present retrospective study, a voxel dosimetry analysis was performed to investigate heterogeneity in distribution of the absorbed dose. The aim of this work was to compare dosimetric and radiobiological evaluations derived from average absorbed dose vs. voxel absorbed dose approaches. We evaluated 14 patients who were injected with avidin into the tumour bed after conservative surgery and 1 day later received an intravenous injection of 3.7 GBq of {sup 90}Y-biotin (together with 185 MBq {sup 111}In-biotin for imaging). Sequential images were used to estimate the absorbed dose in the target region according to the standard dosimetry method (SDM) and the voxel dosimetry method (VDM). The biologically effective dose (BED) distribution was also evaluated. Dose/volume and BED volume histograms were generated to derive equivalent uniform BED (EUBED) and equivalent uniform dose (EUD) values. No ''cold spots'' were highlighted by voxel dosimetry. The median absorbed-dose in the target region was 20 Gy (range 15-27 Gy) by SDM, and the median EUD was 20.4 Gy (range 16.5-29.4 Gy) by the VDM; SDM and VDM estimates differed by about 6 %. The EUD/mean voxel absorbed dose ratio was >0.9 in all patients, indicative of acceptable uniformity in the target. The median BED and EUBED values were 21.8 Gy (range 15.9-29.3 Gy) and 22.8 Gy (range 17.3-31.8 Gy), respectively. VDM highlighted the absence of significant

  5. Clinical evaluation of radionuclide cisternography and x-ray CT in normal pressure hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Osamu; Maeda, Toshio; Matsuda, Hiroshi; Ishida, Hiroko; Michigishi, Takatoshi (Kanazawa Univ. (Japan). School of Medicine)

    1983-06-01

    The retrospective reevaluation of the radionuclide cisternogram and X-ray CT were studied in 14 cases in whom cerebrospinal fluid shunt were installed under the diagnosis of normal pressure hydrocephalus after these examinations. Only half of these cases showed clinical improvement after shunt operation. The most reliable finding of the cisternography was the persistent ventricular visualization with bilateral block at subarachnoid space on 48 hour image. These findings were observed in seven cases, and all of them but one case showed clinical improvement after shunt installation. The exceptional one case in whom shunt was not effective. The cisternogram of the other case whose shunt was effective showed the transient ventricular visualization upto 24 hour, the unilateral subarachnoidal space block upto 48 hour and the prominently delayed clearance of radionuclide from the head. The cisternographic findings of the delayed radionuclide clearance and the ventricular visualization on 24 hour-image were insufficient to help the shunt effect. The most hopeful findings of the X-ray CT was the poor-visualization of Sylvian fissure at least on two cross sections. These findings were observed in eight cases, and six out of them showed clinical improvement after shunt operation. But the poor-visualization of Sylvian fissure is not a specific sign for normal pressure hydrocephalus. We concluded that the abnormal findings on 48 hour-image of cisternography are correlated well with the effect of cerebrospinal fluid shunt in normal pressure hydrocephalus, and the cisternography is still very useful in the chosen patients with clinical and X-ray CT findings.

  6. Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Krenning, Eric P.; Jong, Marion De; Valkema, Roelf; Kwekkeboom, Dik J. [Dept. of Nuclear Medicine, Erasmus MC, ' s Gravendijkwal 230, Rotterdam (Netherlands)

    2007-08-15

    Peptide Receptor Radionuclide Therapy (PRRT) with radiolabelled somatostatin analogues is a promising treatment option for patients with inoperable or metastasised neuroendocrine tumours. Symptomatic improvement may occur with all of the various {sup 111}In, {sup 90}Y, or {sup 177}Lu-labelled somatostatin analogues that have been used. Since tumour size reduction was seldom achieved with {sup 111}Indium labelled somatostatin analogues, radiolabelled somatostatin analogues with beta-emitting isotopes like {sup 90}Y and {sup 177}Lu were developed. Reported anti-tumour effects of [{sup 90}Y-DOTA0,Tyr3]octreotide vary considerably between various studies: Tumour regression of 50% or more was achieved in 9 to 33% (mean 22%). With [{sup 177}Lu-DOTA0,Tyr3]octreotate treatments, tumour regression of 50% or more was achieved in 28% of patients and tumour regression of 25 to 50% in 19% of patients, stable disease was demonstrated in 35% and progressive disease in 18%. Predictive factors for tumour remission were high tumour uptake on somatostatin receptor scintigraphy and limited amount of liver metastases. The side-effects of PRRT are few and mostly mild, certainly when using renal protective agents: Serious side-effects like myelodysplastic syndrome or renal failure are rare. The median duration of the therapy response for [{sup 90}Y-DOTA0,Tyr3]octreotide and [{sup 177}Lu-DOTA0,Tyr3]octreotate is 30 months and more than 36 months respectively. Lastly, quality of life improves significantly after treatment with [{sup 177}Lu-DOTA0,Tyr3]octreotate. These data compare favourably with the limited number of alternative treatment approaches, like chemotherapy. If more widespread use of PRRT is possible, such therapy might become the therapy of first choice in patients with metastasised or inoperable gastroenteropancreatic neuroendocrine tumours. Also the role in somatostatin receptor expressing non-GEP tumours, like metastasised paraganglioma/pheochromocytoma and non

  7. Accelerator based production of auger-electron-emitting isotopes for radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Thisgaard, H.

    2008-08-15

    In this research project the focus has been on the identification and production of new, unconventional Auger-electron-emitting isotopes for targeted radionuclide therapy of cancer. Based on 1st principles dosimetry calculations on the subcellular level, the Auger-emitter 119Sb has been identified as a potent candidate for therapy. The corresponding imaging analogue 117Sb has been shown from planar scintigraphy and single-photon emission computed tomography (SPECT) to be suitable for SPECT-based dosimetry of a future Sb-labeled radiopharmaceutical. The production method of these radioisotopes has been developed using a low-energy cyclotron via the nuclear reactions 119Sn(p,n)119Sb and 117Sn(p,n)117Sb including measurements of the excitation function for the former reaction. Moreover, a new high-yield radiochemical separation method has been developed to allow the subsequent separation of the produced 119Sb from the enriched 119Sn target material with high radionuclidic- and chemical purity. A method that also allows efficient recovery of the 119Sn for recycling. To demonstrate the ability of producing therapeutic quantities of 119Sb and other radioisotopes for therapy with a low-energy cyclotron, two new 'High Power' cyclotron targets were developed in this study. The target development was primarily based on theoretical thermal modeling calculations using finite-element-analysis software. With these targets, I have shown that it will be possible to produce several tens of GBq of therapeutics isotopes (e.g. 119Sb or 64Cu) using the PETtrace cyclotron commonly found at the larger PET-centers in the hospitals. Finally, research in a new method to measure the radiotoxicity of Auger-emitters invitro using cellular microinjection has been carried out. The purpose of this method is to be able to experimentally evaluate and compare the potency of the new and unconventional Auger-emitters (e.g. 119Sb). However, due to experimental complications, the development

  8. Evaluation of new iodinated acridine derivatives for targeted radionuclide therapy of melanoma using 125I, an Auger electron emitter.

    Science.gov (United States)

    Gardette, Maryline; Papon, Janine; Bonnet, Mathilde; Desbois, Nicolas; Labarre, Pierre; Wu, Ting-Dee; Miot-Noirault, Elisabeth; Madelmont, Jean-Claude; Guerquin-Kern, Jean-Luc; Chezal, Jean-Michel; Moins, Nicole

    2011-12-01

    The increasing incidence of melanoma and the lack of effective therapy on the disseminated form have led to an urgent need for new specific therapies. Several iodobenzamides or analogs are known to possess specific affinity for melanoma tissue. New heteroaromatic derivatives have been designed with a cytotoxic moiety and termed DNA intercalating agents. These compounds could be applied in targeted radionuclide therapy using (125)I, which emits Auger electrons and gives high-energy, localized irradiation. Two iodinated acridine derivatives have been reported to present an in vivo kinetic profile conducive to application in targeted radionuclide therapy. The aim of the present study was to perform a preclinical evaluation of these compounds. The DNA intercalating property was confirmed for both compounds. After radiolabeling with (125)I, the two compounds induced in vitro a significant radiotoxicity to B16F0 melanoma cells. Nevertheless, the acridine compound appeared more radiotoxic than the acridone compound. While cellular uptake was similar for both compounds, SIMS analysis and in vitro protocol showed a stronger affinity for melanin with acridone derivative, which was able to induce a predominant scavenging process in the melanosome and restrict access to the nucleus. In conclusion, the acridine derivative with a higher nuclear localization appeared a better candidate for application in targeted radionuclide therapy using (125)I.

  9. Proton therapy in the clinic.

    Science.gov (United States)

    DeLaney, Thomas F

    2011-01-01

    The clinical advantage for proton radiotherapy over photon approaches is the marked reduction in integral dose to the patient, due to the absence of exit dose beyond the proton Bragg peak. The integral dose with protons is approximately 60% lower than that with any external beam photon technique. Pediatric patients, because of their developing normal tissues and anticipated length of remaining life, are likely to have the maximum clinical gain with the use of protons. Proton therapy may also allow treatment of some adult tumors to much more effective doses, because of normal tissue sparing distal to the tumor. Currently, the most commonly available proton treatment technology uses 3D conformal approaches based on (a) distal range modulation, (b) passive scattering of the proton beam in its x- and y-axes, and (c) lateral beam-shaping. It is anticipated that magnetic pencil beam scanning will become the dominant mode of proton delivery in the future, which will lower neutron scatter associated with passively scattered beam lines, reduce the need for expensive beam-shaping devices, and allow intensity-modulated proton radiotherapy. Proton treatment plans are more sensitive to variations in tumor size and normal tissue changes over the course of treatment than photon plans, and it is expected that adaptive radiation therapy will be increasingly important for proton therapy as well. While impressive treatment results have been reported with protons, their cost is higher than for photon IMRT. Hence, protons should ideally be employed for anatomic sites and tumors not well treated with photons. While protons appear cost-effective for pediatric tumors, their cost-effectiveness for treatment of some adult tumors, such as prostate cancer, is uncertain. Comparative studies have been proposed or are in progress to more rigorously assess their value for a variety of sites. The utility of proton therapy will be enhanced by technological developments that reduce its cost

  10. Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with 68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy

    OpenAIRE

    Wolfgang Luboldt; Holger Hartmann; Bärbel Wiedemann; Klaus Zöphel; Hans-Joachim Luboldt

    2010-01-01

    The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) during the course of somatostatin receptor radionuclide therapy (SRRT). In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA) and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax) of normal liver and hepatic metastases we...

  11. Clinical aspects of phage therapy.

    Science.gov (United States)

    Międzybrodzki, Ryszard; Borysowski, Jan; Weber-Dąbrowska, Beata; Fortuna, Wojciech; Letkiewicz, Sławomir; Szufnarowski, Krzysztof; Pawełczyk, Zdzisław; Rogóż, Paweł; Kłak, Marlena; Wojtasik, Elżbieta; Górski, Andrzej

    2012-01-01

    Phage therapy (PT) is a unique method of treatment of bacterial infections using bacteriophages (phages)-viruses that specifically kill bacteria, including their antibiotic-resistant strains. Over the last decade a marked increase in interest in the therapeutic use of phages has been observed, which has resulted from a substantial rise in the prevalence of antibiotic resistance of bacteria, coupled with an inadequate number of new antibiotics. The first, and so far the only, center of PT in the European Union is the Phage Therapy Unit (PTU) established at the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland in 2005. This center continues the rich tradition of PT in Poland, which dates from the early 1920s. The main objective of this chapter is to present a detailed retrospective analysis of the results of PT of 153 patients with a wide range of infections resistant to antibiotic therapy admitted for treatment at the PTU between January 2008 and December 2010. Analysis includes the evaluation of both the efficacy and the safety of PT. In general, data suggest that PT can provide good clinical results in a significant cohort of patients with otherwise untreatable chronic bacterial infections and is essentially well tolerated. In addition, the whole complex procedure employed to obtain and characterize therapeutic phage preparations, as well as ethical aspects of PT, is discussed.

  12. Clinical efficacy of photodynamic therapy

    Science.gov (United States)

    Park, Ye-Kyu

    2016-01-01

    Objective The management of cervical intraepithelial neoplasia (CIN) and early invasive cancer of the uterine cervix is very difficult to approach, especially in case of young woman who wants to preserve her fertility. Conization of the cervix may have various kinds of disadvantage. The objective of this clinical retrospective study is to investigate the therapeutic effects and clinical efficacy of photodynamic therapy (PDT) including combined chemo-photodynamic therapy in patients with pre-malignant CIN and malignant invasive cervical cancer. Methods Total number of PDT trial case was 50 cases and total number of patient was 22 patients who registered to PDT clinic. We used photogem sensitizer and 632 nm diode laser in early two cases. After then we performed PDT using photofrin sensitizer and 630 nm diode laser in other cases. We used flat-cut, microlens, cylindrical diffuser, and interstitial type optic fibers in order to irradiate the lesions. 240 J/cm2 energy was irradiated to the lesions. Results CIN 2 were 4 cases (18.2%) and CIN 3 were 15 (68.2%) and invasive cervical cancer were 3 (13.6%). Complete remission (CR) was found in 20 patients (91%). One case of 19 patients with CIN lesion recurred at 18 months after PDT treatment. CR was found in 18 cases in the patients with CIN lesions (95%). CR was found in 2 cases in the patients with invasive cervical cancer (67%). Conclusion Our data showed that CR rate was fantastic in CIN group (95%). This study suggests that PDT can be recommended as new optimistic management modality on the patients with pre-malignant CIN lesions including carcinoma in situ and relatively early invasive cancer of the uterine cervix. Combined chemo-photodynamic therapy is essential in case of invasive cervical cancer. For the young age group who desperately want to preserve their fertility and have a healthy baby, PDT can be a beacon of hope. PMID:27896250

  13. Development of drug delivery systems for radionuclide therapy using a combination therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, On Hee; Choi, Sun Ju [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2005-07-01

    For the development of new controlled drug delivery systems, the application of combination therapy using angiogenesis inhibitor and tumor static agents has drawn great attention. This approach would be very beneficial for cancer treatment especially when a new drug deliver system utilizing biodegradable polymers is developed. Therefore, the present study for the combination therapy of angiogenesis inhibitor and chemotherapeutic agents was to carry out prior to the development of the novel drug delivery. In present study, the ability of inhibition on cell growth was investigated with treatment of anti-angiogenetic agent and anticancer agent. Thalidomide was used as an antivasculatory agents and Doxorubicine was treated as a chemotherapeutic agent. To demonstrate apoptotic process in in-vitro study, TUNEL assay was carried out. Also, the alteration of p53 level was examined by using western blotting. For the cell lines, NIH:OVCAR3, MKN45, SNU719, C6, L929, T98G, Hep3B and Calu6 were applied. Results showed that Thalidomide inhibited cell growth in tumor cell lines in a dose-dependent manner and Doxorubicin as well. A significant synergistic effect on the apoptotic was noticed in the combination treatment of Thalidomide and Doxorubicin compared to a single treatment of either drug. Therefore, it can be concluded that the mechanism of cytotoxicity was due to the enhancement of apoptosis in early cell death with combination treatment in tumor cell lines.

  14. 内放射治疗肝细胞癌%Radionuclide therapy of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    许颖

    2011-01-01

    肝细胞癌(HCC)的恶性程度非常高,全球每年大约有五十万人死于HCC,且亚洲为高发地区.针对不宜行手术的患者,内放射治疗是一种有效的手段.目前临床内放射治疗较常用的放射性核素有钇-90(90Y)微球、碘-131 (131I)和铼-188 (188Re)碘化油等.本文综述其特点及研究现状,并重点讨论90Y微球内放射治疗与动脉化疗栓塞(TACE)治疗的比较.%Hepatocellular carcinoma (HCC) is a high-grade malignant tumour of the hepatocyte. It causes almost half a million deaths annually, Asia is a high risk area. Radionuclide therapy is an effective treatment for the most patients who are not eligible for surgery. Radiopharmaceuticals used for transarterial treatment of HCC were Yttrium-90 microspheres, Iodine-131 lipiodol and Rhenium-188 lipiodol. This review summarizes characteristics and research of these radiopharmaceuticals for HCC with an emphasis on Yttrium-90 microspheres compared with transcatheter arterial chemoembolization.

  15. Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy.

    Science.gov (United States)

    Grzmil, Michal; Seebacher, Jan; Hess, Daniel; Behe, Martin; Schibli, Roger; Moncayo, Gerald; Frank, Stephan; Hemmings, Brian A

    2016-09-01

    Current standard-of-care treatment for malignant cancers includes radiotherapy and adjuvant chemotherapy. Here, we report increased MAP kinase-interacting kinase (MNK)-regulated phosphorylation of translation initiation factor 4E (eIF4E) in glioma cells upon temozolomide (TMZ) treatment and in medullary thyroid carcinoma (MTC) cells in response to targeted radionuclide therapy. Depletion of MNK activity by using two MNK inhibitors, CGP57380 or cercosporamide, as well as by MNK1-specific knockdown sensitized glioblastoma (GBM) cells and GBM-derived spheres to TMZ. Furthermore, CGP57380 treatment enhanced response of MTC cells to (177)Lu-labeled gastrin analogue. In order to understand how MNK signaling pathways support glioma survival we analyzed putative MNK substrates by quantitative phosphoproteomics in normal condition and in the presence of TMZ. We identified MNK inhibitor-sensitive phosphorylation sites on eIF4G1, mutations of which either influenced eIF4E phosphorylation or glioma cell response to TMZ, pointing to altered regulation of translation initiation as a resistance mechanism. Pharmacological inhibition of overexpressed MNK1 by CGP57380 reduced eIF4E phosphorylation and induced association of inactive MNK1 with eIF4G1. Taken together, our data show an activation of MNK-mediated survival mechanisms in response to either glioma chemotherapy or MTC targeted radiation and suggest that inhibition of MNK activity represents an attractive sensitizing strategy for cancer treatments.

  16. Radionuclide therapy (radiation synovectomy) in rheumatology and orthopaedics; Nuklearmedizinische Therapie (Radiosynoviorthese) in Rheumatologie und Orthopaedie

    Energy Technology Data Exchange (ETDEWEB)

    Moedder, G. [Praxis fuer Nuklearmedizin, Koeln (Germany)

    1995-02-01

    An overview is given over those diseases being an indication for radiosynovectomy, especially inflammatory rheumatoid diseases and the activated arthrosis. In the diagnostic field of nuclear medicine arthrosonography and soft tissue scintigraphy of joints is absolutely therapy-relevant. Hints are offered, technique, results and problems are presented. Baker`s cyst and progressive state of rheumatoid arthritis are no contraindication against radiosynovectomy. (orig./VHE) [Deutsch] Es wird ein Ueberblick ueber die Erkrankungen, die eine Indikation zur Radiosynoviorthese darstellen, insbesondere entzuendlich-rheumatische Erkrankungen und die aktivierte Arthrose gegeben. An diagnostischen Verfahren sind fuer den Nuklearmediziner die Arthrosonographie und die Weichteilszintigraphie der Gelenke absolut therapierelevant. Hinweise werden hierzu gegeben, Technik, Ergebnisse, Probleme werden abgehandelt. So sind die Bakerzyste und ein fortgeschrittenes Stadium der chronischen Polyarthritis keineswegs eine Kontraindikation zur Radiosynoviorthese. (orig./VHE)

  17. The application of polymer gel dosimeters to dosimetry for targeted radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gear, J I [Joint Department of Physics, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey (United Kingdom); Flux, G D [Joint Department of Physics, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey (United Kingdom); Charles-Edwards, E [Clinical Magnetic Research Group, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey (United Kingdom); Partridge, M [Joint Department of Physics, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey (United Kingdom); Cook, G [Department of Nuclear Medicine, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey (United Kingdom); Ott, R J [Joint Department of Physics, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey (United Kingdom)

    2006-07-21

    There is a lack of standardized methodology to perform dose calculations for targeted radionuclide therapy and at present no method exists to objectively evaluate the various approaches employed. The aim of the work described here was to investigate the practicality and accuracy of calibrating polymer gel dosimeters such that dose measurements resulting from complex activity distributions can be verified. Twelve vials of the polymer gel dosimeter, 'MAGIC', were uniformly mixed with varying concentrations of P-32 such that absorbed doses ranged from 0 to 30 Gy after a period of 360 h before being imaged on a magnetic resonance scanner. In addition, nine vials were prepared and irradiated using an external 6 MV x-ray beam. Magnetic resonance transverse relaxation time, T{sub 2}, maps were obtained using a multi-echo spin echo sequence and converted to R{sub 2} maps (where T{sub 2} = 1/R{sub 2}). Absorbed doses for P-32 irradiated gel were calculated according to the medical internal radiation dose schema using EGSnrc Monte Carlo simulations. Here the energy deposited in cylinders representing the irradiated vials was scored. A relationship between dose and R{sub 2} was determined. Effects from oxygen contamination were present in the internally irradiated vials. An increase in O{sub 2} sensitivity over those gels irradiated externally was thought to be a result of the longer irradiation period. However, below the region of contamination dose response appeared homogenous. Due do a drop-off of dose at the periphery of the internally irradiated vials, magnetic resonance ringing artefacts were observed. The ringing did not greatly affect the accuracy of calibration, which was comparable for both methods. The largest errors in calculated dose originated from the initial activity measurements, and were approximately 10%. Measured R{sub 2} values ranged from 5-35 s{sup -1} with an average standard deviation of 1%. A clear relationship between R{sub 2} and dose was

  18. Radionuclide therapy of patients with metastastic bone pain%放射性核素治疗癌转移性骨痛

    Institute of Scientific and Technical Information of China (English)

    程爱萍; 陈绍亮

    2008-01-01

    癌性骨转移原发病灶常见于前列腺癌、乳腺癌、肺癌等,转移发生的病理生理机制、疼痛机制目前不十分明确.止痛治疗尤其是对广泛骨转移性疼痛的治疗是临床医师面对的主要挑战,放射性核素及其标记药物治疗是一种有效、价廉、不良反应较小的治疗方法,对广泛转移的止痛治疗及微转移患者的治疗独具优势,目前有待充分利用.%Bone metastases are often the first sign of distant spread in breast, prostate, and lung cancers. The pathophysiology of bone metastasis is poorly understood and related complications is complex.Bone pain consequent to metastatic cancer continues to be a major therapeutic challenge for clinicians and its alleviation is crucial to improving the patient's quality of life. Targeted radionuclide therapy is an effective and cost efficient treatment for multi-site metastatic bone pain, its advantages may also include therapy for subclinical micro-or oligometastatic disease before clinical manifestation. But radionuclides remain underutilized in such treatments.

  19. Radionuclide venography of lower limbs by subcutaneous injection; A clinical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chung-Chieng; Jong, Shiang-Bin (Kaohsiung Medical Coll., Taiwan (China))

    1993-02-01

    SC-RNV, radionuclide venography by subcutaneous injection of Tc-99m pertechnetate at acupuncture points K-3, a new alternative of lower limb venography, was recently developed in our clinical laboratory. In some of the previous studies, we have proved its superiority to radionuclide venography by intravenous injection. The current investigation was conducted to understand the reliability of SC-RNV in the diagnosis of deep vein thrombosis (DVT). Fifty-seven cases with lower leg edema, from November 1989 through October 1990, received both SC-RNV and duplex US for causative evaluation. As a result of duplex US, 26 were considered normal (non-DVT), 19 were classified as unilateral DVT, and 12 as bilateral DVT. In nineteen cases (61%, 19/31) with DVT also a XCT and/or a CV (contrast venography) was taken, that showed compatible results. All of the non-DVT had a normal pattern of SC-RNV, all of the unilateral DVT had unilateral impairment of deep vein drainage in SC-RNV, and all of the bilateral DVT had impaired deep venous drainage bilaterally in SC-RNV. It is therefore, concluded that SC-RNV is one of the best choices among available non-invasive lower-limb venographic methods. (author).

  20. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Michael Bzorek

    2013-10-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.

  1. Lymphocytic Thyroiditis - is cytological grading significant? A correlation of grades with clinical, biochemical, ultrasonographic and radionuclide parameters

    Directory of Open Access Journals (Sweden)

    Bhatia Alka

    2007-01-01

    Full Text Available Background: Clinical, biochemical, ultrasonographic, radionuclide and cytomorphological observations in Lymphocytic thyroiditis (LT, to define the cytological grading criteria on smears and correlation of grades with above parameters. Methods: This prospective study was conducted on 76 patients attending the Fine needle aspiration cytology clinic of a tertiary care institute in North India. The various parameters like patients′ clinical presentation, thyroid antimicrosomal antibodies, hormonal profiles, radionuclide thyroid scan and thyroid ultrasound were studied. Fine needle aspiration of thyroid gland and grading of thyroiditis was done on smears. The grades were correlated with above parameters and the correlation indices were evaluated statistically. Results: Most of the patients were females (70, 92.11% who presented with a diffuse goiter (68, 89.47%. Hypothyroid features (56, 73.68% and elevated TSH (75, 98.68% were common, but radioiodide uptake was low or normal in majority of patients. Thyroid antimicrosomal antibody was elevated in 46/70 (65.71% patients. Cytomorphology in fine needle aspirates was diagnostic of lymphocytic thyroiditis in 75 (98.68% patients. Most of them had grade I/II disease by cytology. No correlation was observed between grades of cytomorphology and clinical, biochemical, ultrasonographic and radionuclide parameters. Conclusion: Despite the availability of several tests for diagnosis of LT, FNAC remains the gold standard. The grades of thyroiditis at cytology however do not correlate with clinical, biochemical, radionuclide and ultrasonographic parameters.

  2. Lymphocytic Thyroiditis – is cytological grading significant? A correlation of grades with clinical, biochemical, ltrasonographic and radionuclide parameters

    Directory of Open Access Journals (Sweden)

    Dash Radharaman

    2007-01-01

    Full Text Available Abstract Background Clinical, biochemical, ultrasonographic, radionuclide and cytomorphological observations in Lymphocytic thyroiditis (LT, to define the cytological grading criteria on smears and correlation of grades with above parameters. Methods This prospective study was conducted on 76 patients attending the Fine needle aspiration cytology clinic of a tertiary care institute in North India. The various parameters like patients' clinical presentation, thyroid antimicrosomal antibodies, hormonal profiles, radionuclide thyroid scan and thyroid ultrasound were studied. Fine needle aspiration of thyroid gland and grading of thyroiditis was done on smears. The grades were correlated with above parameters and the correlation indices were evaluated statistically. Results Most of the patients were females (70, 92.11% who presented with a diffuse goiter (68, 89.47%. Hypothyroid features (56, 73.68% and elevated TSH (75, 98.68% were common, but radioiodide uptake was low or normal in majority of patients. Thyroid antimicrosomal antibody was elevated in 46/70 (65.71% patients. Cytomorphology in fine needle aspirates was diagnostic of lymphocytic thyroiditis in 75 (98.68% patients. Most of them had grade I/II disease by cytology. No correlation was observed between grades of cytomorphology and clinical, biochemical, ultrasonographic and radionuclide parameters. Conclusion Despite the availability of several tests for diagnosis of LT, FNAC remains the gold standard. The grades of thyroiditis at cytology however do not correlate with clinical, biochemical, radionuclide and ultrasonographic parameters.

  3. [Clinical trials with advanced therapy medicinal products].

    Science.gov (United States)

    Schüssler-Lenz, M; Schneider, C K

    2010-01-01

    For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.

  4. α放射核素靶向治疗研究进展%The Research Progress of Alpha-emitting Radionuclides Targeted Therapy

    Institute of Scientific and Technical Information of China (English)

    李明起; 潘俊男; 段玉春; 邓启民; 王邦金

    2014-01-01

    Alpha‐emitting radionuclides provide effective cell‐killing properties in vivo and have been shown to be effective in cancer treatment .Its short‐range make little effect on normal tissues ,thus alpha‐emitting radionuclides drugs is one of the important research focus areas and radiopharmaceutical research .T he excellent nature of the radi‐onuclide (right half life ,ray energy ,etc .) ,stable supply of high purity nuclides ,suit‐able radionuclide carrier base and excellent kinetics in vivo are necessary to the produc‐tion and research of alpha‐emitting radionuclides .At present ,the alpha‐emitting radio‐nuclidesinclude223Ra,225Ac,213Bi,211At,212Bi,149Tband227Thwereinvestagated.The preparation and sources of the above radionuclides and the latest developments for targe‐ted cancer therapy were described .The existing problems ,status and clinical applica‐tion were briefly discussed .%α放射核素在内照射时具有极强的细胞毒性,对肿瘤细胞具有较强的杀灭作用,而其短射程对正常组织影响较小,因此α放射核素类药物是放射性药物研究的重要领域和研究热点之一。α放射核素类药物的生产和研究关键在于核素的选择、高纯度核素的稳定可靠供应、核素载体及合适的体内动力学。目前国内外研究比较活跃的α放射核素主要包括223 Ra、225 Ac、213 Bi、211 At、212 Bi、149 Tb和227 Th等。本文主要介绍了以上核素的来源制备及用于肿瘤靶向治疗的最新进展,对存在的问题、现状及临床应用前景进行了简要的探讨。

  5. 68Ga-DOTA-NOC PET and peptide receptor radionuclide therapy in management of bilateral ovarian metastases from gastrointestinal carcinoid.

    Science.gov (United States)

    Singla, Suhas; Gupta, Santosh; Reddy, Rama Mohan; Durgapal, Prashant; Bal, C S

    2012-12-01

    The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

  6. The clinical case for proton beam therapy

    Directory of Open Access Journals (Sweden)

    Foote Robert L

    2012-10-01

    Full Text Available Abstract Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence Proton beam therapy is a technically advanced and promising form of radiation therapy.

  7. Therapeutic radionuclides in nuclear medicine: current and future prospects.

    Science.gov (United States)

    Yeong, Chai-Hong; Cheng, Mu-hua; Ng, Kwan-Hoong

    2014-10-01

    The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

  8. Production and dosimetric aspects of the potent Auger emitter Co-58m for targeted radionuclide therapy of small tumours

    DEFF Research Database (Denmark)

    Thisgaard, Helge; Elema, Dennis Ringkjøbing; Jensen, Mikael

    2011-01-01

    Based on theoretical calculations, the Auger emitter 58mCo has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long-lived ground state 58gCo is unfortunately unavoidable, as is ingrowth of the gr......Based on theoretical calculations, the Auger emitter 58mCo has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long-lived ground state 58gCo is unfortunately unavoidable, as is ingrowth...... of the ground state following the isomeric decay of 58mCo. The impact of 58gCo as a bþ- and c-emitting impurity should be included in the dosimetric analysis. The purpose of this study was to investigate this critical part of dosimetry based on experimentally determined production yields of 58mCo and 58g...

  9. Radionuclide angiocardiography in the clinical evaluation of cardiac malpositions in situs solitus in adults.

    Science.gov (United States)

    Guit, G L; Kroon, H M; Chin, J G; Pauwels, E K; van Voorthuisen, A E

    1986-04-01

    A right-sided position of the heart in the chest in situs solitus is an abnormal feature easily discernible from a plain chest radiograph. This cardiac malposition may be due to cardiac displacement (dextroposition), which is usually a feature of lung disease, or a structural abnormality of the heart (dextrocardia). Because each condition has different clinical pathologic implications, it is important to distinguish them. Chest films, however, often provide no conclusive information. We performed radionuclide angiocardiography (RNA) in six adults with a cardiac malposition in situs solitus. It was found that morphologic data obtained from the serial images may distinguish dextroposition from dextrocardia. In addition, these images permitted us to diagnose congenitally corrected transposition, a cardiac anomaly which occurs with increased frequency in situs solitus with dextrocardia. Quantitative shunt detection performed during this procedure is helpful in the differential diagnosis of dextroposition and able to distinguish uncomplicated dextrocardia from dextrocardia associated with other cardiac abnormalities. RNA therefore is a valuable and easily performed method in the analysis of cardiac malpositions in adults.

  10. 肿瘤核素靶向治疗的研究进展%Research progess on treatment of cancer with targeted radionuclide therapy

    Institute of Scientific and Technical Information of China (English)

    罗佳文; 张彩霞

    2008-01-01

    对近年来肿瘤核素靶向治疗的现状及进展进行了论述,包括放射免疫治疗、受体介导的靶向治疗、基因靶向治疗及化疗药物联合核素治疗四个大类,侧重介绍了这些治疗方法的常用标记载体的应用研究.同时,突出介绍了吲哚美辛的最新研究进展,并展望该药与核素靶向治疗联合应用的潜在研究价值.%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.

  11. The role of patient-based treatment planning in peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hardiansyah, Deni; Attarwala, Ali Asgar [Heidelberg University, Medical Radiation Physics/Radiation Protection, Universitaetsmedizin Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Universitaetsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Department of Radiation Oncology, Mannheim (Germany); Maass, Christian; Glatting, Gerhard [Heidelberg University, Medical Radiation Physics/Radiation Protection, Universitaetsmedizin Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Mueller, Berthold [University Hospital, RWTH Aachen University, Klinik fuer Nuklearmedizin, Aachen (Germany); Kletting, Peter [Universitaet Ulm, Klinik fuer Nuklearmedizin, Ulm (Germany); Mottaghy, Felix M. [University Hospital, RWTH Aachen University, Klinik fuer Nuklearmedizin, Aachen (Germany); Maastricht University Medical Center (MUMC+), Department of Nuclear Medicine, Maastricht (Netherlands)

    2016-05-15

    Accurate treatment planning is recommended in peptide-receptor radionuclide therapy (PRRT) to minimize the toxicity to organs at risk while maximizing tumor cell sterilization. The aim of this study was to quantify the effect of different degrees of individualization on the prediction accuracy of individual therapeutic biodistributions in patients with neuroendocrine tumors (NETs). A recently developed physiologically based pharmacokinetic (PBPK) model was fitted to the biokinetic data of 15 patients with NETs after pre-therapeutic injection of {sup 111}In-DTPAOC. Mathematical phantom patients (MPP) were defined using the assumed true (true MPP), mean (MPP 1A) and median (MPP 1B) parameter values of the patient group. Alterations of the degree of individualization were introduced to both mean and median patients by including patient-specific information as a priori knowledge: physical parameters and hematocrit (MPP 2A/2B). Successively, measurable individual biokinetic parameters were added: tumor volume V{sub tu} (MPP 3A/3B), glomerular filtration rate GFR (MPP 4A/4B), and tumor perfusion f{sub tu} (MPP 5A/5B). Furthermore, parameters of MPP 5A/5B and a simulated {sup 68}Ga-DOTATATE PET measurement 60 min p.i. were used together with the population values used as Bayesian parameters (MPP 6A/6B). Therapeutic biodistributions were simulated assuming an infusion of {sup 90}Y-DOTATATE (3.3 GBq) over 30 min to all MPPs. Time-integrated activity coefficients were predicted for all MPPs and compared to the true MPPs for each patient in tumor, kidneys, spleen, liver, remainder, and whole body to obtain the relative differences RD. The large RD values of MPP 1A [RD{sub tumor} = (625 ± 1266)%, RD{sub kidneys} = (11 ± 38)% ], and MPP 1B [RD{sub tumor} = (197 ± 505)%, RD{sub kidneys} = (11 ± 39)% ] demonstrate that individual treatment planning is needed due to large physiological differences between patients. Although addition of individual patient parameters reduced the

  12. Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry.

    Science.gov (United States)

    Baechler, Sébastien; Hobbs, Robert F; Prideaux, Andrew R; Wahl, Richard L; Sgouros, George

    2008-03-01

    In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high alpha/beta), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the

  13. Tumor Immunotargeting Using Innovative Radionuclides

    Directory of Open Access Journals (Sweden)

    Françoise Kraeber-Bodéré

    2015-02-01

    Full Text Available This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

  14. Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90 microspheres for unresectable primary and metastatic liver tumors

    Directory of Open Access Journals (Sweden)

    Ozkan Elgin

    2011-08-01

    Full Text Available Abstract Background The aim of this study was to evaluate the success of selective intraarterial radionuclide therapy (SIRT with Yttrium-90 (Y-90 microspheres in liver metastases of different tumors. We also interpreted the contribution of SIRT to survival times according to responder- non responder and hepatic- extra hepatic disease. Methods The clinical and follow-up data of 124 patients who were referred to our department for SIRT between June 2006 and October 2010 were evaluated retrospectively. SIRT has been applied to 78 patients who were suitable for treatment. All the patients had primary liver tumor or unresectable liver metastasis of different malignancies. The treatment was repeated at least one more time in 5 patients to the same or other lobes. Metabolic treatment response evaluated by fluorine-18 fluorodeoxyglucose (F18-FDG positron emission tomography/computed tomography (PET/CT in the 6th week after treatment. F18-FDG PET/CT was repeated in per six weeks periods. The response criterion had been described as at least 20% decrease of SUV value. Also in patients with neuroendocrine tumor serial Gallium-68 (Ga-68 PET/CT was used for evaluation of response. Patients were divided into 2 groups according to their treatment response. Results 68 patients received treatment for the right lobe, seven patients received treatment for the left lobe and 3 patients for both lobes. The mean treatment dose was estimated at 1.62 GBq. In the evaluation of treatment response; 43(55% patients were responder (R and 35 (45% patients were non-responder (NR in the sixth week F18-FDG PET/CT. Mean pretreatment SUVmax value of R group was 11.6 and NR group was 10.7. While only 11 (31% out of 35 NR patients had H disease, 30 (69% out of 43 R patients had H disease (p Conclusions SIRT is a useful treatment method which can contribute to the lengthening of survival times in patients with primary or metastatic unresectable liver malignancies. Also F18-FDG PET

  15. Validation of an amino-acid-based radionuclide therapy plus external beam radiotherapy in heterotopic glioblastoma models

    Energy Technology Data Exchange (ETDEWEB)

    Israel, Ina [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany); Blass, Georg [Department of Radiotherapy and Radiooncology, Saarland University Medical Center, Homburg (Germany); Reiners, Christoph [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany); Samnick, Samuel, E-mail: samnick_s@klinik.uni-wuerzburg.d [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany)

    2011-05-15

    Background and purpose: Malignant gliomas represent a major therapeutic challenge because no efficient treatment is currently available. p-[{sup 131}I]iodo-L-phenylalanine ([{sup 131}I]IPA) is a glioma avid radiopharmaceutical that demonstrated antiproliferative and tumoricidal effects in gliomas. The present study validated the therapeutic efficiency of [{sup 131}I]IPA combined with external beam radiotherapy in experimental gliomas. Materials and methods: Glioma cells derived from the primary human A1207, T5135, Tx3868 and M059K glioblastoma cell lines or rat F98 glioma cell line were treated with various doses of [{sup 131}I]IPA, external photon irradiation (RT) or combined [{sup 131}I]IPA/RT treatment. Responsiveness of glioma cells to the different therapy modalities was investigated at 24, 48 and 72 h after treatments by trypan blue, WST-1 assay, propidium iodide and bisbenzimide staining as well as by clonogenic assay. In addition, the therapy-induced DNA damage and repair were evaluated using phosphorylated histone H2AX ({gamma}-H2AX). In vivo, the effectiveness of the combination treatment was validated in human Tx3868 and A1207 glioblastoma xenografts in CD1 nu/nu mice and RNU rats. Results: In vitro, the combination treatment resulted in a greater than additive increase in cytotoxic effect in glioma cell lines. Cell survival rate following a treatment with 1.0 {mu}Ci (37 kBq) of [{sup 131}I]IPA amounted to 70%{+-}15% and 60%{+-}10% after 48 and 72 h, respectively, and decreased under 20% after additional RT with 5 Gy. At higher RT doses, cell survival rate decreased below 5%. As a measure of DNA double-strand break, nuclear {gamma}-H2AX foci were determined as a function of time. Within 24 h, the number of {gamma}-H2AX foci per cell was significantly greater after combined modality compared with the individual treatments. In vivo, when combined with RT, the radionuclide therapy with [{sup 131}I]IPA resulted in an extended tumor growth delay, a reduction

  16. Clinical Application of Photodynamic Therapy

    Institute of Scientific and Technical Information of China (English)

    LIU Hui-long; LIU Duan-qi

    2005-01-01

    Photodynamic therapy(PDT) is a new medical technology, the study on photodynamic therapy was in full swing in the past two decade. Scientists have made great progress in it. Photosensitizer,oxygen and light source play important role in photodynamic therapy.PDT is a light activated chemotherapy. A photon is adsorbed by a photosensitizer which moves the drug into an excited state. The excited drug can then pass its energy to oxygen to create a chemical radical called "singlet oxygen". Singlet oxygen attacks cellular structures by oxidation. Such oxidative damage might be oxidation of cell membranes or proteins. When the accumulation of oxidative damage exceeds a threshold level,the cell begins to die.Photodynamic therapy allows selective treatment of localized cancer. PDT involves administration of a photosensitizer to the patients, followed by delivery of light to the cancerous region. The light activates the agent which kills the cancer cells. Without light,the agent is harmless.As a new therapy,photodynamic Therapy has great Advantage in treating cancers. 1. PDT avoids systemic treatment. The treatment occurs only where light is delivered, hence the patient does not undergo go needless systemic treatment when treating localized disease. Side-effects are avoided, from losing hair or suffering nausea to more serious complications. 2. PDT is selective. The photosensitizing agent will selectively accumulate in cancer cells and not in surrounding normal tissues.Hence ,there is selective targeting of the cancer and sparing of surrounding tissues.3. when surgery is not possible. PDT kills cancer cells but does not damage collagenous tissue structures,and normal cells will repopulate these structures. Hence,if a patient has cancer in a structure that cannot be removed surgically(eg. ,the upper bronchi of the lung) ,PDT can still treat the site. 4. PDT is repeatable. Unilke radiation therapy, PDT can be used again and again. Hence,it offers a means of longterm management

  17. CLINICAL APPLICATION OF ACUPUNCTURE THERAPY

    Institute of Scientific and Technical Information of China (English)

    张玉倩; 李云芳; 王廷华

    2004-01-01

    In the present paper, the authors review some major effects of acupuncture in the treatment of clinical diseases and sum up some results of experimental researches on the mechanisms of acupuncture. Up to now, clinical practice and experimental researches demonstrate that acupuncture possesses good analgesic effect, integrative regulation effect on the functional activities of the body and defense-immune-potentiation effect.

  18. Ozone therapy: A clinical review

    OpenAIRE

    Elvis, A. M.; Ekta, J. S.

    2011-01-01

    Ozone (O3) gas discovered in the mid-nineteenth century is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. Although O3 has dangerous effects, yet researchers believe it has many therapeutic effects. Ozone therapy has been utilized and heavily studied for more than a century. Its effects are proven, consistent, safe and with minimal and preventable side effects. Medical O3 is used to disinfect and treat disease. Mechan...

  19. Chemo-radionuclide therapy for thyroid cancer. Initial experimental study with cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Misaki, Takashi; Iwata, Masahiro; Iida, Yasuhiro; Kasagi, Kanji; Konishi, Junji [Kyoto Univ. (Japan). Graduate School of Medicine

    2002-09-01

    Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initial in vitro evaluation with 4 thyroid cancer cell lines. Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity. Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 {mu}g/ml for CDDP, 0.3 {mu}g/ml for Dox, and 3 {mu}g/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4-14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone. In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible. (author)

  20. Designing for Anxiety Therapy, Bridging Clinical and Non-Clinical

    DEFF Research Database (Denmark)

    Bertelsen, Olav Wedege; Kramp, Gunnar

    2012-01-01

    In this position paper we discuss, in terms of the concept of boundary objects, how a mobile application, the MIKAT.app, bridge between clinical intervention in anxiety therapy, and life and coping strategies outside the clinic and across phases of being a person suffering from, or having suffered...

  1. Prostate specific membrane antigen- a target for imaging and therapy with radionuclides

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Choyke, Peter L; Capala, Jacek

    2010-01-01

    Prostate cancer continues to represent a major health problem, and yet there is no effective treatment available for advanced metastatic disease. Thus, there is an urgent need for the development of more effective treatment modalities that could improve the outcome. Because prostate specific...... membrane antigen (PSMA), a transmembrane protein, is expressed by virtually all prostate cancers, and its expression is further increased in poorly differentiated, metastatic, and hormone-refractory carcinomas, it is a very attractive target. Molecules targeting PSMA can be labelled with radionuclides...... to become both diagnostic and/or therapeutic agents. The use of PSMA binding agents, labelled with diagnostic and therapeutic radio-isotopes, opens up the potential for a new era of personalized management of metastatic prostate cancer....

  2. Clinical adenoviral gene therapy for prostate cancer.

    Science.gov (United States)

    Schenk, Ellen; Essand, Magnus; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Danielsson, Angelika; Dautzenberg, Iris J C; Dzojic, Helena; Erbacher, Patrick; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Hoeben, Rob; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Lindholm, Leif; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nilsson, Berith; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schooten, Erik; Seymour, Len; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; Veldhoven-Zweistra, Joke L M; de Vrij, Jeroen; van Weerden, Wytske; Wagner, Ernst; Willemsen, Ralph

    2010-07-01

    Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.

  3. Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

    Science.gov (United States)

    Severi, Stefano; Grassi, Ilaria; Nicolini, Silvia; Sansovini, Maddalena; Bongiovanni, Alberto; Paganelli, Giovanni

    2017-01-01

    Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided. PMID:28203088

  4. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  5. Radionuclide synovectomy - essentials for rheumatologists.

    Science.gov (United States)

    Chojnowski, Marek M; Felis-Giemza, Anna; Kobylecka, Małgorzata

    2016-01-01

    Radionuclide synovectomy is a minimally invasive method of treating persistent joint inflammation. It involves intra-articular injection of radioactive colloids which induce necrosis and fibrosis of hypertrophic synovial membrane. The most common indication for radiosynovectomy is rheumatoid arthritis, although patients with seronegative spondyloarthropathies, unclassified arthritis, haemophilic arthropathy and other less common arthropathies can also benefit from this method. Radiosynovectomy is safe, well tolerated and efficacious. About 70-80% of patients respond well to the therapy. However, the therapeutic effects are considerably worse in patients with co-existent osteoarthritis and advanced joint degeneration. Despite its advantages, radionuclide synovectomy is not performed as often as it could be, so greater knowledge and understanding of this method are needed. The authors present the most important facts about radiosynovectomy that may help rheumatologists in their daily clinical practice.

  6. Ion beam therapy fundamentals, technology, clinical applications

    CERN Document Server

    2012-01-01

    The book provides a detailed, up-to-date account of the basics, the technology, and the clinical use of ion beams for radiation therapy. Theoretical background, technical components, and patient treatment schemes are delineated by the leading experts that helped to develop this field from a research niche to its current highly sophisticated and powerful clinical treatment level used to the benefit of cancer patients worldwide. Rather than being a side-by-side collection of articles, this book consists of related chapters. It is a common achievement by 76 experts from around the world. Their expertise reflects the diversity of the field with radiation therapy, medical and accelerator physics, radiobiology, computer science, engineering, and health economics. The book addresses a similarly broad audience ranging from professionals that need to know more about this novel treatment modality or consider to enter the field of ion beam therapy as a researcher. However, it is also written for the interested public an...

  7. Documenting Clinical Events in Adventure Therapy.

    Science.gov (United States)

    Gray, Sky; Yerkes, Rita

    1995-01-01

    Stresses the need for documenting the application and outcomes of specific adventure activities with specific client groups and documenting critical therapeutic/clinical incidents in adventure therapy programs. Overviews current trends in documentation of therapeutic adventure programs and provides recommendations from the medical and mental…

  8. Development of Reagents for Application of At-211 to Targeted Radionuclide Therapy of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, D. Scott

    2011-12-23

    This grant covered only a period of 4 months as the major portion of the award was returned to DOE due to an award of funding from NIH that covered the same research objectives. A letter regarding the termination of the research is attached as the last page of the Final Report. The research conducted was limited due to the short period of this grant, but the results obtained in that period are outlined in the Final Report. The studies addressed in the research effort were directed at a problem that is of critical importance to the in vivo application of the alpha-particle emitting radionuclide At-211. That problem, low in vivo stability of many astatinated molecules, severely limits the use of At-211 in therapeutic applications. The advances sought in the studies were expected to expand the types of biomolecules that can be used as carriers of At-211, and provide improved in vivo targeting of the radiation dose compared with the dose delivered to normal tissue.

  9. Radionuclide cystogram

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003832.htm Radionuclide cystogram To use the sharing features on this page, please enable JavaScript. A radionuclide cystogram is a special imaging test called a nuclear ...

  10. Clinical application of radionuclide cardiac study to the right heart diseases

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Tatsuro; Ozaki, Masaharu; Ikezono, Tohru (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1984-12-01

    We experienced the four cases of rare right heart diseases: those are two-chambered right ventricle, ball thrombus in right ventricle, right ventricular hypertrophy and tricuspid valve regurgitation due to multiple pulmonary infarction, and right ventricular and right atrial infarction. The preoperative or ante mortem diagnosis of these diseases is difficult, especially by use of a noninvasive technique. This report shows the usefulness of radionuclide cardiac study for diagnosis of these cases. In the two-chambered right ventricle, abnormal muscle bundle was visualized by /sup 201/TlCl and was observed as the filling defect by sup(99m)Tc-HSA radionuclide angiography. The ball thrombus showed the filling defect of sup(99m)Tc-HSA in the right ventricle but was not extracted by /sup 201/TlCl in the site of the defect area. In the multiple pulmonary infarction, the right ventricular free wall was visualized by /sup 201/TlCl, and during right ventricular systole, regurgitation from right atrium to inferior vena cava was noticed by means of sup(99m)Tc-HSA radionuclide angiography. These findings suggested right ventricular hypertrophy and tricuspid valve regurgitation. In the right ventricular and right atrial infarction, right ventricular ejection fraction and right atrial fractional emptying were lower than those of normal controls.

  11. Application of 212Pb for Targeted α-particle Therapy (TAT: Pre-clinical and Mechanistic Understanding through to Clinical Translation

    Directory of Open Access Journals (Sweden)

    Kwon Yong

    2015-08-01

    Full Text Available Targeted α-particle therapy (TAT, in which an α-particle emitting radionuclide is specifically directed to a biological target, is gaining more attention to treat cancers as new targets are validated. Bio-vectors such as monoclonal antibodies are able to selectively transport α-particles to destroy targeted cancer cells. TAT has the potential for an improved therapeutic ratio over β-particle targeted conjugate therapy. The short path length and the intense ionization path generated render α-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking. 212Pb is the longer-lived parent radionuclide of 212Bi and serves as an in vivo generator of 212Bi. 212Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of 212Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of 212Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of 212Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer.

  12. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy

    Directory of Open Access Journals (Sweden)

    Gann Ting

    2010-01-01

    Full Text Available Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, α-, β-, and γ-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients.

  13. Effect of interferon therapy on radionuclide imaging in chronic liver diseases due to HCV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ghaffar, Y.; Dorgham, L.; Lotfy, N. [Ain Shams Univ., Imbaba, Giza (Egypt)]|[Menofia Unif., Shebin El Kom (Egypt)] [and others

    1995-09-01

    Interferon (alpha-IFN) exerts a modulating effect on the immune system. Kupffer cells of the liver play an important immunological role by their uptake of various agents and particles, including colloids. We sought to discover if alpha-IFN could enhance the colloid uptake function of the Kupffer cells. The effect of alpha-IFN therapy on radioisotope scans of the liver was studied in 20 patients with chronic liver disease due to hepatitic C virus (HCV) infection who received therapy at a dose of 3 million IU for 6 mo, in another patients who received the same therapy for 12 mo and in matched control groups (10 patients with HCV infection for each study group) who did not received alpha-IFN. A {sup 99m}Tc-sulfur colloid scan of the liver was obtained for each group before and after therapy and, for control subjects, at the start and end of the study periods. The liver-to-spleen geometric mean ratio of colloid uptake was assessed. In the first study group, the mean rate of improvement in the liver-to-spleen ratio was 48% in 70% of the patients, compared to 8% in 20% of controls (p<0.05). In the second study group, mean liver-to-spleen ratio was 88% in 85% of patients, compared to 12% in 40% of controls (p<0.001). Alpha-IFN therapy appears to enhance the colloidal uptake function of Kupffer cells, which adds a new dimension to the immunomodulatory effect of interferon. 13 refs., 2 tabs.

  14. Huntington's disease: clinical characteristics, pathogenesis and therapies.

    Science.gov (United States)

    Nakamura, Ken; Aminoff, Michael J

    2007-02-01

    Huntington's disease is a devastating disorder with no known cure. The disease results from an expanded sequence of CAG repeats in the huntingtin gene and leads to a movement disorder with associated cognitive and systemic deficits. Huntington's disease is diagnosed by genetic testing and disease progression can be followed with a variety of imaging modalities. The accumulation of aggregated huntingtin with associated striatal degeneration is evident at autopsy. The pathophysiology of Huntington's disease remains unknown, although protein aggregation, excitotoxicity, deficits in energy metabolism, transcriptional dysregulation and apoptosis may all be involved. Current pharmacologic therapy for Huntington's disease is limited and exclusively symptomatic. However, the disease is being heavily researched, and a wide range of disease-modifying therapies is currently under development. The efficacy of these therapies is being evaluated in transgenic models of Huntington's disease and in preliminary clinical trials.

  15. Clinical concepts for regenerative therapy in furcations.

    Science.gov (United States)

    Sanz, Mariano; Jepsen, Karin; Eickholz, Peter; Jepsen, Søren

    2015-06-01

    Furcation involvements present one of the greatest challenges in periodontal therapy because furcation-involved molar teeth respond less favorably to conventional periodontal therapy compared with noninvolved molar or nonmolar teeth. Various regenerative procedures have been proposed and applied with the aim of eliminating the furcation defect or reducing the furcation depth. An abundance of studies and several systematic reviews have established the effectiveness of membrane therapy (guided tissue regeneration) for buccal Class II furcation involvement of mandibular and maxillary molars compared with open flap surgery. Bone grafts/substitutes may enhance the results of guided tissue regeneration. However, complete furcation closure is not a predictable outcome. Limited data and no meta-analyses are available on the effects of enamel matrix proteins for furcation regeneration. Enamel matrix protein therapy has demonstrated clinical improvements in the treatment of buccal Class II furcation defects in mandibular molars; however, complete closure of the furcation lesion is achieved only in a minority of cases. Neither guided tissue regeneration nor enamel matrix protein therapy have demonstrated predictable results for approximal Class II and for Class III furcations. Promising preclinical data from furcation regeneration studies in experimental animals is available for growth factor- and differentiation factor-based technologies, but very limited data are available from human clinical studies. Although cell-based therapies have received considerable attention in regenerative medicine, their experimental evaluation in the treatment of periodontal furcation lesions is at a very early stage of development. In summary, the indications and the limitations for currently available treatment modalities for furcation defects are well established. New regenerative treatments are clearly needed to improve the predictability of a complete resolution of furcation defects.

  16. The prognostic influence of the proliferative discordance in metastatic pancreatic neuroendocrine carcinoma revealed by peptide receptor radionuclide therapy

    Science.gov (United States)

    Montanier, Nathanaëlle; Joubert-Zakeyh, Juliette; Pétorin, Caroline; Montoriol, Pierre François; Maqdasy, Salwan; Kelly, Antony

    2017-01-01

    Abstract Rationale: Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors. Diagnoses and interventions: We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (177Lu DOTATATE). Outcomes: Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%–70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2. Lessons: This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy. PMID:28178157

  17. Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with 68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Wolfgang Luboldt

    2010-11-01

    Full Text Available The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs during the course of somatostatin receptor radionuclide therapy (SRRT. In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax of normal liver and hepatic metastases were calculated. In addition, the volumes of hepatic metastases (volume of interest [VOI] were measured using four cut-offs to separate normal liver tissue from metastases (SUVmax of the normal liver plus 10% [VOIliver+10%], 20% [VOIliver+20%], 30% [VOIliver+30%] and SUV = 10 [VOI10SUV]. The SUVmaxof the normal liver was below 10 (7.2 ± 1.3 in all patients and without significant changes. Overall therapy changes (Δ per patient (mean [95% CI] were statistically significant with p < .01 for ΔCgA = −43 (−69 to −17, ΔSUVmax = −22 (−29 to −14, and ΔVOI10SUV = −53 (−68 to −38% and significant with p < .05 for ΔVOIliver+10% = −29 (−55 to −3%, ΔVOIliver+20% = −32 (−62 to −2 and ΔVOIliver+30% = −37 (−66 to −8. Correlations were found only between ΔCgA and ΔVOI10SUV (r = .595; p < .01, ΔSUVmax and ΔVOI10SUV (0.629, p < .01, and SUVmax and ΔSUVmax (r = .446; p < .05. 68Ga-DOTATOC PET/CT allows volumetric therapy monitoring via an SUV-based cut-off separating hepatic metastases from normal liver tissue (10 SUV recommended.

  18. Personalization of prostate cancer prevention and therapy: are clinically qualified biomarkers in the horizon?

    Directory of Open Access Journals (Sweden)

    Yap Timothy A

    2012-01-01

    Full Text Available Abstract Prostate cancer remains the most common malignancy among men and the second leading cause of male cancer-related mortality. Death from this disease is invariably due to resistance to androgen deprivation therapy. Our improved understanding of the biology of prostate cancer has heralded a new era in molecular anticancer drug development, with multiple novel anticancer drugs for castration resistant prostate cancer now entering the clinic. These include the taxane cabazitaxel, the vaccine sipuleucel-T, the CYP17 inhibitor abiraterone, the novel androgen receptor antagonist MDV-3100 and the radionuclide alpharadin. The management and therapeutic landscape of prostate cancer has now been transformed with this growing armamentarium of effective antitumor agents. This review discusses strategies for the prevention and personalization of prostate cancer therapy, with a focus on the development of predictive and intermediate endpoint biomarkers, as well as novel clinical trial designs that will be crucial for the optimal development of such anticancer therapeutics.

  19. Differences among Monte Carlo codes in the calculations of voxel S values for radionuclide targeted therapy and analysis of their impact on absorbed dose evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Pacilio, M.; Lanconelli, N.; Lo Meo, S.; Betti, M.; Montani, L.; Torres Aroche, L. A.; Coca Perez, M. A. [Department of Medical Physics, Azienda Ospedaliera S. Camillo Forlanini, Piazza Forlanini 1, Rome 00151 (Italy); Department of Physics, Alma Mater Studiorum University of Bologna, Viale Berti-Pichat 6/2, Bologna 40127 (Italy); Department of Medical Physics, Azienda Ospedaliera S. Camillo Forlanini, Piazza Forlanini 1, Rome 00151 (Italy); Department of Medical Physics, Azienda Ospedaliera Sant' Andrea, Via di Grotarossa 1035, Rome 00189 (Italy); Department of Medical Physics, Center for Clinical Researches, Calle 34 North 4501, Havana 11300 (Cuba)

    2009-05-15

    Several updated Monte Carlo (MC) codes are available to perform calculations of voxel S values for radionuclide targeted therapy. The aim of this work is to analyze the differences in the calculations obtained by different MC codes and their impact on absorbed dose evaluations performed by voxel dosimetry. Voxel S values for monoenergetic sources (electrons and photons) and different radionuclides ({sup 90}Y, {sup 131}I, and {sup 188}Re) were calculated. Simulations were performed in soft tissue. Three general-purpose MC codes were employed for simulating radiation transport: MCNP4C, EGSnrc, and GEANT4. The data published by the MIRD Committee in Pamphlet No. 17, obtained with the EGS4 MC code, were also included in the comparisons. The impact of the differences (in terms of voxel S values) among the MC codes was also studied by convolution calculations of the absorbed dose in a volume of interest. For uniform activity distribution of a given radionuclide, dose calculations were performed on spherical and elliptical volumes, varying the mass from 1 to 500 g. For simulations with monochromatic sources, differences for self-irradiation voxel S values were mostly confined within 10% for both photons and electrons, but with electron energy less than 500 keV, the voxel S values referred to the first neighbor voxels showed large differences (up to 130%, with respect to EGSnrc) among the updated MC codes. For radionuclide simulations, noticeable differences arose in voxel S values, especially in the bremsstrahlung tails, or when a high contribution from electrons with energy of less than 500 keV is involved. In particular, for {sup 90}Y the updated codes showed a remarkable divergence in the bremsstrahlung region (up to about 90% in terms of voxel S values) with respect to the EGS4 code. Further, variations were observed up to about 30%, for small source-target voxel distances, when low-energy electrons cover an important part of the emission spectrum of the radionuclide

  20. Radionuclide diagnosis and therapy of neural crest tumors using iodine-131 metaiodobenzylguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A.; Voute, P.A.; de Kraker, J.; Marcuse, H.R.

    1987-03-01

    The successful application of (/sup 131/I)metaiodobenzylguanidine (MIBG) in diagnosis and therapy of pheochromocytoma has led to its use in other tumors which derive from the neural crest and potentially concentrate this radiopharmaceutical as well. In the present series, (/sup 131/)MIBG total-body scintigraphy was used for detection of neuroblastoma in 47 patients and 47 cases of other neural crest tumors. The method was found to be as reliable in neuroblastoma (sensitivity 95%, specificity 100%), as it is in pheochromocytoma. Although other neural crest tumors may concentrate (/sup 131/I)MIBG, this is not a consistent finding; however, it is useful to investigate which tumors do, as this may provide an alternative treatment modality for some patients. Although followup is still very short, preliminary results of therapeutic use of (/sup 131/I) MIBG in 21 patients indicate that this treatment modality may be effective in neuroblastoma and malignant pheochromocytoma.

  1. Occupational Therapy clinical documentation: a literature review

    Directory of Open Access Journals (Sweden)

    Carla Simon Benevides Panzeri

    2013-12-01

    Full Text Available Occupational therapy clinical documentation comprises all recorded information about a client/patient/user, from forwarding to discharge, and it may integrate the patient’s record or serve as support for the exclusive practice of occupational therapy. In Brazil, despite being a mandatory and routine practice, little scientific-technical material on the subject is available for the support of professionals. This study aimed to identify, through literature review, information for greater understanding and support to the practice of professional activity. The data were analyzed and presented according to the different themes identified, seeking common, complementary and divergent points on each theme. Twelve articles were included in the study. The information obtained addressed themes such as registration methods, perception and attitudes of professionals, communication and language, quality, and others. It was possible to achieve a preliminary approach to the subject and have an overview of aspects related to occupational therapy clinical documentation, but some segmented information and several weaknesses were found

  2. Negative pressure wound therapy: clinical utility

    Directory of Open Access Journals (Sweden)

    Sandoz H

    2015-04-01

    Full Text Available Heidi Sandoz Accelerate CIC, Mile End Hospital, London, UK Abstract: Negative pressure wound therapy (NPWT, also known as topical negative pressure therapy, has been increasingly used in health care for the management of a wide variety of wounds over the last 2–3 decades. It is an advanced therapy that can be helpful to accelerate wound healing in both acute and chronic wounds by delivering negative pressure (suction to the wound bed. More recent advancements in the application of NPWT have provided clinicians with wider choices of utilization. There are now devices available that can deliver irrigation to the wound bed, be used for closed surgical incisions, or are disposable and highly portable. Systematic reviews considering NPWT have been published previously. These usually focus on one wound group or device and fail to offer practical clinical guidance due to the scrutiny offered to the evidence via a systematic review process. Here, an overview of the history of NPWT, the varieties of device available, their wide clinical application, and the evidence to support its use are explored in a pragmatic way. Keywords: negative pressure, wound, incision, healing, pain 

  3. Cosmogenic radionuclides

    CERN Document Server

    Beer, Jürg; Von Steiger, R

    2012-01-01

    Cosmogenic radionuclides are radioactive isotopes which are produced by natural processes and distributed within the Earth system. With a holistic view of the environment the authors show in this book how cosmogenic radionuclides can be used to trace and to reconstruct the history of a large variety of processes. They discuss the way in which cosmogenic radionuclides can assist in the quantification of complex processes in the present-day environment. This book aims to demonstrate to the reader the strength of analytic tools based on cosmogenic radionuclides, their contribution to almost any f

  4. Radiation protection of staff in 111In radionuclide therapy--is the lead apron shielding effective?

    Science.gov (United States)

    Lyra, M; Charalambatou, P; Sotiropoulos, M; Diamantopoulos, S

    2011-09-01

    (111)In (Eγ = 171-245 keV, t1/2 = 2.83 d) is used for targeted therapies of endocrine tumours. An average activity of 6.3 GBq is injected into the liver by catheterisation of the hepatic artery. This procedure is time-consuming (4-5 min) and as a result, both the physicians and the technical staff involved are subjected to radiation exposure. In this research, the efficiency of the use of lead apron has been studied as far as the radiation protection of the working staff is concerned. A solution of (111)In in a cylindrical scattering phantom was used as a source. Close to the scattering phantom, an anthropomorphic male Alderson RANDO phantom was positioned. Thermoluminescent dosemeters were located in triplets on the front surface, in the exit and in various depths in the 26th slice of the RANDO phantom. The experiment was repeated by covering the RANDO phantom by a lead apron 0.25 mm Pb equivalent. The unshielded dose rates and the shielded photon dose rates were measured. Calculations of dose rates by Monte Carlo N-particle transport code were compared with this study's measurements. A significant reduction of 65 % on surface dose was observed when using lead apron. A decrease of 30 % in the mean absorbed dose among the different depths of the 26th slice of the RANDO phantom has also been noticed. An accurate correlation of the experimental results with Monte Carlo simulation has been achieved.

  5. COMBINATION THERAPY FOR PROSTATE CANCER: CLINICAL OBSERVATIONS

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-08-01

    Full Text Available Prostate cancer (PC is one of the urgent problems of modern urological oncology. The incidence of this pathology is steadily growing worldwide. Despite the fact that PSA diagnosis is extensively used and programs for the early detection of this disease are introduced, the rate of dia gnosis of advanced PC forms remains high. Furthermore, a number of aspects of therapy for this disease remain controversial so far. The 7 th Congress of the Russian Society of Urological Oncologists, which dealt with some issues of combination therapy for locally advanced PC, was held in Moscow in October 3 to 5, 2012. The paper covers a number of controversial issues in the management of patients with PC in different clinical situations.

  6. Synthesis of Poly[APMA]-DOTA-64Cu Conjugates for Interventional Radionuclide Therapy of Prostate Cancer: Assessment of Intratumoral Retention by Micro–Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Jianchao Yuan

    2007-01-01

    Full Text Available To develop new radiopharmaceuticals for interventional radionuclide therapy of locally recurrent prostate cancer, poly[N-(3-aminopropylmethacrylamide] [poly(APMA] polymers were synthesized by free radical precipitation polymerization in acetonedimethylsulfoxide using N,N‘-azobis(isobutyronitrile as the initiator. The polymers were characterized with nuclear magnetic resonance, size exclusion chromatography, and dynamic light scattering (Mn 5 2.40 × 104, Mw/Mn = 1.87. Subsequently, poly[APMA] was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA using 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride as an activator, followed by conjugation with 64Cu radionuclide. Prolonged retention of poly[APMA]-DOTA-64Cu conjugates within the tumor tissues was demonstrated by micro–positron emission tomography at 24 hours following intra-tumoral injection of the conjugates to human prostate xenografts in mice. The data suggest that the poly[APMA]-DOTA-64Cu conjugates might be useful for interventional radionuclide therapy of locally recurrent prostate cancer in humans.

  7. Selective intraarterial radionuclide therapy with yttrium-90 (Y-90 microspheres for hepatic neuroendocrine metastases: Initial experience at a single center

    Directory of Open Access Journals (Sweden)

    Arslan Nuri

    2011-01-01

    Full Text Available Background/Aim. Selective intraarterial radionuclide therapy (SIRT with Yttrium-90 (Y-90 microspheres is also known as radioembolization and delivers high doses of radiation to hepatic tumors with minimum healthy liver exposure. The aim of this study was to present our preliminary experience in the role of liver directed radiotherapy with Y-90 microspheres for the treatment of unresectable hepatic metastases from neuroendocrine tumors (NET. Methods. The results of SIRT in 10 patients (5 males, 5 females; mean age 48.7 years; age range 24-73 years with metastatic liver disease from NETs during the period from April 2008 through August 2010 were reviewed. All patients had meticulous pre- and post-imaging studies as a part of their work-up procedure, as well as serologic tests of liver function to determine the extent of liver function damage. The patients who were eligible for SIRT had pretreatment visceral angiography to define and occlude non-target arteries. Results. The mean ± SD administered SIR-Spheres® activity was 1.49 ± 0.42 GBq (range 0.72-2.21 GBq in all the patients. These treatments delivered a dose of 99.73 ± 66.36 Gy (range 49- 420.8 Gy to the target tumors. The estimated dose to the lungs and normal liver was 4.45 ± 1.95 Gy (range 2.4-8.5 Gy and 26.73 ± 14.19 Gy (range 5-58.9 Gy, respectively. Overall response rate of 90% and patient tolerance was satisfactory for most patients. Conclusion. From our limited experience, we can conclude that SIRT with Y-90 microspheres is a safe and efficacious treatment option for patients with liver metastasis of NET without any serious side effects.

  8. A novel {sup 125}I-labeled daunorubicin derivative for radionuclide-based cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ickenstein, Ludger M. [Department of Physical and Analytical Chemistry, Uppsala University, P.O. Box 579, 75121 Uppsala (Sweden); Edwards, Katarina [Department of Physical and Analytical Chemistry, Uppsala University, P.O. Box 579, 75121 Uppsala (Sweden); Sjoeberg, Stefan [Department of Biochemistry and Organic Chemistry, Uppsala University, P.O. Box 576, 75123 Uppsala (Sweden); Carlsson, Joergen [Rudbeck Laboratory, Division of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, 75185 Uppsala (Sweden); Gedda, Lars [Rudbeck Laboratory, Division of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, 75185 Uppsala (Sweden) and Rudbeck Laboratory, Division of Experimental Urology, Department of Surgery, Uppsala University, 75185 Uppsala (Sweden)]. E-mail: lars.gedda@bms.uu.se

    2006-08-15

    Introduction: Auger electron emitters, such as {sup 125}I, are getting increasingly wider recognition as alternatives to current anticancer treatments. The effectiveness of Auger electrons is strongly dependent on their proximity to DNA and is therefore considered as harmless outside the nucleus. Methods: {sup 125}I or {sup 127}I was conjugated with Comp1, Comp2 or Comp3 - three derivatives of the chemotherapeutic drug daunorubicin. Their capacity factors, DNA-binding constants and exclusion parameters, and the degree of DNA fragmentation after incubating isolated DNA with our {sup 127}I- or {sup 125}I-conjugated daunorubicin derivatives were determined. Human breast adenocarcinoma (SK-BR-3) cells were incubated with the derivatives; fluorescent microscopy and autoradiography images were generated; and cell growth was monitored. Results and Discussion: The capacity factor of {sup 127}I-Comp1 was similar to those of daunorubicin and doxorubicin, whereas lower capacity factors of {sup 127}I-Comp2 and {sup 127}I-Comp3 suggested reduced interactions with lipid membranes. DNA exclusion parameters and binding constants of {sup 127}I-Comp1 and {sup 127}I-Comp2, but not of {sup 127}I-Comp3, were similar to those of doxorubicin. Fluorescent microscopy and autoradiography images of SK-BR-3 cells revealed that {sup 127}I-Comp1 and {sup 125}I-Comp1 accumulated in tumor cell nuclei, whereas {sup 127}I-Comp2 and {sup 127}I-Comp3 were present predominantly in other cell compartments. The binding of {sup 125}I-Comp1 to isolated chromosomal DNA led to major fragmentation. Incubation of SK-BR-3 cells with {sup 125}I-Comp1 inhibited cell growth, whereas doxorubicin or {sup 127}I-Comp1 administered at the same concentration had no effect on cell growth. Our results thus suggest that {sup 125}I-Comp1 has the potential to become a new tool for anticancer therapy.

  9. Radionuclide diagnosis of allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    George, E.A.

    1982-10-01

    Interaction with one or more anatomical and physiopathological characteristics of the rejecting renal allograft is suggested by those radioagents utilized specifically for the diagnosis of allograft rejection. Rejection, the most common cause of declining allograft function, is frequently mimicked clinically or masked by other immediate or long term post transplant complications. Understanding of the anatomical pathological features and kinetics of rejection and their modification by immunosuppressive maintenance and therapy are important for the proper clinical utilization of these radioagents. Furthermore, in selecting these radionuclides, one has to consider the comparative availability, preparatory and procedural simplicity, acquisition and display techniques and the possibility of timely report. The clinical utilities of radiofibrinogen, /sup 99m/Tc sulfur colloid and /sup 67/Ga in the diagnosis of allograft rejection have been evaluated to a variable extent in the past. The potential usefulness of the recently developed preparations of /sup 111/In labeled autologous leukocytes and platelets are presently under investigation.

  10. Preparation and use of 131I magic gel as a dosimeter for targeted radionuclide therapy.

    Science.gov (United States)

    Courbon, Frédéric; Love, Peter; Chittenden, Sarah; Flux, Glen; Ravel, Patrice; Cook, Gary

    2006-10-01

    Clinical interest in targeted radiotherapy is increasing, but accurate dosimetry studies are difficult to achieve. The aim of this study was to investigate the preparation and use of a "normoxic" polymer gel (with a tissue-equivalent density), known as MAGIC gel, and magnetic resonance imaging (MRI) for nonsealed source dosimetry. MAGIC gel samples were mixed with deionized water (MAGIC95) or a solution of 131I (131I-MAGIC95). By measuring the radioinduced variations of R2 values (relaxivity) of irradiated gels, we analyzed the response of MAGIC95 and MAGIC samples to external photon beam or 131I irradiation (131I-MAGIC95). MRI showed that a homogeneous dose distribution from 131I can be achieved if the MAGIC gel, at a temperature of approximately 35 degrees C, is mixed in 131I solution and the resulting mixture shaken gently for 30 minutes. It is important that the vials are completely filled, as residual air reduces polymerization and causes spontaneous polymerization stripes. Responses of MAGIC95 or MAGIC gels to external photon beam irradiation are similar. The variations of R2 values for 131I-MAGIC95 gel depend on the absorbed dose and not on the duration of the irradiation being reproducible from one batch of gel to another. MAGIC gel responses to 131I or external beam irradiation (EBI) are different. Our preliminary results suggest that radiolabeled "normoxic" polymer can be easily and safely produced. Radiolabeled MAGIC gel may, therefore, be suitable for the creation of phantoms dedicated to nonsealed source dosimetry.

  11. [Diagnostic validity of radionuclide phlebography in the detection of clinically occult deep venous thrombosis in patients with thromboembolism].

    Science.gov (United States)

    Markovic, S; Baskot, B; Ajdinovic, B; Pervulov, S; Gligic, B; Perovanovic, M

    2001-01-01

    Diagnostic reliability of radionuclide phlebography (RNP) compared to contrast phlebography in the detection of deep veins' thrombosis (DVT) in patients with confirmed thromboembolism of the lungs (TEL) was evaluated. RNP. These findings were compared to contrast phlebography (CP), performed in the group of 25 patients in whom TEL was confirmed clinically, radiologically, scintigraphically and biochemically, but without clinical signs and symptoms of DVT. In 15 patients where RNP revealed unilateral DVT, CP finding was confirmed in all: in 6 (40%) on the left, and in 9 (60%) on the right side. In 10 patients with bilateral signs of DVT observed by scintigraphy, DVT finding was confirmed in 7 (70%), while in 3 (30%) patients, scintigraphic signs of DVT were falsely positive. In the segments of deep venous system, specificity of RNP in the detection of DVT in the lower leg was 60%, sensitivity was 100%, accuracy was 64% with 62% falsely positive findings. In the upper legs specificity was 79%, sensitivity was 100%, and accuracy was 86% with 24% falsely positive findings, while in the pelvis specificity was 87%, sensitivity was 100%, accuracy was 83% with 14% falsely positive findings.

  12. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with {sup 177}Lu-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [Charite, University Medicine Berlin, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Berlin (Germany); Nagarajah, James [University Hospital, Department of Nuclear Medicine, Essen (Germany)

    2014-03-15

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with {sup 177}Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by {sup 99m}Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m{sup 2} per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m{sup 2} per year) and 16 patients (22 %) a significant (>10 ml/min/m{sup 2} per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m{sup 2} per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of

  13. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE: the IEO phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M.; Baio, Silvia M.; Lombardo, Dario; Chinol, Marco; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta; Ferrari, Mahila E. [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Fazio, Nicola [European Institute of Oncology, Division of Medical Oncology, Milan (Italy); Iodice, Simona [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Bartolomei, Mirco [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); M. Bufalini Hospital, Division of Nuclear Medicine, Cesena, FC (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Unit of Radiometabolic Medicine, Meldola, FC (Italy)

    2011-12-15

    Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst{sub 2}), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of {sup 177}Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst{sub 2}-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of {sup 177}Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. {sup 177}Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. (orig.)

  14. Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Latifa Rbah-Vidal

    2017-01-01

    Full Text Available PURPOSE: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound. METHODS: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT. TRT efficacy was assessed by tumor volume measurement, with mechanistics and dosimetry parameters being determined in the B16BL6 model. Intracellular localization of ICF15002 was characterized by secondary ion mass spectrometry (SIMS. RESULTS: PET imaging with [18F]ICF15002 evidenced tumoral uptake of 14.33 ± 2.11%ID/g and 4.87 ± 0.93%ID/g in pigmented B16BL6 and SK-MEL-3 models, respectively, at 1 hour post inoculation. No accumulation was observed in the unpigmented A375 melanoma. SIMS demonstrated colocalization of ICF15002 signal with melanin polymers in melanosomes of the B16BL6 tumors. TRT with two doses of 20 MBq [131I]ICF15002 delivered an absorbed dose of 102.3 Gy to B16BL6 tumors, leading to a significant tumor growth inhibition [doubling time (DT of 2.9 ± 0.5 days in treated vs 1.8 ± 0.3 in controls] and a prolonged median survival (27 days vs 21 in controls. P53S15 phosphorylation and P21 induction were associated with a G2/M blockage, suggesting mitotic catastrophe. In the human SK-MEL-3 model, three doses of 25 MBq led also to a DT increase (26.5 ± 7.8 days vs 11.0 ± 3.8 in controls and improved median survival (111 days vs 74 in controls. CONCLUSION: Results demonstrate that ICF15002 fulfills suitable properties for bimodal imaging/TRT management of patients with pigmented melanoma.

  15. uPAR Targeted Radionuclide Therapy with 177Lu-DOTA-AE105 Inhibits Dissemination of Metastatic Prostate Cancer

    DEFF Research Database (Denmark)

    Persson, Morten; Juhl, Karina; Rasmussen, Palle

    2014-01-01

    value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted 177Lu groups (p bioluminescence imaging...... with bioluminescence imaging in a cohort of animals during the treatment study. In conclusion, uPAR targeted radiotherapy resulted in a significant reduction in the number of metastatic lesions in a human metastatic prostate cancer model. Furthermore, we have provided the first evidence of the potential...

  16. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC, Department of Pathology, Rotterdam (Netherlands)

    2007-05-15

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Male Lewis rats were injected with 278 or 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of {sup 99m}Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of {sup 99m}Tc-DMSA SPECT scintigrams at 130 days after [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate therapy correlated well with 1/creatinine (r {sup 2} = 0.772, p < 0.001). Amifostine and lysine effectively decreased functional renal damage caused by high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well

  17. 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

  18. [Study and prospects for clinical diseases treated with scraping therapy].

    Science.gov (United States)

    Wang, Ying-ying; Yang, Jin-sheng

    2009-02-01

    In order to explore characteristics of clinical diseases treated by scraping therapy, summarize laws of clinical application of scraping therapy, and prospect for research direction of scraping therapy in future, collect 437 articles about scraping therapy between 1994-2007 and analyze and summarize the treated diseases and methods of scraping therapy. Results indicate that scraping therapy has been widely applied to commonly encountered diseases and frequently encountered diseases in departments of internal medicine, surgery, gynecology and pediatrics, etc. with more obvious therapeutic effects. Clinically, it can combine with acupuncture and moxibustion, cupping, massage, blood-letting puncture and other methods. In future, the studies on standardization of manipulation and standards for assessment of therapeutic effect, suitable diseases and the mechanisms of scraping therapy, and development of tools and media, etc. of scraping therapy should be strengthened.

  19. New hepatitis C therapies in clinical development

    Directory of Open Access Journals (Sweden)

    Vermehren Johannes

    2011-07-01

    Full Text Available Abstract With the current standard of care for the treatment of chronic hepatitis C, a combination of pegylated interferon alfa and ribavirin, sustained virologic response rates can be achieved in approximately 50% of patients only. Improved understanding of the viral life cycle has led to the identification of numerous potential targets for novel, direct-acting antiviral compounds. Inhibitors of the NS3/4A protease are currently the most advanced in clinical development. Recently completed phase 3 studies of the two protease inhibitors telaprevir and boceprevir, each given in combination with standard of care, yielded sustained virologic response rates in the range of 66-75% in treatment-naive patients and 59-66% in treatment-experienced patients with HCV genotype 1 infection. Studies of second-generation protease inhibitors, with the potential advantage of improved potency, drug metabolism and pharmacokinetics profile, are already underway. Inhibitors of the HCV NS5A protein and NS5B polymerase are potentially active across different HCV genotypes and have shown promising antiviral efficacy in early clinical studies. Other emerging mechanisms include silymarin components and inhibitors of cell proteins required for HCV replication. While improved formulations of current HCV therapies are also being developed, future hopes lie on the combination of direct-acting antivirals with the eventual possibility of interferon-free treatment regimens.

  20. Peptide receptor radionuclide therapy with {sup 90}Y/{sup 177}Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours)

    Energy Technology Data Exchange (ETDEWEB)

    Puranik, Ameya D.; Kulkarni, Harshad R.; Singh, Aviral; Baum, Richard P. [Zentralklinik Bad Berka, THERANOSTICS Centre for Molecular Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka (Germany)

    2015-07-15

    Head and neck paragangliomas (HNPGLs) are rare tumours arising from autonomic nervous system ganglia. Although surgery offers the best chance of complete cure, there is associated morbidity due to the crucial location of these tumours. Radiotherapy arrests tumour growth and provides symptomatic improvement, but has long-term consequences. These tumours express somatostatin receptors (SSTR) and hence peptide receptor radionuclide therapy (PRRT) is now a treatment option. We assessed the molecular, morphological and clinical responses of inoperable HNPGLs to PRRT. Nine patients with inoperable HNPGL assessed between June 2006 and June 2014 were included. Four patients had a solitary lesion, four had multifocal involvement and one had distant metastases (bone and lungs). The patients were treated with PRRT using {sup 90}Y/{sup 177}Lu-labelled peptides after positive confirmation of SSTR expression on {sup 68}Ga-DOTATOC PET/CT. All patients received two to four courses of PRRT. Subsequent serial imaging with {sup 68}Ga-DOTATOC PET/CT was carried out every 6 months to assess response to treatment. Clinical (symptomatic) response was also assessed. Based on molecular response (EORTC) criteria, four of the nine patients showed a partial molecular response to treatment seen as significant decreases in SUV{sub max}, accompanied by a reduction in tumour size. Five patients showed stable disease on both molecular and morphological criteria. Six out of nine patients were symptomatic at presentation with manifestations of cranial nerve involvement, bone destruction at the primary site and metastatic bone pain. Molecular responses were correlated with symptomatic improvement in four out of these six patients; while two patients showed small reductions in tumour size and SUV{sub max}. The three asymptomatic patients showed no new lesions or symptomatic worsening. PRRT was effective in all patients, with no disease worsening seen, either in the form of neurological symptoms or

  1. [Clinical perfectionism and cognitive behavioral therapy].

    Science.gov (United States)

    Papadomarkaki, E; Portinou, S

    2012-01-01

    The present study constitutes a brief literature overview, in which the term of clinical perfectionism, its etiopathology, its assessment and its relation to psychopathology, as well as the therapeutic interventions based on the Cognitive Behavioral Model are discussed. According to Frost, perfectionism is associated with one's desire to achieve the greatest degree of performance and it is accompanied by an extremely strict evaluation of that particular performance. The relationship with oneself as well as the relationship with others are both characterised by high standards and demands which tend to exhaust one individual and dramatically toughen the development of proximity with the others. Perfectionism, as a personality trait, presents functional and dysfunctional elements for a person. Dysfunctional, clinical perfectionism -a term recently coined by researchers- has been linked to a number of disorders, such as social phobia, obsessive-compulsive disorder, eating disorders -anorexia and bulimia nervosa- depression and personality disorders. From a perfectionist's point of view, perfection exists and its attaintment is feasible. The existence of a particularly high and often unrealistic goal can lead the person to severe disappointment when this specific goal is not finally reached. A person with functional perfectionism is possible to set another, more achievable, goal next time, while a person with clinical perfectionism will interpret this failure as a sign of personal inadequacy and will either make another attempt to reach the same goal or will abandon the effort altogether. A sense of weakness and subsequent negative automatic thoughts are the aftermath of both the first and the second choice. Cognitive Behavioral Therapy focuses on the realisation that clinical perfectionism is undesirable, on the dispute of negative automatic thoughts and on the replacement of unfunctional cognitive schemas with other, more functional ones. In the therapeutic process

  2. PLGA nanoparticles for peptide receptor radionuclide therapy of neuroendocrine tumors: a novel approach towards reduction of renal radiation dose.

    Directory of Open Access Journals (Sweden)

    Geetanjali Arora

    Full Text Available BACKGROUND: Peptide receptor radionuclide therapy (PRRT, employed for treatment of neuroendocrine tumors (NETs is based on over-expression of Somatostatin Receptors (SSTRs on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, (177Lu-DOTATATE loaded PLGA nanoparticles (NPs were formulated in the present study, as a potential therapeutic model for NETs. METHODOLOGY AND FINDINGS: DOTATATE was labeled with Lutetium-177 ((177Lu (labeling efficiency 98%; R(f∼0.8. Polyethylene Glycol (PEG coated (177Lu-DOTATATE-PLGA NPs (50:50 and 75:25 formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated and 303.8±67.2 and 494.3±71.8 nm (coated for PLGA(50:50 and PLGA(75:25 respectively. Encapsulation efficiency (EE and In-vitro release kinetics for uncoated and coated NPs of PLGA (50:50 & 75:25 were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated and 65.385±5.67% & 58.495±5.35% (coated. NPs showed initial burst release between 16.64-21.65% with total 42.83-44.79% over 21 days. The release increased with coating to 20.4-23.95% initially and 60.97-69.12% over 21 days. In-vivo studies were done in rats injected with (177Lu-DOTATATE and (177Lu-DOTATATE-NP (uncoated and PEG-coated by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With (177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated (177Lu-DOTATATE-NP. The high liver uptake with uncoated (177Lu-DOTATATE-NP (13.68±3.08% ID/g, reduced to 7.20±2.04%ID/g (p = 0.02 with PEG coating. CONCLUSION: PLGA NPs were easily formulated and modified for desired release properties. PLGA

  3. Application of a whole-body pharmacokinetic model for targeted radionuclide therapy to NM404 and FLT

    Science.gov (United States)

    Grudzinski, Joseph J.; Floberg, John M.; Mudd, Sarah R.; Jeffery, Justin J.; Peterson, Eric T.; Nomura, Alice; Burnette, Ronald R.; Tomé, Wolfgang A.; Weichert, Jamey P.; Jeraj, Robert

    2012-03-01

    We have previously developed a model that provides relative dosimetry estimates for targeted radionuclide therapy (TRT) agents. The whole-body and tumor pharmacokinetic (PK) parameters of this model can be noninvasively measured with molecular imaging, providing a means of comparing potential TRT agents. Parameter sensitivities and noise will affect the accuracy and precision of the estimated PK values and hence dosimetry estimates. The aim of this work is to apply a PK model for TRT to two agents with different magnitudes of clearance rates, NM404 and FLT, explore parameter sensitivity with respect to time and investigate the effect of noise on parameter precision and accuracy. Twenty-three tumor bearing mice were injected with a ‘slow-clearing’ agent, 124I-NM404 (n = 10), or a ‘fast-clearing’ agent, 18F-FLT (3‧-deoxy-3‧-fluorothymidine) (n = 13) and imaged via micro-PET/CT pseudo-dynamically or dynamically, respectively. Regions of interest were drawn within the heart and tumor to create time-concentration curves for blood pool and tumor. PK analysis was performed to estimate the mean and standard error of the central compartment efflux-to-influx ratio (k12/k21), central elimination rate constant (kel), and tumor influx-to-efflux ratio (k34/k43), as well as the mean and standard deviation of the dosimetry estimates. NM404 and FLT parameter estimation results were used to analyze model accuracy and parameter sensitivity. The accuracy of the experimental sampling schedule was compared to that of an optimal sampling schedule found using Cramer-Rao lower bounds theory. Accuracy was assessed using correlation coefficient, bias and standard error of the estimate normalized to the mean (SEE/mean). The PK parameter estimation of NM404 yielded a central clearance, kel (0.009 ± 0.003 h-1), normal body retention, k12/k21 (0.69 ± 0.16), tumor retention, k34/k43 (1.44 ± 0.46) and predicted dosimetry, Dtumor (3.47 ± 1.24 Gy). The PK parameter estimation of FLT

  4. Radionuclide synovectomy – essentials for rheumatologists

    Science.gov (United States)

    Felis-Giemza, Anna; Kobylecka, Małgorzata

    2016-01-01

    Radionuclide synovectomy is a minimally invasive method of treating persistent joint inflammation. It involves intra-articular injection of radioactive colloids which induce necrosis and fibrosis of hypertrophic synovial membrane. The most common indication for radiosynovectomy is rheumatoid arthritis, although patients with seronegative spondyloarthropathies, unclassified arthritis, haemophilic arthropathy and other less common arthropathies can also benefit from this method. Radiosynovectomy is safe, well tolerated and efficacious. About 70–80% of patients respond well to the therapy. However, the therapeutic effects are considerably worse in patients with co-existent osteoarthritis and advanced joint degeneration. Despite its advantages, radionuclide synovectomy is not performed as often as it could be, so greater knowledge and understanding of this method are needed. The authors present the most important facts about radiosynovectomy that may help rheumatologists in their daily clinical practice. PMID:27504020

  5. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Kidd, M. [Wren Laboratories, Branford, CT (United States); Modlin, I.M. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Yale School of Medicine, New Haven, CT (United States); Severi, S.; Nicolini, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Drozdov, I. [Bering Limited, London (United Kingdom); Kwekkeboom, D.J.; Krenning, E.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Erasmus Medical Center, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2016-05-15

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with {sup 177}Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 {sup 18}FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ{sup 2} = 27.4; p = 1.2 x 10{sup -7}) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0

  6. The efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong-Jang; Pak, Kyoungjune [Pusan National University Hospital, Department of Nuclear Medicine and Biomedical Research Institute, Busan (Korea, Republic of); Koo, Phillip J.; Kwak, Jennifer J.; Chang, Samuel [University of Colorado School of Medicine, Department of Radiology, Aurora, CO (United States)

    2015-12-15

    This study was performed to evaluate the efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of ''neuroendocrine'', ''{sup 177}Lu'' and ''prognosis''. All published studies of neuroendocrine tumours treated with {sup 177}Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8 % with a pooled effect of 29 % [95 % confidence interval (CI) 24-34 %]. Disease control rates ranged from 71.8 to 100 %. The random-effects model showed an average disease control rate of 81 % (95 % CI 71-91 %). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5 % with a pooled effect of 23 % (95 % CI 11-38 %). Disease control rates ranged from 73.9 to 89.1 %. The random-effects model showed an average disease control rate of 82 % (95 % CI 71-91 %). {sup 177}Lu-labelled PRRT is an effective treatment

  7. Clinical comparison of radionuclide cisternography and computed tomography in CSF circulatory disturbance

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, M.; Futatsuki, M. (Tazuke Kofukai Medical Research Inst., Osaka (Japan). Kitano Hospital); Tanaka, H.

    1980-12-01

    Forty-three patients with abnormal cisternograms were classified into (1) NPH, (2) Postmeningitic hydrocephalus, (3) Posttraumatic hydrocephalus, (4) Postoperative hydrocephalus (tumor) (5) Postoperative hydrocephalus (vascular disease), (6) Meningitis, (7) Tumor, (8) Vascular disease, (9) Degenerative disease and (10) Miscellaneous. Cisternography was done by a scinticamera with /sup 111/In-DTPA and all groups were scanned by IInd generation CT scanner. The result of the cisternography was not always compatible with the CT findings. We found a case of anatomically normal but functionally abnormal cisterns and ventricular system. In all classified disorder groups, the cisternography detected functioning cisterns in CSF dynamics but the CT visualized anatomically open cisterns. By the combined use of these two examinations, a local cisternal block was detected. Ten in 20 cases with operated (V-P shunt) hydrocephalus clinically improved. But the result of these techniques, failed to assess the effectiveness of the V-P shunt. V-P shunt was effective in 8 out of 14 cases with persistent ventricular reflux and delayed clearance, and in 9 out of 17 cases with total ventricular dilatation. We concluded that the combined use of the RI cisternography and the computed tomography was better than single examination to detect CSF circulatory disturbance but we were not satisfied with the joint use in the evaluation of the effect of V-P shunt. No adverse reaction was experienced in the 43 patients with /sup 111/In-DTPA.

  8. Clinical and microbiological effects of the initial periodontal therapy

    Directory of Open Access Journals (Sweden)

    Predin Tanja

    2014-01-01

    Full Text Available Introduction. Periodontitis is a destructive inflammatory disease of the tooth-supporting tissues, primarily caused by Gram-negative microorganisms. Thus, the primary objective of cause-related initial periodontal therapy is disruption and removal of the subgingival biofilm. Objective. The aim of this study was to evaluate the clinical and microbiological effects of the initial therapy in patients diagnosed with chronic periodontitis. Methods. Forty patients with chronic periodontitis were included in the study. As a part of the clinical assessment undertaken prior to the initial therapy, as well as one month and three months post-therapy, plaque index, gingival index, papilla bleeding index, probing pocket depth and clinical attachment level were recorded. Microbiological testing was performed prior to the initial therapy and three months after therapy. Polymerase chain reaction assays were used to determine the presence of Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans. Results. All clinical parameters were significantly reduced after therapy. The prevalence of Aggregatibacter actinomycetemcomitans was reduced by 22.5%, which was a statistically significant decrease compared to the baseline. The prevalence of Porphyromonas gingivalis, Tannerella forsythensis and Prevotella intermedia tended to decrease after therapy; however, the difference did not reach statistical significance. Conclusion. The results of the present study demonstrated the beneficial effects of the initial periodontal therapy on both the clinical and microbiological parameters. [Projekat Ministarstva nauke Republike Srbije, br. 175075

  9. Factors influencing radiation therapy student clinical placement satisfaction

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Pete; Carmichael, Mary-Ann [School of Clinical Sciences, Queensland University of Technology, Brisbane (Australia)

    2014-02-15

    Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning.

  10. Peptide receptor radionuclide therapy with lutetium-177 DOTATATE in a case of recurrent extradrenal retroperitoneal malignant paraganglioma with nodal and bone metastasis

    Directory of Open Access Journals (Sweden)

    Koramadai Karuppusamy Kamaleshwaran

    2015-01-01

    Full Text Available Extra-adrenal retroperitoneal paragangliomas (PGLs are rare tumors causing considerable difficulty in both, diagnosis and treatment. They can be unicentric or multicentric, tend to be locally invasive and therefore have a high incidence of local recurrence. PGLs shows somatostatin receptor positivity, which can be imaged with technetium-99m (Tc-99m-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC and can be treated with lutetium-177 (Lu-177 DOTATATE. We present a case of recurrent unresectable retroperitoneal PGL with nodal and bone metastases in a 27-year-old male, 6 months postsurgery detected with Tc-99m-HYNIC-TOC and was administered with peptide receptor radionuclide therapy using Lu-177 DOTATATE.

  11. Outcome of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Ezziddin, Samer; Khalaf, Feras; Vanezi, Maria; Haslerud, Torjan; Zreiqat, Abdullah Al; Biersack, Hans-Juergen; Sabet, Amir [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Willinek, Winfried [University Hospital, Department of Radiology, Bonn (Germany)

    2014-05-15

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with {sup 177}Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with {sup 177}Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial {sup 99m}Tc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis

  12. Postmenopausal hormone replacement therapy--clinical implications

    DEFF Research Database (Denmark)

    Ravn, S H; Rosenberg, J; Bostofte, E

    1994-01-01

    in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin....... Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke...... suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular...

  13. Antiresorptive therapies for osteoporosis: a clinical overview.

    Science.gov (United States)

    Chen, Jian Sheng; Sambrook, Philip N

    2011-09-06

    Antiresorptive therapies are used to increase bone strength in individuals with osteoporosis and include five principal classes of agents: bisphosphonates, estrogens, selective estrogen receptor modulators (SERMs), calcitonin and monoclonal antibodies such as denosumab. However, no head-to-head studies have compared different antiresorptive agents using fracture as an end point. Bisphosphonates, which have proven antifracture efficacy and a good safety profile, are the most widely used first-line antiresorptive therapy and are recommended for patients with osteoporosis, a prior fragility fracture or osteopenia, as well as individuals with a high risk of fracture. Denosumab, which also has good antifracture efficacy, is another possible first-line therapy, although long-term safety data are lacking. However, no single antiresorptive therapy is currently appropriate for all patients or clearly superior to other therapies. Antiresorptive agents such as estrogens, SERMs (in postmenopausal women) and calcitonin are considered to be second-line agents that are appropriate in special circumstances. Clinicians should determine the most appropriate pharmacological therapy after a careful assessment of the risk:benefit profiles of these drugs in each patient. In addition, patients should receive a detailed explanation of the treatment goals, so that the therapeutic benefit can be maximized through good compliance and persistence.

  14. Clinical experience of radiation therapy for Graves` ophthalmopathy

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Takeo; Mitsuhashi, Norio; Nagashima, Hisako; Sakurai, Hideyuki; Murata, Osamu; Ishizeki, Kei; Shimaya, Sanae; Hayakawa, Kazushige; Niibe, Hideo [Gunma Univ., Maebashi (Japan). School of Medicine

    1996-11-01

    The effect of radiation therapy for Graves` ophthalmopathy was evaluated. Ten patients with Graves` ophthalmopathy were treated with radiation therapy between 1992 and 1993 in Gunma University Hospital. All patients had a past history of hyperthyroidism and received 2,000 cGy to the retrobulbar tissues in 20 fractions. Nine of ten patients were treated with radiation therapy after the failure of corticosteroids. Six patients (60%) showed good or excellent responses. The exophthalmos type was more responsive to radiation therapy than the double vision type in this series. Two of five patients with the exophthalmos type demonstrated excellent responses, and their symptoms disappeared almost completely. The improvement of symptoms appeared within 3-6 months, and obvious clinical effects were demonstrated after 6 months of radiotherapy. Radiation therapy was well tolerated, and we have not observed any side effects of radiation therapy. In conclusion, radiation therapy is effective treatment for Graves` ophthalmopathy. (author)

  15. [Co-therapy in intercultural clinical psychology].

    Science.gov (United States)

    Pocreau, Jean-Bernard; Martins-Borges, Lucienne

    2013-01-01

    Numerous clinicians practicing systemic psychotherapy have recognized the relevance of co-therapy, an intervention model involving at least two clinicians. Intercultural psychology and ethnopsychiatry have been inspired by the principles of co-therapy and have adapted it to the intercultural context. Our objective is to illustrate how co-therapy works in intercultural psychology, as it has been developed by the Specialized Psychological Services for Immigrants and for Refugees (SAPSIR). This intervention model facilitates the working through processes of mourning and of identity, important issues with migrant individuals. Finally, this practice cannot be reduced to the mere application of techniques including some cultural elements; it implies a special way of being in relationship with others, with oneself and with one's knowledge.

  16. Clinical experience with electron pseudoarc therapy

    Energy Technology Data Exchange (ETDEWEB)

    McKenzie, M.R.; Freeman, C.R.; Pla, M.; Guerra, J.; Souhami, L.; Podgorsak, E.B. (McGill Univ., Montreal, PQ (Canada). Dept. of Oncology)

    1993-03-01

    Between November 1986 and June 1990, 24 patients were treated with electron pseudoarc therapy at McGill University. There were 21 females and three males aged 27 to 81 years (median 62 years). Electron pseudoarc therapy is a treatment option for selected breast carcinoma patients for palliation of extensive chest wall disease, although morbidity may be considerable. The technique may, however, play a more useful role in other situations where the superficial portion of large curved surfaces is to be treated with curative intent, such as chest wall lymphoma and sarcoma, scalp angiosarcoma, scalp lymphoma and posterior cervical soft tissue sarcoma. (Author).

  17. Cellular Therapies for Muscular Dystrophies: Frustrations and Clinical Successes.

    Science.gov (United States)

    Negroni, Elisa; Bigot, Anne; Butler-Browne, Gillian S; Trollet, Capucine; Mouly, Vincent

    2016-02-01

    Cell-based therapy for muscular dystrophies was initiated in humans after promising results obtained in murine models. Early trials failed to show substantial clinical benefit, sending researchers back to the bench, which led to the discovery of many hurdles as well as many new venues to optimize this therapeutic strategy. In this review we summarize progress in preclinical cell therapy approaches, with a special emphasis on human cells potentially attractive for human clinical trials. Future perspectives for cell therapy in skeletal muscle are discussed, including the perspective of combined therapeutic approaches.

  18. Therapy of nephrolithiasis: where is the evidence from clinical trials?

    Science.gov (United States)

    Pachaly, Maria Aparecida; Baena, Cristina Pellegrino; Carvalho, Mauricio de

    2016-03-01

    The prevalence of kidney stone disease is increasing worldwide with significant health and economic burden. Newer research is finding that stones are associated with several serious morbidities. Yet, few randomized clinical trials or high quality observational studies have assessed whether clinical interventions decrease the recurrence of kidney stones. Therefore, in this review we analyze the available evidence on medical expulsive therapy for ureteral stones; describe the evidence about non-pharmacological stone therapy including dietary modifications and citrus juice-based therapy; and discuss the efficacy of thiazide diuretics for the treatment of hypercalciuria in recurrent nephrolithiasis.

  19. The clinical applicability of music therapy research

    DEFF Research Database (Denmark)

    Wigram, Anthony Lewis

    practitioners in all three areas (and beyond) can demonstrate, through previous and current research, that the music therapy service and interventions they provide are relevant and effective (Ansdell, Pavicevic & Proctor, 2004; Gold, Voracek and Wigram, 2004; Vink, 2003; Wigram 2002). Documentation of research...

  20. Clinical Application of Vascular Regenerative Therapy for Peripheral Artery Disease

    Directory of Open Access Journals (Sweden)

    Hiroshi Suzuki

    2013-01-01

    Full Text Available Prognosis of peripheral artery disease (PAD, especially critical limb ischemia, is very poor despite the development of endovascular therapy and bypass surgery. Many patients result in leg amputation and, therefore, vascular regenerative therapy is expected in this field. Gene therapy using vascular endothelial growth factor is the first step of vascular regenerative therapy, but did not confirm effectiveness in a large-scale randomized comparative study. Based on animal experiments, bone marrow mononuclear cells (MNCs, peripheral blood MNCs were used as the cell source for regenerative therapy. Those cells were confirmed to be effective to decrease rest pain and ulcer size, but its effect was not fully satisfied. Mesenchymal stem cells (MSCs are expected as an effective cell source for vascular regeneration and clinical studies are ongoing, because the cells are able to differentiate into various cell types and produce a significant amount of vascular growth factors. Of vascular regeneration therapy, peripheral MNCs and bone marrow MNCs were recognized as advanced medical technology but do not attain to the standard therapy. However, clinical use of MSCs have already started, and induced pluripotent stem cells are surely promising tool for vascular regeneration therapy although further basic studies are required for clinical application.

  1. Clinical applications of bovine colostrum therapy

    DEFF Research Database (Denmark)

    Rathe, Mathias; Müller, Klaus; Sangild, Per Torp

    2014-01-01

    to populations, outcomes, and methodological quality, as judged by the Jadad assessment tool. Many studies used surrogate markers to study the effects of bovine colostrum. Studies suggesting clinical benefits of colostrum supplementation were generally of poor methodological quality, and results could...... not be confirmed by other investigators. Bovine colostrum may provide gastrointestinal and immunological benefits, but further studies are required before recommendations can be made for clinical application. Animal models may help researchers to better understand the mechanisms of bovine colostrum supplementation......, the dosage regimens required to obtain clinical benefits, and the optimal methods for testing these effects in humans....

  2. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  3. Clinical Studies of Biofield Therapies: Summary, Methodological Challenges, and Recommendations.

    Science.gov (United States)

    Jain, Shamini; Hammerschlag, Richard; Mills, Paul; Cohen, Lorenzo; Krieger, Richard; Vieten, Cassandra; Lutgendorf, Susan

    2015-11-01

    Biofield therapies are noninvasive therapies in which the practitioner explicitly works with a client's biofield (interacting fields of energy and information that surround living systems) to stimulate healing responses in patients. While the practice of biofield therapies has existed in Eastern and Western cultures for thousands of years, empirical research on the effectiveness of biofield therapies is still relatively nascent. In this article, we provide a summary of the state of the evidence for biofield therapies for a number of different clinical conditions. We note specific methodological issues for research in biofield therapies that need to be addressed (including practitioner-based, outcomes-based, and research design considerations), as well as provide a list of suggested next steps for biofield researchers to consider.

  4. Clinical Studies of Biofield Therapies: Summary, Methodological Challenges, and Recommendations

    Science.gov (United States)

    Hammerschlag, Richard; Mills, Paul; Cohen, Lorenzo; Krieger, Richard; Vieten, Cassandra; Lutgendorf, Susan

    2015-01-01

    Biofield therapies are noninvasive therapies in which the practitioner explicitly works with a client's biofield (interacting fields of energy and information that surround living systems) to stimulate healing responses in patients. While the practice of biofield therapies has existed in Eastern and Western cultures for thousands of years, empirical research on the effectiveness of biofield therapies is still relatively nascent. In this article, we provide a summary of the state of the evidence for biofield therapies for a number of different clinical conditions. We note specific methodological issues for research in biofield therapies that need to be addressed (including practitioner-based, outcomes-based, and research design considerations), as well as provide a list of suggested next steps for biofield researchers to consider. PMID:26665043

  5. Clinical study on radiofrequency combined with 131I therapy for dedifferentiated thyroid carcinomas%射频联合131I治疗失分化甲状腺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    Hengping Li; Qinjiang Liu; Feng Dong

    2011-01-01

    Objective: The aim of this study was to explore clinical efficiency of radio frequency combined with 131I therapy for dedifferentiated thyroid carcinoma. Methods:All patients have been treated by radiofrequency connected with 1311 in 29 cases of dedifferentiated thyroid carcinoma which performed radionuclide imaging and Ig array of blood serum before and after therapy, respectively. Results: There were 4 (4/29) positive cases of radionuclide imaging before treatment and 19 (19/29) cases 2 weeks after therapy, 25 (25/29) cases of overall efficacy and 15 (15/29) curative cases. Conclusion: Radiofrequency connected with 131I improve clinical efficacy of 131I treatment for dedifferentiated thyroid cancer of thyroid in view of higher absorbing 131I of thyroid cancerous cell.

  6. [Changing surgical therapy because of clinical studies?].

    Science.gov (United States)

    Schwenk, W; Haase, O; Müller, J M

    2002-04-01

    The randomised controlled clinical trial (RCT) is a powerful instrument to evaluate different therapeutic regimens. In a survey among 115 physicians visiting the 25th annual meeting of the Surgical Society of Berlin and Brandenburg, the RCT was judged to be very important when changes of therapeutic strategies are discussed. 90 % of all participants claimed to use data from RCTs in the clinical routine and 89 % would participate in such a trial. In official (e. g. discussions during coffee breaks at scientific meetings) or non-medical (e. g. non-scientific press or media) sources of information were assessed as irrelevant for decisions regarding therapeutic strategies. However, in contrast to this view laparoscopic cholecystectomy was introduced into clinical practice rapidly because patients informed by external (non-medical) sources preferred to be operated on with the "modern" technique. Clinical trials with a high level of evidence had no relevant influence on the rapid distribution of laparoscopic cholecystectomy. Controversial discussions concerning the extent of lymphadenectomy with gastric resection for carcinoma demonstrate that the value of excellent clinical RCTs is low if their results challenge a stable paradigma of the surgical scientific society. To allow a rational judgement, new surgical technologies should undergo a scientific gradual evaluation in agreement with the principles of evidence based medicine.

  7. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting {sup 223}Ra-dichloride

    Energy Technology Data Exchange (ETDEWEB)

    Pacilio, Massimiliano [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Medical Physics; Ventroni, Guido; Mango, Lucio [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Nuclear Medicin; De Vincentis, Giuseppe; Di Castro, Elisabetta; Frantellizzi, Viviana; Follacchio, Giulia Anna; Garkavaya, Tatiana [Rome Univ. (Italy). Dept. of Radiological, Oncological and Anatomo Pathological Sciences; Cassano, Bartolomeo; Lorenzon, Leda [Rome Univ. (Italy). Postgraduate School of Medical Physics; Pellegrini, Rosanna; Pani, Roberto [Rome Univ. (Italy). Dept. of Molecular Medicine; Ialongo, Pasquale [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Radiology

    2016-01-15

    percent uptake of {sup 99m}Tc and {sup 223}Ra (activity extrapolated to t = 0) were significantly correlated. The feasibility of in vivo quantitative imaging in {sup 223}Ra therapy was confirmed. The lesion uptake of {sup 223}Ra-dichloride was significantly correlated with that of {sup 99m}Tc-MDP. The D{sub RBE} to lesions per unit administered activity was much higher than that of other bone-seeking radiopharmaceuticals, but considering a standard administration of 21 MBq (six injections of 50 kBq/kg to a 70-kg patient), the mean cumulative value of D{sub RBE} was about 19 Gy, and was therefore in the range of those of other radiopharmaceuticals. The macrodosimetry of bone metastases in treatments with {sup 223}Ra-dichloride is feasible, but more work is needed to demonstrate its helpfulness in predicting clinical outcomes. (orig.)

  8. Gene therapy clinical trials worldwide to 2012 - an update.

    Science.gov (United States)

    Ginn, Samantha L; Alexander, Ian E; Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo

    2013-02-01

    To date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our June 2012 update, we have entries on 1843 trials undertaken in 31 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are available on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in clinical trials of gene therapy approaches around the world and discuss the prospects for the future.

  9. Current status of clinical laser applications in periodontal therapy.

    Science.gov (United States)

    Aoki, Akira; Mizutani, Koji; Takasaki, Aristeo Atsushi; Sasaki, Katia Miyuki; Nagai, Shigeyuki; Schwarz, Frank; Yoshida, Itaru; Eguro, Toru; Zeredo, Jorge Luis; Izumi, Yuichi

    2008-01-01

    Periodontal disease is a chronic inflammatory disorder caused by bacterial infection. Laser treatment demonstrates specific characteristics that may be valuable in managing periodontal disease. In addition, lasers reduce stress and uncomfortable conditions for patients during and after treatment compared to other conventional tools. This article reviews the literature to describe the current clinical applications of lasers for gingival tissue management-including esthetic treatment, non-surgical and surgical periodontal pocket therapy, osseous surgery, and implant therapy.

  10. Clinical Applications of Gene Therapy for Primary Immunodeficiencies

    OpenAIRE

    2015-01-01

    Primary immunodeficiencies (PIDs) have represented a paradigmatic model for successes and pitfalls of hematopoietic stem cells gene therapy. First clinical trials performed with gamma retroviral vectors (γ-RV) for adenosine deaminase severe combined immunodeficiency (ADA-SCID), X-linked SCID (SCID-X1), and Wiskott–Aldrich syndrome (WAS) showed that gene therapy is a valid therapeutic option in patients lacking an HLA-identical donor. No insertional mutagenesis events have been observed in mor...

  11. Clinical results of radiation therapy for thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Sasai, Keisuke; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Tsutsui, Kazushige; Fushiki, Masato

    1992-05-01

    From August 1968 to December 1989, 58 patients with thymoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiothrapy alone, 1 by preoperative radiotheapy, 43 by postoperative radiotherapy, and 3 in combination with intraoperative radiotherapy. The following points were clarified: (a) Postoperative and intraoperative radiotherapy were effective; (b) For postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy; (c) The patients with complicating myasthenia gravis had a longer survival time and better local control rate than those without it. Radiation pneumonitis was observed in 17 patients, and none of them died of this complication. In all cases in combination with intraoperative radiotherapy, dry desquamation was observed within the irradiated field. (author).

  12. [Celiac disease : Pathogenesis, clinics, epidemiology, diagnostics, therapy].

    Science.gov (United States)

    Schuppan, Detlef

    2016-07-01

    Celiac disease is induced by the consumption of gluten containing cereals (wheat, spelt, barley, rye). With a prevalence of ~ 1 %, it is the most common non-infectious chronic inflammatory intestinal disease worldwide. It manifests in all age groups, either classically with abdominal pain, diarrhoea and growth failure or weight loss, more commonly with indirect consequences of malabsorption, such as anaemia and osteoporosis, or with associated autoimmune diseases like type 1 diabetes, autoimmune thyroiditis or dermatitis herpetiformis. The pathogenesis of celiac disease is well explored. Gluten, the cereal storage protein, is not completely digested and reaches the intestinal mucosa where it activates inflammatory T cells, which cause atrophy of the resorptive villi. This T‑cell activation requires a genetic predisposition (the molecules HLA-DQ2 or -DQ8 on antigen-presenting immune cells). Moreover, the enzyme tissue transglutaminase (TG2) which is released in the mucosa increases the immunogenicity of the gluten peptides by a deamidation reaction. The test for serum antibodies to the autoantigen TG2 is one of the best diagnostic markers in medicine, which in combination with endoscopically obtained biopsies, secures the diagnosis of celiac disease. Despite these tools celiac disease is severely underdiagnosed, with 80-90 % of those affected being undetected. The untreated condition can lead to grave complications. These include the consequences of malabsorption, cancers (especially intestinal T‑cell lymphoma), and likely also the promotion of autoimmune diseases. The therapy of celiac disease, a strict gluten-free diet, is difficult to maintain and not always effective. Alternative, supporting pharmacological therapies are urgently needed and are currently in development.

  13. Liposomal anticancer therapy: pharmacokinetic and clinical aspects.

    Science.gov (United States)

    Di Paolo, A

    2004-11-01

    Liposomes, which are vesicles composed of a phospholipid bilayer surrounding an aqueous milieu, represent a new strategy for anticancer drug delivery. Extravasation and accumulation of liposomal drugs within neoplastic tissues are possible because of the leaky vasculature and scarce lymphatic vessels of tumours (the enhanced permeability and retention effect). Furthermore, liposomal chemotherapeutic agents display distinctive pharmacokinetic characteristics, because they possess longer elimination half-lives, reduced clearance and smaller volume of distribution with respect to corresponding free drugs. Taken together, these features lead to highest levels of cytotoxic agents in tumours, as demonstrated in preclinical models and clinical trials, whereas healthy tissues are spared from toxicity. In fact, liposomal drugs (i.e., doxorubicin), alone or in combination with other cytotoxic agents, lead to improved clinical effectiveness and ameliorated toxicity profile with respect to corresponding free drugs when they are used for the treatment of metastatic breast and ovarian cancers, and Kaposi's sarcoma.

  14. Clinical applications of gene therapy for primary immunodeficiencies.

    Science.gov (United States)

    Cicalese, Maria Pia; Aiuti, Alessandro

    2015-04-01

    Primary immunodeficiencies (PIDs) have represented a paradigmatic model for successes and pitfalls of hematopoietic stem cells gene therapy. First clinical trials performed with gamma retroviral vectors (γ-RV) for adenosine deaminase severe combined immunodeficiency (ADA-SCID), X-linked SCID (SCID-X1), and Wiskott-Aldrich syndrome (WAS) showed that gene therapy is a valid therapeutic option in patients lacking an HLA-identical donor. No insertional mutagenesis events have been observed in more than 40 ADA-SCID patients treated so far in the context of different clinical trials worldwide, suggesting a favorable risk-benefit ratio for this disease. On the other hand, the occurrence of insertional oncogenesis in SCID-X1, WAS, and chronic granulomatous disease (CGD) RV clinical trials prompted the development of safer vector construct based on self-inactivating (SIN) retroviral or lentiviral vectors (LVs). Here we present the recent results of LV-mediated gene therapy for WAS showing stable multilineage engraftment leading to hematological and immunological improvement, and discuss the differences with respect to the WAS RV trial. We also describe recent clinical results of SCID-X1 gene therapy with SIN γ-RV and the perspectives of targeted genome editing techniques, following early preclinical studies showing promising results in terms of specificity of gene correction. Finally, we provide an overview of the gene therapy approaches for other PIDs and discuss its prospects in relation to the evolving arena of allogeneic transplant.

  15. Testicular radionuclide angiography and sttatic imaging: anatomy, scintigraphic interpretation, and clinical indications. [/sup 99m/Tc tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Holder, L.E.; Martire, J.R.; Holmes, E.R. III.; Wagner, H.N. Jr.

    1977-12-01

    Radionuclide testicular angiography and static imaging is an easy, rapidly performed study. Its usefulness in separating acute testicular torsion from acute epididymitis has been confirmed. Increased angiographic perfusion with definition of the testicular and deferential arteries in the spermatic cord and the pudendal artery posteriorly is equated with inflammation. Intense increased vascularity on the blood pool image is seen in abscess and acute inflammation, while cases of tumor and trauma have mild increases. Acute or missed testicular torsion, uncomplicated hydroceles, and spermatoceles show absent vascularity. On the static images, decreased activity is characteristic of the shape and location of the avascular structure. Technical factors are stressed.

  16. Aquatic therapy: scientific foundations and clinical rehabilitation applications.

    Science.gov (United States)

    Becker, Bruce E

    2009-09-01

    The aquatic environment has broad rehabilitative potential, extending from the treatment of acute injuries through health maintenance in the face of chronic diseases, yet it remains an underused modality. There is an extensive research base supporting aquatic therapy, both within the basic science literature and clinical literature. This article describes the many physiologic changes that occur during immersion as applied to a range of common rehabilitative issues and problems. Because of its wide margin of therapeutic safety and clinical adaptability, aquatic therapy is a very useful tool in the rehabilitative toolbox. Through a better understanding of the applied physiology, the practitioner may structure appropriate therapeutic programs for a diverse patient population.

  17. Repeated Radionuclide therapy in metastatic paraganglioma leading to the highest reported cumulative activity of 131I-MIBG

    Directory of Open Access Journals (Sweden)

    Ezziddin Samer

    2012-01-01

    Full Text Available Abstract 131I-MIBG therapy for neuroendocrine tumours may be dose limited. The common range of applied cumulative activities is 10-40 GBq. We report the uneventful cumulative administration of 111 GBq (= 3 Ci 131I-MIBG in a patient with metastatic paraganglioma. Ten courses of 131I-MIBG therapy were given within six years, accomplishing symptomatic, hormonal and tumour responses with no serious adverse effects. Chemotherapy with cisplatin/vinblastine/dacarbazine was the final treatment modality with temporary control of disease, but eventually the patient died of progression. The observed cumulative activity of 131I-MIBG represents the highest value reported to our knowledge, and even though 12.6 GBq of 90Y-DOTATOC were added intermediately, no associated relevant bone marrow, hepatic or other toxicity were observed. In an individual attempt to palliate metastatic disease high cumulative activity alone should not preclude the patient from repeat treatment.

  18. 'Crescent Sign': Phase abnormality in radionuclide multigated study in tricuspid regurge: Description and clinical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ziada, G.; Abdel-Dayem, H.M.; Shafy, M.Z.; Constantinides, C.; Yousif, A.M.; Nair, N.

    1987-08-01

    A phase abnormality in radionuclide multigated studies (MUGA) in patients with tricuspid regurge (TR) is being described. In this condition of TR, as the right ventricle contracts, if causes the blood to regurge through the tricuspid valve to the right atrium and through the inferior Vena cava and hepatic veins to the adjacent liver tissue. As a result the right atrium and the liver will be in the same delayed phase forming a Crescent to the right side of the heart representing the right atrium and extending below the heart into the region of the liver. This Crescent has been graded according to how far it is extending in the liver and below the heart. In 15 patients with cardiac cath finding of TR (done within 2-3 days of the MUGA study), the phase displays of the radionuclide MUGA studies were analysed in order to find out the sensitivity of the Crescent Sign in the detection of TR and whether there is a relationship between the grade of the Crescent and the severity of the regurgitation. The Crescent was found in 13 of the 15 patients (sensitivity = 87%). We have not found a correlation between the severity of TR and the grade of the Crescent. We conclude that the presence of the Crescent Sign in phase display of the MUGA study should direct the attention of the clinician towards the recognition of TR, a condition which is sometimes difficult to diagnose non-invasively.

  19. Predictors of sudden death and death from pump failure in congestive heart failure are different. Analysis of 24 h Holter monitoring, clinical variables, blood chemistry, exercise test and radionuclide angiography

    DEFF Research Database (Denmark)

    Madsen, B K; Rasmussen, Verner; Hansen, J F

    1997-01-01

    One hundred and ninety consecutive patients discharged with congestive heart failure were examined with clinical evaluation, blood chemistry, 24 h Holter monitoring, exercise test and radionuclide angiography. Median left ventricular ejection fraction was 0.30, 46% were in New York Heart Associat......One hundred and ninety consecutive patients discharged with congestive heart failure were examined with clinical evaluation, blood chemistry, 24 h Holter monitoring, exercise test and radionuclide angiography. Median left ventricular ejection fraction was 0.30, 46% were in New York Heart...

  20. Relationship between internal dosimetry and DNA double strand breaks in lymphocytes after radionuclide therapy; Zusammenhang zwischen physikalischer Dosimetrie und DNA Doppelstrangbruechen in Lymphozyten nach Radionuklidtherapie

    Energy Technology Data Exchange (ETDEWEB)

    Eberlein, Uta

    2015-09-30

    In radionuclide therapy radiopharmaceuticals are administered mostly systemically. Primarily, beta-emitters are used because of their short range in tissue. As a result the radiopharmaceutical distributes within the human body and accumulates in organs and target structures. Thus, the body is irradiated internally, in contrast to external irradiation in radiotherapy. The pattern of the activity distribution within the human body is determined by the physical and chemical properties of the radiopharmaceutical. Furthermore, the amount of activity and its accumulation in organs or tissues is essential for the calculation of the absorbed dose which defines the energy deposited in the body by ionizing radiation. During internal or external irradiation, patients are exposed to ionizing radiation which does not only destroy the malignant cells but also damages healthy tissue and cells. This is mainly caused by direct and indirect interaction of the radiation with the DNA which damages the DNA structure. Most frequently, there are single strand breaks and base damages. DNA double strand breaks (DSBs) are rare; nevertheless, they are the most critical lesions for cells as repairing the damage is difficult. Unrepaired or misrepaired DNA could cause mutations, chromosomal aberrations or lead to cell death. The formation of a DNA DSB in nuclear chromatin results in the rapid phosphorylation of the histone H2 variant H2AX, then called gamma-H2AX. Furthermore, DSBs also recruit the damage sensor 53BP1 to the chromatin surrounding the DSBs, which leads to 53BP1 and gamma-H2AX co-localization in the chromatin surrounding a DSB. By immunofluorescence staining with gamma-H2AX and 53BP1 antibodies those biomarkers can be addressed by microscopically visible DNA damage protein foci, this is also known as the DNA damage focus assay. With progression of DSB repair, gamma-H2AX and 53BP1 foci disappear. It is assumed that one focus corresponds to one DSB. Therefore, the number of foci per

  1. Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA

    Science.gov (United States)

    Pereira, Edgar; Do Quental, Letícia; Palma, Elisa; Oliveira, Maria Cristina; Mendes, Filipa; Raposinho, Paula; Correia, Isabel; Lavrado, João; di Maria, Salvatore; Belchior, Ana; Vaz, Pedro; Santos, Isabel; Paulo, António

    2017-02-01

    A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners.

  2. Individualized dosimetry-based activity reduction of {sup 90}Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Binnebeek, Sofie van; Baete, Kristof; Vanbilloen, Bert; Terwinghe, Christelle; Mortelmans, Luc [University Hospitals Leuven, Nuclear Medicine, Leuven (Belgium); KU Leuven, Department of Imaging and Pathology, Leuven (Belgium); Koole, Michel [University Medical Centre Groningen, Department of Nuclear Medicine, Groningen (Netherlands); Mottaghy, Felix M. [University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Clement, Paul M. [University Hospitals Leuven, Medical Oncology, Leuven (Belgium); KU Leuven, Laboratory of Experimental Oncology, Leuven (Belgium); Haustermans, Karin [University Hospitals Leuven, Radiation Oncology, Leuven (Belgium); KU Leuven, Department of Oncology, Leuven (Belgium); Cutsem, Eric van; Verslype, Chris [KU Leuven, Department of Oncology, Leuven (Belgium); University Hospitals Leuven, Division of Digestive Oncology, Leuven (Belgium); Verbruggen, Alfons [KU Leuven, Laboratory for Radiopharmacy, Leuven (Belgium); Bogaerts, Kris [KU Leuven, Division of Public Health and Primary Care (I-Biostat), Leuven (Belgium); Deroose, Christophe M. [University Hospitals Leuven, Nuclear Medicine, Leuven (Belgium); KU Leuven, Department of Imaging and Pathology, Leuven (Belgium); UZ Leuven, Nuclear Medicine, Leuven (Belgium)

    2014-06-15

    Assessment of kidney function evolution after {sup 90}Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney. In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq {sup 111}In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using {sup 51}Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL). Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33 % was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT. Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for {sup 90}Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity. (orig.)

  3. 肺癌的放射性核素分子靶向治疗%Radionuclide molecular target therapy for lung cancer

    Institute of Scientific and Technical Information of China (English)

    张富海; 孟召伟; 谭建

    2012-01-01

    肺癌严重危害民众的生命和健康,目前国内外肺癌的发病率和病死率还在不断上升.在城市中,肺癌的病死率占男性恶性肿瘤患者病死率的38%,占女性恶性肿瘤患者病死率的16%,均居首位.尤其是非小细胞肺癌的治疗效果多年来一直没有显著提高.近年来,随着医学分子生物学技术和理论的发展以及对肺癌发病机制认识的不断深入,转染钠/碘转运体基因及分子靶向药物介导的肺癌放射性核素治疗成为治疗晚期肺癌新的研究方向.%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.

  4. Clinical features, epidemiology, and therapy of lymphangioleiomyomatosis

    Directory of Open Access Journals (Sweden)

    Taveira-DaSilva AM

    2015-04-01

    only affect the activity of mTOR complex 1, therapies targeting RhoA GTPases with simvastatin, which inhibits Rho GTPases and promotes apoptosis, are being investigated. As in the case of cancer, LAM may be best treated with multiple drugs targeting signaling pathways considered important in the pathogenesis of disease.   Keywords: lymphangioleiomyomatosis, tuberous sclerosis, TSC1 and TSC2 mutations, mammalian target of rapamycin signaling pathway

  5. Clinical advance in radionuclide imaging of pulmonary cancer%肺肿瘤核素显像的临床应用进展

    Institute of Scientific and Technical Information of China (English)

    邓智勇; 杨丽春

    2008-01-01

    核素显像在肺癌的诊断、分期、治疗后复发转移的监测、疗效和预后的判断等方面展示了重要的临床价值,日益受到临床的重视.对临床较为常用的67Ga、201Tl、99Tcm和18F等放射性核素及其标记化合物的显像原理、临床应用、优缺点及进展情况进行介绍,并重点介绍了99Tcm-甲氧基异丁基异腈(99Tcm-MIBI)、99Tcm-HL91、18F.氟脱氧葡萄糖(18F-FDG)肺肿瘤核素显像的临床应用进展.%Radionuclide imaging of pulmonary cancer develops very rapidly in recent years. Its important value on the diagnosis, staging, monitoring recur and metastasis after treatment, and judging the curative effect and prognosis has been demonstrated. Clinicians pay more attention to it than before. This present article introduces the imaging principle, clinical use, good and bad points, progress situation of 67Ga, 201Tl, 99Tcm, 18F and their labelled compounds, which are more commonly used in clinical. And introduces the clinical progress of radionuclide imaging of pulmonary neoplasm concerning 99Tcm-sestamibi (99Tcm-MIBI),99Tcm-HL91and 18F-fluoredeoxyglucose (18F-FDG) with emphasis.

  6. Transcatheter therapies for resistant hypertension: Clinical review

    Institute of Scientific and Technical Information of China (English)

    Adil; Lokhandwala; Abhijeet; Dhoble

    2014-01-01

    Resistant hypertension(RHTN) is a commonly encountered clinical problem and its management remains a challenging task for healthcare providers. The prevalence of true RHTN has been difficult to assess due to pseudoresistance and secondary hypertension. Atherosclerotic renal artery stenosis(RAS) has been associated as a secondary cause of RHTN. Initial studies had shown that angioplasty and stenting for RAS were a promising therapeutic option when added to optimal medical management. However, recent randomized controlled trials in larger populations have failed to show any such benefit. Sympathetic autonomic nervous system dysfunction is commonly noted in individuals with resistant hypertension. Surgical sympathectomy was the treatment of choice for malignant hypertension and it significantly improved mortality. However, postsurgical complications and the advent of antihypertensive drugs made this approach less desirable and it was eventually abandoned. Increasing prevalence of RHTN in recent decades has led to the emergence of minimally invasive interventions such as transcatheter renal denervation for better control of blood pressure. It is a minimally invasive procedure which uses radiofrequency energy for selective ablation of renal sympathetic nerves located in the adventitia of the renal artery. It is a quick procedure and has a short recovery time. Early studies in small population showed significant reduction in blood pressure. The most recent Symplicity HTN-3 study, which is the largest randomized control trial and the only one to use a sham procedure in controls, failed to show significant BP reduction at 6 mo.

  7. [Clinical symptomps, diagnosis and therapy of feline allergic dermatitis].

    Science.gov (United States)

    Favrot, C; Rostaher, A; Fischer, N

    2014-07-01

    Allergies are often suspected in cats and they are mainly hypersensitivity reactions against insect bites, food- or environmental allergens. Cats, with non flea induced atopic dermatitis, normally present with one oft he following reaction patterns: miliary dermatitis, eosinophilic dermatitis, selfinduced alopecia or head and neck excoriations. None of these reaction patterns is nevertheless pathognomonic for allergic dermatitis, therefore the diagnosis is based on the one hand on the exclusion of similar diseases on the other hand on the successful response on a certain therapy. Recently a study on the clinical presentation of cats with non flea induced atopic dermatitis was published. In this study certain criteria for diagnosing atopy in cats were proposed. For therapy of allergic cats cyclosporin, glucocorticoids, antihistamines, hypoallergenic diets and allergen specific immunotherapy are used. This article should provide a recent overview on the clinical symptoms, diagnosis and therapy of feline allergic dermatitis.

  8. COMPLICATIONS OF THROMBOLYTIC THERAPY IN ACTUAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    A. F. Sharafutdinova

    2014-07-01

    Full Text Available Reperfusion therapy, in particular, thrombolysis in acute myocardial infarction involves development of serious complications. This clinical situation demonstrates the complexity of treatment of patients with hemorrhagic complications after thrombolysis and makes questions on the application of antiplatelet agents and anticoagulants in such cases.

  9. COMPLICATIONS OF THROMBOLYTIC THERAPY IN ACTUAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    A. F. Sharafutdinova

    2011-01-01

    Full Text Available Reperfusion therapy, in particular, thrombolysis in acute myocardial infarction involves development of serious complications. This clinical situation demonstrates the complexity of treatment of patients with hemorrhagic complications after thrombolysis and makes questions on the application of antiplatelet agents and anticoagulants in such cases.

  10. Simulated Family Therapy Interviews in Clinical Social Work Education

    Science.gov (United States)

    Mooradian, John K.

    2007-01-01

    This article describes a learning method that employed theatre students as family clients in an advanced social work practice course. Students were provided with an opportunity to integrate and apply their learning of theory, clinical skills, and professional conduct in full-length family therapy sessions that occurred in the classroom and were…

  11. Clinical considerations of anticoagulation therapy for patients with atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    Shu ZHANG

    2012-01-01

    Atrial fibrillation (AF) increases the risk of stroke.New anticoagulation agents have recently provided alternative and promising approaches.This paper reviews the current state of anticoagulation therapy in AF patients,focusing on various clinical scenarios and on comparisons,where possible,between western and eastern populations.

  12. Active Interventions in Clinical Practice: Contributions of Gestalt Therapy.

    Science.gov (United States)

    Lammert, Marilyn; Dolan, Mary M.

    1983-01-01

    Describes two dimensions of Gestalt therapy that can enhance clinical practice--orientation to the present and active-experimental style--and examines them in relation to some traditional principles of practice. Gestalt theory offers a method of discovery that is a combination of phenomenology and behaviorism. (JAC)

  13. [Clinical and pharmacological aspects of pancreatic enzyme substitution therapy].

    Science.gov (United States)

    Löser, C; Fölsch, U R

    1991-03-01

    The adequate therapy of pancreatic enzyme replacement in patients with exocrine pancreatic insufficiency is still a difficult clinical problem especially in patients following pancreatectomys, with chronic alcoholic pancreatitis or cystic fibrosis. The substitution of lipase to eliminate steatorrhoea is the most important aim but due to its acid lability even the most serious problem in pancreatic enzyme replacement therapy. Various different medications are meanwhile available: conventional preparations from porcine pancreatin or fungal enzymes as rizolipase, enteric-coated tablets or even enteric-coated microspheres or adjunctive therapy with H2-receptor antagonists. While dosage requirements vary widely and therefore have to be tried out individually, the choice of the adequate preparation should be influenced by the realization of the physiological and pathophysiological characteristics of the individual patient and the pharmaceutical characteristics of the different supplements. The advantages and disadvantages of the various medications for enzyme replacement therapy in patients with exocrine pancreatic insufficiency are reviewed in this article.

  14. Acupressure therapy for morning sickness. A controlled clinical trial.

    Science.gov (United States)

    Hyde, E

    1989-01-01

    A prospective, controlled clinical trial examined the efficacy of acupressure therapy for morning sickness, using a two group, random assignment, crossover design. Subjects in Group 1 (N = 8) used acupressure wristbands for five days, followed by five days without therapy. Subjects in Group 2 (N = 8) had no therapy for five days, followed by five days use of wristbands. The Multiple Affect Adjective Checklist and Sickness Impact Profile were used, and extent of nausea was assessed at baseline, day five, and day ten. Use of acupressure wristbands relieved morning sickness for 12 of 16 subjects (chi 2 = 5.31 with Yates' correction factor, df = 1, p less than .025). Acupressure therapy resulted in statistically significant (p less than .05) reductions in anxiety, depression, behavioral dysfunction, and nausea. Limitations of the study and suggestions for future research are presented.

  15. [Pathogenesis, clinical picture, and current therapy of rosacea].

    Science.gov (United States)

    Gonser, L I; Gonser, C E; Schaller, M

    2016-01-01

    Rosacea is a common chronic inflammatory disease, especially in patients with fair skin and positive family history. Typical locations are forehead, nose, cheeks and chin; the periorbital region is usually not involved. Clinical features can be very heterogeneous. Besides different subtypes (erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea), which often overlap, various special forms of rosacea exist. Up to 60% of patients with cutaneous rosacea suffer from ocular rosacea. In Germany, brimonidine, metronidazol, azelaic acid, and ivermectin are approved for topical therapy of rosacea; for systemic therapy, doxycycline at a subantimicrobial dose (40 mg/day) is the only approved substance. In case of resistance to this therapy, contraindications or side effects, various alternative therapies are available, however off-label.

  16. State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications.

    Science.gov (United States)

    Wang, Dan; Gao, Guangping

    2014-09-01

    In Part I of this Review (Wang and Gao, 2014), we introduced recent advances in gene delivery technologies and explained how they have powered some of the current human gene therapy applications. In Part II, we expand the discussion on gene therapy applications, focusing on some of the most exciting clinical uses. To help readers to grasp the essence and to better organize the diverse applications, we categorize them under four gene therapy strategies: (1) gene replacement therapy for monogenic diseases, (2) gene addition for complex disorders and infectious diseases, (3) gene expression alteration targeting RNA, and (4) gene editing to introduce targeted changes in host genome. Human gene therapy started with the simple idea that replacing a faulty gene with a functional copy can cure a disease. It has been a long and bumpy road to finally translate this seemingly straightforward concept into reality. As many disease mechanisms unraveled, gene therapists have employed a gene addition strategy backed by a deep knowledge of what goes wrong in diseases and how to harness host cellular machinery to battle against diseases. Breakthroughs in other biotechnologies, such as RNA interference and genome editing by chimeric nucleases, have the potential to be integrated into gene therapy. Although clinical trials utilizing these new technologies are currently sparse, these innovations are expected to greatly broaden the scope of gene therapy in the near future.

  17. AARC Clinical Practice Guideline. Surfactant replacement therapy: 2013.

    Science.gov (United States)

    Walsh, Brian K; Daigle, Brandon; DiBlasi, Robert M; Restrepo, Ruben D

    2013-02-01

    We searched the MEDLINE, CINAHL, and Cochrane Library databases for English-language randomized controlled trials, systematic reviews, and articles investigating surfactant replacement therapy published between January 1990 and July 2012. By inspection of titles, references having no relevance to the clinical practice guideline were eliminated. The update of this clinical practice guideline is based on 253 clinical trials and systematic reviews, and 12 articles investigating surfactant replacement therapy. The following recommendations are made following the Grading of Recommendations Assessment, Development, and Evaluation scoring system: 1: Administration of surfactant replacement therapy is strongly recommended in a clinical setting where properly trained personnel and equipment for intubation and resuscitation are readily available. 2: Prophylactic surfactant administration is recommended for neonatal respiratory distress syndrome (RDS) in which surfactant deficiency is suspected. 3: Rescue or therapeutic administration of surfactant after the initiation of mechanical ventilation in infants with clinically confirmed RDS is strongly recommended. 4: A multiple surfactant dose strategy is recommended over a single dose strategy. 5: Natural exogenous surfactant preparations are recommended over laboratory derived synthetic suspensions at this time. 6: We suggest that aerosolized delivery of surfactant not be utilized at this time.

  18. Osteopetrosis: radiological & radionuclide imaging.

    Science.gov (United States)

    Sit, Cherry; Agrawal, Kanhaiyalal; Fogelman, Ignac; Gnanasegaran, Gopinath

    2015-01-01

    Osteopetrosis is a rare inherited bone disease where bones harden and become abnormally dense. While the diagnosis is clinical, it also greatly relies on appearance of the skeleton radiographically. X-ray, radionuclide bone scintigraphy and magnetic resonance imaging have been reported to identify characteristics of osteopetrosis. We present an interesting case of a 59-year-old man with a history of bilateral hip fractures. He underwent (99m)Tc-methylene diphosphonate whole body scan supplemented with single-photon emission computed tomography/computed tomography of spine, which showed increased uptake in the humeri, tibiae and femora, which were in keeping with osteopetrosis.

  19. Heart failure gene therapy: the path to clinical practice.

    Science.gov (United States)

    Pleger, Sven T; Brinks, Henriette; Ritterhoff, Julia; Raake, Philip; Koch, Walter J; Katus, Hugo A; Most, Patrick

    2013-08-30

    Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.

  20. Treatment planning for internal emitter therapy: Methods, applications and clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Sgouros, G. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    1999-01-01

    Treatment planning involves three basic steps: (1) a procedure must be devised that will provide the most relevant information, (2) the procedure must be applied and (3) the resulting information must be translated into a definition of the optimum implementation. There are varying degrees of treatment planning that may be implemented in internal emitter therapy. As in chemotherapy, the information from a Phase 1 study may be used to treat patients based upon body surface area. If treatment planning is included on a patient-specific basis, a pretherapy, trace-labeled, administration of the radiopharmaceutical is generally required. The data collected following the tracer dose may range from time-activity curves of blood and whole-body for use in blood, marrow or total body absorbed dose estimation to patient imaging for three-dimensional internal emitter dosimetry. The most ambitious approach requires a three-dimensional set of images representing radionuclide distribution (SPECT or PET) and a corresponding set of images representing anatomy (CT or MRI). The absorbed dose (or dose-rate) distribution may be obtained by convolution of a point kernel with the radioactivity distribution or by direct Monte Carlo calculation. A critical requirement for both techniques is the development of an overall structure that makes it possible, in a routine manner, to input the images, to identify the structures of interest and to display the results of the dose calculations in a clinically relevant manner. 52 refs., 4 figs., 1 tab.

  1. Interventricular delay measurement using equilibrium radionuclide angiography before resynchronization therapy should be performed outside the area of segmental wall motion abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Courtehoux, Maxime [Service EFMP CHU Trousseau, Chambray les Tours (France); Zannad, Noura; Fauchier, Laurent; Babuty, Dominique [Service Cardiologie B CHU Trousseau, Tours (France); Eder, Veronique [Service EFMP CHU Trousseau, Chambray les Tours (France); EA3852 University Francois Rabelais, Tours (France)

    2011-02-15

    The aim of this study was to demonstrate that only mechanical dyssynchrony outside the area of segmental wall motion abnormalities (WMA) can be reduced by cardiac resynchronization therapy (CRT). Included in the study were 28 consecutive patients with nonischaemic cardiomyopathy selected for CRT. Equilibrium radionuclide angiography (ERNA) was carried out before and after implantation of a multisite pacemaker. Patients were separated into two groups depending on the presence or absence of segmental WMA. A reduction in QRS duration was observed in all patients after CRT. The interventricular delay (IVD) decreased significantly after CRT only in patients without WMA (homogeneous contraction, HG group; IVD 44 {+-} 11.4 vs. 17 {+-} 3.1 , p = 0.04). In contrast, no significant decrease was observed in patients with WMA (WMA group; IVD 51 {+-} 6 vs. 38 {+-} 6 , p NS). However, when dyssynchrony was considered outside the WMA area, a significant reduction in IVD was obtained, in the same range as in the HG group (IVD 32 {+-} 3 vs. 19 {+-} 3 , p = 0.04). In 9 of 15 patients (60%) with a reduction in IVD after CRT, the left ventricle ejection fraction (LVEF) increased by about +10%. In contrast, in 13 of 13 patients (100%) with no reduction in IVD, no modification of LVEF was obtained. In the presence of segmental WMA without significant delays outside the WMA area, no reduction in IVD was observed and LVEF did not increase (IVD 34 {+-} 5 before CRT vs. 37 {+-} 7 after CRT; LVEF 19 {+-} 4% before CRT vs. 22 {+-} 3% after CRT, p NS). ERNA can be used to predict good mechanical resynchronization (decrease in IVD) in patients after pacing. IVD has to be determined excluding the area of WMA in order to select patients who will show an increase in their left ventricle function after CRT. (orig.)

  2. [Structure and process quality of multimodal pain therapy. Results of a survey of pain therapy clinics].

    Science.gov (United States)

    Nagel, B; Pfingsten, M; Brinkschmidt, T; Casser, H-R; Gralow, I; Irnich, D; Klimczyk, K; Sabatowski, R; Schiltenwolf, M; Sittl, R; Söllner, W; Arnold, B

    2012-12-01

    Multimodal therapy has demonstrated good clinical effectiveness in the treatment of chronic pain syndromes. However, within the German health system a comprehensive and nationwide access to multimodal therapy is not available and further improvement is therefore necessary. In order to analyze the current status of multimodal therapy and specifically its structural and procedural requirements and qualities, a survey was carried out in 37 pain clinics with established multimodal treatment programs. An anonymous questionnaire was used for data collection. Results demonstrated that a substantial accordance was found between all pain clinics concerning requirements for space, facilities and staff. Structured multidisciplinary assessments were carried out by all pain clinics even though the amount of time allocated for this varied widely. The main focus of multimodal therapy in all facilities was based on a common philosophy with a cognitive-behavioral approach to reduce patient helplessness and avoidance behavior and to increase physical and psychosocial activities as well as to strengthen self-efficacy. Some differences in the ways and means to achieve these goals could be demonstrated in the various programs.

  3. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

    Directory of Open Access Journals (Sweden)

    LM Benneker

    2014-05-01

    Full Text Available Intervertebral disc (IVD degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

  4. On-Line Adaptive Radiation Therapy: Feasibility and Clinical Study

    Directory of Open Access Journals (Sweden)

    Taoran Li

    2010-01-01

    Full Text Available The purpose of this paper is to evaluate the feasibility and clinical dosimetric benefit of an on-line, that is, with the patient in the treatment position, Adaptive Radiation Therapy (ART system for prostate cancer treatment based on daily cone-beam CT imaging and fast volumetric reoptimization of treatment plans. A fast intensity-modulated radiotherapy (IMRT plan reoptimization algorithm is implemented and evaluated with clinical cases. The quality of these adapted plans is compared to the corresponding new plans generated by an experienced planner using a commercial treatment planning system and also evaluated by an in-house developed tool estimating achievable dose-volume histograms (DVHs based on a database of existing treatment plans. In addition, a clinical implementation scheme for ART is designed and evaluated using clinical cases for its dosimetric qualities and efficiency.

  5. Facilitating case studies in massage therapy clinical education.

    Science.gov (United States)

    Baskwill, Amanda

    2013-01-01

    The integration of evidence into reflective health care practice has been on the rise in recent years and is a phenomenon that has affected all health care professions, including massage therapy. Clinical case studies are a research design that follows one patient or subject, making the studies ideal for use in clinical practice. They are valuable for communicating information from clinical practice to the broader community. Case studies have face validity that may be more valuable to individual practitioners than homogeneous randomized controlled trials, as the practitioner may recognize a complex patient in the case report. At Humber College, Student Massage Therapists (SMTs) create, conduct, and communicate results of a clinical case study prior to graduation. This article describes the process and experience.

  6. Imaging and Data Acquisition in Clinical Trials for Radiation Therapy.

    Science.gov (United States)

    FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Followill, David S; Galvin, James; Knopp, Michael V; Michalski, Jeff M; Rosen, Mark A; Bradley, Jeffrey D; Shankar, Lalitha K; Laurie, Fran; Cicchetti, M Giulia; Moni, Janaki; Coleman, C Norman; Deye, James A; Capala, Jacek; Vikram, Bhadrasain

    2016-02-01

    Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.

  7. Technical basis of radiation therapy. Practical clinical applications. 5. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Levitt, Seymour H. [Karolinska Institutet Stockholm (Sweden). Dept. of Oncol-Pathol; Perez, Carlos A. [Washington Univ. Medical Center, St. Louis, MO (United States). Dept. of Radiation Oncology; Purdy, James A. [California Univ., Sacramento, CA (United States). Dept. of Radiation Oncology; Poortmans, Philip [Institute Verbeeten, Tilburg (Netherlands). Dept. of Radiation Oncology

    2012-07-01

    This well-received book, now in its fifth edition, is unique in providing a detailed description of the technological basis of radiation therapy. Another novel feature is the collaborative writing of the chapters by North American and European authors. This considerably broadens the book's perspective and increases its applicability in daily practice throughout the world. The book is divided into two sections. The first covers basic concepts in treatment planning, including essential physics and biological principles related to time-dose-fractionation, and explains the various technological approaches to radiation therapy, such as intensity-modulated radiation therapy, tomotherapy, stereotactic radiotherapy, and high and low dose rate brachytherapy. Issues relating to quality assurance, technology assessment, and cost-benefit analysis are also reviewed. The second part of the book discusses in depth the practical clinical applications of the different radiation therapy techniques in a wide range of cancer sites. All of the chapters have been written by leaders in the field. This book will serve to instruct and acquaint teachers, students, and practitioners in the various fields of oncology with the basic technological factors and approaches in radiation therapy. (orig.)

  8. CELL THERAPY FOR INTERVERTEBRAL DISC REPAIR: ADVANCING CELL THERAPY FROM BENCH TO CLINICS

    Science.gov (United States)

    Benneker, L.M.; Andersson, G.; Iatridis, J.C.; Sakai, D.; Härtl, R.; Ito, K.; Grad, S.

    2016-01-01

    Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encourageing results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium “Where Science meets Clinics”, sponsored by the AO Foundation and held in Davos, Switzerland, from September 5–7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imageing methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neurogenesis. Discogenic pain, originating from “black discs” or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in outline order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects. PMID:24802611

  9. 75 FR 54351 - Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop

    Science.gov (United States)

    2010-09-07

    ... HUMAN SERVICES Food and Drug Administration Cell and Gene Therapy Clinical Trials in Pediatric... public workshop entitled ``Cell and Gene Therapy Clinical Trials in Pediatric Populations.'' The purpose... therapy clinical researchers, and other stakeholders regarding best practices related to cell and...

  10. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.

    Science.gov (United States)

    Wicki, Andreas; Witzigmann, Dominik; Balasubramanian, Vimalkumar; Huwyler, Jörg

    2015-02-28

    Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology towards the development of nanomedicine products holds great promise to improve therapeutic strategies against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multi-functionality. They can improve the pharmacokinetic and pharmacodynamic profiles of conventional therapeutics and may thus optimize the efficacy of existing anti-cancer compounds. In this review, we discuss state-of-the-art nanoparticles and targeted systems that have been investigated in clinical studies. We emphasize the challenges faced in using nanomedicine products and translating them from a preclinical level to the clinical setting. Additionally, we cover aspects of nanocarrier engineering that may open up new opportunities for nanomedicine products in the clinic.

  11. Radionuclides in nephrology

    Energy Technology Data Exchange (ETDEWEB)

    Lausanne, A.B.D.

    1987-01-01

    In 47 expert contributions, this volume provides a summary of the latest research on radionuclides in nephro-urology together with current and new clinical applications especially in renovascular hypertension, kidney transplantation, and metabolic and urological diseases. In addition, attention is given to aspects of basic renal physiology and function and possible applications of nuclear magnetic resonance and spectroscopy in nephro-urology. New testing procedures which promise to improve diagnosis, and new radiopharmaceuticals are described. The reports are divided into eight sections, the first of which features studies on the renin-angiotensin system, cisplatin, atrial natriuretic factor and determining plasma oxalate. Four papers describe a number of new radiopharmaceuticals which have the potential to replace hippuran. In the third section, radionuclide methods for the measurement of renal function parameters are discussed. The book then focuses on the potential role of captopril in the improved diagnosis of renovascular hypertension. Applications of nuclear magnetic resonance and spectroscopy are demonstrated in the diagnosis of acute pyelonephritis, kidney assessment after lithotripsy, kidney evaluation prior to transplantation, and in monitoring renal ischemia during hypotension.

  12. Nontyphoid salmonella infection: microbiology, clinical features, and antimicrobial therapy.

    Science.gov (United States)

    Chen, Hung-Ming; Wang, Yue; Su, Lin-Hui; Chiu, Cheng-Hsun

    2013-06-01

    Nontyphoid Salmonella is the most common bacterial pathogen causing gastrointestinal infection worldwide. Most nontyphoid Salmonella infection is limited to uncomplicated gastroenteritis that seldom requires antimicrobial treatment. Nevertheless, invasive infections, such as bacteremia, osteomyelitis, and meningitis, may occur and require antimicrobial therapy. Continuous genetic and genomic evolution in Salmonella leading to increased virulence and resistance to multiple drugs are of significant public health concern. Two major changes in the epidemiology of nontyphoid salmonellosis in Europe and in the USA occurred in the second half of the 20(th) century: the emergence of foodborne human infections caused by Salmonella enterica serotype Enteriditis and by multidrug-resistant strains of Salmonella enterica serotype Typhimurium. In the 21(st) century, a worsening situation is the increasing resistance to fluoroquinolones and third-generation cephalosporins in nontyphoid Salmonella. Clinical isolates showing carbapenem resistance also have been identified. Although antimicrobial therapy is usually not indicated for uncomplicated Salmonella gastroenteritis, recent studies indicated that a short-course ceftriaxone therapy (3-5 days) for patients with severe gastroenteritis would lead to a faster clinical recovery. Continuous surveillance of Salmonella in both humans and animals is mandatory. A better understanding of the mechanisms that lead to the emergence of antimicrobial resistance in Salmonella may help in the devising of better interventional strategies to reduce the spread of resistant Salmonella between humans and reservoirs along the food chain.

  13. How Clinical Instructors Can Enhance the Learning Experience of Physical Therapy Students in an Introductory Clinical Placement

    Science.gov (United States)

    Cole, Beverley; Wessel, Jean

    2008-01-01

    Purpose: There is little understanding of how physical therapy students are influenced by clinical instructors (CIs) particularly at the outset of their clinical learning. The purpose of this study was to evaluate physical therapy students' perceptions of their learning experiences during an introductory clinical placement. Methods: Subjects were…

  14. Use of magnetic therapy in clinical neurology: literature review

    Energy Technology Data Exchange (ETDEWEB)

    Shogam, I.I.; Lenchin, V.N.; Baranovskaya, A.V.

    1985-01-01

    A literature survey is presented on the current status of magnetic therapy in clinical neurology. It is generally accepted that the high susceptibility of the nervous system to the magnetic field is due to a large extent to the automatic component. Furthermore, it has also become clear that glial cells are far more susceptible to magnetic fields than are neurons. Controversy prevails on the question of whether the therapeutic effectiveness of magnetic fields involves a direct mechanism of action or an indirect one via reflex mechanisms. Nevertheless, effectiveness of magnetic therapy has been demonstrated and generally accepted in cases dealing with lagophthalmia, ptosis, various neuralgia, radiculitis, neuritis, vascular and infectious pathology of the brain, and so forth. Basically, the effectiveness of such therapy is strongly dependent on the location and the nature of the pathologic process, as well as on the functional status of the autonomic nervous system. In view of this, effective magnetic therapy is highly dependent on individualization of a given approach. 111 References.

  15. Clinical applications of laser therapy on the dental practice

    Science.gov (United States)

    Pinheiro, Antonio L. B.

    2004-09-01

    Dental practice consists of a series of laboring procedures which demands the use of several types of equipment and materials. Usually patient"s fears brings additional burden to the Dentists. The use of Lasers for treating and diagnosis in Dentistry is quite new comparing to other medical areas. Initially Laser technology was used as an alternative method for treating dental caries in order to substitute the use of the drill. Lately surgical Lasers have shown themselves very useful for treating several pathologies and began to be used as a powerful tool on the treatment of several conditions affecting the maxillofacial complex and later on, the era of the use of Laser therapy began. The advent of the diode Lasers made possible the introduction of small units at the dental office and Laser therapy was used to improve healing and later included also caries diagnosis. This paper discuss the use of Laser therapy on Restorative Dentistry, Periodondology, Oral and Maxillofacial Surgery, Oral implantology and other. Clinical and laboratorial experience has demonstrated that Laser therapy does improve the healing of both mineralized and soft tissues, reduces pain and inflammation, and also reduces both cost and length of the dental treatment.

  16. Internal radionuclide therapy in pancreatic cancer:current status and progress%胰腺癌放射性核素内照射治疗现状及进展

    Institute of Scientific and Technical Information of China (English)

    王颖(综述); 李亚明(审校)

    2015-01-01

    Pancreatic cancer is a digestive system tumor with high degree of malignancy, rapid progress and poor prognosis. The early detection of pancreatic cancer is difficult, so that most patients are diagnosed at an advanced stage, have lost the opportunity for surgical therapy, and can only receive adjuvant chemoradiotherapy to help relieve symptoms and control the disease. In recent years, internal radionuclide therapy, with its constant development along with the continuous renewal of treatment strategy, has been increasingly noted in treatment of pancreatic cancer. In this paper, the authors address the advances of internal radionuclide therapy in pancreatic cancer.%胰腺癌是恶性程度高、进展迅速、预后极差的消化系统肿瘤,早期诊断困难,多数患者发现时已属晚期,失去手术治疗的机会,只能采取放化疗等辅助治疗手段来缓解症状及控制疾病。近年来随着放射性核素内照射治疗的不断发展,治疗策略的不断更新,其在胰腺癌的治疗中的作用越来越受到重视,笔者就其在胰腺癌治疗中的进展进行综述。

  17. Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2015-07-15

    Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with {sup 177}Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with {sup 177}Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were

  18. Bone marrow dosimetry in peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Krenning, Eric P.; Kooij, Peter P.; Bernard, Bert F.; Bakker, Willem H.; Teunissen, Jaap J.M.; Jong, Marion de; Kwekkeboom, Dik J. [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Konijnenberg, Mark [Mallinckrodt Medical BV, Research and Development, Petten (Netherlands); Lom, Kirsten van [Erasmus MC Rotterdam, Department of Haematology, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus MC Rotterdam, Department of Internal Medicine, Rotterdam (Netherlands)

    2009-07-15

    Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called ''remainder of the body'' to the bone marrow. Bone marrow aspirates were drawn in 15 patients after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose. (1) After PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone

  19. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Ianniello, Annarita; Sansovini, Maddalena; Severi, Stefano; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Unit, Meldola (Italy); Grana, Chiara Maria [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy); Massri, Katrin [Ospedale San Luca, Nuclear Medicine, Department of Radiology, Lucca (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Antonuzzo, Lorenzo [AOU Careggi, SC Oncologia Medica 1, Firenze (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela; Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2016-06-15

    Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and {sup 18}F-FDG PET as prognostic factors in patients with advanced TC or AC. A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients. The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group. Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of

  20. Clinical management of chronic nightmares: imagery rehearsal therapy.

    Science.gov (United States)

    Krakow, Barry; Zadra, Antonio

    2006-01-01

    Problems with nightmares are reported by a sizable proportion of individuals with a history of trauma and by approximately 5% to 8% of the general population. Chronic nightmares may represent a primary sleep disorder rather than a symptom of a psychiatric disorder, and direct targeting of nightmares is a feasible clinical approach to the problem. Of the treatments proposed, imagery rehearsal therapy (IRT) has received the most empirical support. An up-to-date account of this cognitive-imagery approach shows how to treat nightmares during 4 roughly 2-hr sessions. The main points covered in each therapy session and their underlying rationale are presented. Dismantling protocols are suggested to discern active ingredients of IRT and to develop flexible applications based on patients' needs.

  1. Experimental and clinical evidence of antioxidant therapy in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Mukaddes Esrefoglu

    2012-01-01

    Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP).Antioxidants,alone or in combination with conventional therapy,should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery.In recent years,substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents.Some of these antioxidants have been found beneficial in the treatment of AP in humans; however,at present there is insufficient clinical data to support the benefits of antioxidants,alone or in combination with conventional therapy,in the management of AP in humans.Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species.Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP.Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants.The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP.

  2. Clinical impact of checkpoint inhibitors as novel cancer therapies.

    Science.gov (United States)

    Shih, Kent; Arkenau, Hendrik-Tobias; Infante, Jeffrey R

    2014-11-01

    Immune responses are tightly regulated via signaling through numerous co-stimulatory and co-inhibitory molecules. Exploitation of these immune checkpoint pathways is one of the mechanisms by which tumors evade and/or escape the immune system. A growing understanding of the biology of immune checkpoints and tumor immunology has led to the development of monoclonal antibodies designed to target co-stimulatory and co-inhibitory molecules in order to re-engage the immune system and restore antitumor immune responses. Anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies were among the first to be tested in the clinic, and ipilimumab was the first immune checkpoint inhibitor approved for an anticancer indication. Agents targeting the programmed death 1 (PD-1) pathway, either PD-1 or one of its ligands, programmed death ligand 1, are in active clinical development for numerous cancers, including advanced melanoma and lung cancer. Understanding the different mechanisms of action, safety profiles, and response patterns associated with inhibition of the CTLA-4 and PD-1 pathways may improve patient management as these therapies are moved in to the clinical practice setting and may also provide a rationale for combination therapy with different inhibitors. Additional immune checkpoint molecules with therapeutic potential, including lymphocyte activation gene-3 and glucocorticoid-induced tumor necrosis factor receptor-related gene, also have inhibitors in early stages of clinical development. Clinical responses and safety data reported to date on immune checkpoint inhibitors suggest these agents may have the potential to markedly improve outcomes for patients with cancer.

  3. Nanoshell-enabled photothermal cancer therapy: impending clinical impact.

    Science.gov (United States)

    Lal, Surbhi; Clare, Susan E; Halas, Naomi J

    2008-12-01

    Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanoscale applications in cancer diagnostics and therapy. Because of their strongly resonant light-absorbing and light-scattering properties that depend on shape, noble metal nanoparticles provide a new and powerful tool for innovative light-based approaches. Nanoshellsspherical, dielectric core, gold shell nanoparticleshave been central to the development of photothermal cancer therapy and diagnostics for the past several years. By manipulating nanoparticle shape, researchers can tune the optical resonance of nanoshells to any wavelength of interest. At wavelengths just beyond the visible spectrum in the near-infrared, blood and tissue are maximally transmissive. When nanoshell resonances are tuned to this region of the spectrum, they become useful contrast agents in the diagnostic imaging of tumors. When illuminated, they can serve as nanoscale heat sources, photothermally inducing cell death and tumor remission. As nanoshell-based diagnostics and therapeutics move from laboratory studies to clinical trials, this Account examines the highly promising achievements of this approach in the context of the challenges of this complex disease. More broadly, these materials present a concrete example of a highly promising application of nanochemistry to a biomedical problem. We describe the properties of nanoshells that are relevant to their preparation and use in cancer diagnostics and therapy. Specific surface chemistries are necessary for passive uptake of nanoshells into tumors and for targeting specific cell types by bioconjugate strategies. We also describe the photothermal temperature increases that can be achieved in surrogate structures known as tissue phantoms and the accuracy of models of this effect using heat transport analysis. Nanoshell-based photothermal therapy in several animal models of human tumors have produced highly promising results, and we include

  4. Alteration in the absorption cell dose arising from the use of gold nanoparticle associated with the radionuclides of clinical application: simulate study; Alteracao na absorcao de dose celular decorrente da utilizacao de nanoparticulas de ouro associadas a radionuclideos de aplicacao clinica: estudo simulado

    Energy Technology Data Exchange (ETDEWEB)

    Culik, Lucas; Schwarcke, Marcelo, E-mail: mschwarcke@unifra.br [Centro Universitario Franciscano (UNIFRA), Santa Maria, RS (Brazil)

    2015-12-15

    The present work is a proposal to assess, which is the efficiency in the use of radionuclides of clinical application in nuclear medicine service conjugated system with gold nanoparticles.To obtain the results needed for the interpretation of this combination, was using the Monte Carlo simulation code PENELOPE, where was the main structures of a simulated eukaryote cell. To simulate irradiation on cellular structures was used the emission spectrum of main radionuclide clinical use in nuclear medicine service. The material containing gold nanoparticles was modeled according the stoichiometric proportions found in the literature. The results obtained, present for the simulated energies to smaller bodies than 2,0μm, no substantial response to the use of nanoparticles in the reinforcement of locally absorbed dose. Is observed a small decrease in locally dose absorbed due to emission of charged particles, it is believed that causes an increase in the emission secondary range to be placed outside the study body. But this effect is small when comparing to the increase of energy absorbed due to interaction with the bodies containing nanoparticles, so demonstrating an increase in the locally dose absorbed. Being observed that there is an increase in dose absorbed locally due to the use of nanoparticles. For protocols based on the principle of target radionuclide therapy, the imaging of the treaty sit will be affected in their statistical accuracy, since the gamma radiation will be attenuated by the nanoparticles present in the material. Being necessary to know if this increase in the locally absorbed dose has greater importance in the treatment protocol than the image of the absorption of the radioactive material in the target organ. (author)

  5. Engineering adeno-associated viruses for clinical gene therapy.

    Science.gov (United States)

    Kotterman, Melissa A; Schaffer, David V

    2014-07-01

    Clinical gene therapy has been increasingly successful owing both to an enhanced molecular understanding of human disease and to progressively improving gene delivery technologies. Among these technologies, delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective and, in one recent case, have led to regulatory approval. Although shortcomings in viral vector properties will render extension of such successes to many other human diseases challenging, new approaches to engineer and improve AAV vectors and their genetic cargo are increasingly helping to overcome these barriers.

  6. Photodynamic therapy of port wine stain: preliminary clinical studies

    Science.gov (United States)

    Nelson, J. Stuart

    1993-07-01

    The broad, long term objective of this work is the development of Photodynamic Therapy (PDT) for application in the clinical management of patients with port wine stain (PWS). PDT involves the use of an exogenous drug which is concentrated in a targeted tissue. When irradiated at wavelengths specifically absorbed by the drug, selective destruction of the targeted tissue, without the production of heat, occurs. The results of this preliminary study demonstrate in human PWS patients that a photosensitizer, such as PHOTOFRINR, activated by red light at the appropriate therapeutic wavelength, can cause destruction of subsurface blood vessels in the skin with a high degree of specificity, and further study appears warranted.

  7. Therapeutic radionuclides: Making the right choice

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1996-08-01

    Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article.

  8. Bibliometric Analysis: Mirror Therapy as an Occupational Therapy Intervention Strategy in the Clinical Setting

    Directory of Open Access Journals (Sweden)

    Elvis Siprián Castro Alzate

    2016-01-01

    Full Text Available Objective: To determine the national and international scientific evidence regarding the use of mirror therapy, as an occupational therapy intervention tool in the clinical setting, in order to acquire knowledge and implement this strategy in professional practice. Materials and methods: A descriptive study was conducted in which the research strategy was held through medical subject headings (MeSH, such as “mirror neuron”, ”occupational therapy”, “physical rehabilitation” and “motor imagery”. Through the use of the bolean and combinations in five different databases were performed: Embase, Ebsco, OTseeker, Science Direct and Medline. The analysis was elaborated by establishing frequencies of different variables such as journal, country, study type and publish­ing year. Conclusions: In the evidence analysis it was found that mirror therapy is an interven­tion modality recently used by different rehabilitation professionals. Since 2004, an increase in the generation of high impact scientific evidence about this subject has been recognized, due in part to the reported effectiveness in clinical practices, mainly the treatment of health conditions secondary to stroke, limb amputations, chronic pain syndromes, and post-surgical rehabilitation. During the reviewed period, an increase in high level academic evidence was observed: 35.7 % of the analyzed publications correspond to randomized controlled trials and 42.9 % are system­atic reviews. The use of mirror therapy in occupational therapy is an intervention modality that facilitates functional rehabilitation processes, promotes independence in performing activities of daily living (adl and allows social participation and environment adaptation processes to happen.

  9. Clinical aspects of patients with sarcoglycanopathies under steroids therapy

    Directory of Open Access Journals (Sweden)

    Marco A. V. Albuquerque

    2014-10-01

    Full Text Available Patients with sarcoglycanopathies, which comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies, usually present with progressive weakness leading to early loss of ambulation and premature death, and no effective treatment is currently available. Objective To present clinical aspects and outcomes of six children with sarcoglycanopathies treated with steroids for at least one year. Method Patient files were retrospectively analyzed for steroid use. Results Stabilization of muscle strength was noted in one patient, a slight improvement in two, and a slight worsening in three. In addition, variable responses of forced vital capacity and cardiac function were observed. Conclusions No overt clinical improvement was observed in patients with sarcoglycanopathies under steroid therapy. Prospective controlled studies including a larger number of patients are necessary to determine the effects of steroids for sarcoglycanopathies.

  10. Neuropathic pain due to malignancy: Mechanisms, clinical manifestations and therapy

    Directory of Open Access Journals (Sweden)

    Pjević Miroslava

    2004-01-01

    Full Text Available Introduction Neuropathic pain in cancer patients requires a focused clinical evaluation based on knowledge of common neuropathic pain syndromes. Definition Neuropathic pain is a non-nociceptive pain or "differentiation" pain, which suggests abnormal production of impulses by neural tissue that is separated from afferent input. Impulses arise from the peripheral nervous system or central nervous system. Causes of neuropathic pain due to malignancy Neuropathic pain is caused directly by cancer-related pathology (compression/infiltration of nerve tissue, combination of compression/infiltration or by diagnostic and therapeutic procedures (surgical procedures, chemotherapy, radiotherapy. Mechanisms Pathophysiological mechanisms are very complex and still not clear enough. Neuropathic pain is generated by electrical hyperactivity of neurons along the pain pathways. Peripheral mechanisms (primary sensitization of nerve endings, ectopically generated action potentials within damaged nerves, abnormal electrogenesis within sensory ganglia and central mechanisms (loss of input from peripheral nociceptors into dorsal horn, aberrant sprouting within dorsal horn, central sensitization, loss of inhibitory interneurons, mechanisms at higher centers are involved. Diagnosis The quality of pain presents as spontaneous pain (continuous and paroxysmal, abnormal pain (allodynia, hyperalgesia, hyperpathia, paroxysmal pain. Clinical manifestations Clinically, neuropathic pain is described as the pain in the peripheral nerve (cranial nerves, other mononeuropathies, radiculopathy, plexopathy, paraneoplastic peripheral neuropathy and relatively infrequent, central pain syndrome. Therapy Treatment of neuropathic pain remains a challenge for clinicians, because there is no accepted algorithm for analgesic treatment of neuropathic pain. Pharmacotherapy is considered to be the first line therapy. Opioids combined with non-steroidal antiinflammatory drugs are warrented. If

  11. Clinical Opportunities in Combining Immunotherapy with Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Steven Eric Finkelstein

    2012-11-01

    Full Text Available Preclinical work in murine models suggests that local radiotherapy plus intratumoral syngeneic DC injection can mediate immunologic tumor eradication. Radiotherapy affects the immune response to cancer, besides the direct impact on the tumor cells, and other ways to coordinate immune modulation with radiotherapy have been explored. We review here the potential for immune mediated anticancer activity of radiation on tumors. This is mediated by antigen acquisition and presentation by dendritic cells, and through changes of lymphocytes’ activity. Recent work has implemented the combination of external beam radiation (EBRT with intratumoral injection of dendritic cells (DC. This included a pilot study of coordinated intraprostatic, autologous DC injection together with radiation therapy with five HLA-A2(+ subjects with high-risk, localized prostate cancer; the protocol used androgen suppression, external beam radiation therapy (25 fractions, 45 Gy, DC injections after fractions 5, 15, and 25, and then interstitial radioactive implant. Another was a phase II trial using neo-adjuvant cell death-inducing EBRT plus intra-tumoral DC in soft tissue sarcoma, to test if this would increase immune activity toward soft tissue sarcoma associated antigens. Clinical experience using radiation therapies combined with other systemic immune treatments are additionally surveyed, including use of investigational recombinant vaccinia and fowlpox, interleukin-2, toll like receptor 9 (TLR9 agonists and lymphocyte checkpoint inhibitors directed at PD1 and at CTLA4.

  12. [The sacroiliac joint dysfunction: clinical manifestations, diagnostics and manual therapy].

    Science.gov (United States)

    Grgić, Vjekoslav

    2005-01-01

    Sacroiliac joint dysfunction is one of the proved causes of sacroiliac joint syndrome. We are talking about the restricted mobility of sacrum opposite to ilium the type of "reversible blockage of movement". Main characteristics of dysfunction are as follows: restricted "joint play", referred pain, normal radiological finding, normal lab results and disappearance of clinical symptoms after deblocking of articular bodies. Pain from a blocked joint can be referred to lower back, buttocks, hip, groin, thigh, calf and lower part of abdomen. Dispersion of painful regions is a consequence of a complex and variable innervation of articular capsule. Blocked position of articular bodies and protracted tension of articular capsule causes a stimulus of nociceptors by which a capsule is protected. Nociceptive activity is manifested with referred pains in innervational region of stimulated sensitive nerves. In the article, besides the clinical manifestations, there is described a diagnostics and manual therapy of dysfunction. Springing tests by means of which a passive mobility ("joint play") is being tested, are most valuable in dysfunction diagnostics. Manual therapy (mobilization/manipulation) is indicated and efficacious with the patients suffering from dysfunction.

  13. Review on Clinical and Mechanism Studies of Moxibustion Therapy for Chronic Gastritis

    Institute of Scientific and Technical Information of China (English)

    Zhu Hui-wen; Ruan Chun-xun; Cao Shu-fei; Wu Huan-gan; Li Jing

    2014-01-01

    By computer research, the literature of clinical and experimental studies on moxibustion therapy for chronic gastritis in the recent fifteen years was collected, sorted and analyzed, in order to understand the general situation about the clinical and experimental studies on moxibustion therapy for chronic gastritis, summarize the regularity of moxibustion therapy for chronic gastritis, so as to guide the treatment of chronic gastritis.

  14. Music Therapy with Children: A Review of Clinical Utility and Application to Special Populations.

    Science.gov (United States)

    Yeaw, John David Andrew

    This paper reviews the effectiveness of music therapy in treating children with psychiatric and developmental problems. The clinical utility of music therapy is first evaluated by examining the foundational effects of music on affect and behavior. Next, the two broad approaches to music therapy, active and passive music therapy, are discussed.…

  15. Clinical trial designs for testing biomarker-based personalized therapies

    Science.gov (United States)

    Lai, Tze Leung; Lavori, Philip W; Shih, Mei-Chiung I; Sikic, Branimir I

    2014-01-01

    Background Advances in molecular therapeutics in the past decade have opened up new possibilities for treating cancer patients with personalized therapies, using biomarkers to determine which treatments are most likely to benefit them, but there are difficulties and unresolved issues in the development and validation of biomarker-based personalized therapies. We develop a new clinical trial design to address some of these issues. The goal is to capture the strengths of the frequentist and Bayesian approaches to address this problem in the recent literature and to circumvent their limitations. Methods We use generalized likelihood ratio tests of the intersection null and enriched strategy null hypotheses to derive a novel clinical trial design for the problem of advancing promising biomarker-guided strategies toward eventual validation. We also investigate the usefulness of adaptive randomization (AR) and futility stopping proposed in the recent literature. Results Simulation studies demonstrate the advantages of testing both the narrowly focused enriched strategy null hypothesis related to validating a proposed strategy and the intersection null hypothesis that can accommodate to a potentially successful strategy. AR and early termination of ineffective treatments offer increased probability of receiving the preferred treatment and better response rates for patients in the trial, at the expense of more complicated inference under small-to-moderate total sample sizes and some reduction in power. Limitations The binary response used in the development phase may not be a reliable indicator of treatment benefit on long-term clinical outcomes. In the proposed design, the biomarker-guided strategy (BGS) is not compared to ‘standard of care’, such as physician’s choice that may be informed by patient characteristics. Therefore, a positive result does not imply superiority of the BGS to ‘standard of care’. The proposed design and tests are valid asymptotically

  16. Quantitative radionuclide angiocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Scholz, P.M.; Rerych, S.K.; Moran, J.F.; Newman, G.E.; Douglas, J.M.; Sabiston, D.C. Jr.; Jones, R.H.

    1980-01-01

    This study introduces a new method for calculating actual left ventricular volumes and cardiac output from data recorded during a single transit of a radionuclide bolus through the heart, and describes in detail current radionuclide angiocardiography methodology. A group of 64 healthy adults with a wide age range were studied to define the normal range of hemodynamic parameters determined by the technique. Radionuclide angiocardiograms were performed in patients undergoing cardiac catherization to validate the measurements. In 33 patients studied by both techniques on the same day, a close correlation was documented for measurement of ejection fraction and end-diastolic volume. To validate the method of volumetric cardiac output calcuation, 33 simultaneous radionuclide and indocyanine green dye determinations of cardiac output were performed in 18 normal young adults. These independent comparisons of radionuclide measurements with two separate methods document that initial transit radionuclide angiocardiography accurately assesses left ventricular function.

  17. Cyclotron production of cesium radionuclides as analogues for francium-221 biodistribution

    Science.gov (United States)

    Finn, R.; McDevitt, M.; Sheh, Y.; Lom, C.; Qiao, J.; Cai, S.; Burnazi, E.; Nacca, A.; Pillarsetty, N.; Jaggi, J.; Scheinberg, D.

    2005-12-01

    In our clinical investigations focussing on improved therapeutic treatment of specific tumors we have concentrated on a targeted therapy approach utilizing designed radiolabeled monoclonal antibodies as the cytotoxic reagent. The physical characteristics of the alpha particle emitting radionuclide bismuth-213 including the short half-life of 45.6 min, has shown promise for the treatment of specific cancers such as leukemias and lymphomas or micrometastatic carcinomas. In an effort to increase the cytocidal effect of the HuM195, a humanized monoclonal antibody carrier to the CD33 antigen expressed on leukemia cells, our focus is directed toward an "internal" nano-generator composed of Ac-225 radionuclide, the parent of the bismuth-213. The actinium-225 radionuclide decays through several short-lived, alpha emitting daughters including francium-221, astatine-217 and bismuth-213. In order to study the biodistribution and the pharmacokinetics of the individual daughter nuclide, francium-221, the cyclotron production and separation of cesium radionuclides, specifically cesium-132, from a natural xenon gas target was undertaken. The choice of cesium as an analogue for francium was predicated upon both elements being in Group 1A alkali metals and cesium radionuclide possesses a sufficient half-life to allow biodistribution studies to be performed. The preliminary experimental results of this investigation are presented.

  18. Development of Clinic Specific Physical Therapy Efficiency Targets Based on Clinic Specific Metrics

    Science.gov (United States)

    2009-04-24

    efficiency ratings in the PBAM model which inflates the monetary budget adjustment for the MTF under the orthopedic product line. Developing individual... Veterinarians IF Fellow-Medical 1R Resident-Medical IS Intern-Dental IT Fellow-Dental 1U Resident-Dental IV Veterinarian 2 Direct Care Professional 2P...concerned with the Physical Therapy clinic under the Orthopedic (ORTHO) primary product line within the ambulatory section of the Product Line

  19. Gene therapy clinical trials worldwide 1989-2004-an overview.

    Science.gov (United States)

    Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo; Edelstein, Richard M

    2004-06-01

    In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918

  20. Clinical evidence of statin therapy in non-dyslipidemic disorders.

    Science.gov (United States)

    Ferri, Nicola; Corsini, Alberto

    2014-10-01

    The clinical benefits of statins are strongly related to their low density lipoprotein cholesterol (LDL-C) lowering properties. However, considering that the pharmacological target of statins, the 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase, is one of the upstream enzyme of the mevalonate pathway, its inhibition may determine a substantial impoverishment of additional lipid moieties required for a proper cellular function. From this hypothesis, several experimental and clinical evidences have been reported indicating additional effects of statins beyond the LDL-C lowering, in particular anti-inflammatory and immunomodulatory effects. Thus statin therapy, indicated for hyperlipidemic patients for primary and secondary prevention of coronary heart disease (CHD) has begun to be considered effective in other diseases not necessarily linked to altered lipid profile. In the present review we summarized the current clinical evidence of the efficacy and safety profile of statins in a variety of diseases, such as rheumatoid arthritis, venous thromboembolism, liver diseases, polycystic ovary syndrome, and age-related macular degeneration. As discussed in the review, pending large, well designed, randomized trials, it is reasonable to conclude that there is no definitive evidence for the use of statins in the aforementioned diseases.

  1. [Research advance on clinical blood transfusion and tumor therapy].

    Science.gov (United States)

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  2. Radiation therapy plan checks in a paperless clinic.

    Science.gov (United States)

    Siochi, R Alfredo; Pennington, Edward C; Waldron, Timothy J; Bayouth, John E

    2009-01-27

    Traditional quality assurance checks of a patient's radiation therapy plan involve printing out treatment parameters from the treatment planning system and the "record and verify" (R&V) system and visually checking the information for one-to-one correspondence. In a paperless environment, one can automate this process through independent software that can read the treatment planning data directly and compare it against the parameters in the R&V system's database. In addition to verifying the data integrity, it is necessary to check the logical consistency of the data and the accuracy of various calculations. The results are then imported into the patient's electronic medical record. Appropriate workflows must be developed to ensure that no steps of the QA process are missed. This paper describes our electronic QA system (EQS), consisting of in-house software and workflows. The EQS covers 3D conformal and intensity modulated radiation therapy, electrons, stereotactic radiosurgery, total body irradiation, and clinical set ups with and without virtual simulation. The planning systems handled by our EQS are ADAC Pinnacle and Varian FASTPLAN, while the R&V systems are LANTIS and VARIS. The improvement in our plan check process over the paperless system is described in terms of the types of detected errors. The potential problems with the implementation and use of the EQS, as well as workarounds for data that are not easily accessible through electronic means, are described.

  3. Basics of particle therapy II biologic and dosimetric aspects of clinical hadron therapy.

    Science.gov (United States)

    Rong, Yi; Welsh, James

    2010-12-01

    Besides photons and electrons, high-energy particles like protons, neutrons, ⁴He ions or heavier ions (C, Ne, etc) have been finding increasing applications in the treatment of radioresistant tumors and tumors located near critical structures. The main difference between photons and hadrons is their different biologic effect and depth-dose distribution. Generally speaking, protons are superior in dosimetric aspects whereas neutrons have advantages in biologic effectiveness because of the high linear energy transfer. In 1946 Robert Wilson first published the physical advantages in dose distribution of ion particles for cancer therapy. Since that time hadronic radiotherapy has been intensively studied in physics laboratories worldwide and clinical application have gradually come to fruition. Hadron therapy was made possible by the advances in accelerator technology, which increases the particles' energy high enough to place them at any depth within the patient's body. As a follow-up to the previous article Introduction to Hadrons, this review discusses certain biologic and dosimetric aspects of using protons, neutrons, and heavy charged particles for radiation therapy.

  4. Furcation therapy with bioabsorbable collagen membrane: a clinical trial.

    Science.gov (United States)

    Pruthi, Vijay K; Gelskey, Shirley C; Mirbod, Sayed M

    2002-11-01

    This study compared the effectiveness of 2 barrier membranes, expanded polytetrafluoroethylene (e-PTFE) and collagen, in treating Class II furcation defects of mandibular molars in humans. Seventeen nonsmoking subjects with no history of systemic disease each presenting with Class II furcation defects in 2 mandibular molars were selected and underwent initial therapy. At the time of the surgery and at 8-month follow-up, soft-tissue measurements consisting of the gingival index, vertical and horizontal probing depth, recession and clinical attachment level were obtained at the midfurcation level. At the time of membrane placement and at 12-month re-entry, horizontal midfurcation probing depth and hard-tissue measurement of vertical fill (from the crown to the depth of the pocket) were also obtained. According to the surgical protocol, both membranes were completely covered with a coronally positioned flap, and in all cases healing was uneventful. Data were analyzed first by comparing baseline measurements (at surgery) with measurements at 8-month follow-up and 12-month re-entry for both e-PTFE and collagen membranes according to repeated-measures analysis of variance. The changes from surgery to follow-up and re-entry were then compared between the 2 treatment modalities with paired Wilcoxon rank-sum tests. No statistically significant differences were found between e-PTFE and collagen membranes with respect to gingival index, reduction in probing depth, gain in clinical attachment or filling of the horizontal defect. However, the improvement in vertical fill at 12-month re-entry was more substantial for the teeth treated with collagen membrane than those treated with e-PTFE (p collagen is a beneficial material for regenerative therapy of Class II furcation defects in humans, yielding results that are similar to or better than (vertical fill) those for e-PTFE membrane.

  5. Clinical research evidence of cupping therapy in China: a systematic literature review

    OpenAIRE

    Wang Qian; Shang Yongmei; Dong Shangjuan; Li Xun; Han Mei; Cao Huijuan; Xu Shu; Liu Jianping

    2010-01-01

    Abstract Background Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it. This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies. Methods We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping...

  6. Clinical Implementation of Intensity Modulated Proton Therapy for Thoracic Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Heng; Zhu, X. Ronald [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing; Zhao, Lina [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Amy [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Yupeng [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Applied Research, Varian Medical Systems, Palo Alto, California (United States); Sahoo, Narayan; Poenisch, Falk [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wu, Richard; Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhang, Xiaodong, E-mail: xizhang@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-11-15

    Purpose: Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance. Methods and Materials: Thirty-four consecutive patients with lung/mediastinal cancers received IMPT to a median 66 Gy(relative biological equivalence [RBE]). All patients were able to undergo definitive radiation therapy. IMPT was used when the treating physician judged that IMPT conferred a dosimetric advantage; all patients had minimal tumor motion (<5 mm) and underwent individualized tumor-motion dose-uncertainty analysis and 4-dimensional (4D) computed tomographic (CT)-based treatment simulation and motion analysis. Plan robustness was optimized by using a worst-case scenario method. All patients had 4D CT repeated simulation during treatment. Results: IMPT produced lower mean lung dose (MLD), lung V{sub 5} and V{sub 20}, heart V{sub 40}, and esophageal V{sub 60} than did IMRT (P<.05) and lower MLD, lung V{sub 20}, and esophageal V{sub 60} than did passive scattering proton therapy (PSPT) (P<.05). D{sub 5} to the gross tumor volume and clinical target volume was higher with IMPT than with intensity modulated radiation therapy or PSPT (P<.05). All cases were analyzed for beam-angle-specific motion, water-equivalent thickness, and robustness. Beam angles were chosen to minimize the effect of respiratory motion and avoid previously treated regions, and the maximum deviation from the nominal dose-volume histogram values was kept at <5% for the target dose and met the normal tissue constraints under a worst-case scenario. Patient-specific quality assurance measurements showed that a median 99% (range, 95% to 100%) of the pixels met the 3% dose/3 mm distance criteria for the

  7. Radionuclide salivary gland imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mishkin, F.S.

    1981-10-01

    Salivary gland imaging with 99mTc as pertechnetate provides functional information concerning trapping and excretion of the parotid and submandibular glands. Anatomic information gained often adds little to clinical evaluation. On the other hand, functional information may detect subclinical involvement, which correlates well with biopsy of the minor labial salivary glands. Salivary gland abnormalities in systemic disease such as sarcoidosis, rheumatoid arthritis, lupus erythematosus, and other collagenvascular disorders may be detected before they result in the clinical manifestaions of Sjoegren's syndrome. Such glands, after initially demonstrating increased trapping in the acute phase, tend to have decreased trapping and failure to discharge pertechnetate in response to an appropriate physiologic stimulus. Increased uptake of gallium-67 citrate often accompanies these findings. Inflammatory parotitis can be suspected when increased perfusion is evident on radionuclide angiography with any agent. The ability of the salivary gland image to detect and categorize mass lesions, which result in focal areas of diminished activity such as tumors, cysts, and most other masses, is disappointing, while its ability to detect and categorize Warthin's tumor, which concentrates pertechnetate, is much more valuable, although not specific.

  8. Clinical relevance of stem cell therapies in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Amit K Srivastava

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS, characterized by the progressive loss of both upper and lower motor neurons, is a fatal neurodegenerative disorder. This disease is often accompanied by a tremendous physical and emotional burden not only for the patients, but also for their families and friends as well. There is no clinically relevant treatment available for ALS. To date, only one Food and Drug Administration (FDA-approved drug, Riluzole, licensed 18 years ago, has been proven to marginally prolong patients′ survival without improving the quality of their lives. Because of the lack of an effective drug treatment and the promising outcomes from several preclinical studies, researchers have highlighted this disease as a suitable candidate for stem cell therapy. This review article highlights the finding of key preclinical studies that present a rationale for the use of different types of stem cells for the treatment of ALS, and the most recent updates on the stem cell-based ALS clinical trials around the world.

  9. The influence of punctural millimeter wave therapy on clinical presentation of patients with essential hypertention

    Directory of Open Access Journals (Sweden)

    Kotenko К.V.

    2013-12-01

    Full Text Available Aim: to estimate the influence of punctural millimeter wave therapy on clinical presentation. Material and methods. This study includes 102 patients with essential hypertension the I and II stage. Patients were divided into three equal groups depending on the method of treatment: some of them received procedures of punctural millimeter wave therapy, some of them received these procedures as the "placebo" and those who had not received specified procedures. Dynamics of clinical symptomatology and condition of eye bottom vessels was estimated. It was shown that addition of punctural millimeter wave therapy in complex therapy of patients with essential hypertension promotes the expressed regress of clinical symptomatology and state normalization the retinal vessels at these patients. Results. Addition of punctural millimeter wave therapy into the complex therapy was shown to lead to pronounced regress of clinical symptoms. Conclusion. The received results allow to recommend this method to be used in clinical practice for treating patients with essential hypertension.

  10. Clinical effects of acupuncture therapy for vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Lei Zhao; Yi Guo; Jun Xiong; Wei Wang; Yuanhao Du; Lijuan Yan

    2011-01-01

    OBJECTIVE: To evaluate clinical acupuncture treatment studies for vascular dementia, as well as to collect high-quality evidence related to clinical acupuncture treatment for clinical diagnosis.DATA SOURCES: PubMed database(1966-2010), Embase database(1986-2010), Cochrane Library(Issue 1,2010), Chinese Biomedical Literature Database(1979-2010), China HowNet database(1979-2010), VI P Journals Database(1989-2010), and Wanfang database(1998-2010)were analyzed by computer.DATA SELECTION: Any form of acupuncture(needles, electro-acupuncture, laser acupuncture,pointer, or ear acupuncture), as well as blank, placebo, Western medicine, acupuncture therapy combined with other therapies, and randomized or quasi-randomized controlled studies were included. The priority was given to high-quality randomized, controlled trials. Data were independently extracted from two reviewers and cross-checked in accordance with high to low standards utilizing evidence-based medicine to answer five relevant clinical questions. Statistical outcome indicators were measured using RevMan 5.0.20 software, such as overall function,Hasegawa Dementia Scale score, Functional Activities Questionnaire score, Mini Mental State Examination, and efficacy of daily living activities.MAIN OUTCOME MEASURES: The present study assessed standards of efficacy, including Hasegawa Dementia Scale score, Functional Activities Questionnaire score, Mini Mental State Examination, and efficacy of daily living activities.RESULTS: A total of 11 articles were included, including one with systematic reviews/meta-analysis,one with Cochrane A level, eight with Cochrane B level, and one with Cochrane C level evidence.Acupuncture resulting in improved overall function and cognitive function was superior than Western medicine. A system evaluation showed the following: weighted mean difference(WMD)=5.64, 95% confidence interval(CI): 2.87-11.09, P <0.01; WMD = 6.07, 95% CI:3.76-8.38, P<0.01.Two articles with Class B evidences

  11. Coenzyme Q10 therapy in current clinical practice

    Directory of Open Access Journals (Sweden)

    Abhishek Soni

    2015-04-01

    Full Text Available Coenzyme Q10 (CoQ10 is a naturally occurring, lipid soluble, essential compound and is also known as ubiquinone. CoQ10 acts as an intermediate of the electron transport chain situated in membrane of mitochondria and vital for ATP production and cellular respiration. CoQ10 also serves as an intercellular antioxidant. All the clinical use of CoQ10 are based upon these two functions. CoQ10 levels are altered in a number of oncological as well as non-oncological diseases. Furthermore, recent data indicate that CoQ10 has an impact on the expression of many genes involved in metabolism, cellular transport, transcription control, and cell signaling, making CoQ10 a potent gene regulator. CoQ10 supplementation is useful in diseases associated with CoQ10 deficiency which includes primary and secondary CoQ10 deficiencies, fibromyalgia, diabetes mellitus, mitochondrial diseases, neurodegenerative diseases, cardiovascular disease, cancer, male infertility and periodontal disease. Clinical presentations of severe CoQ10 deficiency include severe infantile multisystemic disease, encephalomyopathy, isolated myopathy cerebellar ataxia and Leigh syndrome with growth retardation. Oral CoQ10 administration can correct CoQ10 deficiency since it increases CoQ10 tissue levels. CoQ10 therapy has no serious side effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Future trends involving CoQ10 in many diseases needs more clinical trials for better understanding of CoQ10 efficacy. [Int J Res Med Sci 2015; 3(4.000: 817-825

  12. Clinical significance of metallothioneins in cell therapy and nanomedicine

    Directory of Open Access Journals (Sweden)

    Sharma S

    2013-04-01

    Full Text Available Sushil Sharma,1 Afsha Rais,1 Ranbir Sandhu,1 Wynand Nel,1 Manuchair Ebadi21Saint James School of Medicine, Bonaire, The Netherlands; 2Department of Pharmacology, Physiology, and Therapeutics, Center of Excellence in Neuroscience, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USAAbstract: Mammalian metallothioneins (MTs are low molecular weight (6–7 kDa cysteine-rich proteins that are specifically induced by metal nanoparticles (NPs. MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide–ubiquinone oxidoreductase (complex-1, a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimine-induced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs

  13. New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177Lu-DOTA-AE105 targeting uPAR in human colorectal cancer xenografts

    DEFF Research Database (Denmark)

    Persson, Morten; Rasmussen, Palle; Madsen, Jacob;

    2012-01-01

    -of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. MethodsA DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64Cu and 177Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29...... by recording mouse weight and by H&E staining of kidneys in each treatment group. ResultsuPAR-positive HT-29 xenograft was clearly visualized by PET/CT imaging using 64Cu-DOTA-AE105. Subsequently, these xenograft transplants were locally irradiated using 177Lu-DOTA-AE105, where a significant effect on tumor...... size and the number of uPAR-positive cells in the tumor was found (p

  14. Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda

    Directory of Open Access Journals (Sweden)

    Namagala Elizabeth

    2009-08-01

    Full Text Available Abstract Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%, 24 of 40 clinical officers (60%, 16 of 114 nurses (14% and 13 of 54 midwives (24% who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p Conclusion Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.

  15. Clinical Study of Therapy for Intractable Ulcer of Skin

    Institute of Scientific and Technical Information of China (English)

    NING Jian; MO Xiaofeng; BU Jie; ZHANG Xianglan; RUI Yunzhen

    2002-01-01

    Objective Exploring therapy of skin ulcer. Method Using gauze with high - osmoticmetronidazole and glucose fluid fill up ulcer after conventional therapy. Observing proliferation of bacteriabefore and 1 week after therapy and comparing the healing time beween experimental and control group.Result Experintal group can inhibit proliferation of becteria and reduce healing time. ConclusionsHigh- osmotic metronidazole and glucose fluid is a safe and effective therapy to skin ulcer.

  16. Radionuclides in US coals

    Energy Technology Data Exchange (ETDEWEB)

    Bisselle, C. A.; Brown, R. D.

    1984-03-01

    The current state of knowledge with respect to radionuclide concentrations in US coals is discussed. Emphasis is placed on the levels of uranium in coal (and lignite) which are considered to represent a concern resulting from coal combustion; areas of the US where such levels have been found; and possible origins of high radionuclide levels in coal. The report reviews relevant studies and presents new data derived from a computerized search of radionuclide content in about 4000 coal samples collected throughout the coterminous US. 103 references, 5 figures, 5 tables.

  17. HYPERPHAGIA REACTIONS WITHIN EATING DISORDERS. CLINICAL FEATURES AND THERAPY

    Directory of Open Access Journals (Sweden)

    O. A. Gladyshev

    2015-09-01

    Full Text Available Aim. To evaluate clinical features of hyperphagia reactions, their significance in attraction abnormities within eating disorders and treatment options for these conditions with escitalopram.Material and methods. Mental state of 39 women (age 19-50 years with psychogenic overeating and obesity (body mass index of 30 to 53 kg/m2 was studied. Patients were admitted to the Institute of Nutrition of the Russian Academy of Medical Sciences. Diagnostic criteria for International Classification of Diseases, 10th edition, as well as Eating Disorder Inventory (EDI, Hospital Anxiety and Depression Scale (HADS and Ferreri Anxiety Rating Diagram (FARD were used for syndrome qualifications. Patient Global Impression of Change was also studied using a 4-point scale of results (excellent, good, fair, and negative.Results. Clinical features of hyperphagic reactions were found. Escitalopram treatment course was completed with excellent and good results in 80% of patients. 50%-reduction in HADS score for anxiety was found in 74% of patients, for depression – in 63%, and for Ferreri scale – in 68% of patients. Escitalopram promoted more intensive body weight loss: 11% vs 8% of baseline weight in active and control groups, respectively. Adverse events occurred only in 7 (36% patients; they were transient and did not require therapy discontinuation.Conclusion: Significant differences of premanifest disorders were often observed in patients history. Escitalopram in these patients showed efficacy in improvement of both mental and somatic symptoms of anxiety. It decreased dependence on food as a factor mitigating affect and stress, thus provided better results in body weight reduction.

  18. HYPERPHAGIA REACTIONS WITHIN EATING DISORDERS. CLINICAL FEATURES AND THERAPY

    Directory of Open Access Journals (Sweden)

    O. A. Gladyshev

    2014-01-01

    Full Text Available Aim. To evaluate clinical features of hyperphagia reactions, their significance in attraction abnormities within eating disorders and treatment options for these conditions with escitalopram.Material and methods. Mental state of 39 women (age 19-50 years with psychogenic overeating and obesity (body mass index of 30 to 53 kg/m2 was studied. Patients were admitted to the Institute of Nutrition of the Russian Academy of Medical Sciences. Diagnostic criteria for International Classification of Diseases, 10th edition, as well as Eating Disorder Inventory (EDI, Hospital Anxiety and Depression Scale (HADS and Ferreri Anxiety Rating Diagram (FARD were used for syndrome qualifications. Patient Global Impression of Change was also studied using a 4-point scale of results (excellent, good, fair, and negative.Results. Clinical features of hyperphagic reactions were found. Escitalopram treatment course was completed with excellent and good results in 80% of patients. 50%-reduction in HADS score for anxiety was found in 74% of patients, for depression – in 63%, and for Ferreri scale – in 68% of patients. Escitalopram promoted more intensive body weight loss: 11% vs 8% of baseline weight in active and control groups, respectively. Adverse events occurred only in 7 (36% patients; they were transient and did not require therapy discontinuation.Conclusion: Significant differences of premanifest disorders were often observed in patients history. Escitalopram in these patients showed efficacy in improvement of both mental and somatic symptoms of anxiety. It decreased dependence on food as a factor mitigating affect and stress, thus provided better results in body weight reduction.

  19. Clinical application of shock wave therapy (SWT) in musculoskeletal disorders.

    Science.gov (United States)

    Ioppolo, F; Rompe, J D; Furia, J P; Cacchio, A

    2014-04-01

    Currently the application of shock wave therapy (SWT) in musculoskeletal disorders has been primarily used in the treatment of tendinopathies (proximal plantar fasciopathy, lateral elbow tendinopathy, calcific tendinopathy of the shoulder, and patellar tendinopathy, etc.) and bone defects (delayed- and non-union of bone fractures, avascular necrosis of femoral head, etc.). Although the mechanism of their therapeutic effects are still unknown, the majority of published papers have shown positive and beneficial effects of using SWT as a treatment for musculoskeletal disorders, with a success rate ranging from 65% to 91%, while the complications are low or negligible. The purpose of this paper is to inform the reader about the published data on the clinical application of SWT in the treatment of musculoskeletal disorders. In this paper, with the help of a literature review, indications and success rates for SWT in the treatment of musculoskeletal disorders are outlined, while adequate SWT parameters (e.g., rate of impulses, energy flux density, etc.) are defined according to the present state of knowledge.

  20. Clinical characteristics and current therapies for inherited retinal degenerations.

    Science.gov (United States)

    Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

    2014-10-16

    Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307-316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod-cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances.

  1. [Calcium polycarbophil in clinical practice. The therapy of constipation].

    Science.gov (United States)

    Pallotta, N; Rubinetto, M P; Zaccaro, C; Gizzi, G; Villani, V; Barbara, L

    1993-12-01

    The clinical efficacy of polycarbophil calcium was assessed in 57 patients of both sexes aged between 18 and 77 years old affected by chronic non-organic constipation. The multicentre study was performed using a single blind and cross-over protocol for 8 weeks, 4 with placebo and 4 with the drug (2 c.p.s 3 t.i.d). Thirteen patients failed to complete the study, 8 of them for reasons not related to the drug. In comparison to placebo, the drug caused a significant reduction in the consistency of stool and evacuatory force during the first week of stool therapy. Medical judgement was that efficacy was "very good" in 73% and "good" in 18%, whereas the drug was thought to be "non efficacious" in 9% of cases. The statistical analysis of data confirmed the efficacy of the drug. The hematochemical parameters evaluated before, during and after treatment only showed a slight increase in calcemia and calciuria which did not reach statistical significance. The therapeutic efficacy and lack of undesired effects confirm the value of polycarbophyl calcium in the treatment of chronic constipation.

  2. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    Science.gov (United States)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  3. Radiation protection measures for reduction of incorporations of iodine-131 by the staff of a radionuclide therapy ward; Strahlenschutzmassnahmen zur Verringerung der Inkorporation von JOD-131 beim Personal einer Radionuklidtherapiestation

    Energy Technology Data Exchange (ETDEWEB)

    Petzold, J.; Meyer, K.; Lincke, T.; Sabri, O. [Universitaetsklinikum Leipzig (Germany); Alborzi, H. [LfULG Sachsen (Germany); Lorenz, J. [SMUL Sachsen (Germany); Schoenmuth, T. [VKTA Rossendorf (Germany); Keller, A. [Strahlenschutzseminar Thueringen e.V. (Germany)

    2009-07-01

    The air in patient's rooms with thyroid therapies is loaded with iodine 131, which is to be seen as a cause for the incorporation of iodine 131 by the staff. The patients exhale a part of the iodine applied for their intended radionuclide therapy. The activity is concentrated in the saliva and, thereby, the breath air is moistened and iodine reaches the exhaled and compartment air. The detection of iodine in the form of contaminations and/or incorporations with the staff succeeds only after a longer stay in the patient's room. With this, a clear relation between the particular type of work performed in the room and therapy of malignant thyroid disease with high amounts of radioactivity can be found. The measured values of incorporations, obtained with an whole-body counter, are in the range of up to 400Bq. The activity concentration in the compartment air some hours after application of the therapeutic activity reaches a maximum and then decreases with a half-life of about 15 hours. As a protection measure we asked the patients wearing a mask up to 30 hours after application to (orig.)

  4. Gender differences in clinical outcomes for cocaine dependence: Randomized clinical trials of behavioral therapy and disulfiram✩

    Science.gov (United States)

    DeVito, Elise E.; Babuscio, Theresa A.; Nich, Charla; Ball, Samuel A.; Carroll, Kathleen M.

    2014-01-01

    Background Despite extensive research on gender differences in addiction, there are relatively few published reports comparing treatment outcomes for women versus men based on evidence-based treatments evaluated in randomized clinical trials. Methods An aggregate sample comprised of data from five randomized clinical trials of treatment for cocaine dependence (N = 434) was evaluated for gender differences in clinical outcomes. Secondary analyses compared gender differences in outcome by medication condition (disulfiram versus no medication) and across multiple behavioral treatment conditions. Results Women, compared with men, had poorer treatment outcomes on multiple measures of cocaine use during treatment and at post-treatment follow-up. These results appear to be primarily accounted for by disulfiram being less effective in women compared with men. There was no evidence of meaningful gender differences in outcome as a function of the behavioral therapies evaluated. Conclusions These findings suggest that women and men may benefit to similar degrees from some empirically validated behavioral treatments for addiction. Conversely, some addiction pharmacotherapies, such as disulfiram, may be associated with poorer outcomes among women relative to men and point to the need for careful assessment of pharmacological treatments in both sexes prior to widespread clinical implementation. PMID:25457739

  5. [Collaborative study on regulatory science for facilitating clinical development of gene therapy products for genetic diseases].

    Science.gov (United States)

    Uchida, Eriko; Igarashi, Yuka; Sato, Yoji

    2014-01-01

    Gene therapy products are expected as innovative medicinal products for intractable diseases such as life-threatening genetic diseases and cancer. Recently, clinical developments by pharmaceutical companies are accelerated in Europe and the United States, and the first gene therapy product in advanced countries was approved for marketing authorization by the European Commission in 2012. On the other hand, more than 40 clinical studies for gene therapy have been completed or ongoing in Japan, most of them are conducted as clinical researches by academic institutes, and few clinical trials have been conducted for approval of gene therapy products. In order to promote the development of gene therapy products, revision of the current guideline and/or preparation of concept paper to address the evaluation of the quality and safety of gene therapy products are necessary and desired to clearly show what data should be submitted before First-in-Human clinical trials of novel gene therapy products. We started collaborative study with academia and regulatory agency to promote regulatory science toward clinical development of gene therapy products for genetic diseases based on lentivirus and adeno-associated virus vectors; National Center for Child Health and Development (NCCHD), Nippon Medical School and PMDA have been joined in the task force. At first, we are preparing pre-draft of the revision of the current gene therapy guidelines in this project.

  6. The entry-level occupational therapy clinical doctorate: advantages, challenges, and international issues to consider.

    Science.gov (United States)

    Brown, Ted; Crabtree, Jeffrey L; Mu, Keli; Wells, Joe

    2015-04-01

    Internationally, occupational therapy education has gone through several paradigm shifts during the last few decades, moving from certificate to diploma to bachelors to masters and now in some instances to clinical doctorate as the entry-level professional credential to practice. In the United States there is a recommendation under consideration by the American Occupational Therapy Association (AOTA) that by 2025, all occupational therapy university programs will move to the clinical doctorate level. It should be noted, however, that the AOTA Board can only make recommendations and it is the Accreditation Council for Occupational Therapy Education (ACOTE) who has regulatory authority to approve such a change. What are the potential implications for the profession, our clients, and funders of occupational therapy services? What are the primary drivers for the move towards the clinical doctorate being the educational entry point? Is the next step in the evolution of occupational therapy education globally a shift to the entry-level clinical doctorate? This article reviews current literature and discusses issues about the occupational therapy entry-level clinical doctorate. The published evidence available about the occupational therapy entry-level clinical doctorate is summarized and the perceived or frequently cited pros and cons of moving to the clinical doctorate as the singular entry point to occupational therapy practice are considered. The potential impacts of the introduction of the clinical doctorate as the entry-to-practice qualification across the United States on the occupational therapy community internationally will be briefly discussed. If the United States moves toward the entry-level clinical doctorate as the only educational starting point for the profession, will other jurisdictions follow suit? Further discourse and investigation of this issue both inside and outside of the United States is needed so that informed decisions can be made.

  7. Changing the culture of clinical education in massage therapy.

    Science.gov (United States)

    Baskwill, Amanda

    2011-01-01

    Much within the profession of massage therapy is done according to tradition. From an epistemological viewpoint, tradition is a way of knowing or, by extension, being, that is based upon both tenacity and authority and not always in best practices. As the profession of massage therapy moves in the direction of evidence-based medicine, or evidence-informed practice, the opportunity to re-evaluate massage therapy education presents itself.

  8. Abnormal Bleeding During Menopause Hormone Therapy: Insights for Clinical Management

    OpenAIRE

    2013-01-01

    Objective Our objective was to review the involved mechanisms and propose actions for controlling/treating abnormal uterine bleeding during climacteric hormone therapy. Methods A systemic search of the databases SciELO, MEDLINE, and Pubmed was performed for identifying relevant publications on normal endometrial bleeding, abnormal uterine bleeding, and hormone therapy bleeding. Results Before starting hormone therapy, it is essential to exclude any abnormal organic condition, identify women a...

  9. Lubiprostone in constipation: clinical evidence and place in therapy.

    Science.gov (United States)

    Wilson, Nicholas; Schey, Ron

    2015-03-01

    Constipation is one of the most common function bowel disorders encountered by primary care providers and gastroenterologists. Disorders of chronic constipation, including irritable bowel syndrome with constipation, chronic idiopathic constipation, and opioid-induced chronic constipation, are associated with significant medical costs and a negative impact on quality of life. Although there is evidence supporting the effectiveness of some over-the-counter laxatives in chronic constipation, currently there is no evidence supporting lifestyle modification, dietary change or over-the-counter laxatives as effective long-term therapy for patients with chronic constipation. Lubiprostone is a prostaglandin-derived bicyclic fatty acid available to use for long-term treatment of constipation. Lubiprostone works by increasing intraluminal chloride ion secretion, which results in a passive influx of water and sodium, leading to increased intestinal peristalsis and colonic laxation with decreased intestinal stool transit time. Randomized, double-blind, placebo-controlled trials of lubiprostone in patients with chronic constipation, irritable bowel syndrome and opioid-induced constipation have shown it to be effective and free of serious adverse effects. The most common side effects associated with lubiprostone are mild to moderate nausea and diarrhea. Currently lubiprostone is approved for treatment of chronic constipation and opioid-induced constipation for men and women at 24 µg twice daily and for treatment of irritable bowel syndrome with constipation in women at 8 µg twice daily. Additional research continues to shed light on the molecular mechanisms of lubiprostone and further work may expand its clinical applications.

  10. Evolution of targeted therapies in cancer: opportunities and challenges in the clinic.

    Science.gov (United States)

    Santhosh, Sam; Kumar, Prasanna; Ramprasad, Vedam; Chaudhuri, Amitabha

    2015-01-01

    Targeted therapies have changed the course of cancer treatment in recent years. By reducing toxicity and improving outcome, these new generations of precision medicines have extended patient lives beyond what could be achieved by the use of nontargeted therapies. In the last 2 years, several new molecular entities targeting signaling proteins and immune pathways have gone through successful clinical development resulting in their approval. These new targeted therapies require patient selection and the discovery of biomarkers of response. This review discusses the evolution of targeted therapies in cancer and challenges in translating the concepts into clinical practice.

  11. Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study

    Directory of Open Access Journals (Sweden)

    Benjamin M Davies

    2014-09-01

    Full Text Available There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

  12. Quantitative Single-Particle Digital Autoradiography with α-Particle Emitters for Targeted Radionuclide Therapy using the iQID Camera

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Brian W.; Frost, Sophia; Frayo, Shani; Kenoyer, Aimee L.; Santos, E. B.; Jones, Jon C.; Green, Damian J.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Orozco, Johnnie J.; Press, Oliver W.; Pagel, John M.; Sandmaier, B. M.

    2015-07-01

    Abstract Alpha emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50–80 μm) causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with alpha emitters may inactivate targeted cells with minimal radiation damage to surrounding tissues. For accurate dosimetry in alpha-RIT, tools are needed to visualize and quantify the radioactivity distribution and absorbed dose to targeted and non-targeted cells, especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, iQID (ionizing-radiation Quantum Imaging Detector), for use in alpha-RIT experiments. Methods: The iQID camera is a scintillator-based radiation detection technology that images and identifies charged-particle and gamma-ray/X-ray emissions spatially and temporally on an event-by-event basis. It employs recent advances in CCD/CMOS cameras and computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, we evaluated this system’s characteristics for alpha particle imaging including measurements of spatial resolution and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 (211At) activity distributions in cryosections of murine and canine tissue samples. Results: The highest spatial resolution was measured at ~20 μm full width at half maximum (FWHM) and the alpha particle background was measured at a rate of (2.6 ± 0.5) × 10–4 cpm/cm2 (40 mm diameter detector area). Simultaneous imaging of multiple tissue sections was performed using a large-area iQID configuration (ø 11.5 cm

  13. Quantitative single-particle digital autoradiography with α-particle emitters for targeted radionuclide therapy using the iQID camera

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Brian W., E-mail: brian.miller@pnnl.gov [Pacific Northwest National Laboratory, Richland, Washington 99354 and College of Optical Sciences, The University of Arizona, Tucson, Arizona 85719 (United States); Frost, Sofia H. L.; Frayo, Shani L.; Kenoyer, Aimee L.; Santos, Erlinda; Jones, Jon C.; Orozco, Johnnie J. [Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 (United States); Green, Damian J.; Press, Oliver W.; Pagel, John M.; Sandmaier, Brenda M. [Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 and Department of Medicine, University of Washington, Seattle, Washington 98195 (United States); Hamlin, Donald K.; Wilbur, D. Scott [Department of Radiation Oncology, University of Washington, Seattle, Washington 98195 (United States); Fisher, Darrell R. [Dade Moeller Health Group, Richland, Washington 99354 (United States)

    2015-07-15

    Purpose: Alpha-emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50–80 μm), causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with α emitters may thus inactivate targeted cells with minimal radiation damage to surrounding tissues. Tools are needed to visualize and quantify the radioactivity distribution and absorbed doses to targeted and nontargeted cells for accurate dosimetry of all treatment regimens utilizing α particles, including RIT and others (e.g., Ra-223), especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, the ionizing-radiation quantum imaging detector (iQID) camera, for use in α-RIT experiments. Methods: The iQID camera is a scintillator-based radiation detection system that images and identifies charged-particle and gamma-ray/x-ray emissions spatially and temporally on an event-by-event basis. It employs CCD-CMOS cameras and high-performance computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, the authors evaluated its characteristics for α-particle imaging, including measurements of intrinsic detector spatial resolutions and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 ({sup 211}At) activity distributions in cryosections of murine and canine tissue samples. Results: The highest spatial resolution was measured at ∼20 μm full width at half maximum and the α-particle background was measured at a rate as low as (2.6 ± 0.5) × 10{sup −4} cpm/cm{sup 2} (40 mm diameter detector area

  14. Reflections on clinical reasoning in mental health occupational therapy: the case of the occupational therapy dynamic method

    Directory of Open Access Journals (Sweden)

    Taís Quevedo Marcolino

    2014-12-01

    Full Text Available The Clinical Reasoning Study supported by the American Occupational Therapy Association/AOTA and the American Occupational Therapy Foundation/AOTF in the United States in the late 1980s, had inaugurated the scientific production in the field and offered an initial framework on clinical reasoning for understanding and conducting clinical cases in Occupational Therapy. Most of the researches in this field have focused on reasoning processes, and point out the need to understand the contents of clinical thoughts, or how occupational therapists act and elaborate hypotheses, based on their background knowledge, in order to produce an explanatory theory. In this direction, this article presents the results of two studies from the author focused on understanding aspects of clinical reasoning of occupational therapists who work sustained by Occupational Therapy Dynamic Method/ MTOD, highlighting similarities and differences on diagnostic and procedural reasoning. The discussion points out need to expand the production of this type of research, in particular with Brazilian professionals, as well as the dissemination and study of this subject in the initial and continuing training of occupational therapists.

  15. Comparison of clinical results of pharmaceutical and surgical therapy in patients with severe chronic heart failure

    Directory of Open Access Journals (Sweden)

    Kotsoeva О.Т.

    2016-06-01

    Full Text Available The aim of the presented paper is a meta-analysis of clinical studies on the comparative effectiveness of pharmaceutical therapy and surgical treatment such as cardiac resynchronization therapy (CRT, cardiac resynchronization therapy with cardioversion-defibrillation (CRT-D, circulatory support system and heart transplantation in patients with severe chronic heart failure (CHF. Material and Methods. Results of 41 clinical studies (29799 patients with severe CHF were included in a meta-analysis. Data search was conducted in the following databases: Medline, Medscape, Pubmed, and websites dedicated to clinical research (National Institutes of Health, Clinical Center, ClinicalStudyResults.org, ClinicalTrials.gov. Results. As compared with pharmaceutical therapy, surgical treatment of severe CHF is better to reduce fatal risk, incidence of decompensation of CHF, frequency of cardiac arrhythmias, the need to perform or re-perform heart transplantation. It is also shown that CRT better reduced the mortality from progression of heart failure than heart transplantation. Both pharmaceutical therapy and surgical treatment improved functional class of CHF and quality of patients' life, but does not affect the left ventricular ejection fraction. Conclusion. It was found out that there was a number of significant advantages of surgical treatment of severe CHF, compared with pharmaceutical therapy. However, it is still a number of unresolved issues (particularly in relation to heart transplantation on the effectiveness comparing pharmaceutical and surgical therapies of severe CHF

  16. Clinical implications of antithrombotic therapy in dentistry: a literature review

    OpenAIRE

    Seguro, Joel David Martinho

    2016-01-01

    Tese de mestrado, Medicina Dentária, Universidade de Lisboa, Faculdade de Medicina Dentária, 2016 Introduction: The therapeutical approach of patients under chronic antithrombotic therapy needing dental procedures causes great controversy. The increased hemorrhage risk associated with these procedures when the patient is undergoing this therapy must be taken into account relatively to the increased thrombotic risk caused by its interruption. The aim of this study was to review the current ...

  17. A prospective 9-month human clinical evaluation of Laser-Assisted New Attachment Procedure (LANAP) therapy.

    Science.gov (United States)

    Nevins, Marc; Kim, Soo-Woo; Camelo, Marcelo; Martin, Ignacio Sanz; Kim, David; Nevins, Myron

    2014-01-01

    This investigation was designed and implemented as a single-center, prospective study to evaluate the clinical response to the Laser-Assisted New Attachment Procedure (LANAP). Eight patients with advanced periodontitis were enrolled and treated with full-mouth LANAP therapy and monitored for 9 months. Fullmouth clinical measurements, including clinical attachment level (CAL), probing depth (PD), and recession, were provided at baseline and after 9 months of healing by a single calibrated examiner, including a total of 930 sites and 444 sites with initial PD equal to or greater than 5 mm. Clinical results for the 930 sites measured pre- and postoperatively revealed that mean PD was reduced from 4.62 ± 2.29 mm to 3.14 ± 1.48 mm after 9 months (P LANAP therapy should be further investigated with long-term clinical trials to compare the stability of clinical results with conventional therapy.

  18. Radionuclides in house dust

    CERN Document Server

    Fry, F A; Green, N; Hammond, D J

    1985-01-01

    Discharges of radionuclides from the British Nuclear Fuel plc (BNFL) reprocessing plant at Sellafield in Cumbria have led to elevated concentrations radionuclides in the local environment. The major routes of exposure of the public are kept under review by the appropriate Government departments and monitoring is carried out both by the departments and by BNFL itself. Recently, there has been increasing public concern about general environmental contamination resulting from the discharges and, in particular, about possible exposure of members of the public by routes not previously investigated in detail. One such postulated route of exposure that has attracted the interest of the public, the press and Parliament arises from the presence of radionuclides within houses. In view of this obvious and widespread concern, the Board has undertaken a sampling programme in a few communities in Cumbria to assess the radiological significance of this source of exposure. From the results of our study, we conclude that, alt...

  19. Rational-Emotive Therapy: Research Data That Supports the Clinical and Personality Hypotheses of Ret and Other Modes of Cognitive-Behavior Therapy

    Science.gov (United States)

    Ellis, Albert

    1977-01-01

    This article examines 32 important clinical and personality hypotheses of rational-emotive therapy (RET) and other modes of cognitive-behavior therapy and lists a large number of research studies that provide empirical confirmation of these hypotheses. (Author)

  20. Towards combinatorial targeted therapy in melanoma: from pre-clinical evidence to clinical application (review).

    Science.gov (United States)

    Grazia, Giulia; Penna, Ilaria; Perotti, Valentina; Anichini, Andrea; Tassi, Elena

    2014-09-01

    Over the last few years, clinical trials with BRAF and mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors have shown significant clinical activity in melanoma, but only a fraction of patients respond to these therapies, and development of resistance is frequent. This has prompted a large set of preclinical studies looking at several new combinatorial approaches of pathway- or target-specific inhibitors. At least five main drug association strategies have been verified in vitro and in preclinical models. The most promising include: i) vertical targeting of either MEK or phosphoinositide-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways, or their combined blockade; ii) association of receptor tyrosine kinases (RTKs) inhibitors with other pro-apoptotic strategies; iii) engagement of death receptors in combination with MEK-, mTOR/PI3K-, histone deacetylase (HDAC)-inhibitors, or with anti-apoptotic molecules modulators; iv) strategies aimed at blocking anti-apoptotic proteins belonging to B-cell lymphoma (Bcl-2) or inhibitors of apoptosis (IAP) families associated with MEK/BRAF/p38 inhibition; v) co-inhibition of other molecules important for survival [proteasome, HDAC and Signal transducers and activators of transcription (Stat)3] and the major pathways activated in melanoma; vi) simultaneous targeting of multiple anti-apoptotic molecules. Here we review the anti-melanoma efficacy and mechanism of action of the above-mentioned combinatorial strategies, together with the potential clinical application of the most promising studies that may eventually lead to therapeutic benefit.

  1. Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome

    DEFF Research Database (Denmark)

    Claesson, J; Freundlich, M; Gunnarsson, I

    2016-01-01

    BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according...

  2. Implant therapy for a patient with Down syndrome and oral habits: A clinical report.

    Science.gov (United States)

    Saponaro, Paola C; Deguchi, Toru; Lee, Damian J

    2016-09-01

    This clinical report describes prosthodontic therapy with an implant-supported partial fixed dental prosthesis for a patient with Down syndrome and concomitant oral habits, including tongue thrusting and thumb sucking.

  3. ACC/AHA CLOPIDOGREL CLINICAL ALERT. WHAT MUST BE MODERN ANTIPLATELET THERAPY?

    OpenAIRE

    S. J. Martsevich

    2010-01-01

    The ACC/AHA clopidogrel clinical alert about the possibility of ineffective treatment with clopidogrel is discussed. The reason of this resistance to clopidogrel therapy and possible ways to overcome it is considered.

  4. Clinical observation on common peroneal nerve palsy treated with comprehensive therapy

    Institute of Scientific and Technical Information of China (English)

    杨丽娟

    2014-01-01

    Objective To compare the difference of the clinical efficacy on common peroneal nerve palsy between the comprehensive therapy of electroacupuncture,moxibustion and moving cupping method and western medication.Methods Ninety cases of common peroneal nerve palsy were randomized into a comprehensive therapy group and a western medication group,45 cases in each

  5. Art Therapy for an Individual with Late Stage Dementia: A Clinical Case Description

    Science.gov (United States)

    Tucknott-Cohen, Tisah; Ehresman, Crystal

    2016-01-01

    This article describes the healing benefits of art therapy for an individual with dementia of the Alzheimer's type. In this clinical case description, a woman diagnosed with Alzheimer's disease received individual art therapy for 17 weeks. The treatment concerns that arose, altered view of reality, agitation, and retrogenesis provide insight on…

  6. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  7. Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

    Science.gov (United States)

    Tendler, Rabbi Moshe D.; Loike, John D.

    2015-01-01

    The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal. PMID:26241230

  8. Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

    Directory of Open Access Journals (Sweden)

    Rabbi Moshe D. Tendler

    2015-07-01

    Full Text Available The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal.

  9. Loading technique for preparing radionuclide containing nanoparticles

    DEFF Research Database (Denmark)

    2011-01-01

    Source: US2012213698A The present invention relates to a novel composition and method for loading delivery systems such as liposome compositions with radionuclides useful in targeted diagnostic and/or therapy of target site, such as cancerous tissue and, in general, pathological conditions associ...... of positron emission tomography (PET) imaging technique. One specific aspect of the invention is directed to a method of producing nanoparticles with desired targeting properties for diagnostic and/or radio-therapeutic applications....

  10. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

    Science.gov (United States)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  11. Laser Assisted Non-surgical Periodontal Therapy: A Double Blind, Randomized Clinical Trial

    Science.gov (United States)

    Everett, Joseph D.; Rossmann, Jeffrey A.; Kerns, David G.; Al-Hashimi, Ibtisam

    2017-01-01

    The objective of this study was to examine potential benefits of using laser therapy for secular decontamination in conjunction with scaling and root planing in the treatment of chronic periodontitis. The study was performed on 173 teeth in 14 patients in a split-mouth design, one side received scaling and root planing followed by laser therapy using a carbon dioxide (CO2) laser with an ablative handpiece (test group); the contralateral side received scaling and root planing without laser (control group). Clinical and laboratory parameters were evaluated prior to treatment and at 3 and 6 months following therapy; clinical measurements were performed by two blinded examiners. The clinical parameters included measurement of gingival recession (REC), bleeding on probing (BOP), clinical attachment level (CAL), pocket depth (PD), furcation involvement (FUR), and tooth mobility (MOB). Laboratory testing to determine the levels of periodontal pathogens was performed using PCR techniques. The results of the study revealed statistically significant differences in clinical and laboratory parameters at 3 and 6 months after therapy for both test and control groups, but no significant difference was observed between the two groups. However, sites receiving laser therapy tended to show a greater decrease in probing depths, gain in clinical attachment level, and reduced bacterial levels. In conclusion, the overall results of the study suggest a potential benefit of using laser therapy in conjunction with scaling and root planing for the treatment of chronic periodontitis. PMID:28357001

  12. Radionuclide diagnostics of right ventricle; Diagnostyka radioizotopowa prawej komory serca

    Energy Technology Data Exchange (ETDEWEB)

    Zaorska-Rajca, J.

    1993-12-31

    Difficulties in evaluating the right ventricle function motivate to making research into new non-invasive methods. Four radionuclide methods that are used to access the right ventricle have been discussed in this paper: first-pass angiocardiography, gated equilibrium ventriculography with red blood cells labelled in vivo technetium-{sup 99}Tc, ventriculography with radioactive xenon 133 and a computerized single probe. Advantages and disadvantages of using each method have been discussed. RNV {sup 99m}Tc method has been recognized as the best one to evaluate RV function. Results of the right ventricle assessment in patients have been discussed in the following clinical groups: chronic cor pulmonale (CP), chronic lung disease without pulmonary arterial hypertension (LD), coronary artery disease (CAD), in patients after infarction (IMA and IMi), dilated cardiomyopathy (KZ) and valvular heart diseases (Wm and Wa). Abnormals in right ventricle function occur with different intensity in all groups, although they no specificity. The highest abnormality occurs in patients with KZ, CP, IMi and Wm, the lowest one - in patients with CAD. Abnormalities are higher in patients with congestive heart failure. In most pathological groups the right ventricle dysfunction is connected with the left ventricle insufficiency. The interdependence between the dysfunction of both ventricles is differs in particular diseases. Assessment of right ventricle function with radionuclide methods plays an important role in diagnosis and control therapy of cardiopulmonary diseases. (author). 385 refs, 48 figs, 6 tabs.

  13. Preparation of Radiopharmaceuticals Labeled with Metal Radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    2012-02-16

    The overall goal of this project was to develop methods for the production of metal-based radionuclides, to develop metal-based radiopharmaceuticals and in a limited number of cases, to translate these agents to the clinical situation. Initial work concentrated on the application of the radionuclides of Cu, Cu-60, Cu-61 and Cu-64, as well as application of Ga-68 radiopharmaceuticals. Initially Cu-64 was produced at the Missouri University Research Reactor and experiments carried out at Washington University. A limited number of studies were carried out utilizing Cu-62, a generator produced radionuclide produced by Mallinckrodt Inc. (now Covidien). In these studies, copper-62-labeled pyruvaldehyde Bis(N{sup 4}-methylthiosemicarbazonato)-copper(II) was studied as an agent for cerebral myocardial perfusion. A remote system for the production of this radiopharmaceutical was developed and a limited number of patient studies carried out with this agent. Various other copper radiopharmaceuticals were investigated, these included copper labeled blood imaging agents as well as Cu-64 labeled antibodies. Cu-64 labeled antibodies targeting colon cancer were translated to the human situation. Cu-64 was also used to label peptides (Cu-64 octriatide) and this is one of the first applications of a peptide radiolabeled with a positron emitting metal radionuclide. Investigations were then pursued on the preparation of the copper radionuclides on a small biomedical cyclotron. A system for the production of high specific activity Cu-64 was developed and initially the Cu-64 was utilized to study the hypoxic imaging agent Cu-64 ATSM. Utilizing the same target system, other positron emitting metal radionuclides were produced, these were Y-86 and Ga-66. Radiopharmaceuticals were labeled utilizing both of these radionuclides. Many studies were carried out in animal models on the uptake of Cu-ATSM in hypoxic tissue. The hypothesis is that Cu-ATSM retention in vivo is dependent upon the

  14. Clinical infection control in gene therapy : A multidisciplinary conference

    NARCIS (Netherlands)

    Evans, ME; Jordan, CT; Chang, SMW; Conrad, C; Gerberding, JL; Kaufman, HL; Mayhall, CG; Nolta, JA; Pilaro, AM; Sullivan, S; Weber, DJ; Wivel, NA

    2000-01-01

    Gene therapy is being studied for the treatment of a variety of acquired and inherited disorders. Retroviruses, adenoviruses, poxviruses, adeno-associated viruses, herpesviruses, and others are being engineered to transfer genes into humans. Treatment protocols using recombinant viruses are being in

  15. Clinical Guide to Music Therapy in Physical Rehabilitation Settings

    Science.gov (United States)

    Wong, Elizabeth

    2004-01-01

    Elizabeth Wong, MT-BC presents tools and information designed to arm the entry-level music therapist (or an experienced MT-BC new to rehabilitation settings) with basic knowledge and materials to develop or work in a music therapy program treating people with stroke, brain injury, and those who are ventilator dependent. Ms. Wong offers goals and…

  16. Clinical outcome of surgical periodontal therapy: a short-term retrospective study.

    Science.gov (United States)

    Hayakawa, Hiroki; Fujinami, Koushu; Ida, Atsushi; Furusawa, Masahiro; Nikaido, Masahiko; Yamashita, Shuichiro; Saito, Atsushi

    2012-01-01

    This study aimed to investigate retrospectively the outcome of surgical periodontal therapy. Periodontal surgeries implemented at General Dentistry, Tokyo Dental College Suidobashi Hospital during the period of April 2010 through March 2012 were subjected to data analysis. After initial periodontal therapy, 17 clinicians performed a total of 138 periodontal surgeries in 80 patients with moderate to advanced periodontitis (31 men and 49 women; mean age 54). Cases (sites) operated were as follows: open flap debridement=102, periodontal regenerative therapy=29 (17 for intrabony defects, 12 for furcation involvements) and periodontal plastic surgery=7. Enamel matrix derivative or bone graft was used for regenerative therapy. Clinical data were analyzed focusing on the comparison between open flap debridement and regenerative therapy. At 5 months after open flap debridement, mean reduction in probing depth (PD) and gain in clinical attachment level (CAL) was 3.9 mm (range -1.0-9.0) and 2.3 mm (range -1.0-9.0), respectively. The corresponding values with regenerative therapy were 4.0 mm (range 0-8.0) and 2.8 mm (-1.0-6.0), respectively. At sites with initial PD≥8 mm, a significantly greater gain in CAL was obtained with the regenerative therapy than with flap surgery (mean CAL gain 4.3 mm vs. 2.9 mm, pPeriodontal surgery performed in our clinical setting demonstrated a favorable short-term outcome. Our data suggest the efficacy of regenerative therapy, in particular for the treatment of deep pockets.

  17. Clinical evolution of mediastinitis in patients undergoing adjuvant hyperbaric oxygen therapy after coronary artery bypass surgery

    Science.gov (United States)

    do Egito, Julyana Galvão Tabosa; Abboud, Cely Saad; de Oliveira, Aline Pâmela Vieira; Máximo, Carlos Alberto Gonçalves; Montenegro, Carolina Moreira; Amato, Vivian Lerner; Bammann, Roberto; Farsky, Pedro Silvio

    2013-01-01

    ABSTRACT Objective: To evaluate the use of hyperbaric oxygen therapy as an adjunctive treatment in mediastinitis after coronary artery bypass surgery. Methods: This is a retrospective descriptive study, performed between October 2010 and February 2012. Hyperbaric oxygen therapy was indicated in difficult clinical management cases despite antibiotic therapy. Results: We identified 18 patients with mediastinitis during the study period. Thirty three microorganisms were isolated, and polymicrobial infection was present in 11 cases. Enterobacteriaceae were the most prevalent pathogens and six were multi-resistant agents. There was only 1 hospital death, 7 months after the oxygen therapy caused by sepsis, unrelated to hyperbaric oxygen therapy. This treatment was well-tolerated. Conclusion: The initial data showed favorable clinical outcomes. PMID:24136762

  18. Clinical application of dendritic cells in cancer vaccination therapy

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Soot, Mette Line; Buus, Søren

    2003-01-01

    During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols...... for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...... endpoints, including toxicity and response evaluation. This paper aims to review the technical aspects and clinical impact of vaccination trials, focusing on the generation of DC-based vaccines, evaluation of immunologic parameters and design of clinical trials necessary to meet the need for good laboratory...

  19. 甲亢性心脏病应用碘131核素辅以普萘洛尔的临床研究%Clinical Study of 131 Hyperthyroid Heart Disease Application of Ra-dionuclide Combined with Propranolol

    Institute of Scientific and Technical Information of China (English)

    张丽莉

    2016-01-01

    Objective To analyze the application of iodine 131 radionuclide combined with the clinical effects of pro-pranolol treatment of hyperthyroid heart disease. Methods March 2015 to March 2016 in our hospital for treatment of 84 cases of hyperthyroid patients with heart disease, the application of computer sampling group, the control group of 42 cases were treated by propranolol,the observation group of 42 cases of application of radionuclide iodine 131 treat-ment with propranolol,observe clinical efficacy and adverse reactions. Results The total study group was 92.86%higher than 73.81%, P0.05. Conclusion Iodine 131 radionuclide combined with propranolol to treat hyperthyroidism heart disease can sig-nificantly reduce the amount of thyroid hormone, promote clinical efficacy.%目的:研究分析应用碘131核素辅以普萘洛尔治疗甲亢性心脏病的临床效果。方法选择2015年3月—2016年3月期间在该院进行治疗的84例甲亢性心脏病患者,应用计算机抽样法进行分组,对照组42例应用普萘洛尔进行治疗,观察组42例应用碘131核素辅以普萘洛尔进行治疗,观察临床疗效和不良反应。结果研究组总有效率92.86%高于对照组73.81%,P0.05。结论应用碘131核素辅以普萘洛尔治疗甲亢性心脏病可明显降低甲状腺激素的含量,促进临床疗效的提高。

  20. {sup 213}Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

    Energy Technology Data Exchange (ETDEWEB)

    Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Boll, R.; Murphy, K. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    2014-11-15

    Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as {sup 90}Y/{sup 177}Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with {sup 213}Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with {sup 90}Y/{sup 177}Lu-DOTATOC were treated with an intraarterial infusion of {sup 213}Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of {sup 213}Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and {sup 68}Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of {sup 213}Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)

  1. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice.

    Science.gov (United States)

    Lee, Ho Sup; Min, Chang-Ki

    2016-09-01

    Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice.

  2. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  3. Strategies used in the clinical trials of gene therapy for cancer.

    Science.gov (United States)

    Ajith, Thekkuttuparambil Ananthanarayanan

    2015-01-01

    Advances in understanding and manipulating genes have set the stage for scientists to alter a person's genetic material to prevent or treat diseases. Over the past decade, somatic gene therapy has been increasingly applied in clinical trials where the genetic material (DNA and RNA) introduced into a person's cell. Mutation and inactivation of the tumor suppressor genes are the unified concept of the development of tumor in humans. Therefore, researchers have discovered potential of gene therapies in the treatment of cancer. Among the clinical trials of gene therapy conducted so far, approximately 66% were for the treatment of cancer which includes cancer of prostate, head and neck, kidneys, lungs, breast and skin. Introducing a wild type p53 gene, enhancing the immune system to protect against the cancer cells, enhancing the apoptosis of cancer cells and inhibiting the process of angiogenesis in the tumor are some of the clinical trials that are achieved through the gene therapy. Broad spectrum of delivery constructs, including viral vectors, liposomes, cationic polymers and dendrimers, cell-penetrating peptides, semiconductor quantum dots, and gold and magnetic nanoparticles have been investigated. A well designed vector is the most forward approach to increase the safety of gene therapy. Though, Gendicine and Oncorine have been marketed, gene therapy is still in its infancy stages in cancer research. More experimental and clinical trials using well-designed and effective doses of vectors are needed to ensure the therapeutic efficacy of gene therapy for its clinical use against a wide variety of cancers. This review article discuses about the various strategies used in clinical trials of gene therapy for cancer.

  4. Comparison of gated radionuclide scans and chest radiographs. Assessment of left ventricular impairment in patients with coronary disease.

    Science.gov (United States)

    Bianco, J A; Reinke, D B; Makey, D G; Shafer, R B

    1980-03-01

    Diagnostic efficacy of gated cardiac blood pool imaging was studied in 41 consecutive patients with LV ejection fractions (LVEF) less than or equal to 0.50. Eighty percent of patients were receiving therapy for LV failure at the time of the study. All patients had documented coronary-artery disease (CAD). Chest x-ray films were interpreted blindly by a senior radiologist. Cardiothoracic ratio of less than or equal to 0.50 was recorded as normal. Radionuclide assessment of LV function contributes importantly to the diagnostic and screening value of chest x-ray films. Patients with coronary disease and clinical evidence of heart failure should have radioisotopic studies even if chest x-ray film findings are normal. In patients with coronary artery disease and enlarged LV on chest films, radionuclide study of left ventricular performance aids in defining LV impairment, and in the prognostication of subsequent clinical course.

  5. The clinical use of regenerative therapy in COPD.

    Science.gov (United States)

    Lipsi, Roberto; Rogliani, Paola; Calzetta, Luigino; Segreti, Andrea; Cazzola, Mario

    2014-01-01

    Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation.

  6. Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Koch-Henriksen, Nils; Petersen, Thor;

    2014-01-01

    A number of studies have reported flare-up of multiple sclerosis (MS) disease activity after cessation of natalizumab, increasing to a level beyond the pre-natalizumab treatment level. Our aim was to describe the development in clinical disease activity following cessation of natalizumab therapy...... in a large unselected cohort of highly active patients. We studied 375 highly active patients who had suffered at least two significant relapses within 1 year or three relapses within 2 years, or had been treated with mitoxantrone for highly active disease. All patients had discontinued therapy...... with natalizumab after at least 24 weeks on therapy, and had been followed 3-12 months (mean 8.9 months) after cessation of natalizumab therapy. The annualised relapse rate before start of natalizumab therapy was 0.94 (95 % confidence interval [CI] 0.88-1.00), 0.47 (95 % CI 0.43-0.52) during natalizumab therapy, 0...

  7. The clinical use of regenerative therapy in COPD

    OpenAIRE

    Lipsi R; Rogliani P; Calzetta L; Segreti A; Cazzola M

    2014-01-01

    Roberto Lipsi,1 Paola Rogliani,1 Luigino Calzetta,2 Andrea Segreti,1 Mario Cazzola1 1Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 2Department of Pulmonary Rehabilitation, San Raffaele Pisana Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy Abstract: Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat disea...

  8. Acute pancreatitis: etiology, clinical presentation, diagnosis, and therapy.

    Science.gov (United States)

    Cappell, Mitchell S

    2008-07-01

    Acute pancreatitis is a relatively common disease that affects about 300,000 patients per annum in America with a mortality of about 7%. About 75% of pancreatitis is caused by gallstones or alcohol. Other important causes include hypertriglyceridemia, medication toxicity, trauma from endoscopic retrograde cholangiopancreatography, hypercalcemia, abdominal trauma, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown after thorough investigation. This article discusses the causes, diagnosis, imaging findings, therapy, and complications of acute pancreatitis.

  9. Schema Therapy for Emotional Dysregulation: Theoretical Implication and Clinical Applications.

    Science.gov (United States)

    Dadomo, Harold; Grecucci, Alessandro; Giardini, Irene; Ugolini, Erika; Carmelita, Alessandro; Panzeri, Marta

    2016-01-01

    The term emotional dysregulation refers to an impaired ability to regulate unwanted emotional states. Scientific evidence supports the idea that emotional dysregulation underlies several psychological disorders as, for example: personality disorders, bipolar disorder type II, interpersonal trauma, anxiety disorders, mood disorders and post-traumatic stress disorder. Emotional dysregulation may derive from early interpersonal traumas in childhood. These early traumatic events create a persistent sensitization of the central nervous system in relation to early life stressing events. For this reason, some authors suggest a common endophenotypical origin across psychopathologies. In the last 20 years, cognitive behavioral therapy has increasingly adopted an interactive-ontogenetic view to explain the development of disorders associated to emotional dysregulation. Unfortunately, standard Cognitive Behavior Therapy (CBT) methods are not useful in treating emotional dysregulation. A CBT-derived new approach called Schema Therapy (ST), that integrates theory and techniques from psychodynamic and emotion focused therapy, holds the promise to fill this gap in cognitive literature. In this model, psychopathology is viewed as the interaction between the innate temperament of the child and the early experiences of deprivation or frustration of the subject's basic needs. This deprivation may lead to develop early maladaptive schemas (EMS), and maladaptive Modes. In the present paper we point out that EMSs and Modes are associated with either dysregulated emotions or with dysregulatory strategies that produce and maintain problematic emotional responses. Thanks to a special focus on the therapeutic relationship and emotion focused-experiential techniques, this approach successfully treats severe emotional dysregulation. In this paper, we make several comparisons between the main ideas of ST and the science of emotion regulation, and we present how to conceptualize pathological

  10. MEDECOR--a medical decorporation tool to assist first responders, receivers, and medical reach-back personnel in triage, treatment, and risk assessment after internalization of radionuclides.

    Science.gov (United States)

    Waller, Ed; Wilkinson, Diana

    2010-10-01

    After a radiological dispersal device (RDD) event, it is possible for radionuclides to enter the human body through inhalation, ingestion, and skin and wound absorption. From a health physics perspective, it is important to know the magnitude of the intake to perform dosimetric assessments. From a medical perspective, removal of radionuclides leading to dose aversion (hence risk reduction) is of high importance. The efficacy of medical decorporation strategies is extremely dependent upon the time of treatment delivery after intake. The "golden hour," or more realistically 3-4 h, is optimal when attempting to increase removal of radionuclides from extracellular fluids prior to cellular incorporation. To assist medical first response personnel in making timely decisions regarding appropriate treatment delivery modes, it is desirable to have a software tool that compiles existing radionuclide decorporation therapy data and allows a user to perform simple diagnosis leading to optimized decorporation treatment strategies. In its most simple application, the software is a large database of radionuclide decorporation strategies and treatments. The software can also be used in clinical interactive mode, in which the user inputs the radionuclide, estimated activity, route of intake and time since exposure. The software makes suggestions as to the urgency of treatment (i.e., triage) and the suggested therapy. Current developments include risk assessment which impacts the potential risk of delivered therapy and resource allocation of therapeutic agents. The software, developed for the Canadian Department of National Defence (DND), is titled MEDECOR (MEdical DECORporation). The MEDECOR tool was designed for use on both personal digital assistant and laptop computer environments. The tool was designed using HTML/Jscript, to allow for ease of portability amongst different computing platforms. This paper presents the features of MEDECOR, results of testing at a major NATO

  11. The clinical use of regenerative therapy in COPD

    Directory of Open Access Journals (Sweden)

    Lipsi R

    2014-12-01

    Full Text Available Roberto Lipsi,1 Paola Rogliani,1 Luigino Calzetta,2 Andrea Segreti,1 Mario Cazzola1 1Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 2Department of Pulmonary Rehabilitation, San Raffaele Pisana Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy Abstract: Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. Keywords: chronic obstructive pulmonary disease, stem cells, regenerative therapy, all-trans retinoic acid, photobiostimulation

  12. Differentiated thyroid carcinoma : treatment and clinical consequences of therapy

    NARCIS (Netherlands)

    Hoftijzer, Hendrieke Catherijn

    2011-01-01

    The first chapters of this thesis describe the treatment of radioiodine non-avid thyroid carcinoma with the tyrosine kinase inhibitor sorafenib. The remainder of the thesis describes the clinical consequences of the treatment of thyroid carcinoma.

  13. Clinical pharmacist interventions to support adherence to thrombopreventive therapy

    DEFF Research Database (Denmark)

    Hedegaard, Ulla

    individualised interventions and team-based care, e.g. integrating a clinical pharmacist with particular focus on patients’ drug-related problems. One approach with growing evidence of improving medication adherence is motivational interviewing (MI). So far, no clinical pharmacist intervention using MI has...... to the different results in the two trials is that the stroke patients - compared to the hypertension patients - may have been more motivated for taking their medication as they just experienced a serious event. Another factor is that a secondary prevention clinic was established during the stroke study, which may...... by the clinical pharmacists and the patients.  Sensitivity and specificity for the two scales of the adherence questionnaire demonstrating the best agreement with prescription-based measures were about 90% and 30%, and the agreement with refill data was fairly low with kappa values below 0.3, suggesting...

  14. EGFR-Targeting as a Biological Therapy: Understanding Nimotuzumab's Clinical Effects

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Rolando, E-mail: rolando@cim.sld.cu; Moreno, Ernesto; Garrido, Greta; Crombet, Tania [Center of Molecular Immunology, P.O. Box 16040, Havana 11600 (Cuba)

    2011-04-18

    Current clinical trials of epidermal growth factor receptor (EGFR)-targeted therapies are mostly guided by a classical approach coming from the cytotoxic paradigm. The predominant view is that the efficacy of EGFR antagonists correlates with skin rash toxicity and induction of objective clinical response. Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity. Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile. Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.

  15. In vivo molecular imaging and radionuclide (131I therapy of human nasopharyngeal carcinoma cells transfected with a lentivirus expressing sodium iodide symporter.

    Directory of Open Access Journals (Sweden)

    Shuo Shi

    Full Text Available Despite recent improvements in the survival rates for nasopharyngeal carcinoma (NPC, novel treatment strategies are required to improve distant metastasis-free survival. The sodium iodine symporter (NIS gene has been applied for in vivo imaging and cancer therapy. In this study, we examined the potential of NIS gene therapy as a therapeutic approach in NPC by performing non-invasive imaging using 125I and 131I therapy in vivo.We constructed a lentiviral vector expressing NIS and enhanced green fluorescent protein (EGFP under the control of the human elongation factor-1α (EF1α promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE-2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT imaging; the therapeutic effects of treatment with 131I were assessed over 25 days by measuring tumor volume and immunohistochemical staining of the excised tumors.qPCR, immunofluorescence and Western blotting confirmed that CNE-2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and xenografts took up and accumulated significantly more 125I than CNE-2Z cells and xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells expressed higher levels of NIS and caspase-3 and lower levels of Ki-67.Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC. NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.

  16. EBS Radionuclide Transport Abstraction

    Energy Technology Data Exchange (ETDEWEB)

    R. Schreiner

    2001-06-27

    The purpose of this work is to develop the Engineered Barrier System (EBS) radionuclide transport abstraction model, as directed by a written development plan (CRWMS M&O 1999a). This abstraction is the conceptual model that will be used to determine the rate of release of radionuclides from the EBS to the unsaturated zone (UZ) in the total system performance assessment-license application (TSPA-LA). In particular, this model will be used to quantify the time-dependent radionuclide releases from a failed waste package (WP) and their subsequent transport through the EBS to the emplacement drift wall/UZ interface. The development of this conceptual model will allow Performance Assessment Operations (PAO) and its Engineered Barrier Performance Department to provide a more detailed and complete EBS flow and transport abstraction. The results from this conceptual model will allow PA0 to address portions of the key technical issues (KTIs) presented in three NRC Issue Resolution Status Reports (IRSRs): (1) the Evolution of the Near-Field Environment (ENFE), Revision 2 (NRC 1999a), (2) the Container Life and Source Term (CLST), Revision 2 (NRC 1999b), and (3) the Thermal Effects on Flow (TEF), Revision 1 (NRC 1998). The conceptual model for flow and transport in the EBS will be referred to as the ''EBS RT Abstraction'' in this analysis/modeling report (AMR). The scope of this abstraction and report is limited to flow and transport processes. More specifically, this AMR does not discuss elements of the TSPA-SR and TSPA-LA that relate to the EBS but are discussed in other AMRs. These elements include corrosion processes, radionuclide solubility limits, waste form dissolution rates and concentrations of colloidal particles that are generally represented as boundary conditions or input parameters for the EBS RT Abstraction. In effect, this AMR provides the algorithms for transporting radionuclides using the flow geometry and radionuclide concentrations

  17. EBS Radionuclide Transport Abstraction

    Energy Technology Data Exchange (ETDEWEB)

    J. Prouty

    2006-07-14

    The purpose of this report is to develop and analyze the engineered barrier system (EBS) radionuclide transport abstraction model, consistent with Level I and Level II model validation, as identified in Technical Work Plan for: Near-Field Environment and Transport: Engineered Barrier System: Radionuclide Transport Abstraction Model Report Integration (BSC 2005 [DIRS 173617]). The EBS radionuclide transport abstraction (or EBS RT Abstraction) is the conceptual model used in the total system performance assessment (TSPA) to determine the rate of radionuclide releases from the EBS to the unsaturated zone (UZ). The EBS RT Abstraction conceptual model consists of two main components: a flow model and a transport model. Both models are developed mathematically from first principles in order to show explicitly what assumptions, simplifications, and approximations are incorporated into the models used in the TSPA. The flow model defines the pathways for water flow in the EBS and specifies how the flow rate is computed in each pathway. Input to this model includes the seepage flux into a drift. The seepage flux is potentially split by the drip shield, with some (or all) of the flux being diverted by the drip shield and some passing through breaches in the drip shield that might result from corrosion or seismic damage. The flux through drip shield breaches is potentially split by the waste package, with some (or all) of the flux being diverted by the waste package and some passing through waste package breaches that might result from corrosion or seismic damage. Neither the drip shield nor the waste package survives an igneous intrusion, so the flux splitting submodel is not used in the igneous scenario class. The flow model is validated in an independent model validation technical review. The drip shield and waste package flux splitting algorithms are developed and validated using experimental data. The transport model considers advective transport and diffusive transport

  18. Clinical value of radionuclide bone imaging in 343 primary nasopharyngeal carcinoma cases%鼻咽癌343例放射性核素骨显像的临床分析

    Institute of Scientific and Technical Information of China (English)

    邱素芳; 潘建基; 唐明灯; 林少俊; 杨凌; 林端瑜

    2008-01-01

    Objective To analyze the radionuclide bone imaging in 343 primary nasopharyngeal carcinoma cases and to know the positive ratio and its prognosis. Methods 343 cases with primary NPC were examined by radionuclide bone imaging in order to find if there was bone metastases and analyze in single and multi factors, and then to know its prognosis. Results The positive ratio of 343 NPC cases was 32.9 %, men 37.5%, women 17.7%. There was significant statistic value in sex, age and staging through Binary Logistic Regress analysis. Men, the more advanced staging, the older people, the earlier to metastases.The overall accumulate survival ratio was 1 year 92.1%, 2 year 83.9 %, 3 year 78.8 %. Conclusion Nasopharyngeal carcinoma is easy to metastases. Radionuclide bone imaging should be performed in the patients with NPC because it is important to evaluate the staging and therapy.%目的 通过分析鼻咽癌初治患者放射性核素骨显像资料,了解骨转移发生情况及其预后.方法 对343例鼻咽癌初治患者均行常规放射性核素骨显像检查,对其进行单因素及多因素分析,并在治疗后1、2、3年进行随访.结果 343例患者初诊时骨转移发生率为32.9%,其中男性37.5%,女性17.7%,多因素分析结果显示不同性别、年龄、病期间差异有统计学意义.总体累计生存率为:1年92.1%,2年83.9%,3年78.8%.结论 鼻咽癌放射性核素骨显像灵敏度较高,对鼻咽癌的诊断、分期、治疗及预后判断有重要作用,应作为鼻咽癌患者的常规检查.

  19. Chronic edema of the lower extremities: international consensus recommendations for compression therapy clinical research trials.

    Science.gov (United States)

    Stout, N; Partsch, H; Szolnoky, G; Forner-Cordero, I; Mosti, G; Mortimer, P; Flour, M; Damstra, R; Piller, N; Geyer, M J; Benigni, J-P; Moffat, C; Cornu-Thenard, A; Schingale, F; Clark, M; Chauveau, M

    2012-08-01

    Chronic edema is a multifactorial condition affecting patients with various diseases. Although the pathophysiology of edema varies, compression therapy is a basic tenant of treatment, vital to reducing swelling. Clinical trials are disparate or lacking regarding specific protocols and application recommendations for compression materials and methodology to enable optimal efficacy. Compression therapy is a basic treatment modality for chronic leg edema; however, the evidence base for the optimal application, duration and intensity of compression therapy is lacking. The aim of this document was to present the proceedings of a day-long international expert consensus group meeting that examined the current state of the science for the use of compression therapy in chronic edema. An expert consensus group met in Brighton, UK, in March 2010 to examine the current state of the science for compression therapy in chronic edema of the lower extremities. Panel discussions and open space discussions examined the current literature, clinical practice patterns, common materials and emerging technologies for the management of chronic edema. This document outlines a proposed clinical research agenda focusing on compression therapy in chronic edema. Future trials comparing different compression devices, materials, pressures and parameters for application are needed to enhance the evidence base for optimal chronic oedema management. Important outcomes measures and methods of pressure and oedema quantification are outlined. Future trials are encouraged to optimize compression therapy in chronic edema of the lower extremities.

  20. Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

    Science.gov (United States)

    Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

    2015-01-01

    In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

  1. Natural Killer Cells: Biology and Clinical Use in Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    WilliamH.D.Hallett; WilliamJ.Murphy

    2004-01-01

    Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.

  2. Natural Killer Cells: Biology and Clinical Use in Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    William H. D. Hallett; William J. Murphy

    2004-01-01

    Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.

  3. The Effect of Cognitive Behavior Therapy in Insomnia due to Methadone Maintenance Therapy: A Randomized Clinical Trial

    OpenAIRE

    Robabeh Soleimani; Mohammad Jafar Modabbernia; Sharareh Habibi; Maryam Habibi Roudsary; Masoumeh Elahi

    2015-01-01

    Background: Sleep disturbance is a common complaint of patients undergoing methadone maintenance therapy (MMT). There are limited studies about the effect of different treatments on insomnia due to MMT. In this study, we evaluated the effect of cognitive-behavioral treatment for insomnia (CBTI) on sleep disorders in patients undergoing MMT. Methods: Twenty-two patients with insomnia due to MMT (aged 18-60 years) participated in this randomized double-blind clinical trial. The intervention ...

  4. ACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient.

    Science.gov (United States)

    McClave, Stephen A; DiBaise, John K; Mullin, Gerard E; Martindale, Robert G

    2016-03-01

    The value of nutrition therapy for the adult hospitalized patient is derived from the outcome benefits achieved by the delivery of early enteral feeding. Nutritional assessment should identify those patients at high nutritional risk, determined by both disease severity and nutritional status. For such patients if they are unable to maintain volitional intake, enteral access should be attained and enteral nutrition (EN) initiated within 24-48 h of admission. Orogastric or nasogastric feeding is most appropriate when starting EN, switching to post-pyloric or deep jejunal feeding only in those patients who are intolerant of gastric feeds or at high risk for aspiration. Percutaneous access should be used for those patients anticipated to require EN for >4 weeks. Patients receiving EN should be monitored for risk of aspiration, tolerance, and adequacy of feeding (determined by percent of goal calories and protein delivered). Intentional permissive underfeeding (and even trophic feeding) is appropriate temporarily for certain subsets of hospitalized patients. Although a standard polymeric formula should be used routinely in most patients, an immune-modulating formula (with arginine and fish oil) should be reserved for patients who have had major surgery in a surgical ICU setting. Adequacy of nutrition therapy is enhanced by establishing nurse-driven enteral feeding protocols, increasing delivery by volume-based or top-down feeding strategies, minimizing interruptions, and eliminating the practice of gastric residual volumes. Parenteral nutrition should be used in patients at high nutritional risk when EN is not feasible or after the first week of hospitalization if EN is not sufficient. Because of their knowledge base and skill set, the gastroenterologist endoscopist is an asset to the Nutrition Support Team and should participate in providing optimal nutrition therapy to the hospitalized adult patient.

  5. Music Therapy with Traumatized Refugees in a Clinical Setting

    Directory of Open Access Journals (Sweden)

    Jaap Orth

    2005-07-01

    Full Text Available As music therapists now deal more often with traumatized refugees, and the demand for documentation, research, and a methodical description has grown, in this article I would like to make a contribution to the development of a methodology in music therapy with traumatized refugees. Various methods used by music therapists in trauma treatment will be described. An overview of the development of a set of methods at Phoenix, a highly specialized inpatient treatment facility for refugees and asylum seekers, will be presented and I will focus on four approaches I developed in my work with traumatized refugees.

  6. Radionuclide transfer. Radionuklid Transfer

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, G.B.

    1993-01-01

    The research project described here had the aim to obtain further information on the transfer of nuclides during pregnancy and lactation. The tests were carried out in mini-pigs and rats receiving unchanging doses of radionuclides with the food. The following findings were revealed for the elements examined: Fe, Se, Cs and Zn were characterized by very high transfer levels in the mother, infant and foetus. A substantial uptake by the mother alone was observed for Co, Ag and Mn. The uptake by the foetus and infant here was 1 to 10 times lower. A preferential concentration in certain tissues was seen for Sr and Tc; the thyroid levels of Tc were about equally high in mothers and infants, while Sr showed less accumulation in the maternal bone. The lanthanide group of substances (Ce, Eu and Gd as well as Y and Ru) were only taken up to a very limited extent. The uptake of the examined radionuclides (Fe, Co, Ag, Ce) with the food ingested was found here to be ten times greater in rats as compared to mini-pigs. This showed that great caution must be observed, if the behaviour of radionuclides in man is extrapolated from relevant data obtained in rodents. (orig./MG)

  7. Requirements for Clinical Trials with Gene Therapy and Transplant Products in Switzerland.

    Science.gov (United States)

    Marti, Andreas

    2015-01-01

    This chapter aims to describe and summarize the regulation of gene and cell therapy products in Switzerland and its legal basis. Product types are briefly described, as are Swiss-specific terminologies such as the term "transplant product," which means products manufactured from cells, tissues, or even whole organs. Although some parts of this chapter may show a guideline character, they are not legally binding, but represent the current thinking of Swissmedic, the Swiss Agency for Therapeutic Products. As so far the experience with marketing approval of gene therapy and cell therapy products in Switzerland is limited, this chapter focuses on the regulation of clinical trials conducted with these products. Quality, nonclinical, and clinical aspects are summarized separately for gene therapy products and transplant products.

  8. Clinical significance of radiation therapy in breast recurrence and prognosis in breast-conserving surgery

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko [Kumamoto City Hospital (Japan)] [and others

    1999-03-01

    Significant risk factors for recurrence of breast cancer after breast-conserving therapy, which has become a standard treatment for breast cancer, are positive surgical margins and the failure to perform radiation therapy. In this study, we evaluated the clinical significance of radiation therapy after primary surgery or breast recurrence. In 344 cases of breast-conserving surgery, disease recurred in 43 cases (12.5%), which were classified as follows: 17 cases of breast recurrence, 13 cases of breast and distant metastasis, and 13 cases of distant metastasis. Sixty-two patients (16.7%) received radiation therapy. A positive surgical margin and younger age were significant risk factors for breast recurrence in patients not receiving postoperative radiation therapy but not in patients receiving radiation therapy. Radiation therapy may be beneficial for younger patients with positive surgical margins. Furthermore, radiation therapy after recurrence was effective in the cases not treated with postoperative radiation but not in cases with inflammatory recurrence. Patients with breast recurrence alone had significantly higher survival rates than did patients with distant metastases regardless of breast recurrence. These findings suggest that the adaptation criteria of radiation therapy for local control must be clarified. (author)

  9. Gene therapy takes a cue from HAART: combinatorial antiviral therapeutics reach the clinic.

    Science.gov (United States)

    Shah, Priya S; Schaffer, David V

    2010-06-16

    For the first time, scientists have tested a combination of three RNA-based gene therapies, delivered via a lentiviral vector, to target HIV in patients. This study not only demonstrates the safety and long-term viability of this approach, but also highlights areas in which focused improvements in gene therapy strategies may provide the most impact in increasingly translating promise in the laboratory to efficacy in the clinic.

  10. A clinical study of topical mucopolysaccharides & polydeoxyribonucleoprotein (Foltene) therapy in alopecia.

    OpenAIRE

    K.S. Lee; Myung, K. B.; Kook, H. I.

    1987-01-01

    We performed clinical trials to evaluate the therapeutic effects of Foltene in patients of the several types of hair fallings. Thirty patients with male pattern baldness, alopecia areata and seborrheic alopecia were included in this study. Foltene was applied every other day for 40 days, and followed by maintenance therapy of twice application a week. The duration of whole therapy was 6 months. We conclude that Foltene is an effective and agent for male pattern baldness, alopecia areata and s...

  11. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    Directory of Open Access Journals (Sweden)

    Silvia Consalvi

    2016-01-01

    Full Text Available In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD.

  12. Clinical considerations for an effective medical therapy in Wilson's disease.

    Science.gov (United States)

    Weiss, Karl Heinz; Stremmel, Wolfgang

    2014-05-01

    Wilson's disease is an autosomal recessively inherited copper overload disorder that leads to hepatic and/or neurologic symptoms. More than a century after the first description of Wilson's disease, the available medical treatment options have not been standardized. The efficacy of the commonly used drugs is satisfactory for hepatic disease, but disappointing in the neurologic patients, including the risk of neurologic deterioration after the initiation of chelation therapy. An approach to overcome this problem is the careful and systematic assessment of biochemical response patterns and the quantitative monitoring of symptoms using validated rating scales. Standardized dosage strategies that address changes in copper pools might improve adherence and reduce side effects. Such an approach may reduce long-term morbidity. In this paper, we discuss considerations for an effective medical treatment and requirements for future studies in Wilson's disease.

  13. Clinical results of radiation therapy for thymic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Fushiki, Masato

    1991-12-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author).

  14. Fluid therapy in neurotrauma: basic and clinical concepts

    Directory of Open Access Journals (Sweden)

    Hernando Raphael Alvis-Miranda

    2014-01-01

    Full Text Available The patient with head trauma is a challenge for the emergency physician and for the neurosurgeon. Currently traumatic brain injury constitutes a public health problem. Knowledge of the various therapeutic strategies to provide support in the prehospital and perioperative are essential for optimal care. Rapid infusion of large volumes of crystalloids to restore blood volume and blood pressure quickly is now the standard treatment for patients with combined TBI and HS The fluid in patients with brain and especially in the carrier of brain injury is a critical topic; we present a review of the literature about the history, physiology of current fluid preparations, and a discussion regard the use of fluid therapy in traumatic brain injury and decompressive craniectomy.http://dx.doi.org/10.7175/rhc.v5i1.636

  15. DUAL ANTIPLATELET THERAPY IN THE REAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    G. N. Guseva

    2015-09-01

    Full Text Available Aim. To evaluate an adequacy of dual antiplatelet therapy (DAPT in patients with acute coronary syndrome (ACS with ST segment elevation and bare metal stent implantation after hospital discharge.Material and methods. 311 patients with ACS with ST segment elevation were included into the study. All of them underwent percutaneous coronary intervention with bare metal stent implantation. The information was obtained by the telephone survey.Results. 54.5% of patients received DAPT during 12 months. 43.8% of patients also received combination of clopidogrel and acetylsalicylic acid, but changed medicinal products of clopidogrel due to different reasons. 1.7% of patients received acetylsalicylic acid only.Conclusion. More than 50% of patients received recommended DAPT at that they preferred generic drugs of clopidogrel original one.

  16. Relapse after oral terbinafine therapy in dermatophytosis: A clinical and mycological study

    Directory of Open Access Journals (Sweden)

    Imran Majid

    2016-01-01

    Full Text Available Background: The incidence of recurrent tinea infections after oral terbinafine therapy is on the rise. Aim: This study aims to identify the appearance of incomplete cure and relapse after 2-week oral terbinafine therapy in tinea corporis and/or tinea cruris. Materials and Methods: A total of 100 consecutive patients clinically and mycologically diagnosed to have tinea corporis and/or tinea cruris were included in the study. The enrolled patients were administered oral terbinafine 250 mg once daily for 2 weeks. All clinically cured patients were then followed up for 12 weeks to look for any relapse/cure. Results: The common dermatophytes grown on culture were Trichophyton rubrum and Trichophyton tonsurans in 55% and 20% patients, respectively. At the end of 2-week oral terbinafine therapy, 30% patients showed a persistent disease on clinical examination while 35% patients showed a persistent positive fungal culture (persisters at this time. These culture positive patients included all the clinically positive cases. Rest of the patients (65/100 demonstrated both clinical and mycological cure at this time (cured. Over the 12-week follow-up, clinical relapse was seen in 22 more patients (relapse among those who had shown clinical and mycological cure at the end of terbinafine therapy. Thus, only 43% patients could achieve a long-term clinical and mycological cure after 2 weeks of oral terbinafine treatment. Majority of the relapses (16/22 were seen after 8 weeks of completion of treatment. There was no statistically significant difference in the body surface area involvement or the causative organism involved between the cured, persister, or relapse groups. Conclusions: Incomplete mycological cure as well as relapse is very common after standard (2-week terbinafine therapy in our patients of tinea cruris/corporis.

  17. Relapse after Oral Terbinafine Therapy in Dermatophytosis: A Clinical and Mycological Study

    Science.gov (United States)

    Majid, Imran; Sheikh, Gousia; Kanth, Farhath; Hakak, Rubeena

    2016-01-01

    Background: The incidence of recurrent tinea infections after oral terbinafine therapy is on the rise. Aim: This study aims to identify the appearance of incomplete cure and relapse after 2-week oral terbinafine therapy in tinea corporis and/or tinea cruris. Materials and Methods: A total of 100 consecutive patients clinically and mycologically diagnosed to have tinea corporis and/or tinea cruris were included in the study. The enrolled patients were administered oral terbinafine 250 mg once daily for 2 weeks. All clinically cured patients were then followed up for 12 weeks to look for any relapse/cure. Results: The common dermatophytes grown on culture were Trichophyton rubrum and Trichophyton tonsurans in 55% and 20% patients, respectively. At the end of 2-week oral terbinafine therapy, 30% patients showed a persistent disease on clinical examination while 35% patients showed a persistent positive fungal culture (persisters) at this time. These culture positive patients included all the clinically positive cases. Rest of the patients (65/100) demonstrated both clinical and mycological cure at this time (cured). Over the 12-week follow-up, clinical relapse was seen in 22 more patients (relapse) among those who had shown clinical and mycological cure at the end of terbinafine therapy. Thus, only 43% patients could achieve a long-term clinical and mycological cure after 2 weeks of oral terbinafine treatment. Majority of the relapses (16/22) were seen after 8 weeks of completion of treatment. There was no statistically significant difference in the body surface area involvement or the causative organism involved between the cured, persister, or relapse groups. Conclusions: Incomplete mycological cure as well as relapse is very common after standard (2-week) terbinafine therapy in our patients of tinea cruris/corporis. PMID:27688443

  18. [Clinical application of moving cupping therapy based on skin reaction observation and syndrome differentiation].

    Science.gov (United States)

    Deng, Xiao-Lan; Chen, Bo; Chen, Ze-Lin

    2014-12-01

    The diagnostic evidence on clinical diseases and theoretic basis of moving cupping therapy were ex- plored in the paper. By the observation of the local reaction, such as skin appearance and color, the affected location, duration of sickness and nature of disease were judged. Different moving cupping methods were selected for different disorders. It was discovered that the property of syndromes should be recognized by the palpation on skin and muscle in the moving cupping therapy so that the pathogenesis and treating principle could be carefully determined. The moving cupping therapy is the important component of body surface therapy. Skin reaction observation and syndrome differentiation is the essential guidance of the moving cupping therapy.

  19. Ambivalent journeys of hope: embryonic stem cell therapy in a clinic in India.

    Science.gov (United States)

    Prasad, Amit

    2015-03-01

    Stem cell therapy in non-Western countries such as India has received a lot of attention. Apart from media reports, there are a number of social science analyses of stem cell policy, therapy, and research, their ethical implications, and impact of advertising on patients. Nevertheless, in the media reports as well as in academic studies, experiences of patients, who undertake overseas journeys for stem cell therapy, have largely been either ignored or presented reductively, often as a "false hope." In this article, I analyze the experiences of patients and their "journeys of hope" to NuTech Mediworld, an embryonic stem cell therapy clinic in New Delhi, India. My analysis, which draws on my observations in the clinic and patients' experiences, instead of seeking to adjudicate whether embryonic stem cell therapy in clinics such as NuTech is right or wrong, true or false, focuses on how patients navigate and contest these concerns. I utilize Gilles Deleuze and Felix Guattari's "concepts," lines of flight and deterritorialization, to highlight how embryonic stem cell therapy's "political economy of hope" embodies deterritorialization of several "regimes of truth" and how these deterritorializations impact patients' experiences.

  20. Cancer therapy with phytochemicals: evidence from clinical studies

    Directory of Open Access Journals (Sweden)

    Ahmad Ghorbani

    2015-02-01

    Full Text Available Cancer is still one of the major causes of mortality in both developing and developed countries. At this time, in spite of intensive interventions, a large number of patients have poor prognosis. Therefore, the effort for finding new anticancer agents with better efficacy and lesser side effects has continued. According to the traditional recommendations and experimental studies, numerous medicinal plants have been reported to have anticancer effect. Also antiproliferative, proapoptotic, antimetastatic and antiangiogenic effects of several phytochemicals have been shown with in vitro experiments or animal studies. However, only a small number of them were tested in cancerous patients and limited evidence exists on their clinical effectiveness. Also, regarding some phytochemicals, only beneficial effects on cancer-related symptoms or on quality of life have been reported and no positive results exist on their antitumor actions. In this review we focus on phytochemicals that their beneficial effects on various types of cancer are supported by clinical trials. Based our literature search, curcumin, green tea, resveratrol and Viscum album had satisfactory instances of clinical evidence for supporting their anticancer effects. The main findings on these phytochemicals are summarized and discussed.

  1. Clinical applications of bovine colostrum therapy: a systematic review.

    Science.gov (United States)

    Rathe, Mathias; Müller, Klaus; Sangild, Per Torp; Husby, Steffen

    2014-04-01

    Bovine colostrum, the first milk that cows produce after parturition, contains high levels of growth factors and immunomodulatory components. Some healthy and diseased individuals may gain health benefits by consuming bovine colostrum as a food supplement. This review provides a systematic, critical evaluation of the current state of knowledge in this area. Fifty-one eligible studies were identified from the following databases: Medline, Embase, Global Health, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature. Studies were heterogeneous with regard to populations, outcomes, and methodological quality, as judged by the Jadad assessment tool. Many studies used surrogate markers to study the effects of bovine colostrum. Studies suggesting clinical benefits of colostrum supplementation were generally of poor methodological quality, and results could not be confirmed by other investigators. Bovine colostrum may provide gastrointestinal and immunological benefits, but further studies are required before recommendations can be made for clinical application. Animal models may help researchers to better understand the mechanisms of bovine colostrum supplementation, the dosage regimens required to obtain clinical benefits, and the optimal methods for testing these effects in humans.

  2. Epigenetic therapies - a new direction in clinical medicine.

    Science.gov (United States)

    Stein, R A

    2014-07-01

    A major biomedical advance from recent years was the finding that gene expression and phenotypic traits may be shaped by potentially reversible and heritable modifications that occur without altering the sequence of the nucleotides, and became known as epigenetic changes. The term 'epigenetics' dates back to the 1940s, when it was first used in context of cellular differentiation decisions that are made during development. Since then, our understanding of epigenetic modifications that govern development and disease expanded considerably. The contribution of epigenetic changes to shaping phenotypes brings at least two major clinically relevant benefits. One of these, stemming from the reversibility of epigenetic changes, involves the possibility to therapeutically revert epigenetic marks to re-establish prior gene expression patterns. The strength and the potential of this strategy are illustrated by the first four epigenetic drugs that were approved in recent years and by the additional candidates that are at various stages in preclinical studies and clinical trials. The second particularity is the finding that epigenetic changes precede the appearance of histopathological modifications. This has the potential to facilitate the emergence of epigenetic biomarkers, some of which already entered the clinical arena, catalysing a major shift in prophylactic and therapeutic strategies, and promising to fill a decades-old gap in preventive medicine.

  3. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    Science.gov (United States)

    Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

    Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

  4. Brief strategic therapy in a child community clinic. A follow-up report.

    Science.gov (United States)

    Eisenberg, J; Wahrman, O

    1994-01-01

    This paper reports the outcome of brief strategic therapy, practiced according to the model described by S. de Shazer, in an out-patient child psychiatry clinic during 4 years. Forty-two clients were interviewed in a span of 6 to 18 months after termination of therapy and asked about symptomatic improvement and satisfaction with the treatment. The results showed that brief strategic therapy achieved lasting complaint resolution in a high percentage of cases, high satisfaction rates with little relapse or need for additional interventions.

  5. Value and Clinical Impact of an Infectious Disease-Supervised Outpatient Parenteral Antibiotic Therapy Program

    Science.gov (United States)

    Petrak, Russell M.; Skorodin, Nathan C.; Fliegelman, Robert M.; Hines, David W.; Chundi, Vishnu V.; Harting, Brian P.

    2016-01-01

    Background. Outpatient parenteral antibiotic therapy (OPAT) is a safe and effective modality for treating serious infections. This study was undertaken to define the value of OPAT in a multicentered infectious disease (ID) private practice setting. Methods. Over a period of 32 months, 6120 patients were treated using 19 outpatient ID offices in 6 states. Analysis included patient demographics, indications of OPAT, diagnoses, therapeutic agent, duration of therapy, and site of therapy initiation. Outcomes were stratified by therapeutic success, clinical relapse, therapeutic complications, and hospitalizations after initiating therapy. Statistical analysis included an ordinal logistic regression analysis. Results. Forty-three percent of patients initiated therapy in an outpatient office, and 57% began therapy in a hospital. Most common diagnoses treated were bone and joint (32.2%), abscesses (18.8%), cellulitis (18.5%), and urinary tract infection (10.8%). Ninety-four percent of patients were successfully treated, and only 3% were hospitalized after beginning therapy. Most common cause of treatment failure was a relapse of primary infection (60%), progression of primary infection (21%), and therapeutic complication (19%). Conclusions. An ID-supervised OPAT program is safe, efficient, and clinically effective. By maximizing the delivery of outpatient care, OPAT provides a tangible value to hospitals, payers, and patients. This program is a distinctive competency available to ID physicians who offer this service to patients.

  6. Clinical Study on the Visceral Differentiation-Based Acupuncture Therapy for Insomnia

    Institute of Scientific and Technical Information of China (English)

    LING Li; JIANG Xin-mei; XUE Jin-wei; WANG Miao; KE Rui

    2008-01-01

    objective;To investigate the clinical effects of acupuncture for insomnia on the basis of visceral differentiation.Methods;Seventy cases of insomnia were randomly divided into a treatment group and a control group,The former was treated by acupuncture based on visceral differentiation and the latter by the routine acupuncture therapy.Results;The clinical effcts were significantly better in the treatment group than that of the control group(P<0.05).Conclusion;The visceral difrerentiation-based acupuncture therapy may enhance the therapeutic effects for insomnia patients.

  7. Clinical Outlook for Type-1 and FOXP3+ T Regulatory Cell-Based Therapy

    Science.gov (United States)

    Gregori, Silvia; Passerini, Laura; Roncarolo, Maria-Grazia

    2015-01-01

    T regulatory cells (Tregs) are subsets of T lymphocytes specialized in modulating antigen-specific immune responses in vivo. Hence, Tregs represent an ideal therapeutic tool to control detrimental immune reactions. Based on solid pre-clinical results, investigators started testing the safety and efficacy of Treg-based therapies in humans. Despite promising results, a number of issues remain to be solved. We will discuss the results obtained from clinical trials and the challenges and risks we are facing in the further development of Treg-based therapies. PMID:26635807

  8. Clinical Study on Kidney-Nourishing and Governor Vessel-Regulating Acupuncture Therapy for Apoplexy Sequela

    Institute of Scientific and Technical Information of China (English)

    LI Yan; PANG Yong; ZOU Zhuo-cheng; XIAO Yuan-chun

    2007-01-01

    To observe the clinical efficacy of kidney-nourishing and governor vessel-regulating therapy for apoplexy sequela.Methods:Sixty subjects were equally randomized into observation group and control group,and respectively treated for 35 days.The scores of survival quality,interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor (TNF) were measured,and the clinical efficacy were compared between two groups.Results and Conclusion:After treatment.all the observational items were improved,with better results in observation group than in control group.This therapy has better effects than regular method in the treatment of apoplexy sequela.

  9. Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

    Directory of Open Access Journals (Sweden)

    Clark Michael E

    2010-04-01

    Full Text Available Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR, and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The

  10. [Musculoskeletal shock wave therapy--current database of clinical research].

    Science.gov (United States)

    Rompe, J D; Buch, M; Gerdesmeyer, L; Haake, M; Loew, M; Maier, M; Heine, J

    2002-01-01

    During the past decade application of extracorporal shock waves became an established procedure for the treatment of various musculoskeletal diseases in Germany. Up to now the positive results of prospective randomised controlled trials have been published for the treatment of plantar fasciitis, lateral elbow epicondylitis (tennis elbow), and of calcifying tendinitis of the rotator cuff. Most recently, contradicting results of prospective randomised placebo-controlled trials with adequate sample size calculation have been reported. The goal of this review is to present information about the current clinical database on extracorporeal shock wave treatment (ESWT).

  11. Clinical Studies on HWANGRYUNHAEDOKTANG Herbal Acupuncture Therapy on Headache

    Directory of Open Access Journals (Sweden)

    Lee, Dae-Yong

    2003-02-01

    Full Text Available Objective: There are many treatments for headache. We suggested the clinical effect and utilization of HWANGRYUNHAEDOKTANG herbal acupuncture on headache. Methods: 1. We injected distillation of HWANGRYUNHAEDOKTANG(2.0cc on Both Pung-Ji(GB20 of patients. In 20 minutes later, We examined therapeutic value of headache. 2. We examined effects of HWANGRYUNHAEDOKTANG Herbal acupuncture by sex , age, area of headache, period of history, degree of headache. Results and Conclusions: 1. There was a significantly effect of HWANGRYUNHAEDOKTANG Herbal acupuncture on headache. 2. In therapeutic value, The effect of HWANGRYUNHAEDOKTANG Herbal acupuncture by each type is significant.

  12. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation.

    Science.gov (United States)

    Rincon, Melvin Y; VandenDriessche, Thierry; Chuah, Marinee K

    2015-10-01

    Gene therapy is a promising modality for the treatment of inherited and acquired cardiovascular diseases. The identification of the molecular pathways involved in the pathophysiology of heart failure and other associated cardiac diseases led to encouraging preclinical gene therapy studies in small and large animal models. However, the initial clinical results yielded only modest or no improvement in clinical endpoints. The presence of neutralizing antibodies and cellular immune responses directed against the viral vector and/or the gene-modified cells, the insufficient gene expression levels, and the limited gene transduction efficiencies accounted for the overall limited clinical improvements. Nevertheless, further improvements of the gene delivery technology and a better understanding of the underlying biology fostered renewed interest in gene therapy for heart failure. In particular, improved vectors based on emerging cardiotropic serotypes of the adeno-associated viral vector (AAV) are particularly well suited to coax expression of therapeutic genes in the heart. This led to new clinical trials based on the delivery of the sarcoplasmic reticulum Ca(2+)-ATPase protein (SERCA2a). Though the first clinical results were encouraging, a recent Phase IIb trial did not confirm the beneficial clinical outcomes that were initially reported. New approaches based on S100A1 and adenylate cyclase 6 are also being considered for clinical applications. Emerging paradigms based on the use of miRNA regulation or CRISPR/Cas9-based genome engineering open new therapeutic perspectives for treating cardiovascular diseases by gene therapy. Nevertheless, the continuous improvement of cardiac gene delivery is needed to allow the use of safer and more effective vector doses, ultimately bringing gene therapy for heart failure one step closer to reality.

  13. Cell therapy in dilated cardiomyopathy: from animal models to clinical trials

    Directory of Open Access Journals (Sweden)

    C. del Corsso

    2011-05-01

    Full Text Available Dilated cardiomyopathy can be the end-stage form and common denominator of several cardiac disorders of known cause, such as hypertensive, ischemic, diabetic and Chagasic diseases. However, some individuals have clinical findings, such as an increase in ventricular chamber size and impaired contractility (classical manifestations of dilated cardiomyopathy even in the absence of a diagnosed primary disease. In these patients, dilated cardiomyopathy is classified as idiopathic since its etiology is obscure. Nevertheless, regardless of all of the advances in medical, pharmacological and surgical procedures, the fate of patients with dilated cardiomyopathy (of idiopathic or of any other known cause is linked to arrhythmic episodes, severe congestive heart failure and an increased risk of sudden cardiac death. In this review, we will summarize present data on the use of cell therapies in animal models of dilated cardiomyopathies and will discuss the few clinical trials that have been published so far involving patients affected by this disease. The animal models discussed here include those in which the cardiomyopathy is produced by genetic manipulation and those in which disease is induced by chemical or infectious agents. The specific model used clearly creates restrictions to translation of the proposed cell therapy to clinical practice, insofar as most of the clinical trials performed to date with cell therapy have used autologous cells. Thus, translation of genetic models of dilated cardiomyopathy may have to wait until the use of allogeneic cells becomes more widespread in clinical trials of cell therapies for cardiac diseases.

  14. Cell therapy in dilated cardiomyopathy: from animal models to clinical trials.

    Science.gov (United States)

    Del Corsso, C; Campos de Carvalho, A C

    2011-05-01

    Dilated cardiomyopathy can be the end-stage form and common denominator of several cardiac disorders of known cause, such as hypertensive, ischemic, diabetic and Chagasic diseases. However, some individuals have clinical findings, such as an increase in ventricular chamber size and impaired contractility (classical manifestations of dilated cardiomyopathy) even in the absence of a diagnosed primary disease. In these patients, dilated cardiomyopathy is classified as idiopathic since its etiology is obscure. Nevertheless, regardless of all of the advances in medical, pharmacological and surgical procedures, the fate of patients with dilated cardiomyopathy (of idiopathic or of any other known cause) is linked to arrhythmic episodes, severe congestive heart failure and an increased risk of sudden cardiac death. In this review, we will summarize present data on the use of cell therapies in animal models of dilated cardiomyopathies and will discuss the few clinical trials that have been published so far involving patients affected by this disease. The animal models discussed here include those in which the cardiomyopathy is produced by genetic manipulation and those in which disease is induced by chemical or infectious agents. The specific model used clearly creates restrictions to translation of the proposed cell therapy to clinical practice, insofar as most of the clinical trials performed to date with cell therapy have used autologous cells. Thus, translation of genetic models of dilated cardiomyopathy may have to wait until the use of allogeneic cells becomes more widespread in clinical trials of cell therapies for cardiac diseases.

  15. Particle beam therapy (hadrontherapy): basis for interest and clinical experience.

    Science.gov (United States)

    Orecchia, R; Zurlo, A; Loasses, A; Krengli, M; Tosi, G; Zurrida, S; Zucali, P; Veronesi, U

    1998-03-01

    The particle or hadron beams deployed in radiotherapy (protons, neutrons and helium, carbon, oxygen and neon ions) have physical and radiobiological characteristics which differ from those of conventional radiotherapy beams (photons) and which offer a number of theoretical advantages over conventional radiotherapy. After briefly describing the properties of hadron beams in comparison to photons, this review discusses the indications for hadrontherapy and analyses accumulated experience on the use of this modality to treat mainly neoplastic lesions, as published by the relatively few hadrontherapy centres operating around the world. The analysis indicates that for selected patients and tumours (particularly uveal melanomas and base of skull/spinal chordomas and chondrosarcomas), hadrontherapy produces greater disease-free survival. The advantages of hadrontherapy are most promisingly realised when used in conjunction with modern patient positioning, radiation delivery and focusing techniques (e.g. on-line imaging, three-dimensional conformal radiotherapy) developed to improve the efficacy of photon therapy. Although the construction and running costs of hadrontherapy units are considerably greater than those of conventional facilities, a comprehensive analysis that considers all the costs, particularly those resulting from the failure of less effective conventional radiotherapy, might indicate that hadrontherapy could be cost effective. In conclusion, the growing interest in this form of treatment seems to be fully justified by the results obtained to date, although more efficacy and dosing studies are required.

  16. Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy.

    Science.gov (United States)

    Thiberville, Simon-Djamel; Moyen, Nanikaly; Dupuis-Maguiraga, Laurence; Nougairede, Antoine; Gould, Ernest A; Roques, Pierre; de Lamballerie, Xavier

    2013-09-01

    Chikungunya virus (CHIKV) is the aetiological agent of the mosquito-borne disease chikungunya fever, a debilitating arthritic disease that, during the past 7years, has caused immeasurable morbidity and some mortality in humans, including newborn babies, following its emergence and dispersal out of Africa to the Indian Ocean islands and Asia. Since the first reports of its existence in Africa in the 1950s, more than 1500 scientific publications on the different aspects of the disease and its causative agent have been produced. Analysis of these publications shows that, following a number of studies in the 1960s and 1970s, and in the absence of autochthonous cases in developed countries, the interest of the scientific community remained low. However, in 2005 chikungunya fever unexpectedly re-emerged in the form of devastating epidemics in and around the Indian Ocean. These outbreaks were associated with mutations in the viral genome that facilitated the replication of the virus in Aedes albopictus mosquitoes. Since then, nearly 1000 publications on chikungunya fever have been referenced in the PubMed database. This article provides a comprehensive review of chikungunya fever and CHIKV, including clinical data, epidemiological reports, therapeutic aspects and data relating to animal models for in vivo laboratory studies. It includes Supplementary Tables of all WHO outbreak bulletins, ProMED Mail alerts, viral sequences available on GenBank, and PubMed reports of clinical cases and seroprevalence studies.

  17. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Hao Hong

    2008-01-01

    Full Text Available Carcinoembryonic antigen (CEA, highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET] have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”.

  18. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Science.gov (United States)

    Hong, Hao; Sun, Jiangtao; Cai, Weibo

    2008-01-01

    Carcinoembryonic antigen (CEA), highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET]) have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc) have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment) has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc) are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In) are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”. PMID:19578524

  19. Proton Radiation Therapy for Head and Neck Cancer: A Review of the Clinical Experience to Date

    Energy Technology Data Exchange (ETDEWEB)

    Holliday, Emma B.; Frank, Steven J., E-mail: sjfrank@mdanderson.org

    2014-06-01

    Proton beam radiation has been used for cancer treatment since the 1950s, but recent increasing interest in this form of therapy and the construction of hospital-based and clinic-based facilities for its delivery have greatly increased both the number of patients and the variety of tumors being treated with proton therapy. The mass of proton particles and their unique physical properties (ie, the Bragg peak) allow proton therapy to spare normal tissues distal to the tumor target from incidental irradiation. Initial observations show that proton therapy is particularly useful for treating tumors in challenging locations close to nontarget critical structures. Specifically, improvements in local control outcomes for patients with chordoma, chonodrosarcoma, and tumors in the sinonasal regions have been reported in series using proton. Improved local control and survival outcomes for patients with cancer of the head and neck region have also been seen with the advent of improvements in better imaging and multimodality therapy comprising surgery, radiation therapy, and chemotherapy. However, aggressive local therapy in the proximity of critical normal structures to tumors in the head and neck region may produce debilitating early and late toxic effects. Great interest has been expressed in evaluating whether proton therapy can improve outcomes, especially early and late toxicity, when used in the treatment of head and neck malignancies. This review summarizes the progress made to date in addressing this question.

  20. EBS Radionuclide Transport Abstraction

    Energy Technology Data Exchange (ETDEWEB)

    J.D. Schreiber

    2005-08-25

    The purpose of this report is to develop and analyze the engineered barrier system (EBS) radionuclide transport abstraction model, consistent with Level I and Level II model validation, as identified in ''Technical Work Plan for: Near-Field Environment and Transport: Engineered Barrier System: Radionuclide Transport Abstraction Model Report Integration'' (BSC 2005 [DIRS 173617]). The EBS radionuclide transport abstraction (or EBS RT Abstraction) is the conceptual model used in the total system performance assessment for the license application (TSPA-LA) to determine the rate of radionuclide releases from the EBS to the unsaturated zone (UZ). The EBS RT Abstraction conceptual model consists of two main components: a flow model and a transport model. Both models are developed mathematically from first principles in order to show explicitly what assumptions, simplifications, and approximations are incorporated into the models used in the TSPA-LA. The flow model defines the pathways for water flow in the EBS and specifies how the flow rate is computed in each pathway. Input to this model includes the seepage flux into a drift. The seepage flux is potentially split by the drip shield, with some (or all) of the flux being diverted by the drip shield and some passing through breaches in the drip shield that might result from corrosion or seismic damage. The flux through drip shield breaches is potentially split by the waste package, with some (or all) of the flux being diverted by the waste package and some passing through waste package breaches that might result from corrosion or seismic damage. Neither the drip shield nor the waste package survives an igneous intrusion, so the flux splitting submodel is not used in the igneous scenario class. The flow model is validated in an independent model validation technical review. The drip shield and waste package flux splitting algorithms are developed and validated using experimental data. The transport

  1. Promoting Clinical Reasoning in Undergraduate Physical Therapy Education: A Review of Strategies and Approaches

    DEFF Research Database (Denmark)

    Brekke, Anders Falk

    2015-01-01

    curricula. Under the broad paradigm of Problem Based Learning (PBL), which is being viewed as the key shift in educations in the last few years, many other models have been proposed. Strategies such as case based teaching, blended learning, co-operative learning, interactive learning, blogging and clinical......Title: Promoting Clinical Reasoning in Undergraduate Physical Therapy Education: A Review of Strategies and Approaches Juneja H1, Brekke A F2 1,2 Physical Therapy Education, University College Zealand, Denmark Background: Clinical reasoning (CR) also referred to as “critical thinking” or “decision...... in this area. This has resulted in diverse methods and strategies to transfer reasoning skills effectively to students. Awareness about recommended pedagogical techniques to enhance clinical reasoning skills can significantly influence the educator’s choice of methods within and beyond the classroom teaching...

  2. Boron neutron capture therapy for malignant melanoma: first clinical case report in China

    Science.gov (United States)

    Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

    2016-01-01

    A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

  3. [Extracorporeal shock-wave therapy. Experimental basis, clinical application].

    Science.gov (United States)

    Rompe, J D; Küllmer, K; Vogel, J; Eckardt, A; Wahlmann, U; Eysel, P; Hopf, C; Kirkpatrick, C J; Bürger, R; Nafe, B

    1997-03-01

    The purpose of our studies was to investigate experimentally the dose-dependent effects of extracorporeal shock waves on tendon and bone and to unveil therapeutic possibilities in tendinopathies and pseudarthroses. In animal experiments, both positive and negative influences were exerted by shock waves, depending on the initial situation and on the power of the applied shock waves. In prospective clinical trials positive effects were found in the treatment of persistent tennis elbow, plantar fasciitis, calcifying tendinitis, and pseudarthrosis. Our data show that extracorporeal shock waves may provide analgesic, resorptive and osteo-inductive reactions with nearly no side effects. However, the high cost of apparatus and staff prevents a routine application. Extracorporeal shock waves thus remain a last alternative before the indication is made for an operative procedure.

  4. Pharmacological basis and clinical evidence of dabigatran therapy

    Directory of Open Access Journals (Sweden)

    Redondo Santiago

    2011-12-01

    Full Text Available Abstract Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves.

  5. Clinical Controversies in Aerosol Therapy for Infants and Children.

    Science.gov (United States)

    DiBlasi, Robert M

    2015-06-01

    Pediatric patients are different from adult patients with respect to airway anatomy and breathing patterns. They are also incapable of following commands and often reject breathing treatments. For these reasons, aerosol drug delivery is one of the most technically challenging aspects for clinicians providing respiratory care to young children. Improvements in nebulizer technology have provided better delivery options for pediatric patients. This review highlights research related to pediatric nebulizer and interface devices and how they can be used to provide the safest and most efficient treatments with the array of treatment delivery options. Also addressed are clinical controversies and debates in pediatric aerosol science, including drug delivery in crying versus resting infants, pressurized metered-dose inhalers and small-volume nebulizers for bronchodilator administration, continuous nebulization, noninvasive drug delivery options, and optimization of nebulizer performance during infant and large pediatric conventional and high-frequency ventilation.

  6. Nutritional therapy for the management of diabetic gastroparesis: clinical review

    Directory of Open Access Journals (Sweden)

    Sadiya A

    2012-09-01

    Full Text Available Amena SadiyaLifestyle Clinic, Rashid Centre for Diabetes and Research, Ministry of Health, Ajman, United Arab EmiratesAbstract: Diabetic gastroparesis (DGP, or slow emptying of the stomach, is a well-established complication of diabetes mellitus and is typically considered to occur in individuals with long-standing type 1 and type 2 diabetes mellitus. Clinical consequences of DGP include induction of gastrointestinal (GI symptoms (early satiety, abdominal distension, reflux, stomach spasm, postprandial nausea, vomiting, alteration in drug absorption, and destabilization of glycemic control (due to mismatched postprandial glycemic and insulin peaks. Effective nutritional management not only helps in alleviating the symptoms, but also in facilitating better glycemic control. Although there have been no evidence-based guidelines pertaining to the nutrition care process of the DGP, the current dietary recommendations are based on expert opinions or observational studies. The dietary management of gastroparesis needs to be tailored according to the severity of malnutrition and kind of upper GI symptom by changing the volume, consistency, frequency, fiber, fat, and carbohydrates in the meal. Small frequent meals, using more liquid calories, reducing high fat or high fiber, consuming bezoar forming foods, and adjusting meal carbohydrates based on medications or insulin helps in improving the upper GI symptoms and glycemic control. Enteral nutrition can be an option for patients who fail to stabilize their weight loss, or for those who cannot gain weight with oral feedings, while total parenteral nutrition is rarely necessary for the patient with gastroparesis.Keywords: diabetic gastroparesis, delayed gastric emptying, diabetes mellitus, bezoar, GI symptoms, glycemic control

  7. Genomic Testing and Therapies for Breast Cancer in Clinical Practice

    Science.gov (United States)

    Haas, Jennifer S.; Phillips, Kathryn A.; Liang, Su-Ying; Hassett, Michael J.; Keohane, Carol; Elkin, Elena B.; Armstrong, Joanne; Toscano, Michele

    2011-01-01

    Purpose: Given the likely proliferation of targeted testing and treatment strategies for cancer, a better understanding of the utilization patterns of human epidermal growth factor receptor 2 (HER2) testing and trastuzumab and newer gene expression profiling (GEP) for risk stratification and chemotherapy decision making are important. Study Design: Cross-sectional. Methods: We performed a medical record review of women age 35 to 65 years diagnosed between 2006 and 2007 with invasive localized breast cancer, identified using claims from a large national health plan (N = 775). Results: Almost all women received HER2 testing (96.9%), and 24.9% of women with an accepted indication received GEP. Unexplained socioeconomic differences in GEP use were apparent after adjusting for age and clinical characteristics; specifically, GEP use increased with income. For example, those in the lowest income category (< $40,000) were less likely than those with an income of $125,000 or more to receive GEP (odds ratio, 0.34; 95% CI, 0.16 to 0.73). A majority of women (57.7%) with HER2-positive disease received trastuzumab; among these women, differences in age and clinical characteristics were not apparent, although surprisingly, those in the lowest income category were more likely than those in the high-income category to receive trastuzumab (P = .02). Among women who did not have a positive HER2 test, 3.9% still received trastuzumab. Receipt of adjuvant chemotherapy increased as GEP score indicated greater risk of recurrence. Conclusion: Identifying and eliminating unnecessary variation in the use of these expensive tests and treatments should be part of quality improvement and efficiency programs. PMID:21886507

  8. SU-E-T-588: Optimization of Imaging Following 223Ra Administration in Targeted Alpha-Emitting Radionuclide Therapy of Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Benabdallah, N; Bernardini, M [Hopital Europeen George Pompidou, Paris, Ile de France (France); Desbree, A [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-roses, Ile-de-France (France); Labriolle-Vaylet, C de [Hopital Trousseau, Paris, Ile de France (France); Franck, D [Institut de Radioprotection et de Suretu Nucleaire, Fontenay Aux Roses, Ile de France (France)

    2015-06-15

    Purpose: With a growing demand of alpha-emitting radiopharmaceuticals, especially Xofigo ({sup 223}RaCl{sub 2}) which is used in the treatment of metastatic bone disease, the optimization of dosimetry becomes necessary. Indeed, in Europe, as stated on the council directive 2013/59/euratom, exposures of target volumes for radiotherapeutic purposes shall be individually planned taking into account that doses to non-target volumes and tissues shall be as low as reasonably achievable. To that aim, the possibility of imaging {sup 223}Ra was first investigated. Methods: The experiments were conducted at the Hopital Europeen Georges Pompidou with an Infinia Hawkeye 4 gamma camera, equipped with a medium-energy collimator. Imaging parameters, such as sensibility, spatial resolution and energy spectrum, were determined using several physical phantoms with a source of 6 MBq of {sup 223}Ra. Bone metastases were modeled with a NEMA Body Phantom to investigate image degradation based on the concentration of {sup 223}Ra. Results: The acquired energy spectrum allowed to visualize several photon peaks: at 85, 154 and 270 keV. Camera sensitivity measured from the phantom study was 102.3 cps/MBq for the 85 keV ± 20 %, 89.9 cps/MBq for the 154 ± 20 % window and 65.4 cps/MBq for the 270 ± 10 % window. The spatial resolution (full-width at half-maximum) was respectively 1.7, 1.9 and 1.8 cm for the three energy windows. SPECT/CT images of NEMA Body Phantom without and with attenuation have permitted to determine the best reconstruction parameters. Conclusion: This study has demonstrated that it is possible to obtain clinically relevant information from images of {sup 223}Ra. All these results will be valuable to analyze biodistribution imaging of the radiopharmaceutical in the patient body and go further in the reconstruction of patient images in order to personalize the dosimetry.

  9. Utilization of therapies for stress management in Chilean clinical dental students.

    Directory of Open Access Journals (Sweden)

    Francisco Pérez

    2015-12-01

    Full Text Available Dental students suffer greater stress than the rest of the university population. In general, most health students seek little assistance to help them cope with stress. The aim of this study is to evaluate the use of therapies to manage stress in Chilean clinical dental students. A cross-sectional study was conducted nationwide; this report is a secondary data analysis. The study population was dental students in clinical years (4th and 5th of 5 Chilean dental schools: Antofagasta, Valparaíso, Viña del Mar, Concepción, and La Frontera. This paper reports the use of therapies for stress management during the past six months considering four options: medical/psychiatric, psychological, self-medication and alternative. Tabulation and analysis were done in STATA 10/SE. Three hundred thirty-seven students were surveyed, 54.01% were men and 64.99% were in fourth year, with an average age of 22.94±2.04. The 48.07% of students have used any of the four types of therapies; women and fourth-year students use more any form of therapy with 53.30% (p=.037 and 48.86% (p=.694, respectively, than men and fifth year students. About half of the students have used some form of therapy to manage stress in the last six months; of the students that received therapy, the percentage of women was significantly higher.

  10. Regulations and ethical codes for clinical cell therapy trials in Iran

    Institute of Scientific and Technical Information of China (English)

    Hooshang Saberi; Nazi Derakhshanrad; Babak Arjmand; Jafar Ai; Masoud Soleymani; Amir Ali Hamidieh; Mohammad Taghi Joghataei; Zahid Hussain Khan; Seyed Hassan Emami Razavi

    2015-01-01

    Objective:The local regulations for conducting experimental and clinical cell therapy studies are dependent on the national and cultural approach to the issue, and may have many common aspects as well as differences with the regulations in other countries. The study reflects the latest national aspects of cell therapy in Iran and relevant regulations. Methods:The following topics are discussed in the article including sources of cell harvest, regulations for cell disposal, stem cell manufacturing, and economic aspects of stem cell, based on current practice in Iran. Results:All cell therapy trials in Iran are required to strictly abide with the ethical codes, national and local regulations, and safety requirements, as well as considering human rights and respect. Adherence to these standards has facilitated the conduct of human cell therapy trials for research, academic advancement, and therapy. Conclusions:The cell therapy trials based on the aforementioned regulations may be assumed to be ethical and they are candidates for clinical translations based on safety and efficacy issues.

  11. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy.

    Science.gov (United States)

    Nowicka, Danuta

    2017-01-01

    Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = -0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.

  12. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy

    Science.gov (United States)

    2017-01-01

    Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = −0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.

  13. Accelerated prompt gamma estimation for clinical proton therapy simulations

    Science.gov (United States)

    Huisman, Brent F. B.; Létang, J. M.; Testa, É.; Sarrut, D.

    2016-11-01

    There is interest in the particle therapy community in using prompt gammas (PGs), a natural byproduct of particle treatment, for range verification and eventually dose control. However, PG production is a rare process and therefore estimation of PGs exiting a patient during a proton treatment plan executed by a Monte Carlo (MC) simulation converges slowly. Recently, different approaches to accelerating the estimation of PG yield have been presented. Sterpin et al (2015 Phys. Med. Biol. 60 4915-46) described a fast analytic method, which is still sensitive to heterogeneities. El Kanawati et al (2015 Phys. Med. Biol. 60 8067-86) described a variance reduction method (pgTLE) that accelerates the PG estimation by precomputing PG production probabilities as a function of energy and target materials, but has as a drawback that the proposed method is limited to analytical phantoms. We present a two-stage variance reduction method, named voxelized pgTLE (vpgTLE), that extends pgTLE to voxelized volumes. As a preliminary step, PG production probabilities are precomputed once and stored in a database. In stage 1, we simulate the interactions between the treatment plan and the patient CT with low statistic MC to obtain the spatial and spectral distribution of the PGs. As primary particles are propagated throughout the patient CT, the PG yields are computed in each voxel from the initial database, as a function of the current energy of the primary, the material in the voxel and the step length. The result is a voxelized image of PG yield, normalized to a single primary. The second stage uses this intermediate PG image as a source to generate and propagate the number of PGs throughout the rest of the scene geometry, e.g. into a detection device, corresponding to the number of primaries desired. We achieved a gain of around 103 for both a geometrical heterogeneous phantom and a complete patient CT treatment plan with respect to analog MC, at a convergence level of 2% relative

  14. Nutritional therapy for the management of diabetic gastroparesis: clinical review.

    Science.gov (United States)

    Sadiya, Amena

    2012-01-01

    Diabetic gastroparesis (DGP), or slow emptying of the stomach, is a well-established complication of diabetes mellitus and is typically considered to occur in individuals with long-standing type 1 and type 2 diabetes mellitus. Clinical consequences of DGP include induction of gastrointestinal (GI) symptoms (early satiety, abdominal distension, reflux, stomach spasm, postprandial nausea, vomiting), alteration in drug absorption, and destabilization of glycemic control (due to mismatched postprandial glycemic and insulin peaks). Effective nutritional management not only helps in alleviating the symptoms, but also in facilitating better glycemic control. Although there have been no evidence-based guidelines pertaining to the nutrition care process of the DGP, the current dietary recommendations are based on expert opinions or observational studies. The dietary management of gastroparesis needs to be tailored according to the severity of malnutrition and kind of upper GI symptom by changing the volume, consistency, frequency, fiber, fat, and carbohydrates in the meal. Small frequent meals, using more liquid calories, reducing high fat or high fiber, consuming bezoar forming foods, and adjusting meal carbohydrates based on medications or insulin helps in improving the upper GI symptoms and glycemic control. Enteral nutrition can be an option for patients who fail to stabilize their weight loss, or for those who cannot gain weight with oral feedings, while total parenteral nutrition is rarely necessary for the patient with gastroparesis.

  15. Nutritional therapy for the management of diabetic gastroparesis: clinical review

    Science.gov (United States)

    Sadiya, Amena

    2012-01-01

    Diabetic gastroparesis (DGP), or slow emptying of the stomach, is a well-established complication of diabetes mellitus and is typically considered to occur in individuals with long-standing type 1 and type 2 diabetes mellitus. Clinical consequences of DGP include induction of gastrointestinal (GI) symptoms (early satiety, abdominal distension, reflux, stomach spasm, postprandial nausea, vomiting), alteration in drug absorption, and destabilization of glycemic control (due to mismatched postprandial glycemic and insulin peaks). Effective nutritional management not only helps in alleviating the symptoms, but also in facilitating better glycemic control. Although there have been no evidence-based guidelines pertaining to the nutrition care process of the DGP, the current dietary recommendations are based on expert opinions or observational studies. The dietary management of gastroparesis needs to be tailored according to the severity of malnutrition and kind of upper GI symptom by changing the volume, consistency, frequency, fiber, fat, and carbohydrates in the meal. Small frequent meals, using more liquid calories, reducing high fat or high fiber, consuming bezoar forming foods, and adjusting meal carbohydrates based on medications or insulin helps in improving the upper GI symptoms and glycemic control. Enteral nutrition can be an option for patients who fail to stabilize their weight loss, or for those who cannot gain weight with oral feedings, while total parenteral nutrition is rarely necessary for the patient with gastroparesis. PMID:23055757

  16. Bisphosphonates and their clinical implications in endodontic therapy.

    Science.gov (United States)

    Moinzadeh, A-T; Shemesh, H; Neirynck, N A M; Aubert, C; Wesselink, P R

    2013-05-01

    This review gives an overview of the factors that may play a role in the development of osteonecrosis of the jaw in patients treated with bisphosphonates (BPs) and undergoing nonsurgical endodontic treatment as well as some recommendations for its prevention. BPs are a widely prescribed group of drugs for diverse bone diseases. The occasional but devastating adverse effect of these drugs has been described as bisphosphonate-related osteonecrosis of the jaw (BRONJ). As this condition is debilitating and difficult to treat, all efforts should be made to prevent its occurence in patients at risk. The main triggering event is considered to be dental extraction. Even though nonsurgical endodontic treatment appears to be a relatively safe procedure, care remains essential. After an overview of this class of drugs, the clinical presentation, epidemiology and pathogenesis of BRONJ, as well as the possible risk factors associated with its development after nonsurgical endodontic treatment will be described. Finally, several strategies will be proposed for the prevention of BRONJ during nonsurgical endodontic treatment.

  17. Non specific aorto-arteritis. Clinical picture, diagnosis and therapy.

    Science.gov (United States)

    Miani, S; De Monti, M; Keller, G; Bordoni, M G; Bianchi, E; Giordanengo, F

    1999-06-01

    This study is aimed at analyzing clinical features, angiographic findings and evolution of Takayasu's arteritis and the criteria adopted to establish the indication for non-surgical versus operative treatment. Eighteen patients affected by non specific aortarteritis were observed and treated at our Department between 1973 and 1996. All patients met the American College of Rheumatology 1990 criteria of classification of Takayasu's arteritis. Sixteen patients were young females. Two patients were males. Nine patients underwent surgical procedures. One young female underwent a PTA. All eight asymptomatic patients were only medically treated. One patient died some days after an aorto-bicarotid bypass graft due to acute myocardial infarction. Two other patients died two and four years after intervention for renal and cardiac failure respectively. One patient after an aorto bicarotid bypass underwent a left hemiplegia due to thrombosis of the right graft branch. All the other 14 patients either surgically or medically treated are well and are under strict surveillance through rigorous follow-up. The 10 patients who underwent surgical or interventional radiological treatment were certainly the most seriously affected patients and were symptomatic (presented neurological disturbances or a severe hypertensive state). This fact explains, to some extent, the mortality and morbidity rate observed in this group. The seven medically treated patients were completely asymptomatic in spite of a major involvement of various vascular districts.

  18. [Multi-national clinical therapy studies. Design, management and costs].

    Science.gov (United States)

    Demol, P; Weihrauch, T R

    1997-02-15

    The development of new drugs requires increasingly the performance of large multinational clinical trials (MCT) with a common protocol. They must be planned when the demonstration of a hypothesis, which requires specific conditions (for example availability of patients with rare diseases, a particular infrastructure or expert knowledge in trial centers) has to be proven in an acceptable time. Our own experience has shown that such multinational trials are more time-consuming in their preparation and their analysis than multicenter trials which are run in one country. MCTs are associated with complex problems due to many differences in medical culture, treatment strategies, administrative guidelines, etc., between countries. When possible MCTs should be realized in countries and centers with relatively similar medical practices. A global coordination is necessary to control the progress of the trial in the different countries. The major requirements for the successful realisation of an MCT, from the writing of the first draft of the protocol until the publication of the results, are a well-coordinated multidisciplinary team and an effective project management.

  19. Attachment-based family therapy for depressed and suicidal adolescents: theory, clinical model and empirical support.

    Science.gov (United States)

    Ewing, E Stephanie Krauthamer; Diamond, Guy; Levy, Suzanne

    2015-01-01

    Attachment-Based Family Therapy (ABFT) is a manualized family-based intervention designed for working with depressed adolescents, including those at risk for suicide, and their families. It is an empirically informed and supported treatment. ABFT has its theoretical underpinnings in attachment theory and clinical roots in structural family therapy and emotion focused therapies. ABFT relies on a transactional model that aims to transform the quality of adolescent-parent attachment, as a means of providing the adolescent with a more secure relationship that can support them during challenging times generally, and the crises related to suicidal thinking and behavior, specifically. This article reviews: (1) the theoretical foundations of ABFT (attachment theory, models of emotional development); (2) the ABFT clinical model, including training and supervision factors; and (3) empirical support.

  20. The efficacy of maggot debridement therapy - a review of comparative clinical trials

    DEFF Research Database (Denmark)

    Zarchi, K.; Jemec, G.B.

    2012-01-01

    Over the last decade, maggot debridement therapy (MDT) has been recognized by many clinicians as a potential adjunct to conventional therapy, and many patients with non healing, chronic ulcers have been treated. Numerous case reports and case series have described the successful use of MDT...... in a variety of ulcers. However, comparative clinical trials and in particular randomized controlled trials investigating the efficacy of MDT are sparse. A systematic search in the literature showed three randomized clinical trials and five non randomized studies evaluating the efficacy of sterile Lucilia...... sericata applied on ulcers with various aetiologies. Of these, seven studies had debridement and/or healing as an outcome variable. When evaluating maggots as debriding agents, the studies report MDT as being significantly more effective than hydrogel or a mixture of conventional therapy modalities...

  1. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy

    NARCIS (Netherlands)

    Lalla, R.V.; Bowen, J.; Barasch, A.; Elting, L.; Epstein, J.; Keefe, D.M.; McGuire, D.B.; Migliorati, C.; Nicolatou-Galitis, O.; Peterson, D.E.; Raber-Durlacher, J.E.; Sonis, S.T.; Elad, S.

    2014-01-01

    BACKGROUND Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for

  2. Group Cognitive-Behavioral Therapy for Insomnia in a VA Mental Health Clinic

    Science.gov (United States)

    Perlman, Lawrence M.; Arnedt, J. Todd; Earnheart, Kristie L.; Gorman, Ashley A.; Shirley, Katherine G.

    2008-01-01

    Effective cognitive-behavioral therapies for insomnia have been developed over the past 2 decades, but they have not been systematically evaluated in some clinical settings. While insomnia is common among veterans with mental health problems, the availability of effective treatments is limited. We report on the group application of a…

  3. Nature and frequency of drug therapy alerts generated by clinical decision support in community pharmacy

    NARCIS (Netherlands)

    Heringa, Mette; Floor-Schreudering, Annemieke; Tromp, P. Chris; de Smet, Peter A G M; Bouvy, Marcel L.

    2016-01-01

    Purpose: The purpose of this study is to investigate the nature, frequency, and determinants of drug therapy alerts generated by a clinical decision support system (CDSS) in community pharmacy in order to propose CDSS improvement strategies. Methods: This is a retrospective analysis of dispensed dru

  4. Cognitive-Behavioral Therapy for Intermittent Explosive Disorder: A Pilot Randomized Clinical Trial

    Science.gov (United States)

    McCloskey, Michael S.; Noblett, Kurtis L.; Deffenbacher, Jerry L.; Gollan, Jackie K.; Coccaro, Emil F.

    2008-01-01

    No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized…

  5. Randomized controlled trial of oral vs intravenous therapy for the clinically diagnosed acute uncomplicated diverticulitis.

    LENUS (Irish Health Repository)

    Ridgway, P F

    2009-11-01

    Despite the high prevalence of hospitalization for left iliac fossa tenderness, there is a striking lack of randomized data available to guide therapy. The authors hypothesize that an oral antibiotic and fluids are not inferior to intravenous (IV) antibiotics and \\'bowel rest\\' in clinically diagnosed acute uncomplicated diverticulitis.

  6. Botulinum therapy for poststroke spasticity of the lower extremity (clinical cases

    Directory of Open Access Journals (Sweden)

    L. V. Krylova

    2014-01-01

    Full Text Available The paper deals with the topical problem – the medical rehabilitation of patients with poststroke spasticity. It describes clinical cases of patients with poststroke spasticity of the upper and lower extremities who have received combined therapy using botulinum toxin type A (Botox injections.

  7. Dissecting the Wilderness Therapy Client: Examining Clinical Trends, Findings, and Patterns

    Science.gov (United States)

    Hoag, Matthew J.; Massey, Katie E.; Roberts, Sean D.

    2014-01-01

    Over the last decade, wilderness therapy research has increased substantially in both quality and quantity and has begun to establish a base of evidence and literature. However, there is still much to be learned about the clients served and their clinical profile. The authors examined diagnostic data from discharge summaries of 929 clients (192…

  8. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy

    DEFF Research Database (Denmark)

    Lalla, Rajesh V; Bowen, Joanne; Barasch, Andrei

    2014-01-01

    BACKGROUND: Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines ...

  9. Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy

    NARCIS (Netherlands)

    Heetla, Herre W; Staal, Michael; Proost, Johannes H; van Laar, Teus

    2014-01-01

    Objective: To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research. Data Sources: PubMed was searched for relevant anatomic, physiological, and pharmacological data available on ITB. Study S

  10. Moving from Efficacy to Effectiveness in Cognitive Behavioral Therapy for Psychosis: A Randomized Clinical Practice Trial

    Science.gov (United States)

    Lincoln, Tania M.; Ziegler, Michael; Mehl, Stephanie; Kesting, Marie-Luise; Lullmann, Eva; Westermann, Stefan; Rief, Winfried

    2012-01-01

    Objective: Randomized controlled trials have attested the efficacy of cognitive behavioral therapy (CBT) in reducing psychotic symptoms. Now, studies are needed to investigate its effectiveness in routine clinical practice settings. Method: Eighty patients with schizophrenia spectrum disorders who were seeking outpatient treatment were randomized…

  11. Telephone-Administered Cognitive Behavioral Therapy for Veterans Served by Community-Based Outpatient Clinics

    Science.gov (United States)

    Mohr, David C.; Carmody, Timothy; Erickson, Lauren; Jin, Ling; Leader, Julie

    2011-01-01

    Objective: Multiple trials have found telephone-administered cognitive behavioral therapy (T-CBT) to be effective for the treatment of depression. The aim of this study was to evaluate T-CBT for the treatment of depression among veterans served by community-based outpatient clinics (CBOCs) outside of major urban areas. Method: Eighty-five veterans…

  12. Setting up the On-Site Marriage and Family Therapy Clinical Training Course

    Science.gov (United States)

    Ratanasiripong, Paul; Ghafoori, Bita

    2009-01-01

    The first clinical training experience or practicum for graduate students in a Marriage and Family Therapy (MFT) program is one of the most important aspects of the entire training program. After a year-long journey through textbook and classroom knowledge, students have the opportunity to finally apply their skills to real life environments with…

  13. Competency-Based Training: Objective Structured Clinical Exercises (OSCE) in Marriage and Family Therapy

    Science.gov (United States)

    Miller, John K.

    2010-01-01

    The field of marriage and family therapy (MFT) has recently engaged in the process of defining core competencies for the profession. Many MFT training programs are adapting their curriculum to develop more competency-based training strategies. The Objective Structured Clinical "Examination" (OSCE) is widely used in the medical profession to assess…

  14. Delivering Parent-Child Interaction Therapy in an Urban Community Clinic

    Science.gov (United States)

    Budd, Karen S.; Hella, Bryce; Bae, Hyo; Meyerson, David A.; Watkin, Sarah C.

    2011-01-01

    Extensive evidence supports the efficacy of Parent-Child Interaction Therapy (PCIT) for reducing behavior problems in young children; however, little is known about the use of PCIT in a community mental health center (CMHC). This paper provides four clinical case examples of families who were referred to and successfully completed PCIT in an urban…

  15. The Clinical Aspects of Mirror Therapy in Rehabilitation: A Systematic Review of the Literature

    Science.gov (United States)

    Rothgangel, Andreas Stefan; Braun, Susy M.; Beurskens, Anna J.; Seitz, Rudiger J.; Wade, Derick T.

    2011-01-01

    The objective of this study was to evaluate the clinical aspects of mirror therapy (MT) interventions after stroke, phantom limb pain and complex regional pain syndrome. A systematic literature search of the Cochrane Database of controlled trials, PubMed/MEDLINE, CINAHL, EMBASE, PsycINFO, PEDro, RehabTrials and Rehadat, was made by two…

  16. Clinical Observation of 82 Cases of Enuresis Treated by Ginger-partitioned Moxibustion plus Cupping Therapy

    Institute of Scientific and Technical Information of China (English)

    ZHU Wei-ping; HUANG Guo-qi

    2003-01-01

    Purpose: To observe the clinical therapeutic effect in the treatment of enuresis by ginger-partitioned moxibustion plus cupping therapy. Methods: Ginger-par -titioned moxibustion was applied on Guanyuan (CV 4)and bilateral Zusanli (ST 36) and cupping therapy was applied on Shenque (CV 8) in the treatment of 82 cases of enuresis, in comparison with 76 cases treated by Chinese herbal medicine. Results: The effective rate was 84.1% in the treatment by ginger-partitioned moxibustion plus cupping therapy and was 64.5% in the treatment by Chinese herbal medicine. Conclusion: Ginger-partitio -ned moxibustion plus cupping therapy was better than Chinese herbal medicine in the treatment of enuresis (P <0.05).

  17. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Ataman, Ozlem U., E-mail: ouataman@hotmail.com [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Sambrook, Sally J. [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Wilks, Chris [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Lloyd, Andrew [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Taylor, Amanda E. [Yellow Delaney Communications Ltd, Wilmslow, Cheshire (United Kingdom); Wedge, Stephen R. [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom)

    2012-11-15

    Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that

  18. Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective

    Directory of Open Access Journals (Sweden)

    Davatgaran-Taghipour Y

    2017-04-01

    bioavailability. Different types of formulations have been designed for the improvement of bioavailability of these compounds, nanonization being one of the most notable approaches among them. This study aimed to review current data on the nanoformulations of natural polyphenols as chemopreventive and chemotherapeutic agents and to discuss their molecular anticancer mechanisms of action. Nanoformulations of natural polyphenols as bioactive agents, including resveratrol, curcumin, quercetin, epigallocatechin-3-gallate, chrysin, baicalein, luteolin, honokiol, silibinin, and coumarin derivatives, in a dose-dependent manner, result in better efficacy for the prevention and treatment of cancer. The impact of nanoformulation methods for these natural agents on tumor cells has gained wider attention due to improvement in targeted therapy and bioavailability, as well as enhancement of stability. Today, several nanoformulations are designed for delivery of polyphenolic compounds, including nanosuspensions, solid lipid nanoparticles, liposomes, gold nanoparticles, and polymeric nanoparticles, which have resulted in better antineoplastic activity, higher intracellular concentration of polyphenols, slow and sustained release of the drugs, and improvement of proapoptotic activity against tumor cells. To conclude, natural polyphenols demonstrate remarkable anticancer potential in pharmacotherapy; however, the obstacles in terms of their bioavailability in and toxicity to normal cells, as well as targeted drug delivery to malignant cells, can be overcome using nanoformulation-based technologies, which optimize the bioefficacy of these natural drugs. Keywords: natural products, flavonoid, anthocyanin, tumor, malignancy

  19. Radionuclide - Soil Organic Matter Interactions

    DEFF Research Database (Denmark)

    Carlsen, Lars

    1985-01-01

    Interactions between soil organic matter, i.e. humic and fulvic acids, and radionuclides of primary interest to shallow land burial of low activity solid waste have been reviewed and to some extent studied experimentally. The radionuclides considered in the present study comprise cesium, strontium...

  20. Cognitive Behavioral Therapy in Practice: Treatment Delivered by Trainees at an Outpatient Clinic Is Clinically Effective

    Science.gov (United States)

    Forand, Nicholas R.; Evans, Susan; Haglin, Dean; Fishman, Baruch

    2011-01-01

    Cognitive-behavioral therapy (CBT) is known to be effective for a number of disorders, and can be delivered effectively by trainees in controlled settings. However, the effectiveness of trainee therapists in general practice compared to that of more experienced therapists is unknown. In this study, the authors used a benchmarking strategy to…

  1. Clinical research evidence of cupping therapy in China: a systematic literature review

    Directory of Open Access Journals (Sweden)

    Wang Qian

    2010-11-01

    Full Text Available Abstract Background Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it. This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies. Methods We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated. Results 550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs, 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies. Conclusions According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice.

  2. Adapting preclinical concepts for use in clinical trials of serosal and interstitial photodynamic therapy.

    Science.gov (United States)

    Cengel, Keith

    2012-10-01

    Photodynamic therapy (PDT) requires an optimal combination of drug and light. To achieve the ideal conditions, a tight bond between the research laboratory and the clinic is essential. This continual 2-way street allows preclinical ideas and concepts to be tested in the clinic and refinements in technique to be made. This article clearly illustrates the close connection between the bench and the bedside, exploring intraoperative pleural PDT, challenges in matching fluence and photosensitizer, improvements in animal models that lead to adjustments in the operating room, and clinical applications for interstitial PDT in prostate cancer and beyond.

  3. [Psychodynamic-multisystemic Therapy of School Phobia due to Separation Anxiety in Day Clinic].

    Science.gov (United States)

    Herbst, Antje; Fernholz, Judith Maria; Strothe, Kay Susanne; Schlund, Sarah

    2015-01-01

    Psychodynamic understanding and systemic approach in the multi-family treatment of a day care clinic are illustrated following the case report of a seven-year old girl with school phobia due to separation anxiety. The treatment modalities of the day clinic at the University Medical Center Muenster are described focussing on the multi-systemic approach. Using psychodynamic and systemic hypotheses the process of treatment is developed. Specific interventions, differentiated into reorganizations of inner and outer world issues, are traced to psychodynamic and systemic hypotheses. In conclusion it is argued that the integration of psychodynamic and multisystemic therapy methods in day clinic parent-child treatment provide a promising treatment approach.

  4. The practice of clinical research in accredited marriage and family therapy programs.

    Science.gov (United States)

    McWey, Lenore M; West, Stacy Hernandez; Ruble, Nikki M; Handy, Amy K; Handy, David G; Koshy, Mathen; Mills, Kathleen

    2002-01-01

    This study aims to explore the prevalence of clinic-based research among accredited marriage and family therapy (MFT) programs and reveal rationales explaining why academic settings may or may not be conducting clinical research. Findings of this project are the result of electronic-mail surveys completed by 26 accredited MFT programs. Approximately one-half of the respondents reported currently conducting clinic-based research. Open-ended responses reveal factors that lead to research success and failure, as well as reasons research was not being conducted at training programs.

  5. Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

    Science.gov (United States)

    Labrador-Velandia, Sonia; Alonso-Alonso, María Luz; Alvarez-Sanchez, Sara; González-Zamora, Jorge; Carretero-Barrio, Irene; Pastor, José Carlos; Fernandez-Bueno, Iván; Srivastava, Girish Kumar

    2016-01-01

    Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells (MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in I/II phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase III-IV. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases. PMID:27928464

  6. [Bibliometrics study on indications of acupuncture therapy based on foreign acupuncture clinical trials].

    Science.gov (United States)

    He, Wei; Tong, Yuan-Yuan; Zhao, Ying-Kai; Rong, Pei-Jing; Wang, Hong-Cai

    2012-10-01

    In the present paper, the authors make a bibliometrics study on clinical indications of acupuncture therapy based on the published foreign articles about acupuncture clinical trials collected from PubMed database and Excerpta Medica database (EMbase). In 1996, 64 acupuncture indications were declared by WHO in Milan conference. But in recent 15 years, clinical trials have been conducted extensively in the foreign countries. Till now, 77 new indications for acupuncture therapy have been found in the foreign journals. The authors recommended that 29 indications (knee osteoarthritis, critique age problems, muscular fasciae ache, anxiety, etc.) should be added to the first class, 4 indications (irritable bowel syndrome, malposition, backache, simple obesity) should be upgraded from the second class to the first class, and the other 3 indications (childbirth pain, male and female barren) should be upgraded from the third class to the first class due to their application frequency in clinical trials. Increase of clinical indications reflects extensive application of acupuncture therapy and may help providing a better service for people's health.

  7. An audit on virological efficacy of anti-retroviral therapy in a specialist infectious disease clinic.

    LENUS (Irish Health Repository)

    Reyad, A

    2009-06-01

    We have assessed the efficacy of anti retroviral therapy (ART) using undetectable viral load (VL) (<50 RNA copies\\/ml) as a marker of virological success, in patients who have Human Immunodeficiency Virus (HIV) attending the Department of Infectious Disease. A cross-sectional review of patients\\' case notes was used to obtain their demographics and treatment details. 79% (253) of the hospital case notes of clinic population was available for analysis, which represents 90% of those receiving ART in the clinic. 166\\/253 of the cohort were receiving treatment at the time of this study and 95% (157\\/166) of these were on treatment for greater than 6 months. The total virological success rate is 93%, which is comparable to other centres and are as good as those from published clinical trials. 56% of those on therapy who have virological failure were Intravenous Drug Users (IVDUs). Case by case investigation for those with treatment failure is warranted.

  8. Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    John F. Flynn

    2009-01-01

    Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

  9. Promoting Clinical Reasoning in Undergraduate Physical Therapy Education: A Review of Strategies and Approaches

    DEFF Research Database (Denmark)

    Brekke, Anders Falk

    2015-01-01

    -deduction and the pattern recognition skills in physical therapy students, focused teaching methods and strategies need to be emphasized and adopted by academicians, clinical educators and of course students. It is also of utmost importance that evaluation systems of physical therapy programs are introspected for inclusion...... in this area. This has resulted in diverse methods and strategies to transfer reasoning skills effectively to students. Awareness about recommended pedagogical techniques to enhance clinical reasoning skills can significantly influence the educator’s choice of methods within and beyond the classroom teaching...... curricula. Under the broad paradigm of Problem Based Learning (PBL), which is being viewed as the key shift in educations in the last few years, many other models have been proposed. Strategies such as case based teaching, blended learning, co-operative learning, interactive learning, blogging and clinical...

  10. The Effect of Cognitive Behavior Therapy in Insomnia due to Methadone Maintenance Therapy: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Robabeh Soleimani

    2015-09-01

    Full Text Available Background: Sleep disturbance is a common complaint of patients undergoing methadone maintenance therapy (MMT. There are limited studies about the effect of different treatments on insomnia due to MMT. In this study, we evaluated the effect of cognitive-behavioral treatment for insomnia (CBTI on sleep disorders in patients undergoing MMT. Methods: Twenty-two patients with insomnia due to MMT (aged 18-60 years participated in this randomized double-blind clinical trial. The intervention group received CBTI from a clinical psychologist for 8 weeks, whereas the control group received behavioral placebo therapy (BPT. The duration of individual sessions was 45 minutes, which was conducted once a week. The primary outcome was sleep disturbance assessed with Pittsburgh Sleep Quality Index (PSQI. Data were analyzed using SPSS software version 19. Results: Eleven patients were assigned to each group. Two groups were matched according to demographic characteristics (age, marital status, education, and daily methadone doses. Although PSQI score was significantly reduced during weeks 5 and 8 after both interventions, there was a significant difference in intervention versus time interaction (P<0.02. The effects of CBTI versus placebo were significantly different (P<0.001. The time course was also significant (P<0.001. Conclusion: This study showed that CBTI is more effective than BPT in overall sleep quality. We recommend further studies, with a larger sample, on CBTI in patients undergoing MMT.

  11. A simulation for teaching the basic and clinical science of fluid therapy.

    Science.gov (United States)

    Rawson, Richard E; Dispensa, Marilyn E; Goldstein, Richard E; Nicholson, Kimberley W; Vidal, Noni Korf

    2009-09-01

    The course "Management of Fluid and Electrolyte Disorders" is an applied physiology course taught using lectures and paper-based cases. The course approaches fluid therapy from both basic science and clinical perspectives. While paper cases provide a basis for application of basic science concepts, they lack key components of genuine clinical cases that, by nature, are diverse, change over time, and respond in unique ways to therapeutic interventions. We developed a dynamic model using STELLA software that simulates normal and abnormal fluid and electrolyte balance in the dog. Students interact, not with the underlying model, but with a user interface that provides sufficient data (skin turgor, chemistry panel, etc.) for the clinical assessment of patients and an opportunity for treatment. Students administer fluids and supplements, and the model responds in "real time," requiring regular reassessment and, potentially, adaptation of the treatment strategy. The level of success is determined by clinical outcome, including improvement, deterioration, or death. We expected that the simulated cases could be used to teach both the clinical and basic science of fluid therapy. The simulation provides exposure to a realistic clinical environment, and students tend to focus on this aspect of the simulation while, for the most part, ignoring an exploration of the underlying physiological basis for patient responses. We discuss how the instructor's expertise can provide sufficient support, feedback, and scaffolding so that students can extract maximum understanding of the basic science in the context of assessing and treating at the clinical level.

  12. Clinical Case Reporting in the Peer-Reviewed Physical Therapy Literature: Time to Move Toward Functioning.

    Science.gov (United States)

    Davenport, Todd E

    2015-12-01

    Physical therapists increasingly are contributing clinical case reports to the health literature, which form the basis for higher quality evidence that has been incorporated into clinical practice guidelines. Yet, few resources exist to assist physical therapists with the basic mechanics and quality standards of producing a clinical case report. This situation is further complicated by the absence of uniform standards for quality in case reporting. The importance of including a concise yet comprehensive description of patient functioning in all physical therapy case reports suggest the potential appropriateness of basing quality guidelines on the World Health Organization's International Classification of Functioning Disability and Health (ICF) model. The purpose of this paper is to assist physical therapists in creating high-quality clinical case reports for the peer-reviewed literature using the ICF model as a guiding framework. Along these lines, current recommendations related to the basic mechanics of writing a successful clinical case report are reviewed, as well and a proposal for uniform clinical case reporting requirements is introduced with the aim to improve the quality and feasibility of clinical case reporting in physical therapy that are informed by the ICF model.

  13. Comparison of clinical characteristics and survival on patients with idiopathic pulmonary arterial hypertension and familial pulmonary arterial hypertension during conventional therapy era and targeted therapy era

    Institute of Scientific and Technical Information of China (English)

    徐希奇

    2014-01-01

    Objective To compare the clinical characteristics and survival on Chinese patients with idiopathic pulmonary arterial hypertension(IPAH)and familiar pulmonary arterial hypertension(FPAH)during conventional therapy era and targeted therapy era.Methods IPAH and FPAH patients who were referred between Jan 1999and Oct 2004 in Fuwai Hospital were defined as conventional therapy era group(before 2005 no PAH-specific drug was available in China).All patients in this group

  14. 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

  15. The development and use of radionuclide generators in nuclear medicine -- recent advances and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.

    1998-03-01

    Although the trend in radionuclide generator research has declined, radionuclide generator systems continue to play an important role in nuclear medicine. Technetium-99m obtained from the molybdenum-99/technetium-99m generator system is used in over 80% of all diagnostic clinical studies and there is increasing interest and use of therapeutic radioisotopes obtained from generator systems. This paper focuses on a discussion of the major current areas of radionuclide generator research, and the expected areas of future research and applications.

  16. Clinical Observation on Treatment of Cervical Spondylosis with Combined Acupuncture and Cupping Therapies

    Institute of Scientific and Technical Information of China (English)

    万学文

    2007-01-01

    目的:观察针刺结合拔罐治疗颈椎病的临床疗效.方法:针罐组(30例)采用针刺结合拔罐治疗,针刺组(30例)采用单纯针刺治疗,治疗30天观察疗效.结果:两组治愈率、总有效率、半年后复发率、平均疗程经χ2检验P<0.01两组有显著性差异.结论:针刺结合拔罐治疗颈椎病疗效好,疗程短,不易复发.%Objective: To observe the clinical efficacy of treating cervical spondylosis with combined acupuncture and cupping therapies. Method: The patients in the treatment group (30 cases) were treated with combined acupuncture and cupping therapies; and the patients in the control group (30 cases) were treated with acupuncture therapy alone. Then the clinical efficacy was observed after 30 days of treatment. Result: The χ2 test showed that there was significant difference (P<0.01) between the two groups in recovery rate, total effective rate, relapse rate after six months, and average treatment course. Conclusion: Combined acupuncture and cupping therapies is a better therapy for cervical spondylosis with a shorter treatment course and low relapse rate.

  17. Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma.

    Science.gov (United States)

    Richter, Joshua; Neparidze, Natalia; Zhang, Lin; Nair, Shiny; Monesmith, Tamara; Sundaram, Ranjini; Miesowicz, Fred; Dhodapkar, Kavita M; Dhodapkar, Madhav V

    2013-01-17

    Natural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of α-galactosylceramide-loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK cells with an increase in NKG2D and CD56 expression. Treatment also led to activation of monocytes with an increase in CD16 expression. Each cycle of therapy was associated with induction of eosinophilia as well as an increase in serum soluble IL2 receptor. Clinical responses correlated with pre-existing or treatment-induced antitumor T-cell immunity. These data demonstrate synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor regression. Combination therapies targeting iNKT cells may be of benefit toward prevention of cancer in humans.

  18. Clinical applications of stereotactic radiation therapy for oligometastatic cancer patients: a disease-oriented approach

    Science.gov (United States)

    Ricardi, Umberto; Badellino, Serena; Filippi, Andrea Riccardo

    2016-01-01

    Oligometastases from solid tumors are currently recognized as a distinct clinical entity, corresponding to an intermediate state between local and widespread disease. It has been suggested that local ablative therapies (including surgery, radiofrequency ablation and radiation therapy) play an important role in this setting, in combination or not with systemic therapies, particularly in delaying disease progression and hopefully in increasing the median survival time. Stereotactic body radiation therapy (SBRT) rapidly emerged in recent years as one of the most effective and less toxic local treatment modalities for lung, liver, adrenal, brain and bone metastases. The aim of this review was to focus on its clinical role for oligometastatic disease in four major cancer subtypes: lung, breast, colorectal and prostate. On the basis of the available evidence, SBRT is able to provide high rates of local tumor control without significant toxicity. Its global impact on survival is uncertain; however, in specific subpopulations of oligometastatic patients there is a trend towards a significant improvement in progression-free and overall survival rates; these important data might be used as a platform for clinical decision-making and establish the basis for the current and future prospective trials investigating its role with or without systemic treatments. PMID:26962198

  19. Extracorporeal shock wave therapy (ESWT) for wound healing: technology, mechanisms, and clinical efficacy.

    Science.gov (United States)

    Mittermayr, Rainer; Antonic, Vlado; Hartinger, Joachim; Kaufmann, Hanna; Redl, Heinz; Téot, Luc; Stojadinovic, Alexander; Schaden, Wolfgang

    2012-01-01

    For almost 30 years, extracorporeal shock wave therapy has been clinically implemented as an effective treatment to disintegrate urinary stones. This technology has also emerged as an effective noninvasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life. Intensive wound care is required, and this places an enormous burden on society in terms of lost productivity and healthcare costs. Therefore, cost-effective, noninvasive, and efficacious treatments are imperative to achieve both (accelerated and complete) healing of problematic wounds and reduce treatment-related costs. Several experimental and clinical studies show efficacy for extracorporeal shock wave therapy as means to accelerate tissue repair and regeneration in various wounds. However, the biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains unclear. Potential mechanisms, which are discussed herein, include initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves. This review aims to provide an overview of shock wave therapy, its history and development as well as its current place in clinical practice. Recent research advances are discussed emphasizing the role of extracorporeal shock wave therapy in soft tissue wound healing.

  20. Clinical implementation of the Peregrine Monte Carlo dose calculations system for photon beam therapy

    Energy Technology Data Exchange (ETDEWEB)

    Albright, N; Bergstrom, P M; Daly, T P; Descalle, M; Garrett, D; House, R K; Knapp, D K; May, S; Patterson, R W; Siantar, C L; Verhey, L; Walling, R S; Welczorek, D

    1999-07-01

    PEREGRINE is a 3D Monte Carlo dose calculation system designed to serve as a dose calculation engine for clinical radiation therapy treatment planning systems. Taking advantage of recent advances in low-cost computer hardware, modern multiprocessor architectures and optimized Monte Carlo transport algorithms, PEREGRINE performs mm-resolution Monte Carlo calculations in times that are reasonable for clinical use. PEREGRINE has been developed to simulate radiation therapy for several source types, including photons, electrons, neutrons and protons, for both teletherapy and brachytherapy. However the work described in this paper is limited to linear accelerator-based megavoltage photon therapy. Here we assess the accuracy, reliability, and added value of 3D Monte Carlo transport for photon therapy treatment planning. Comparisons with clinical measurements in homogeneous and heterogeneous phantoms demonstrate PEREGRINE's accuracy. Studies with variable tissue composition demonstrate the importance of material assignment on the overall dose distribution. Detailed analysis of Monte Carlo results provides new information for radiation research by expanding the set of observables.

  1. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly

    Science.gov (United States)

    Christofides, Elena A

    2016-01-01

    In acromegaly, achieving biochemical control (growth hormone [GH] level acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. PMID:27471378

  2. Gene Therapy of T Helper Cells in HIV Infection. Mathematical Model of the Criteria for Clinical Effect

    DEFF Research Database (Denmark)

    Lund, Ole; Lund, Ole søgaard; Gram, Gregers

    1997-01-01

    The paper presents a mathematical model of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. Our main results are that the therapy should be designed to give the transduced cells a significant but not necessarily total protection against HIV-induced cell...... deaths, and to avoid the production of viral mutants that are insensitive to gene therapy. The transduced cells will not survive if the gene therapy only blocks the spread of virus....

  3. Radioactivity, radionuclides, radiation

    CERN Document Server

    Magill, Joseph

    2005-01-01

    RADIOACTIVITY – RADIONUCLIDES – RADIATION is suitable for a general audience interested in topical environmental and human health radiological issues such as radiation exposure in aircraft, food sterilisation, nuclear medicine, radon gas, radiation dispersion devices ("dirty bombs")… It leads the interested reader through the three Rs of nuclear science, to the forefront of research and developments in the field. The book is also suitable for students and professionals in the related disciplines of nuclear and radiochemistry, health physics, environmental sciences, nuclear and astrophysics. Recent developments in the areas of exotic decay modes (bound beta decay of ‘bare’ or fully ionized nuclei), laser transmutation, nuclear forensics, radiation hormesis and the LNT hypothesis are covered. Atomic mass data for over 3000 nuclides from the most recent (2003) evaluation are included.

  4. Music therapy services in pediatric oncology: a national clinical practice review.

    Science.gov (United States)

    Tucquet, Belinda; Leung, Maggie

    2014-01-01

    This article presents the results of a national clinical practice review conducted in Australia of music therapy services in pediatric oncology hospitals. Literature specifically related to music therapy and symptom management in pediatric oncology is reviewed. The results from a national benchmarking survey distributed to all music therapists working with children with cancer in Australian pediatric hospitals are discussed. Patient and family feedback provided from a quality improvement activity conducted at a major pediatric tertiary hospital is summarized, and considerations for future growth as a profession and further research is proposed.

  5. Clinical Observation of Fire-needle Therapy plus Tuina for Senile Knee Osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    Zhao Jing-jun

    2014-01-01

    Objective: To observe the therapeutic efficacy of fire-needle therapy plus tuina in treating primary knee osteoarthritis (KOA) in the elderly. Methods: Twenty-three patients with KOA were intervened by pricking with fire-needle therapy plus tuina, and evaluated by using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) before and after intervention. Results: After intervention, the total score, scores of pain, rigidity, and activities of daily living of WOMAC dropped significantly (P Conclusion: Pricking with fire needle plus tuina can produce a significant therapeutic efficacy in treating KOA in the elderly, thus worth application in clinic.

  6. Proton therapy of cancer: Potential clinical advantages and cost-effectiveness

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, Jonas; Ekman, Mattias [Stockholm Health Economics, Stockholm (Sweden); Rehn Ericsson, Suzanne [Univ. Hospital, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology; Joensson, Bengt [Stockholm School of Economics, Stockholm (Sweden); Glimelius, Bengt [Karolinska Inst., Stockholm (Sweden). Dept. of Oncology and Pathology; Akademiska sjukhuset, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology

    2005-12-01

    Proton therapy may offer potential clinical advantages compared with conventional radiation therapy for many cancer patients. Due to the large investment costs for building a proton therapy facility, however, the treatment cost with proton radiation is higher than with conventional radiation. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to motivate the higher costs. We assessed the cost-effectiveness of proton therapy in the treatment of four different cancers: left-sided breast cancer, prostate cancer, head and neck cancer, and childhood medulloblastoma. A Markov cohort simulation model was created for each cancer type and used to simulate the life of patients treated with radiation. Cost and quality adjusted life years (QALYs) were used as primary outcome measures. The results indicated that proton therapy was cost-effective if appropriate risk groups were chosen. The average cost per QALY gained for the four types of cancer assessed was about Euro 10,130. If the value of a QALY was set to Euro 55,000, the total yearly net benefit of treating 925 cancer patients with the four types of cancer was about Euro 20.8 million. Investment in a proton facility may thus be cost-effective. The results must be interpreted with caution, since there is a lack of data, and consequently large uncertainties in the assumptions used.

  7. COMPARISON OF DIFFERENT STRATEGIES OF ANTIHYPERTENSIVE THERAPY IN OUT-PATIENT CLINIC

    Directory of Open Access Journals (Sweden)

    O. A. Plejko

    2008-01-01

    Full Text Available Aim. To compare different strategies of start antihypertensive therapy in out-patients.Material and methods. 120 out-patients with arterial hypertension (HT 1-2 stages were included in the study and randomized in 3 groups. Patients of group «A» received start treatment in compliance with age, clinical features and mechanisms of hypertension. Patients of group «B» received step-by-step start antihypertensive therapy based on doses titration and addition of the second (third drug if necessary. Patients of group «C» received fixed drug combination with addition of other antihypertensive medicines if necessary. Decrease of BP level and number of visits were used as criteria of therapy efficacy. Pharmacoeconomic analysis of antihypertensive therapy was done in all groups.Results. Strategy of HT start therapy in group «C» had advantages in speed of blood pressure normalization, number of necessary visits and in pharmacoeconomic efficacy in comparison with the strategies in group «A» and «B».Conclusion. HT start therapy with implementation of fixed low dose combination leads to the best result in comparison with other strategy based on step-by-step drug replacement (as well as their combining or monotherapy dose titration.

  8. Comparison of Photodynamic Therapy versus conventional antifungal therapy for the treatment of denture stomatitis: a randomized clinical trial.

    Science.gov (United States)

    Mima, E G; Vergani, C E; Machado, A L; Massucato, E M S; Colombo, A L; Bagnato, V S; Pavarina, A C

    2012-10-01

    In this randomized clinical trial, the clinical and mycological efficacy of Photodynamic Therapy (PDT) was compared with that of topical antifungal therapy for the treatment of denture stomatitis (DS) and the prevalence of Candida species was identified. Patients were randomly assigned to one of two groups (n = 20 each); in the nystatin (NYT) group patients received topical treatment with nystatin (100,000 IU) four times daily for 15 days and in the PDT group the denture and palate of patients were sprayed with 500 mg/L of Photogem(®), and after 30 min of incubation, were illuminated by light emitting-diode light at 455 nm (37.5 and 122 J/cm(2), respectively) three times a week for 15 days. Mycological cultures taken from dentures and palates and standard photographs of the palates were taken at baseline (day 0), at the end of the treatment (day 15) and at the follow-up time intervals (days 30, 60 and 90). Colonies were quantified (CFU/mL) and identified by biochemical tests. Data were analysed by Fisher's exact test, analysis of variance and Tukey tests and κ test (α = 0.05). Both treatments significantly reduced the CFU/mL at the end of the treatments and on day 30 of the follow-up period (p <0.05). The NYT and PDT groups showed clinical success rates of 53% and 45%, respectively. Candida albicans was the most prevalent species identified. PDT was as effective as topical nystatin in the treatment of DS.

  9. Reporter Gene Imaging in Therapy and Diagnosis

    Directory of Open Access Journals (Sweden)

    Pritha Ray, Abhijit De

    2012-01-01

    Full Text Available Noninvasive molecular imaging using reporter genes is a relatively recent field in biomedical imaging that holds great promises for disease diagnosis and therapy. As modern medicine is moving towards personalized medicine, targeted biomolecule based therapies is gaining popularity that requires careful and systematic validation. Reporter genes have emerged as important generalizable tools to overcome the shortcomings of direct evaluation of individual biomolecules and are being applied in various fields such as cell therapy, stem cell therapy, immune therapy, viral gene delivery through optical, radionuclide, magnetic resonance imaging techniques. New approaches to image protein-protein interaction, protein phosphorylation, protein folding that are crucial parameters for theranostic study using reporter genes are being developed. All these new technologies and relevant preclinical and clinical researches will determine the success of early detection and personalized therapy in the future.

  10. Clinical trial success rates of anti-obesity agents: the importance of combination therapies.

    Science.gov (United States)

    Hussain, H T; Parker, J L; Sharma, A M

    2015-09-01

    The objective of this study was to construct a clinical trial profile assessing the risk of drug failure among anti-obesity agents. Research was conducted by looking at anti-obesity therapies currently on the market or in clinical trials (phases I to III) conducted from 1998 to September 2014, with the exclusion of any drugs whose phase I trial was conducted prior to January 1998. This was completed primarily through a search on http://clinicaltrials.gov where a total of 51 drugs met the search criteria. The transition probabilities were then calculated based on various classifications and compared against industry standards. The transition probability of anti-obesity agents was 8.50% whereas the transition probability of industry standards was 10.40%. Combination therapies had four times the transition probability than monotherapies, 40% and 4.75%, respectively. Therefore, it was determined that 92% of drugs fail during clinical trial testing for this indication and combination therapy appears to improve clinical trial success rates to 10-fold.

  11. Progress and prospects of gene therapy clinical trials for the muscular dystrophies.

    Science.gov (United States)

    Bengtsson, Niclas E; Seto, Jane T; Hall, John K; Chamberlain, Jeffrey S; Odom, Guy L

    2016-04-15

    Clinical trials represent a critical avenue for new treatment development, where early phases (I, I/II) are designed to test safety and effectiveness of new therapeutics or diagnostic indicators. A number of recent advances have spurred renewed optimism toward initiating clinical trials and developing refined therapies for the muscular dystrophies (MD's) and other myogenic disorders. MD's encompass a heterogeneous group of degenerative disorders often characterized by progressive muscle weakness and fragility. Many of these diseases result from mutations in genes encoding proteins of the dystrophin-glycoprotein complex (DGC). The most common and severe form among children is Duchenne muscular dystrophy, caused by mutations in the dystrophin gene, with an average life expectancy around 25 years of age. Another group of MD's referred to as the limb-girdle muscular dystrophies (LGMDs) can affect boys or girls, with different types caused by mutations in different genes. Mutation of the α-sarcoglycan gene, also a DGC component, causes LGMD2D and represents the most common form of LGMD. Early preclinical and clinical trial findings support the feasibility of gene therapy via recombinant adeno-associated viral vectors as a viable treatment approach for many MDs. In this mini-review, we present an overview of recent progress in clinical gene therapy trials of the MD's and touch upon promising preclinical advances.

  12. The reasons for triple therapy in stable COPD patients in Japanese clinical practice

    Directory of Open Access Journals (Sweden)

    Miyazaki M

    2015-06-01

    Full Text Available Masaki Miyazaki,1 Hidetoshi Nakamura,1,2 Saeko Takahashi,1 Shotaro Chubachi,1 Mamoru Sasaki,1 Mizuha Haraguchi,1 Hideki Terai,1 Makoto Ishii,1 Koichi Fukunaga,1 Sadatomo Tasaka,1 Kenzo Soejima,1 Koichiro Asano,3 Tomoko Betsuyaku1 On behalf of the Keio COPD Comorbidity Research (K-CCR group 1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, 2Department of Respiratory Medicine, Saitama Medical University, Saitama, 3Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan Background: Triple combination therapy involving long-acting muscarinic antagonists long-acting β2 agonists, and inhaled corticosteroids has recently become an option for maintenance treatment of COPD. Some add-on clinical trials have reported the benefits of these combinations. However, the process to step up to triple therapy varies for individual cases.Methods: Keio University and affiliated hospitals conducted an observational COPD cohort study, recruiting patients diagnosed as having COPD by pulmonary physicians and those referred for investigation of possible COPD. Their prescription history and clinical course were retrospectively analyzed based on the physicians’ medical records and patient questionnaires. This study was registered with UMIN (UMIN000003470, April 10, 2010.Results: A total of 95 of the 445 COPD patients (21% were treated with inhaled corticosteroids/long-acting β2 agonists/long-acting muscarinic antagonists as maintenance therapy, including 12 in COPD Grade I, 31 in Grade II, 38 in Grade III, and 14 in Grade IV, based on the Global Initiative for Chronic Obstructive Lung Disease spirometric grading. For more than half of the patients on triple therapy, the treatment had been intensified due to unsatisfactory improvement of symptoms, and 32% were treated with triple therapy due to comorbid asthma. In contrast, there were COPD patients whose therapy was

  13. Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders [Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden)

    2012-07-15

    Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom

  14. "Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2006-07-01

    Full Text Available Abstract Background In a significant proportion of metastatic breast cancer (MBC patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance, it is generally believed that the chance of achieving clinical benefit (CB with further endocrine therapy is minimal. Methods Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. Results In oestrogen receptor (ER positive MBC patients with assessable disease, CB was achieved in 159 (71.3% (1st line patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2nd line, 46.1% (on 3rd line and 20% (on 4th line with a median duration of response (DOR in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7% patients had de novo resistance on 1st line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2nd line and 22.2% (on 3rd line with a median DOR in those with CB of 22.7 months and 14 months respectively. Conclusion The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4th line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1st line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances.

  15. Prize reinforcement contingency management for cocaine dependence: integration with group therapy in a methadone clinic.

    Science.gov (United States)

    Petry, Nancy M; Martin, Bonnie; Simcic, Francis

    2005-04-01

    In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes ranging from $1 to $100 for submitting cocainenegative samples and attending therapy. Patients in the CM condition submitted more cocaine-negative samples and attended more groups than patients in standard treatment. The best predictor of cocaine abstinence at follow-up was duration of abstinence during treatment. On average, patients in the CM condition earned $117 in prizes. Data from this study suggest that some aspects of reinforcement can be implemented in group therapy in community-based clinics.

  16. Physical therapy guideline for children with malnutrition in low income countries: clinical commentary

    Science.gov (United States)

    Bekele, Abey; Janakiraman, Balamurugan

    2016-01-01

    Physical therapy intervention along with nutritional rehabilitation has recently become an inevitable combo after recent evidences suggesting a strong interaction between malnutrition and neuro-muscular disabilities which contribute to a significant burden in global settings. Recent studies confirm that appropriate physical assessment of neuro-musculo skeletal system, developmental assessment or cognitive tools along with nutritional assessments followed by exercise rehabilitation will yield positive results in children with malnutrition. There is an obvious need to make available a simple physical therapy exercise guidelines with simple measure and exercise to be used in resource limited settings of developing countries. The purpose of this clinical commentary is to summarize simple assessment tools to evaluate activity impairment, participation restriction, gross motor activity and simple physical therapy intervention program for children with disability secondary to malnutrition. PMID:27656622

  17. Hormono-biological therapy in metastatic breast cancer: preclinical evidence, clinical studies and future directions.

    Science.gov (United States)

    Tonini, Giuseppe; Schiavon, Gaia; Fratto, Maria Elisabetta; Vincenzi, Bruno; Santini, Daniele

    2008-02-01

    Breast cancer growth is regulated by coordinated actions of the estrogen receptor (ER) and various growth factor receptor signalling pathways. This complex interactive signalling potentially explains some of the reasons behind endocrine therapy action and resistance. Recent research into the molecular biology of ER signalling has revealed new molecular targets which, if present in cancer cells, might be additionally targeted using various signal transduction inhibitors to overcome or prevent resistance to endocrine therapy. The dynamic inverse relationship between the expression of ER and growth factor receptors brings more excitement to the potential of restoring ER expression in apparently ER-negative cells by inhibition of growth factor signalling. The multiple pathways involved in activating ERs also provide a rationale for combining endocrine and non-endocrine therapies that block different signalling pathways. Ongoing clinical trials promise to further improve the present care for breast cancer patients.

  18. Endoscopic therapy for chronic pancreatitis: technical success, clinical outcomes, and complications.

    Science.gov (United States)

    Kowalczyk, Lukasz M; Draganov, Peter V

    2009-04-01

    Chronic pancreatitis (CP) can cause failure of both the exocrine and endocrine portions of the gland. Pain is the most recalcitrant clinical complaint in CP. Generally, conservative measures are first attempted to manage pain. These include cessation of alcohol use and smoking, enzyme replacement therapy, and finally, opioid analgesia. Endoscopy can be employed to treat the pain and complications due to CP. The results of the only two prospective randomized controlled trials suggest that surgery has a more durable effect than endoscopic therapy in controlling pain. Both trials suffer from severe limitations, however, and endoscopy remains the preferred approach for many patients because of its minimally invasive nature. Endoscopic ultrasound celiac plexus block has limited value in helping to control pain. More randomized trials are needed, along with further technologic innovation to improve the current treatment modalities. When considering interventional therapy for a patient with CP, a tailored and multidisciplinary therapeutic approach should be taken.

  19. Clinical Comparative Study on Massage Therapy and Cisapride in Treating Functional Dyspepsia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jia-fu; LIN Qiang; LIU Hong-bo; ZHOU Ping; XIAO Yuan-chun

    2007-01-01

    To observe the clinical efficacy of massage therapy and Cisapride in the treatment of functional dyspepsia (FD).Methods:Eighty subjects were randomized into two groups:treatment group in which 40 cases were treated by massage therapy and control group in which 40 cases were treated by Cisapride,with a course of 4 weeks;meanwhile,another 40 healthy people were taken as normal group.Abdominal fullness,acid regurgitation,diminished appetite and anorexia,nausea and vomiting and health survey were observed;symptom scores were recorded.Results:These two treatment methods were effective for FD.Conclusion:Mental disorder is one cause of FD;massage therapy is quite effective for it.

  20. Radionuclide imaging of musculoskeletal infection

    Directory of Open Access Journals (Sweden)

    Christopher J. Palestro

    2007-09-01

    Full Text Available Radionuclide imaging studies are routinely used to evaluate patients suspected of having musculoskeletal infection. Three-phase bone imaging is readily available, relatively inexpensive, and very accurate in the setting of otherwise normal bone. Labeled leukocyte imaging should be used in cases of "complicating osteomyelitis" such as prosthetic joint infection. This test also is useful in clinically unsuspected diabetic pedal osteomyelitis as well as in the neuropathic joint. It is often necessary, however, to perform complementary bone marrow imaging, to maximize the accuracy of labeled leukocyte imaging. In contrast to other regions in the skeleton, labeled leukocyte imaging is not useful for diagnosing spinal osteomyelitis. At the moment, gallium is the preferred radionuclide procedure for this condition and is a useful adjunct to magnetic resonance imaging. FDG-PET likely will play an important role in the evaluation of musculoskeletal infection, especially spinal osteomyelitis, and may replace gallium imaging for this purpose.Estudos através de imagens com o uso de radionuclídeos são rotineiramente usadas para avaliar pacientes suspeitos de terem infecção músculo-esquelética. A imagem óssea em tridimensional é facilmente avaliável, relativamente de baixo custo, e muito precisa na localização de alterações ósseas. Imagem com leucócito marcado poderia ser usada nos casos de "osteomielite com complicações" tais como infecção prostética articular. Esse teste também é útil na não suspeita clinica de osteomielite associada ao pé diabético tanto quanto nas junções neuropáticas. É sempre necessário, por outro lado, realizar imagem complementar da medula óssea para aumentar a precisão da imagem com leucócito marcado. Em contraste com outras regiões no esqueleto, imagem com leucócito marcado não é útil para diagnosticar osteomielite da coluna vertebral. Até agora, o gálio é o radionuclídeo preferido para

  1. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly

    Directory of Open Access Journals (Sweden)

    Christofides EA

    2016-07-01

    Full Text Available Elena A Christofides Endocrinology Associates, Inc., Columbus, OH, USA Abstract: In acromegaly, achieving biochemical control (growth hormone [GH] level <1.0 ng/mL and age- and sex-normalized levels of insulin-like growth factor 1 [IGF-1] through timely diagnosis and appropriate treatment provides an opportunity to improve patient outcomes. Diagnosis of acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. Keywords: disease burden, growth hormone, insulin-like growth factor 1, medical therapy, pituitary

  2. Review of technology development and clinical trials of transcranial laser therapy for acute ischemic stroke treatment

    Science.gov (United States)

    Catanzaro, Brian E.; Streeter, Jackson; de Taboada, Luis

    2010-02-01

    Stroke is the one of the leading causes of mortality in the United States, claiming 600,000 lives each year. Evidence suggests that near infrared (NIR) illumination has a beneficial effect on a variety of cells when these cells are exposed to adverse conditions. Among these conditions is the hypoxic state produced by acute ischemic stroke (AIS). To demonstrate the impact NIR Transcranial Laser Therapy (TLT) has on AIS in humans, a series of double blind, placebo controlled clinical trials were designed using the NeuroThera(R) System (NTS). The NTS was designed and developed to treat subjects non-invasively using 808 nm NIR illumination. TLT, as it applies to stroke therapy, and the NTS will be described. The results of the two clinical trials: NeuroThera(R) Safety and Efficacy Trial 1 (NEST-1) and NeuroThera(R) Safety and Efficacy Trial 2 (NEST-2) will be reviewed and discussed.

  3. Towards clinical evidence in particle therapy: ENLIGHT, PARTNER, ULICE and beyond

    CERN Document Server

    Combs, Stephanie E; Pötter, Richad; Orrechia, Roberto; Haberer, Thomas; Durante, Marco; Fossati, Piero; Parodi, Katia; Balosso, Jacques; Amaldi, Ugo; Baumann, Michael; Debus, Jürgen

    2013-01-01

    Since the middle of the 20th century, particle therapy has been in focus for patient treatments. In 1946, Robert Wilson proposed the use of charged particles for tumor therapy, and since then, the clinical use of protons and heavier ions, mainly carbon ions, has become more widespread. The first clinical evidence was obtained in Berkeley, treating radiation-resistant targets with various ion species. The main advantage of particle beams derive from their physical properties: through an inverted dose profile, regions within the entry channel of the beam can be spared of dose, while a steep dose deposition can be directed in an energydependent manner into the defined treatment volume (Bragg Peak). The following dose fall-off spares tissue behind the target volume, thus reducing integral dose significantly compared to when using photons. Heavier charged particles, such as carbon ions or oxygen, are additionally associated with an increased relative biological effectiveness (RBE), while the RBE of protons is comm...

  4. The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence

    DEFF Research Database (Denmark)

    Gräs, Søren; Lose, Gunnar

    2011-01-01

    Stress urinary incontinence is a common disorder affecting the quality of life for millions of women worldwide. Effective surgical procedures involving synthetic permanent meshes exist, but significant short- and long-term complications occur. Cell-based therapy using autologous stem cells...... or progenitor cells presents an alternative approach, which aims at repairing the anatomical components of the urethral continence mechanism. In vitro expanded progenitor cells isolated from muscle biopsies have been most intensely investigated, and both preclinical trials and a few clinical trials have...... provided proof of concept for the idea. An initial enthusiasm caused by positive results from early clinical trials has been dampened by the recognition of scientific irregularities. At the same time, the safety issue for cell-based therapy has been highlighted by the appearance of new and comprehensive...

  5. Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

    DEFF Research Database (Denmark)

    Haack-Sorensen, M.; Friis, T.; Bindslev, L.

    2008-01-01

    used for MSC cultivation in animal studies simulating clinical stem cell therapy. MATERIAL AND METHODS: Human mononuclear cells (MNCs) were isolated from BM aspirates by density gradient centrifugation and cultivated in a GMP-accepted medium (EMEA medium) or in one of four other media. RESULTS: FACS...... compliant medium for MSC cultivation, expansion and differentiation. The expanded and differentiated MSCs can be used in autologous mesenchymal stromal cell therapy in patients with ischaemic heart disease Udgivelsesdato: 2008......OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under...

  6. Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence.

    Science.gov (United States)

    Kawanami, Daiji; Matoba, Keiichiro; Sango, Kazunori; Utsunomiya, Kazunori

    2016-07-29

    An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications.

  7. Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

    Directory of Open Access Journals (Sweden)

    Daiji Kawanami

    2016-07-01

    Full Text Available An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications.

  8. Reflections on clinical expertise and silent know-how in voice therapy

    DEFF Research Database (Denmark)

    Iwarsson, Jenny

    2014-01-01

    The concept of ‘clinical expertise’ is described as a part of evidence-based practice (EBP) together with ‘external scientific evidence’ and ‘patient values and perspectives’. However, clinical expertise in the management of voice disorders has not been described or discussed in much detail....... The expertise seems to consist partly of silent know-how that, from the outside, may seem improperly related to the personality of the speech-language pathologist or exclusively dependent on the number of years in the field. In this paper, it is suggested that clinical expertise in voice therapy consists...... of specific skills that can be explicitly described and trained. These skills are discussed together with educational aspects that contribute to the development of clinical expertise. The skills are also discussed from the perspectives of the past, present, and future....

  9. Clinical management of a western lowland gorilla (Gorilla gorilla gorilla) with a cardiac resynchronization therapy device.

    Science.gov (United States)

    Rush, Elizabeth Marie; Ogburn, Anna L; Monroe, Denise

    2011-06-01

    A 24-yr-old, male western lowland gorilla (Gorilla gorilla gorilla) was diagnosed with congestive heart failure using transesophageal and transthoracic echocardiology. New York Heart Association (NYHA) Class III was assigned to the severity of the condition. Over 16 mo, this progressed to NYHA Class IV despite increasing medical therapy. Repeated evaluations suggested that implantation of a cardiac resynchronization therapy device with a defibrillator (CRT-D) could benefit this animal based on clinical signs and underlying evidence of dyssynchrony and suspected fibrotic myocardial disease. Surgical implantation of leads into the right atrium, right ventricle, and left ventricle was accomplished. The CRT-D device was placed under the thoracic pectoral muscles during an initial surgical procedure. Improvement in the gorilla's clinical condition after implantation of the CRT-D device was immediate and dramatic. Subsequent scanning of the device was accomplished through operant conditioning. The data from these device interrogations included stored and real-time cardiac data, which were used to minimize recognized environmental stressors and change device settings. Over 4 yr, case management was critical to successful device use in treatment of the clinical disease. This involved medications, training for device interrogation, exercise to increase activity and improve body condition, and phlebotomy attempts. Dietary management was necessary to manipulate caloric and sodium intake and encourage medication compliance. Cardiac resynchronization therapy device implantation, although requiring specialized equipment and surgical skill, appears to be a viable option for treatment of fibrosing cardiomyopathy with systolic dysfunction in gorillas refractory to medical management. In addition to treatment, this device provides cardiovascular data at rest that could allow for early diagnosis and treatment of gorillas with this and other cardiac conditions in the future. This

  10. The laboratory of clinical virology in monitoring patients undergoing monoclonal antibody therapy.

    Science.gov (United States)

    Cavallo, R

    2011-12-01

    The relevant efficacy of monoclonal antibodies (mAbs) has resulted in the successful treatment of several diseases, although susceptibility to infections remains a major problem. This review summarizes aspects of the literature regarding viral infections and mAbs, specifically addressing the risk of infection/reactivation, the measures that can reduce this risk, and the role played by the laboratory of clinical virology in monitoring patients undergoing mAb therapy.

  11. Clinical signs, therapy and zoonotic risk of pet guinea pigs with dermatophytosis.

    Science.gov (United States)

    Kraemer, A; Hein, J; Heusinger, A; Mueller, R S

    2013-03-01

    Systematic studies about pet guinea pigs with dermatophytosis are rare. The aim of this study was to evaluate clinical signs, therapy and zoonotic risk of pet guinea pigs with dermatophytosis. Questionnaires from both owners (n = 74) of pet guinea pigs with dermatophytosis and their veterinarians (n = 101) were analysed regarding clinical signs, therapy and data pertinent to zoonotic potential. Trichophyton (T.) mentagrophytes was found in 97% of cases. In the weeks preceding the onset of the clinical signs, a new guinea pig joined the household in 43% of cases. One third of the affected guinea pigs had lived in the household for less than 3 months. Predominant clinical signs were alopecia (83%), scaling (73%) and crusting (70%). The most commonly affected body site was the head (75%). In approximately one quarter of the cases humans showed clinical signs of dermatophytosis, in half the households, only children were affected. Skin lesions were seen most often on the face, the neck and the arms. Pet guinea pigs carrying dermatophytes must be considered a serious zoonotic risk for their owners, especially for children. A major risk factor for dermatophytosis seems to be a recent acquisition of a new guinea pig.

  12. Development of job standards for clinical nutrition therapy for dyslipidemia patients.

    Science.gov (United States)

    Kang, Min-Jae; Seo, Jung-Sook; Kim, Eun-Mi; Park, Mi-Sun; Woo, Mi-Hye; Ju, Dal-Lae; Wie, Gyung-Ah; Lee, Song-Mi; Cha, Jin-A; Sohn, Cheong-Min

    2015-04-01

    Dyslipidemia has significantly contributed to the increase of death and morbidity rates related to cardiovascular diseases. Clinical nutrition service provided by dietitians has been reported to have a positive effect on relief of medical symptoms or reducing the further medical costs. However, there is a lack of researches to identify key competencies and job standard for clinical dietitians to care patients with dyslipidemia. Therefore, the purpose of this study was to analyze the job components of clinical dietitian and develop the standard for professional practice to provide effective nutrition management for dyslipidemia patients. The current status of clinical nutrition therapy for dyslipidemia patients in hospitals with 300 or more beds was studied. After duty tasks and task elements of nutrition care process for dyslipidemia clinical dietitians were developed by developing a curriculum (DACUM) analysis method. The developed job standards were pretested in order to evaluate job performance, difficulty, and job standards. As a result, the job standard included four jobs, 18 tasks, and 53 task elements, and specific job description includes 73 basic services and 26 recommended services. When clinical dietitians managing dyslipidemia patients performed their practice according to this job standard for 30 patients the job performance rate was 68.3%. Therefore, the job standards of clinical dietitians for clinical nutrition service for dyslipidemia patients proposed in this study can be effectively used by hospitals.

  13. Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect

    DEFF Research Database (Denmark)

    Lund, O; Lund, O S; Gram, G

    1997-01-01

    This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not......This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells...

  14. Overcoming challenges to initiating cell therapy clinical trials in rapidly developing countries: India as a model.

    Science.gov (United States)

    Viswanathan, Sowmya; Rao, Mahendra; Keating, Armand; Srivastava, Alok

    2013-08-01

    Increasingly, a number of rapidly developing countries, including India, China, Brazil, and others, are becoming global hot spots for the development of regenerative medicine applications, including stem cell-based therapies. Identifying and overcoming regulatory and translational research challenges and promoting scientific and ethical clinical trials with cells will help curb the growth of stem cell tourism for unproven therapies. It will also enable academic investigators, local regulators, and national and international biotechnology and biopharmaceutical companies to accelerate stem cell-based clinical research that could lead to effective innovative treatments in these regions. Using India as a model system and obtaining input from regulators, clinicians, academics, and industry representatives across the stem cell field in India, we reviewed the role of key agencies and processes involved in this field. We have identified areas that need attention and here provide solutions from other established and functioning models in the world to streamline and unify the regulatory and ethics approval processes for cell-based therapies. We also make recommendations to check the growth and functioning of clinics offering unproven treatments. Addressing these issues will remove considerable hurdles to both local and international investigators, accelerate the pace of research and development, and create a quality environment for reliable products to emerge. By doing so, these countries would have taken one important step to move to the forefront of stem cell-based therapeutics.

  15. [Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives].

    Science.gov (United States)

    Pinto, F; Calarco, A; Totaro, A; Sacco, E; Volpe, A; Racioppi, M; D'Addessi, A; Bassi, P F

    2010-01-01

    Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

  16. Clinical group supervision in yoga therapy: model effects, and lessons learned.

    Science.gov (United States)

    Forbes, Bo; Volpe Horii, Cassandra; Earls, Bethany; Mashek, Stephanie; Akhtar, Fiona

    2012-01-01

    Clinical supervision is an integral component of therapist training and professional development because of its capacity for fostering knowledge, self-awareness, and clinical acumen. Individual supervision is part of many yoga therapy training programs and is referenced in the IAYT Standards as "mentoring." Group supervision is not typically used in the training of yoga therapists. We propose that group supervision effectively supports the growth and development of yoga therapists-in-training. We present a model of group supervision for yoga therapist trainees developed by the New England School of Integrative Yoga Therapeutics™ (The NESIYT Model) that includes the background, structure, format, and development of our inaugural 18-month supervision group. Pre-and post-supervision surveys and analyzed case notes, which captured key didactic and process themes, are discussed. Clinical issues, such as boundaries, performance anxiety, sense of self efficacy, the therapeutic alliance, transference and counter transference, pacing of yoga therapy sessions, evaluation of client progress, and adjunct therapist interaction are reviewed. The timing and sequence of didactic and process themes and benefits for yoga therapist trainees' professional development, are discussed. The NESIYT group supervision model is offered as an effective blueprint for yoga therapy training programs.

  17. Regulatory considerations in production of a cell therapy medicinal product in Europe to clinical research.

    Science.gov (United States)

    Martín, Patricia Gálvez; Martinez, Adolfina Ruiz; Lara, Visitación Gallardo; Naveros, Beatriz Clares

    2014-02-01

    The development of new drugs using stem cells has become a clinic alternative for the treatment of different diseases such as Alzheimer's, diabetes and myocardial infarction. Similar to conventional medicines, stem cells as new medicinal products for cell therapy are subjected to current legislation concerning their manufacture process. Besides, their legality is determined by the Regulatory Agencies belonging to the Member State of the European Union in which they are being registered. With the evolution of therapy that uses cells as medicines, there is a need to develop the appropriate legislative and regulatory framework capable of ensuring their safety and effectiveness. However, few works have been published regarding the regulations that these products must comply through production and commercialization processes. The present work is focused on the description of key events during clinical development and cell production of stem cells as drugs. Such as the regulations, requirements and directives involved in the production of cell therapy medicinal products, from the clinical design stage to its commercialization in Europe.

  18. Biologic Therapies: From Complexity to Clinical Practice in a Changing Environment

    Directory of Open Access Journals (Sweden)

    Remo Panaccione

    2015-12-01

    Full Text Available This symposium provided an opportunity for global experts to discuss the challenges posed by the introduction of biosimilars. The impact of the manufacturing process on clinical outcomes, maintaining treatment responses over the long term, and issues surrounding patient management in a changing environment were addressed. The symposium was opened by Prof Panaccione describing the evolution of inflammatory bowel disease (IBD treatment in the last 20 years and how biologics have improved outcomes. Prof D’Haens provided an explanation of the complexity surrounding biologic drug development and the hurdles facing drug manufacturers when ensuring high quality and consistently performing products over time. Prof Panaccione discussed the clinical challenges in balancing the transition from induction to maintenance therapy in order to provide a clinically relevant and sustained response to therapy. He also discussed the evidence for long-term outcomes with adalimumab for IBD. Prof Feagan highlighted the issues faced by clinicians treating patients with biologics, including the ability to switch between biologics without loss of efficacy or impact on safety, and the need to consider interchangeability between biologic therapies and the potential risk and impact of immunogenicity.

  19. CLINICAL RESULTS OF THROMBOLYTIC THERAPY WITH ALTEPLASE AND TENECTEPLASE IN PATIENTS WITH MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    L. A. Bondarenko

    2012-01-01

    Full Text Available Aim. To evaluate the clinical results of thrombolytic therapy with thrombolytics (alteplase, tenecteplase in patients with ST segment elevation myocardial infarction (STEMI. Material and methods. Patients with STEMI (n=181 included in the study were split into two groups depending on the thrombolytic agent: patients treated with alteplase - group 1 (n=78; patients treated with tenecteplase — group 2 (n=52. Patients with STEMI who had no thrombolysis due to late treatment-seeking or the presence of contraindications were included into the group 3 (n=51. Thrombolysis took place both in pre-hospital and in-hospital period. Time before the thrombolysis, STEMI clinical course, mortality , and complications were analyzed. Results. The average time pain-thrombolysis was 2.7±0.22 hours. High efficacy of both thrombolytic drugs was proved in the most of patients. Mortality in patients received thrombolysis was 6.4–7.7%; this in patients without thrombolytic therapy — 24%. Thrombolysis performed in the first 3 hours after STEMI onset reduced mortality to 3.4%. No one intracranial hemorrhage or allergic reaction was registered. Conclusion. Thrombolytic therapy with alteplase and tenecteplase in patients with STEMI in the real clinical practice was high efficient, reduced hospital mortality and induced a few adverse reactions.

  20. CLINICAL RESULTS OF THROMBOLYTIC THERAPY WITH ALTEPLASE AND TENECTEPLASE IN PATIENTS WITH MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    L. A. Bondarenko

    2015-12-01

    Full Text Available Aim. To evaluate the clinical results of thrombolytic therapy with thrombolytics (alteplase, tenecteplase in patients with ST segment elevation myocardial infarction (STEMI. Material and methods. Patients with STEMI (n=181 included in the study were split into two groups depending on the thrombolytic agent: patients treated with alteplase - group 1 (n=78; patients treated with tenecteplase — group 2 (n=52. Patients with STEMI who had no thrombolysis due to late treatment-seeking or the presence of contraindications were included into the group 3 (n=51. Thrombolysis took place both in pre-hospital and in-hospital period. Time before the thrombolysis, STEMI clinical course, mortality , and complications were analyzed. Results. The average time pain-thrombolysis was 2.7±0.22 hours. High efficacy of both thrombolytic drugs was proved in the most of patients. Mortality in patients received thrombolysis was 6.4–7.7%; this in patients without thrombolytic therapy — 24%. Thrombolysis performed in the first 3 hours after STEMI onset reduced mortality to 3.4%. No one intracranial hemorrhage or allergic reaction was registered. Conclusion. Thrombolytic therapy with alteplase and tenecteplase in patients with STEMI in the real clinical practice was high efficient, reduced hospital mortality and induced a few adverse reactions.

  1. Clinical Study of the Effects of Juglandis Semen Pharmacopuncture Therapy on Shoulder Pain

    Directory of Open Access Journals (Sweden)

    Han-Na Choi

    2011-12-01

    Full Text Available Objectives: The purpose of this study is to examine the effects of Juglandis Semen Pharmaco-puncture Therapy on Shoulder Pain. Methods & Results: Clinical studies on shoulder pain were carried out on 34 patients who were treated at Department of Acupuncture & Moxibusition, Samse Oriental Medical Hospital from June to October, 2009. Patients were divided into two groups, i.e.Sample group(Group A and Control group(Group B. Group B were treated by body acupuncture and cupping therapies while Group A were added juglandis semen pharmacopuncture therapy to therapies of Group A. All patients of both groups were treated three times a week for three weeks. In order to evaluate pain degree, we apply Shoulder Pain and Disability Index(SPADI, Visual Analogue Scale(VAS and the tool developed by Japan’s Industrial Hygienics Society and modified by Korean Doctor. Evaluations were done after first week, second week and third week during period of treatment. Results: Both groups showed significant pain decreasing tendencies. But Group A showed more efficiency comparing to Group B. Conclusions: According to the above-mentioned results, it seems that Juglandis Semen pharmacopuncture therapy could be applied as the effective method for reducing shoulder pain.

  2. Cell Therapy for Stroke: Review of Previous Clinical Trials and Introduction of Our New Trials

    Science.gov (United States)

    SHICHINOHE, Hideo; HOUKIN, Kiyohiro

    2016-01-01

    Stroke is still a leading cause of death and disability, and despite intensive research, few treatment options exist. A recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. Although some pioneer studies on the use of cell therapy for the treatment of stroke have been reported, certain problems still remain unsolved. We investigated the use of autologous bone marrow stromal cell (BMSC) transplantation for the treatment of stroke, to develop it as the next-generation cell therapy. In this study, we introduce the preparation of a new clinical trial, the Research on Advanced Intervention using Novel Bone marrow stem cell (RAINBOW) study. The trial will start in 2016, and we hope that it will not only be helpful for treating patients but also for clarifying the therapeutic mechanisms. Moreover, we review stem cell therapeutics as an emerging paradigm in stroke (STEPS) and the guidelines for the development of cell therapy for stroke in the United States as well as introduce the development of new guidelines in Japan. These guidelines are expected to encourage the development of cell therapy for stroke management. PMID:27302193

  3. Clinical evaluation of physical therapy in the management of internal derangement of the temporomandibular joint.

    Science.gov (United States)

    Kirk, W S; Calabrese, D K

    1989-02-01

    This clinical cross-sectional study examines the favorable functional improvement in patients undergoing physical therapy for mild to moderate internal disc derangements of the temporomandibular joint. Sixty-eight patients with internal derangements were treated with physical therapeutic modalities as described by Rocabado. A success rate of 86% was achieved in patients with early- to mid-opening and late- to mid-closing clicks of the temporomandibular joint. Approximately one third of these patients required short-term occlusal bite appliances to assist in their management. A success rate of 7% was achieved in patients with late-opening and late-closing clicks. No patient with clicking on mediolateral movement was successfully managed with physical therapy. Likewise, patients with nonreducing anteriorly displaced discs of the temporomandibular joint did not respond well to physical therapy. Pain management was evaluated separately and showed subjective improvement in 82% of patients with mild to moderate disc dysfunction and pain. Only 29% of patients with late-opening clicking or locked joints experienced pain relief. When patients were classified according to occurrence of the clicking phenomenon, interesting trends relating to duration of symptoms were found. Twenty-two patients who did not respond favorably to physical therapy underwent surgical procedures. Findings in these patients offer suggestions about why nonsurgical therapy is not successful in certain cases.

  4. Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial

    Science.gov (United States)

    Ferreira, Luciano Ambrosio; Grossmann, Eduardo; Januzzi, Eduardo; Gonçalves, Rafael Tardin Rosa Ferraz; Mares, Fernando Antonio Guedes; de Paula, Marcos Vinicius Queiroz; Carvalho, Antonio Carlos Pires

    2015-01-01

    Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study) and the use of the occlusal splint plate alone (control). We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p < 0.05). However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p < 0.05) already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term. PMID:26351510

  5. Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Luciano Ambrosio Ferreira

    2015-01-01

    Full Text Available Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study and the use of the occlusal splint plate alone (control. We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p<0.05. However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p<0.05 already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term.

  6. Dependence of the effectiveness of thrombolytic therapy at ischemic stroke from clinical and paraclinical predictors

    Directory of Open Access Journals (Sweden)

    Іванна Михайлівна Мельнічек

    2015-12-01

    Full Text Available The aim of the work. The aim of the work is an assessment of informativeness of several clinical and paraclinical predictors in prognostics of the results of effectiveness of thrombolytic therapy at the most acute period of ishemic stroke with the further definition of the most significant ones for achieving the least neurologic deficiency.Methods of research: There were retrospectively considered 61 patients 60,5±7,8 years old with ishemic stroket who sucsessfully underwent thrombolytic therapy as an intravenous administration of Actilyse. These patients demonstrated the next factors of gemostasis: prothrombin time, prothrombin index, fibrinogen. For the research there were also used the scales of neurological deficiency activisation (Rankin and NIHSS; ultrasound of the magistral arteries and extracranial CT of brain; methods of mathematical statistics (the definition of chances and confidence intervals ratio, Pirson and Student criteria, verification of hypothesis about the law of distribution and equality of the mean values in the both samplings.Results. There were defined the most informative factors in prognostication of the good result after thrombolytic therapy. There was formed the list of output factors that the results of actilyse thrombolytic therapy effectiveness in Lviv region are depending on. There was grounded the necessity of laboratory data monitoring in patients with stroke for receiving the best results of thrombolytic therapy.There was established that thrombolytic therapy of ishemic stroke must begin as early as possible (in computed tomography department if possible for receiving the maximal effectiveness. There was detected that ultrasound of magistral vessels that supply brain with blood is necessary for all patients who are candidates for thrombolytic therapy because the stenosis of the vessel lumen more than 60 % significantly worsens an effectiveness of treatment

  7. Therapeutic radionuclides in nuclear medicine:current and future prospects%核医学放射性核素治疗的研究现状及前景

    Institute of Scientific and Technical Information of China (English)

    Chai-Hong YEONG; Mu-hua CHENG; Kwan-Hoong NG

    2014-01-01

    本文目的:本文综述了临床常用的放射性治疗方式和应用现状以及新的放射性核素从科研至临床应用所存在的问题。  本文概放射性核素的临床应用及研究已历数十载,已有碘-131、磷-32、锶-90及钇-90等众多放射性核素被成功用于治疗良恶性疾病。随着新的放射性核素及药物不断应用于骨转移瘤疼痛治疗、神经内分泌肿瘤及其他良恶性肿瘤治疗,放射性核素治疗得到了快速发展。目前,放射性核素治疗已进入蓬勃发展期;在亚洲,由于甲状腺和肝脏肿瘤的高发病率,促进了放射性核素治疗及其靶向治疗研究的日益发展。随着放射性核素与其他药物的联合应用,放射性核素治疗肿瘤的临床价值必将显著提高。%The potential use of radionuclides in therapy has been recognized for many decades. A number of ra-dionuclides, such as iodine-131 (131I), phosphorous-32 (32P), strontium-90 (90Sr), and yttrium-90 (90Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel de-velopments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

  8. Anthropogenic radionuclides in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Q; Weng, J; Wang, J

    2007-11-15

    Studies of radionuclides in the environment have entered a new era with the renaissance of nuclear energy and associated fuel reprocessing, geological disposal of high-level nuclear wastes, and concerns about national security with respect to nuclear non-proliferation. This work presents an overview of anthropogenic radionuclide contamination in the environment, as well as the salient geochemical behavior of important radionuclides. We first discuss the following major anthropogenic sources and current development that contribute to the radionuclide contamination of the environment: (1) nuclear weapons program; (2) nuclear weapons testing; (3) nuclear power plants; (4) commercial fuel reprocessing; (5) geological repository of high-level nuclear wastes, and (6) nuclear accidents. Then, we summarize the geochemical behavior for radionuclides {sup 99}Tc, {sup 129}I, and {sup 237}Np, because of their complex geochemical behavior, long half-lives, and presumably high mobility in the environment. Biogeochemical cycling and environment risk assessment must take into account speciation of these redox-sensitive radionuclides.

  9. Medication therapy management clinic: perception of healthcare professionals in a University medical center setting

    Directory of Open Access Journals (Sweden)

    Shah M

    2013-09-01

    Full Text Available Objective: To determine the overall perception and utilization of the pharmacist managed medication therapy management (MTM clinic services, by healthcare professionals in a large, urban, university medical care setting.Methods: This was a cross-sectional, anonymous survey sent to 195 healthcare professionals, including physicians, nurses, and pharmacists at The University of Illinois Outpatient Care Center to determine their perception and utilization of the MTM clinic. The survey consisted of 12 questions and was delivered through a secure online application. Results: Sixty-two healthcare professionals (32% completed the survey. 82% were familiar with the MTM clinic, and 63% had referred patients to the clinic. Medication adherence and disease state management was the most common reason for referral. Lack of knowledge on the appropriate referral procedure was the prominent reason for not referring patients to the MTM clinic. Of the providers that were aware of MTM services, 44% rated care as ‘excellent’, 44% as ‘good’, 5% as ‘fair’, and 0% stated ‘poor’. Strengths of MTM clinic identified by healthcare providers included in-depth education to patients, close follow-up, and detailed medication reconciliation provided by MTM clinic pharmacists. Of those familiar with MTM clinic, recommendations included; increase marketing efforts to raise awareness of the MTM clinic service, create collaborative practice agreements between MTM pharmacists and physicians, and ensure that progress notes are more concise.Conclusion: In a large, urban, academic institution MTM clinic is perceived as a valuable resource to optimize patient care by providing patients with in-depth education as it relates to their prescribed medications and disease states. These identified benefits of MTM clinic lead to frequent patient referrals specifically for aid with medication adherence and disease state management.

  10. Predictability of the individual clinical outcome of extracorporeal shock wave therapy for cellulite

    Directory of Open Access Journals (Sweden)

    Schlaudraff KU

    2014-05-01

    Full Text Available Kai-Uwe Schlaudraff,1 Maren C Kiessling,2 Nikolaus BM Császár,2 Christoph Schmitz21Concept Clinic, Geneva, Switzerland; 2Department of Anatomy II, Ludwig-Maximilians-University of Munich, Munich, GermanyBackground: Extracorporeal shock wave therapy has been successfully introduced for the treatment of cellulite in recent years. However, it is still unknown whether the individual clinical outcome of cellulite treatment with extracorporeal shock wave therapy can be predicted by the patient's individual cellulite grade at baseline, individual patient age, body mass index (BMI, weight, and/or height.Methods: Fourteen Caucasian females with cellulite were enrolled in a prospective, single-center, randomized, open-label Phase II study. The mean (± standard error of the mean cellulite grade at baseline was 2.5±0.09 and mean BMI was 22.8±1.17. All patients were treated with radial extracorporeal shock waves using the Swiss DolorClast® device (Electro Medical Systems, S.A., Nyon, Switzerland. Patients were treated unilaterally with 2 weekly treatments for 4 weeks on a randomly selected side (left or right, totaling eight treatments on the selected side. Treatment was performed at 3.5–4.0 bar, with 15,000 impulses per session applied at 15 Hz. Impulses were homogeneously distributed over the posterior thigh and buttock area (resulting in 7,500 impulses per area. Treatment success was evaluated after the last treatment and 4 weeks later by clinical examination, photographic documentation, contact thermography, and patient satisfaction questionnaires.Results: The mean cellulite grade improved from 2.5±0.09 at baseline to 1.57±0.18 after the last treatment (ie, mean δ-1 was 0.93 cellulite grades and 1.68±0.16 at follow-up (ie, mean δ-2 was 0.82 cellulite grades. Compared with baseline, no patient's condition worsened, the treatment was well tolerated, and no unwanted side effects were observed. No statistically significant (ie, P<0

  11. Same-day physical therapy consults in an outpatient neuromuscular disease physician clinic

    Directory of Open Access Journals (Sweden)

    Pucillo EM

    2016-10-01

    Full Text Available Evan M Pucillo,1 Nancy Christensen-Mayer,2 Shelly D Poole,2 Denise M Whitten,2 Danielle Freeman,3 Blake R Bohe,4 Brandon R Swensen,3 A Gordon Smith,1 Nicholas E Johnson1 1Department of Neurology, School of Medicine, 2Department of Physical Medicine & Rehabilitation, 3Outpatient Neurology, University of Utah Hospitals and Clinics, 4Business Support, University of Utah Information Technology, Salt Lake City, UT, USA Background: Team-based care has been shown to offer more comprehensive benefits to patients when compared to standard physician-based care alone in clinics for chronic conditions. However, apart from grant-funded multidisciplinary clinics, there are no reports on the usage of same-day physical therapy (PT consults within a daily outpatient neuromuscular disease (NMD physician clinic.Objective: To determine the impact of same-day PT consults at the University of Utah’s outpatient Clinical Neurosciences Center.Design: A qualitative assessment and survey of patient satisfaction.Methods: An eight question Health Insurance Portability and Accountability Act-compliant patient satisfaction survey using a 5-point Likert scale was administered. Demographic data and Press-Ganey Provider Satisfaction surveys were retrospectively collected from electronic medical records for patients receiving same-day PT encounters in the neuromuscular division over 1 year.Results: Mean (standard deviation age was 54.22 (19.81 years for 134 patient encounters, median age was 60 years, with 76 male (57% and 58 female (43% patients. Mean Likert score for 61 self-reported patient satisfaction surveys for same-day PT consults was 4.87 (97.4%. Press-Ganey Provider Satisfaction scores improved from 89.9% (N=287 for the year prior to 90.8% (N=320 for the corresponding year (P=0.427. A total of 46 (75.4% patients have either never before received PT care or never before received PT care for their NMD, 67.4% of whom were male.Conclusion: Same-day PT consults in an

  12. Paving the way to personalized medicine. Production of some theragnostic radionuclides at Brookhaven National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.

    2011-07-01

    This paper introduces a relatively novel paradigm that involves specific individual radionuclides or radionuclide pairs that have emissions that allow pre-therapy low-dose imaging plus higher-dose therapy in the same patient. We have made an attempt to sort out and organize a number of such theragnostic radionuclides and radionuclide pairs that may potentially bring us closer to the age-long dream of personalized medicine for performing tailored low-dose molecular imaging (SPECT/CT or PET/CT) to provide the necessary pre-therapy information on biodistribution, dosimetry, the limiting or critical organ or tissue, and the maximum tolerated dose (MTD), etc. If the imaging results then warrant it, it would be possible to perform higher-dose targeted molecular therapy in the same patient with the same radiopharmaceutical. A major problem that remains yet to be fully resolved is the lack of availability, in sufficient quantities, of a majority of the best candidate theragnostic radionuclides in a no-carrier-added (NCA) form. A brief description of the recently developed new or modified methods at BNL for the production of four theragnostic radionuclides, whose nuclear, physical, and chemical characteristics seem to show great promise for personalized cancer therapy are described.

  13. Paving the way to personalized medicine: production of some theragnostic radionuclides at Brookhaven National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava S. C.

    2011-06-06

    This paper introduces a relatively novel paradigm that involves specific individual radionuclides or radionuclide pairs that have emissions that allow pre-therapy low-dose imaging plus higher-dose therapy in the same patient. We have made an attempt to sort out and organize a number of such theragnostic radionuclides and radionuclide pairs that may potentially bring us closer to the age-long dream of personalized medicine for performing tailored low-dose molecular imaging (SPECT/CT or PET/CT) to provide the necessary pre-therapy information on biodistribution, dosimetry, the limiting or critical organ or tissue, and the maximum tolerated dose (MTD), etc. If the imaging results then warrant it, it would be possible to perform higher-dose targeted molecular therapy in the same patient with the same radiopharmaceutical. A major problem that remains yet to be fully resolved is the lack of availability, in sufficient quantities, of a majority of the best candidate theragnostic radionuclides in a no-carrier-added (NCA) form. A brief description of the recently developed new or modified methods at BNL for the production of four theragnostic radionuclides, whose nuclear, physical, and chemical characteristics seem to show great promise for personalized cancer therapy are described.

  14. 中枢神经系统核素显像的临床应用与进展%The progress and clinical application of radionuclide neuroimaging

    Institute of Scientific and Technical Information of China (English)

    陈文新; 何品玉

    2008-01-01

    Development of site-specific brain radiopharmaceuticals extends the the functional neuroimaging applications in the diagnosis and monitoring treatments of various neurologic and psychiatric disorders.This article highlights recent advances and clinical applications of the functional neuroimaging in Parkinson disease,epilepsy,dementia,substance abuse,psychiatric disorders and brain functional research.%各种特异性脑显像剂不断被推广应用,使放射性核素显像从诊断中枢神经系统疾病和监测疗效发展到观察特异性变化的阶段.简述了帕金森病、癫痫、痴呆、药物成瘾、精神疾病、脑功能活动等核素显像的临床应用及近期研究进展.

  15. Preparation of radiopharmaceuticals labeled with metal radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1992-06-01

    We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides.

  16. Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Fredriksson, Albin, E-mail: albin.fredriksson@raysearchlabs.com; Hårdemark, Björn [RaySearch Laboratories, Sveavägen 44, Stockholm SE-111 34 (Sweden); Forsgren, Anders [Optimization and Systems Theory, Department of Mathematics, KTH Royal Institute of Technology, Stockholm SE-100 44 (Sweden)

    2015-07-15

    Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goals to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.

  17. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    Energy Technology Data Exchange (ETDEWEB)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy.

  18. Current status of radionuclide scrotal imaging

    Energy Technology Data Exchange (ETDEWEB)

    Holder, L.E.; Melloul, M.; Chen, D.

    1981-10-01

    Scrotal imaging with technetium-99m sodium pertechnetate consists of a radionuclide angiogram and static scrotal scans. Utilization of this study in patients presenting with an acute scrotum can dramatically reduce the number of surgical explorations for acute epididymitis. It can also aid in other aspects of differential diagnosis in patients presenting with either an acutely enlarged and/or painful scrotum or a scrotal mass. Ambiguities in previous descriptions of perfusion through the spermatic and extraspermatic cord vessels are described and distinguished from scrotal perfusion. The clinical and scintigraphic spectrum of testicular torsion, including spontaneous detorsion, early acute testicular torsion, midphase testicular torsion, and late phase or ''missed testicular torsion,'' is discussed and illustrated. The variety of patterns seen in acute epididymitis, including lateral and medial epididymal location, and focal epididymitis are described, as is the appearance of hydrocele as both a primary and secondary entity. The relationship of scrotal imaging to the overall clinical presentation and evaluation of these patients is emphasized in testicular torsion, torsion of the testicular appendages, epididymitis, abscess, trauma, tumor, spermatocele, and varicocele. The techniques, clinical utility, and relationship to radionuclide imaging of Doppler ultrasound and gray scale ultrasound scanning are reviewed. Doppler ultrasound results in many false negative studies in testicular torsion. Gray scale ultrasound is useful in clarifying the nature of scrotal masses.

  19. Heidelberg Ion Therapy Center (HIT): Initial clinical experience in the first 80 patients

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E. (Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)), E-mail: Stephanie.Combs@med.uni-heidelberg.de; Ellerbrock, Malte; Haberer, Thomas (Heidelberger Ionenstrahl Therapiezentrum (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg (Germany)) (and others)

    2010-10-15

    The Heidelberg Ion Therapy Center (HIT) started clinical operation in November 2009. In this report we present the first 80 patients treated with proton and carbon ion radiotherapy and describe patient selection, treatment planning and daily treatment for different indications. Patients and methods. Between November 15, 2009 and April 15, 2010, 80 patients were treated at the Heidelberg Ion Therapy Center (HIT) with carbon ion and proton radiotherapy. Main treated indications consisted of skull base chordoma (n = 9) and chondrosarcoma (n = 18), malignant salivary gland tumors (n=29), chordomas of the sacrum (n = 5), low grade glioma (n=3), primary and recurrent malignant astrocytoma and glioblastoma (n=7) and well as osteosarcoma (n = 3). Of these patients, four pediatric patients aged under 18 years were treated. Results. All patients were treated using the intensity-modulated rasterscanning technique. Seventy-six patients were treated with carbon ions (95%), and four patients were treated with protons. In all patients x-ray imaging was performed prior to each fraction. Treatment concepts were based on the initial experiences with carbon ion therapy at the Gesellschaft fuer Schwerionenforschung (GSI) including carbon-only treatments and carbon-boost treatments with photon-IMRT. The average time per fraction in the treatment room per patient was 29 minutes; for irradiation only, the mean time including all patients was 16 minutes. Position verification was performed prior to every treatment fraction with orthogonal x-ray imaging. Conclusion. Particle therapy could be included successfully into the clinical routine at the Dept. of Radiation Oncology in Heidelberg. Numerous clinical trials will subsequently be initiated to precisely define the role of proton and carbon ion radiotherapy in radiation oncology.

  20. Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study.

    Science.gov (United States)

    Ottaviani, Giulia; Gobbo, Margherita; Sturnega, Mauro; Martinelli, Valentina; Mano, Miguel; Zanconati, Fabrizio; Bussani, Rossana; Perinetti, Giuseppe; Long, Carlin S; Di Lenarda, Roberto; Giacca, Mauro; Biasotto, Matteo; Zacchigna, Serena

    2013-12-01

    Oral mucositis (OM) is a serious and acute side effect in patients with cancer who receive chemotherapy or radiotherapy, often leading to the suspension of therapy and a need for opioid analgesic and enteral/parenteral nutrition, with an effect on patient survival. Among the various interventions proposed in OM management, laser therapy is becoming a recommended treatment option but has limitations due to its heterogeneous laser parameters. Here, we report on our successful clinical experience on the use of class IV laser therapy to treat OM induced by different chemotherapy regimens. To shed light on the mechanisms of action of laser therapy in improving OM resolution, we have developed an animal model of chemotherapy-induced OM, in which we compare the efficacy of the standard low-power laser therapy protocol with an innovative protocol, defined as high-power laser therapy. We show that high-power laser therapy is more effective than low-power laser therapy in improving OM lesion healing, reducing the inflammatory burden, and preserving tissue integrity. In addition, high-power laser therapy has been particularly effective in promoting the formation of new arterioles within the granulation tissue. Our results provide important insights into the mechanism of action of biostimulating laser therapy on OM in vivo and pave a way for clinical experimentation with the use of high-power laser therapy.

  1. May spa therapy be a valid opportunity to treat hand osteoarthritis? A review of clinical trials and mechanisms of action

    Science.gov (United States)

    Fortunati, Nicola Angelo; Fioravanti, Antonella; Seri, Gina; Cinelli, Simone; Tenti, Sara

    2016-01-01