Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

A. Monti Hughes; ECC Pozzi; S. Thorp

Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model.

A Systematic Approach for Evaluation of Capture Zones at Pump and Treat Systems

EPA Science Inventory

This document describes a systematic approach for performing capture zone analysis associated with ground water pump and treat systems. A “capture zone” refers to the three-dimensional region that contributes the ground water extracted by one or more wells or drains. A capture ...

Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

DOEpatents

Miura, Michiko; Slatkin, Daniel N.

1997-03-18

A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na.sub.4 B.sub.12 I.sub.11 SSB.sub.12 I.sub.11, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy.

Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

DOEpatents

Miura, Michiko; Slatkin, Daniel N.

1995-10-03

A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na.sub.4 B.sub.12 I.sub.11 SSB.sub.12 I.sub.11, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy.

Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

DOEpatents

Miura, Michiko; Slatkin, Daniel N.

1997-08-05

A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized. by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na.sub.4 B.sub.12 I.sub.11 SSB.sub.12 I.sub.11, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy.

Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

DOEpatents

Miura, M.; Slatkin, D.N.

1995-10-03

A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na{sub 4}B{sub 12}I{sub 11}SSB{sub 12}I{sub 11}, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy. 1 fig.

Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

DOEpatents

Miura, M.; Slatkin, D.N.

1997-03-18

A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na{sub 4}B{sub 12}I{sub 11}SSB{sub 12}I{sub 11}, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy. 1 fig.

Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

DOEpatents

Miura, M.; Slatkin, D.N.

1997-08-05

A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na{sub 4}B{sub 12}I{sub 11}SSB{sub 12}I{sub 11}, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy. 1 fig.

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

PubMed

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

2005-08-01

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

Theoretical and experimental physical methods of neutron-capture therapy

NASA Astrophysics Data System (ADS)

Borisov, G. I.

2011-09-01

This review is based to a substantial degree on our priority developments and research at the IR-8 reactor of the Russian Research Centre Kurchatov Institute. New theoretical and experimental methods of neutron-capture therapy are developed and applied in practice; these are: A general analytical and semi-empiric theory of neutron-capture therapy (NCT) based on classical neutron physics and its main sections (elementary theories of moderation, diffuse, reflection, and absorption of neutrons) rather than on methods of mathematical simulation. The theory is, first of all, intended for practical application by physicists, engineers, biologists, and physicians. This theory can be mastered by anyone with a higher education of almost any kind and minimal experience in operating a personal computer.

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

2007-10-01

Purpose: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. Methods and Materials: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria andmore » adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). Conclusions: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.« less

Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model.

PubMed

Monti Hughes, A; Pozzi, Ecc; Thorp, S I; Curotto, P; Medina, V A; Martinel Lamas, D J; Rivera, E S; Garabalino, M A; Farías, R O; Gonzalez, S J; Heber, E M; Itoiz, M E; Aromando, R F; Nigg, D W; Trivillin, V A; Schwint, A E

2015-09-01

Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Boron containing compounds and their preparation and use in neutron capture therapy

DOEpatents

Gabel, D.

1992-09-01

The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

Monte Carlo based dosimetry for neutron capture therapy of brain tumors

NASA Astrophysics Data System (ADS)

Zaidi, Lilia; Belgaid, Mohamed; Khelifi, Rachid

2016-11-01

Boron Neutron Capture Therapy (BNCT) is a biologically targeted, radiation therapy for cancer which combines neutron irradiation with a tumor targeting agent labeled with a boron10 having a high thermal neutron capture cross section. The tumor area is subjected to the neutron irradiation. After a thermal neutron capture, the excited 11B nucleus fissions into an alpha particle and lithium recoil nucleus. The high Linear Energy Transfer (LET) emitted particles deposit their energy in a range of about 10μm, which is of the same order of cell diameter [1], at the same time other reactions due to neutron activation with body component are produced. In-phantom measurement of physical dose distribution is very important for BNCT planning validation. Determination of total absorbed dose requires complex calculations which were carried out using the Monte Carlo MCNP code [2].

Therapies for Treating Diabetic Nerve Pain

MedlinePlus

... for PATIENTS and THEIR FAMILIES THERAPIES FOR TREATING DIABETIC NERVE PAIN This fact sheet is provided to help you understand which therapies help diabetic nerve pain. This condition is also known as ...

Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture therapy.

PubMed

Krstic, D; Markovic, V M; Jovanovic, Z; Milenkovic, B; Nikezic, D; Atanackovic, J

2014-10-01

Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A microdosimetric study of {sup 10}B(n,{alpha}){sup 7}Li and {sup 157}Gd(n,{gamma}) reactions for neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, C.K.C.; Sutton, M.; Evans, T.M.

1999-01-01

This paper presents the microdosimetric analysis for the most interesting cell survival experiment recently performed at the Brookhaven National Laboratory (BNL). In this experiment, the cells were first treated with a gadolinium (Gd) labeled tumor-seeking boronated porphyrin (Gd-BOPP) or with BOPP alone, and then irradiated with thermal neutrons. The resulting cell-survival curves indicate that the {sup 157}Gd(n,{gamma}) reactions are very effective in cell killing. The death of a cell treated with Gd-BOPP was attributed to either the {sup 10}B(n,{alpha}){sup 7}Li reactions or the {sup 157}Gd(n,{gamma}) reactions (or both). However, the quantitative relationship between the two types of reaction and themore » cell-survival fraction was not clear. This paper presents the microdosimetric analysis for the BNL experiment based on the measured experimental parameters, and the results clearly suggest a quantitative relationship between the two types of reaction and the cell survival fraction. The results also suggest new research in gadolinium neutron capture therapy (GdNCT) which may lead to a more practical modality than the boron neutron capture therapy (BNCT) for treating cancers.« less

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

PubMed Central

Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Toledo Arruda-Neto, João Dias; Maria-Engler, Silvya Stuchi; Tiago, Manoela; Capelozzi, Vera Luiza; Giorgi, Ricardo Rodrigues; Maria, Durvanei Augusto

2013-01-01

Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and 7Li, with a range of 5 to 9 µm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT. PMID:23527236

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy.

PubMed

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue; Wu, Yuan-Hung

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting.

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy

PubMed Central

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting. PMID:28662135

Design of a boron neutron capture enhanced fast neutron therapy assembly

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhonglu

The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator nearmore » the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm 2 treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm 2 collimation was 21.9% per 100-ppm 10B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm 2 fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm 2 collimator. Five 1.0-cm thick 20x20 cm 2 tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm 10B) to measure dose due to boron neutron capture. The measured dose enhancement at 5.0-cm depth in the head phantom for the 5

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Herrera, María S.; González, Sara J.; Minsky, Daniel M.; Kreiner, Andrés J.

2010-08-01

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a real patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrera, Maria S.; Gonzalez, Sara J.; Minsky, Daniel M.

2010-08-04

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a realmore » patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.« less

Cellular uptake and in vitro antitumor efficacy of composite liposomes for neutron capture therapy.

PubMed

Peters, Tanja; Grunewald, Catrin; Blaickner, Matthias; Ziegner, Markus; Schütz, Christian; Iffland, Dorothee; Hampel, Gabriele; Nawroth, Thomas; Langguth, Peter

2015-02-22

Neutron capture therapy for glioblastoma has focused mainly on the use of (10)B as neutron capture isotope. However, (157)Gd offers several advantages over boron, such as higher cross section for thermal neutrons and the possibility to perform magnetic resonance imaging during neutron irradiation, thereby combining therapy and diagnostics. We have developed different liposomal formulations of gadolinium-DTPA (Magnevist®) for application in neutron capture therapy of glioblastoma. The formulations were characterized physicochemically and tested in vitro in a glioma cell model for their effectiveness. Liposomes entrapping gadolinium-DTPA as neutron capture agent were manufactured via lipid/film-extrusion method and characterized with regard to size, entrapment efficiency and in vitro release. For neutron irradiation, F98 and LN229 glioma cells were incubated with the newly developed liposomes and subsequently irradiated at the thermal column of the TRIGA reactor in Mainz. The dose rate derived from neutron irradiation with (157)Gd as neutron capturing agent was calculated via Monte Carlo simulations and set in relation to the respective cell survival. The liposomal Gd-DTPA reduced cell survival of F98 and LN229 cells significantly. Differences in liposomal composition of the formulations led to distinctly different outcome in cell survival. The amount of cellular Gd was not at all times proportional to cell survival, indicating that intracellular deposition of formulated Gd has a major influence on cell survival. The majority of the dose contribution arises from photon cross irradiation compared to a very small Gd-related dose. Liposomal gadolinium formulations represent a promising approach for neutron capture therapy of glioblastoma cells. The liposome composition determines the uptake and the survival of cells following radiation, presumably due to different uptake pathways of liposomes and intracellular deposition of gadolinium-DTPA. Due to the small range of

L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, eithermore » 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.« less

Sonoporation as an enhancing method for boron neutron capture therapy for squamous cell carcinomas

PubMed Central

2013-01-01

Background Boron neutron capture therapy (BNCT) is a selective radiotherapy that is dependent on the accumulation of 10B compound in tumors. Low-intensity ultrasound produces a transient pore on cell membranes, sonoporation, which enables extracellular materials to enter cells. The effect of sonoporation on BNCT was examined in oral squamous cell carcinoma (SCC) xenografts in nude mice. Materials and methods Tumor-bearing mice were administrated boronophenylalanine (BPA) or boronocaptate sodium (BSH) intraperitoneally. Two hours later, tumors were subjected to sonoporation using microbubbles followed by neutron irradiation. Results The 10B concentration was higher in tumors treated with sonoporation than in untreated tumors, although the difference was not significant in BPA. When tumors in mice that received BPA intraperitoneally were treated with sonoporation followed by exposure to thermal neutrons, tumor volume was markedly reduced and the survival rate was prolonged. Such enhancements by sonoporation were not observed in mice treated with BSH-mediated BNCT. Conclusions These results indicate that sonoporation enhances the efficiency of BPA-mediated BNCT for oral SCC. Sonoporation may modulate the microlocalization of BPA and BSH in tumors and increase their intracellular levels. PMID:24295213

Workshop on neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1986-01-01

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

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: comparison of clinical results obtained with BNCT and conventional treatment.

PubMed

Kageji, Teruyoshi; Nagahiro, Shinji; Mizobuchi, Yoshifumi; Matsuzaki, Kazuhito; Nakagawa, Yoshinobu; Kumada, Hiroaki

2014-01-01

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

Could lengthening minocycline therapy better treat early syphilis?

PubMed

Shao, Li-Li; Guo, Rui; Shi, Wei-Jie; Liu, Yuan-Jun; Feng, Bin; Han, Long; Liu, Quan-Zhong

2016-12-01

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Minocycline, a representative tetracycline derivative, has the greatest antimicrobial activity among all tetracyclines. There are few reports about treating syphilis with minocycline because there is a lack of efficacy data from controlled trials. We compared the rates of serological cure in patients with early syphilis who were treated with minocycline or benzathine penicillin G (BPG).During the study period, a total of 40 syphilis patients received the BPG treatment, which was a single intramuscular dose of 2.4 million units of BPG, and 156 patients were treated with minocycline; 77 patients were placed in the 2-week, standard minocycline therapy group and received 100 mg of minocycline orally, twice daily for 14 days, and 79 patients were placed in the 4-week, lengthened minocycline therapy group and received 100 mg of minocycline orally, twice daily for 28 days. The outcome of interest was the rate of serological cure in these patients.At the end of the 2-year follow-up, the serological cure rate of the 4-week, lengthened minocycline therapy group (87.34%) was higher than that of both the 2-week, standard minocycline therapy group (72.73%) and the BPG treatment group (77.50%). In addition, the curative effect of the 4-week, lengthened minocycline therapy was significantly greater than that of the 2-week, standard minocycline therapy in patients who were aged >40 years; exhibited an initial rapid plasma reagin titer ≥1: 32; or exhibited secondary syphilis (P = 0.000, 0.008, 0.000; <0.05).Minocycline appears to be an effective agent for treating early syphilis, especially when applied as a 4-week, lengthened therapy.

Proceedings of the first international symposium on neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairchild, R.G.; Brownell, G.L.

This meeting was arranged jointly by MIT and BNL in order to illuminate progress in the synthesis and targeting of boron compounds and to evaluate and document progress in radiobiological and dosimetric aspects of neutron capture therapy. It is hoped that this meeting will facilitate transfer of information between groups working in these fields, and encourage synergistic collaboration.

Thiourea derivatives, methods of their preparation and their use in neutron capture therapy of malignant melanoma

DOEpatents

Gabel, D.

1991-06-04

The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.

PubMed

Sasai, Masao; Nakamura, Hiroyuki; Sougawa, Nagako; Sakurai, Yoshinori; Suzuki, Minoru; Lee, Chun Man

2016-03-01

Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells. In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model. HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT. Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Accelerator-driven boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Edgecock, Rob

2014-05-01

Boron Neutron Capture Therapy is a binary treatment for certain types of cancer. It works by loading the cancerous cells with a boron-10 carrying compound. This isotope has a large cross-section for thermal neutrons, the reaction producing a lithium nucleus and alpha particle that kill the cell in which they are produced. Recent studies of the boron carrier compound indicate that the uptake process works best in particularly aggressive cancers. Most studied is glioblastoma multiforme and a trial using a combination of BNCT and X-ray radiotherapy has shown an increase of nearly a factor of two in mean survival over the state of the art. However, the main technical problem with BNCT remains producing a sufficient flux of neutrons for a reasonable treatment duration in a hospital environment. This paper discusses this issue.

Boron neutron capture therapy (BNCT) in Finland: technological and physical prospects after 20 years of experiences.

PubMed

Savolainen, Sauli; Kortesniemi, Mika; Timonen, Marjut; Reijonen, Vappu; Kuusela, Linda; Uusi-Simola, Jouni; Salli, Eero; Koivunoro, Hanna; Seppälä, Tiina; Lönnroth, Nadja; Välimäki, Petteri; Hyvönen, Heini; Kotiluoto, Petri; Serén, Tom; Kuronen, Antti; Heikkinen, Sami; Kosunen, Antti; Auterinen, Iiro

2013-05-01

Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy method developed to treat patients with certain malignant tumours. To date, over 300 treatments have been carried out at the Finnish BNCT facility in various on-going and past clinical trials. In this technical review, we discuss our research work in the field of medical physics to form the groundwork for the Finnish BNCT patient treatments, as well as the possibilities to further develop and optimize the method in the future. Accordingly, the following aspects are described: neutron sources, beam dosimetry, treatment planning, boron imaging and determination, and finally the possibilities to detect the efficacy and effects of BNCT on patients. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels.

PubMed

Molinari, Ana J; Thorp, Silvia I; Portu, Agustina M; Saint Martin, Gisela; Pozzi, Emiliano C C; Heber, Elisa M; Bortolussi, Silva; Itoiz, Maria E; Aromando, Romina F; Monti Hughes, Andrea; Garabalino, Marcela A; Altieri, Saverio; Trivillin, Verónica A; Schwint, Amanda E

2015-01-01

We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control.

An Assessment of the Potential Use of BNNTs for Boron Neutron Capture Therapy.

PubMed

Ferreira, Tiago H; Miranda, Marcelo C; Rocha, Zildete; Leal, Alexandre S; Gomes, Dawidson A; Sousa, Edesia M B

2017-04-12

Currently, nanostructured compounds have been standing out for their optical, mechanical, and chemical features and for the possibilities of manipulation and regulation of complex biological processes. One of these compounds is boron nitride nanotubes (BNNTs), which are a nanostructured material analog to carbon nanotubes, but formed of nitrogen and boron atoms. BNNTs present high thermal stability along with high chemical inertia. Among biological applications, its biocompatibility, cellular uptake, and functionalization potential can be highlighted, in addition to its eased utilization due to its nanometric size and tumor cell internalization. When it comes to new forms of therapy, we can draw attention to boron neutron capture therapy (BNCT), an experimental radiotherapy characterized by a boron-10 isotope carrier inside the target and a thermal neutron beam focused on it. The activation of the boron-10 atom by a neutron generates a lithium atom, a gamma ray, and an alpha particle, which can be used to destroy tumor tissues. The aim of this work was to use BNNTs as a boron-10 carrier for BNCT and to demonstrate its potential. The nanomaterial was characterized through XRD, FTIR, and SEM. The WST-8 assay was performed to confirm the cell viability of BNNTs. The cells treated with BNNTs were irradiated with the neutron beam of a Triga reactor, and the apoptosis caused by the activation of the BNNTs was measured with a calcein AM/propidium iodide test. The results demonstrate that this nanomaterial is a promising candidate for cancer therapy through BNCT.

Boron Neutron Capture Therapy for Malignant Brain Tumors

PubMed Central

MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

2016-01-01

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

Boron Neutron Capture Therapy for Malignant Brain Tumors.

PubMed

Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

2016-07-15

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

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

PubMed

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

2009-07-01

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

Physics of epi-thermal boron neutron capture therapy (epi-thermal BNCT).

PubMed

Seki, Ryoichi; Wakisaka, Yushi; Morimoto, Nami; Takashina, Masaaki; Koizumi, Masahiko; Toki, Hiroshi; Fukuda, Mitsuhiro

2017-12-01

The physics of epi-thermal neutrons in the human body is discussed in the effort to clarify the nature of the unique radiologic properties of boron neutron capture therapy (BNCT). This discussion leads to the computational method of Monte Carlo simulation in BNCT. The method is discussed through two examples based on model phantoms. The physics is kept at an introductory level in the discussion in this tutorial review.

Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS.

PubMed

Andoh, Tooru; Fujimoto, Takuya; Suzuki, Minoru; Sudo, Tamotsu; Sakurai, Yoshinori; Tanaka, Hiroki; Fujita, Ikuo; Fukase, Naomasa; Moritake, Hiroshi; Sugimoto, Tohru; Sakuma, Toshiko; Sasai, Hiroshi; Kawamoto, Teruya; Kirihata, Mitsunori; Fukumori, Yoshinobu; Akisue, Toshihiro; Ono, Koji; Ichikawa, Hideki

2015-12-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B. Unlike conventional gamma-ray irradiation, BNCT significantly suppressed tumor growth without damaging normal tissues, suggesting that it may be a potential new therapeutic option to treat CCS lung metastases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields.

PubMed

Inui, Toshio; Amitani, Haruka; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Mette, Martin

2016-07-01

Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment. We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies. This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects. This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Epithermal neutron beams from the 7 Li(p,n) reaction near the threshold for neutron capture therapy

NASA Astrophysics Data System (ADS)

Porras, I.; Praena, J.; Arias de Saavedra, F.; Pedrosa, M.; Esquinas, P.; L. Jiménez-Bonilla, P.

2016-11-01

Two applications for neutron capture therapy of epithermal neutron beams calculated from the 7Li ( p , n reaction are discussed. In particular, i) for a proton beam of 1920 keV of a 30 mA, a neutron beam of adequate features for BNCT is found at an angle of 80° from the forward direction; and ii) for a proton beam of 1910 keV, a neutron beam is obtained at the forward direction suitable for performing radiobiology experiments for the determination of the biological weighting factors of the fast dose component in neutron capture therapy.

Somatic symptom disorder treated with electroconvulsive therapy.

PubMed

Borisovskaya, Anna; Augsburger, Jay Alan

2017-05-01

Somatic symptom disorder (SSD) is a challenging condition to treat with chronic pain, a common and disabling symptom. We present a patient who received electroconvulsive therapy (ECT) for SSD with significant improvement in pain and gastrointestinal symptoms. We also present a brief literature review of similar cases treated with ECT. Preliminary evidence suggests that ECT should be considered for treatment of SSD comorbid with major depressive disorder, when standard treatments fail. Further research is needed to clarify whether ECT can be used for SSD without associated depression.

Effectiveness of 308-nm Excimer Laser Therapy in Treating Alopecia Areata, Determined by Examining the Treated Sides of Selected Alopecic Patches.

PubMed

Byun, Ji Won; Moon, Jong Hyuk; Bang, Chan Yl; Shin, Jeonghyun; Choi, Gwang Seong

2015-01-01

Some studies have reported the use of 308-nm excimer laser therapy for treating alopecia areata (AA); however, the effectiveness of this therapy on a theoretical basis has not yet been comparatively analyzed. To determine the therapeutic effect of excimer laser therapy on AA. One alopecic patch was divided into control and treated sides in 10 patients with AA. Then, 308-nm excimer laser therapy was administered twice a week for 12 weeks. Photograph and phototrichogram analyses were performed. Photographic assessments by both dermatologists and individuals of the general population showed objective improvements after excimer laser therapy. On the treated side, the hair count and hair diameter had statistically increased after treatment. However, only the hair diameter was found to be significantly high in the treated half when it was compared with the control side. The 308-nm excimer laser has a therapeutic effect on AA, which is proven by photograph and phototrichogram analysis by a side-by-side comparison. © 2015 S. Karger AG, Basel.

A new electrocardiogram algorithm for diagnosing loss of ventricular capture during cardiac resynchronisation therapy.

PubMed

Ganière, Vincent; Domenichini, Giulia; Niculescu, Viviana; Cassagneau, Romain; Defaye, Pascal; Burri, Haran

2013-03-01

The prerequisite for cardiac resynchronization therapy (CRT) is ventricular capture, which may be verified by analysis of the surface electrocardiogram (ECG). Few algorithms exist to diagnose loss of ventricular capture. Electrocardiograms from 126 CRT patients were analysed during biventricular (BV), right ventricular (RV), and left ventricular (LV) pacing. An algorithm evaluating QRS narrowing in the limb leads and increasing negativity in lead I to diagnose changes in ventricular capture was devised, prospectively validated, and compared with two existing algorithms. Performance of the algorithm according to ventricular lead position was also assessed. Our algorithm had an accuracy of 88% to correctly identify the changes in ventricular capture (either loss or gain of RV or LV capture). The algorithm had a sensitivity of 94% and a specificity of 96% with an accuracy of 96% for identifying loss of LV capture (the most clinically relevant change), and compared favourably with the existing algorithms. Performance of the algorithms was not significantly affected by RV or LV lead position. A simple two-step algorithm evaluating QRS width in the limb leads and changes in negativity in lead I can accurately diagnose the lead responsible for intermittent loss of ventricular capture in CRT. This simple tool may be of particular use outside the setting of specialized device clinics.

Treating the sibling subsystem: an adjunct of divorce therapy.

PubMed

Schibuk, M

1989-04-01

Sibling therapy, frequently overlooked as a method of treatment, is particularly appropriate in situations that require a deliberate focus on the "unit of continuity," or the subsystem that remains intact during a process of family reorganization. For this and other reasons it can be an effective tool in treating children of divorce. A case illustrating this use of sibling therapy is presented.

Neutron-beam-shaping assembly for boron neutron-capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaidi, L.; Kashaeva, E. A.; Lezhnin, S. I.

A neutron-beam-shaping assembly consisting of a moderator, a reflector, and an absorber is used to form a therapeutic neutron beam for the boron neutron-capture therapy of malignant tumors at accelerator neutron sources. A new structure of the moderator and reflector is proposed in the present article, and the results of a numerical simulation of the neutron spectrum and of the absorbed dose in a modified Snyder head phantom are presented. The application of a composite moderator and of a composite reflector and the implementation of neutron production at the proton energy of 2.3MeV are shown to permit obtaining a high-qualitymore » therapeutic neutron beam.« less

Universal algorithm for diagnosis of biventricular capture in patients with cardiac resynchronization therapy.

PubMed

Jastrzebski, Marek; Kukla, Piotr; Fijorek, Kamil; Czarnecka, Danuta

2014-08-01

An accurate and universal method for diagnosis of biventricular (BiV) capture using a standard 12-lead electrocardiogram (ECG) would be useful for assessment of cardiac resynchronization therapy (CRT) patients. Our objective was to develop and validate such an ECG method for BiV capture diagnosis that would be independent of pacing lead positions-a major confounder that significantly influences the morphologies of paced QRS complexes. On the basis of an evaluation of 789 ECGs of 443 patients with heart failure and various right ventricular (RV) and left ventricular (LV) lead positions, the following algorithm was constructed and validated. BiV capture was diagnosed if the QRS in lead I was predominantly negative and either V1 QRS was predominantly positive or V6 QRS was of negative onset and predominantly negative (step 1), or if QRS complex duration was <160 ms (step 2). All other ECGs were classified as loss of LV capture. The algorithm showed good accuracy (93%), sensitivity (97%), and specificity (90%) for detection of loss of LV capture. The performance of the algorithm did not differ among apical, midseptal, and outflow tract RV lead positions and various LV lead positions. LV capture leaves diagnostic hallmarks in the fused BiV QRS related to different vectors of depolarization and more rapid depolarization of the ventricles. An accurate two-step ECG algorithm for BiV capture diagnosis was developed and validated. This algorithm is universally applicable to all CRT patients, regardless of the positions of the pacing leads. ©2014 Wiley Periodicals, Inc.

Survival times for canine intranasal sarcomas treated with radiation therapy: 86 cases (1996-2011).

PubMed

Sones, Evan; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Taylor, Kathryn; Haney, Siobhan; Wypij, Jackie; Keyerleber, Michele; Arthur, Jennifer; Hamilton, Terrance; Lawrence, Jessica; Gieger, Tracy; Sellon, Rance; Wright, Zack

2013-01-01

Sarcomas comprise approximately one-third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily-fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily-fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily-fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits. © 2012 Veterinary Radiology & Ultrasound.

Insights into the use of gadolinium and gadolinium/boron-based agents in imaging-guided neutron capture therapy applications.

PubMed

Deagostino, Annamaria; Protti, Nicoletta; Alberti, Diego; Boggio, Paolo; Bortolussi, Silva; Altieri, Saverio; Crich, Simonetta Geninatti

2016-05-01

Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome.

Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joel, D.D.; Coderre, J.A.; Chanana, A.D.

1996-12-31

Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope {sup 10}B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/{sup 10}B reactions ({sup 10}B(n,{alpha}){sup 7}Li) resulting in the production of localized high LET radiation from alpha and {sup 7}Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released ismore » microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams.« less

Operant Reinforcement with Structural Family Therapy in Treating Anorexia Nervosa

ERIC Educational Resources Information Center

Perlman, Lawrence M.; Bender, Sheila S.

1975-01-01

The authors successfully treated two families in which the index patients were anorectic adolescent girls by combining structural family therapy with behavioral modification techniques. Phases which appear to be typical of the treatment are described. A discussion of the value of the operant reinforcement procedure in family therapy follows.…

Tandem-ESQ for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreiner, A. J.; Escuela de Ciencia y Tecnologia, Universidad de Gral San Martin; CONICET,

2007-02-12

A folded tandem, with 1.25 MV terminal voltage, combined with an ElectroStatic Quadrupole (ESQ) chain is being proposed as a machine for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT). The machine is shown to be capable of accelerating a 30 mA proton beam to 2.5 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the on the 7Li(p,n)7Be reaction, to perform BNCT treatment for deep seated tumors in less than an hour.

Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

PubMed Central

Miyatake, Shin-Ichi; Kawabata, Shinji; Nonoguchi, Naosuke; Yokoyama, Kunio; Kuroiwa, Toshihiko; Matsui, Hideki; Ono, Koji

2009-01-01

Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT. PMID:19289492

Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

DOE PAGES

Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.; ...

2017-08-01

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less

Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less

A light therapy for treating Alzheimer's disease

NASA Astrophysics Data System (ADS)

Wang, Xue; Han, Mengmeng; Wang, Qiyan; Zeng, Yuhui; Meng, Qingqiang; Zhang, Jun; Wei, Xunbin

2017-02-01

It is generally believed that there are some connections between Alzheimer's disease and amyloid protein plaques in the brain. The typical symptoms of Alzheimer's disease are memory loss, language disorders, mood swings, loss of motivation and behavioral issues. Currently, the main therapeutic method is pharmacotherapy, which may temporarily reduce symptoms, but has many side effects. Infrared light therapy has been studied in a range of single and multiple irradiation protocols in previous studies and was found beneficial for neuropathology. In our research we have studied the effect of infrared light on Alzheimer's disease through transgenic mouse model. We designed an experimental apparatus for treating mice, which primarily included a therapeutic box and a LED array, which emitted infrared light. After the treatment, we assessed the effects of infrared light by performing two tests: cognitive performance of mice in Morris water maze, and plaque load by immunofluorescence analysis. Immunofluorescence analysis was based on measuring the quantity of plaques in mouse brain slices. Our results show that infrared therapy is able to improve cognitive performance in the mouse model. It might provide a novel and safe way to treat Alzheimer's disease.

Perspectives of boron-neutron capture therapy of malignant brain tumors

NASA Astrophysics Data System (ADS)

Kanygin, V. V.; Kichigin, A. I.; Krivoshapkin, A. L.; Taskaev, S. Yu.

2017-09-01

Boron neutron capture therapy (BNCT) is characterized by a selective effect directly on the cells of malignant tumors. The carried out research showed the perspective of the given kind of therapy concerning malignant tumors of the brain. However, the introduction of BNCT into clinical practice is hampered by the lack of a single protocol for the treatment of patients and the difficulty in using nuclear reactors to produce a neutron beam. This problem can be solved by using a compact accelerator as a source of neutrons, with the possibility of installation in a medical institution. Such a neutron accelerator for BNCT was developed at Budker Institute of Nuclear Physics, Novosibirsk. A neutron beam was obtained on this accelerator, which fully complies with the requirements of BNCT, as confirmed by studies on cell cultures and experiments with laboratory animals. The conducted experiments showed the relative safety of the method with the absence of negative effects on cell cultures and living organisms, and also confirmed the effectiveness of BNCT for malignant brain tumors.

Tension - Type - Headache treated by Positional Release Therapy: a case report.

PubMed

Mohamadi, Marzieh; Ghanbari, Ali; Rahimi Jaberi, Abbas

2012-10-01

Tension Type Headache (T.T.H) is the most prevalent headache. Myofascial abnormalities & trigger points are important in this type of headache which can be managed by Positional Release Therapy (PRT). This is a report of a 47 years old female patient with Tension Type Headache treated by Positional Release Therapy for her trigger points. She had a constant dull headache, which continued all the day for 9 months. A physiotherapist evaluated the patient and found active trigger points in her cervical muscles. Then, she received Positional Release Therapy for her trigger points. After 3 treatment sessions, the patient's headache stopped completely. During the 8 months following the treatment she was without pain, and did not use any medication. Positional Release Therapy was effective in treating Tension Type Headache. This suggests that PRT could be an alternative treatment to medication in patients with T.T.H if the effectiveness of that can be confirmed by further studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Physical Therapy to Treat Torn Meniscus Comparable to Surgery for Many Patients

MedlinePlus

... to Surgery for Many Patients Spotlight on Research Physical Therapy to Treat Torn Meniscus Comparable to Surgery ... to avoid surgery and achieve comparable relief from physical therapy, according to a recent, multisite study funded ...

Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model.

PubMed Central

Yanagië, H.; Tomita, T.; Kobayashi, H.; Fujii, Y.; Takahashi, T.; Hasumi, K.; Nariuchi, H.; Sekiguchi, M.

1991-01-01

An immunoliposome containing a 10B-compound has been examined as a selective drug delivery system in boron neutron-capture therapy. Liposomes, conjugated with monoclonal antibodies specific for carcinoembryonic antigen (CEA) were shown to bind selectively to cells bearing CEA on their surface. The immunoliposomes attached to tumour cells suppressed growth in vitro upon thermal neutron irradiation and suppression was dependent upon the concentration of the 10B-compound in the liposomes and on the density of antibody conjugated to the liposomes. The results suggest that immunoliposomes containing the 10B-compound could act as a selective and efficient carrier of 10B atoms to target tumour cells in boron neutron-capture therapy. Images Figure 1 PMID:2021537

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

PubMed Central

2010-01-01

Background Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis. Results Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E

Boron neutron capture therapy as new treatment for clear cell sarcoma: trial on different animal model.

PubMed

Andoh, Tooru; Fujimoto, Takuya; Sudo, Tamotsu; Suzuki, Minoru; Sakurai, Yoshinori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Takeuchi, Tamotsu; Sonobe, Hiroshi; Epstein, Alan L; Fukumori, Yoshinobu; Ono, Koji; Ichikawa, Hideki

2014-06-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. Copyright © 2013 Elsevier Ltd. All rights reserved.

Treating hearing disorders with cell and gene therapy

NASA Astrophysics Data System (ADS)

Gillespie, Lisa N.; Richardson, Rachael T.; Nayagam, Bryony A.; Wise, Andrew K.

2014-12-01

Hearing loss is an increasing problem for a substantial number of people and, with an aging population, the incidence and severity of hearing loss will become more significant over time. There are very few therapies currently available to treat hearing loss, and so the development of new therapeutic strategies for hearing impaired individuals is of paramount importance to address this unmet clinical need. Most forms of hearing loss are progressive in nature and therefore an opportunity exists to develop novel therapeutic approaches to slow or halt hearing loss progression, or even repair or replace lost hearing function. Numerous emerging technologies have potential as therapeutic options. This paper details the potential of cell- and gene-based therapies to provide therapeutic agents to protect sensory and neural cells from various insults known to cause hearing loss; explores the potential of replacing lost sensory and nerve cells using gene and stem cell therapy; and describes the considerations for clinical translation and the challenges that need to be overcome.

IgE-blocking therapy for difficult-to-treat asthma: a brief review.

PubMed

Marshall, Gailen D; Sorkness, Christine A

2004-03-01

To review the characteristics of difficult-to-treat asthma and describe patients who may benefit from therapy with the recently approved humanized monoclonal antiimmunoglobulin E (IgE) antibody, omalizumab. Up to 20 percent of patients have difficult-to-treat asthma. These patients consume a disproportionate share of asthma care resources. Clinical and economic outcomes can be improved via improved self-management, increased adherence to prescribed therapy, and better compliance to national asthma treatment guidelines. These patients also may benefit from therapies that directly target mechanisms responsible for persistent airway inflammation and elicit favorable clinical responses. Effective asthma control remains difficult in a small cohort of patients with persistent, severe airway inflammation. Management strategies that improve asthma control and reduce exacerbations can improve clinical outcomes and minimize health care resource utilization.

Targeting neutrophils for host-directed therapy to treat tuberculosis.

PubMed

Dallenga, Tobias; Linnemann, Lara; Paudyal, Bhesh; Repnik, Urska; Griffiths, Gareth; Schaible, Ulrich E

2017-10-07

M. tuberculosis is one of the prime killers from infectious diseases worldwide. Infections with multidrug-resistant variants counting for almost half a million new cases per year are steadily on the rise. Tuberculosis caused by extensively drug-resistant variants that are even resistant against newly developed or last resort antibiotics have to be considered untreaTable Susceptible tuberculosis already requires a six-months combinational therapy which requires further prolongation to treat drug-resistant infections. Such long treatment schedules are often accompanied by serious adverse effects causing patients to stop therapy. To tackle the global tuberculosis emergency, novel approaches for treatment need to be urgently explored. Host-directed therapies that target components of the defense system represent such a novel approach. In this review, we put a spotlight on neutrophils and neutrophil-associated effectors as promising targets for adjunct host-directed therapies to improve antibiotic efficacy and reduce both, treatment time and long-term pathological sequelae. Copyright © 2017 Elsevier GmbH. All rights reserved.

CONVECTION ENHANCED DELIVERY OF CARBORANYLPORPHYRINS FOR NEUTRON CAPTURE THERAPY OF BRAIN TUMORS

PubMed Central

Kawabata, Shinji; Yang, Weilian; Wu, Gong; Huo, Tianyao; Binns, Peter J.; Riley, Kent J.; Ongayi, Owendi; Gottumukkala, Vijay; Vicente, M. Graça H.

2010-01-01

Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive 10B is irradiated with low energy thermal neutrons to produce α-particles (10B[n,α]7Li). Carboranylporphyrins are a class of substituted porphyrins containing multiple carborane clusters. Three of these have been evaluated in the present study: 5,10,15,20-tetra-(4-nido-carboranyphenyl)tetrabenzoporphyrin (H2TBP), 5,10,15,20-tetra-(4-nido-carboranylphenyl)porphyrin (H2TCP) and 5,15-di-[3,5-(nido-carboranylmethyl)phenyl]-porphyrin (H2DCP). The goals of this study were two-fold. First, to determine the biodistribution of H2TBP, H2TCP and H2DCP following intracerebral (i.c.) administration by means of short term (30 min) convection enhanced delivery (CED) or sustained delivery over 24 h by osmotic pumps to F98 glioma bearing rats. Second, to determine the efficacy of H2TCP and H2TBP as boron delivery agents for BNCT in F98 glioma bearing rats. Tumor boron concentrations immediately after i.c. osmotic pump delivery were high (36–88 µg/g) and they remained so at 24 h (62–103 µg/g) The corresponding normal brain concentrations were low (0.8–5.2 µg/g) and the blood and liver concentrations were all undetectable. Based on these data, therapy studies were initiated at the Massachusetts Institute of Technology (MIT) Research Reactor (MITRR) with H2TCP and H2TBP 24 h after CED or osmotic pump delivery. Mean survival times (MST) of untreated and irradiated control rats were 23±3 and 27±3 d, respectively, while animals that received H2TCP or H2TBP, followed by BNCT, had a MST of 35±4 d and 44±10 d, respectively, which were better than those obtained following i.v. administration of boronophenylalanine (37±3 d). However, since the tumor boron concentrations of the carboranylporphyrins were 3–5X > i.v. BPA (~25 µg/g), we had expected that the MSTs would have been greater. Histopathologic examination of brains of BNCT treated rats revealed

Exploring Boron Neutron Capture Therapy for non-small cell lung cancer.

PubMed

Farías, Rubén O; Bortolussi, Silva; Menéndez, Pablo R; González, Sara J

2014-12-01

Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high LET radiation. It consists in the enrichment of tumour with (10)B and in the successive irradiation of the target with low energy neutrons producing charged particles that mainly cause non-repairable damages to the cells. The feasibility to treat Non Small Cells Lung Cancer (NSCLC) with BNCT was explored. This paper proposes a new approach to determine treatment plans, introducing the possibility to choose the irradiation start and duration to maximize the tumour dose. A Tumour Control Probability (TCP) suited for lung BNCT as well as other high dose radiotherapy schemes was also introduced. Treatment plans were evaluated in localized and disseminated lung tumours. Semi-ideal and real energy spectra beams were employed to assess the best energy range and the performance of non-tailored neutron sources for lung tumour treatments. The optimal neutron energy is within [500 eV-3 keV], lower than the 10 keV suggested for the treatment of deep-seated tumours in the brain. TCPs higher than 0.6 and up to 0.95 are obtained for all cases. Conclusions drawn from [Suzuki et al., Int Canc Conf J 1 (4) (2012) 235-238] supporting the feasibility of BNCT for shallow lung tumours are confirmed, however discussions favouring the treatment of deeper lesions and disseminated disease are also opened. Since BNCT gives the possibility to deliver a safe and potentially effective treatment for NSCLC, it can be considered a suitable alternative for patients with few or no treatment options. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Characteristics of a heavy water photoneutron source in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Danial, Salehi; Dariush, Sardari; M. Salehi, Jozani

2013-07-01

Bremsstrahlung photon beams produced by medical linear accelerators are currently the most commonly used method of radiation therapy for cancerous tumors. Photons with energies greater than 8-10 MeV potentially generate neutrons through photonuclear interactions in the accelerator's treatment head, patient's body, and treatment room ambient. Electrons impinging on a heavy target generate a cascade shower of bremsstrahlung photons, the energy spectrum of which shows an end point equal to the electron beam energy. By varying the target thickness, an optimum thickness exists for which, at the given electron energy, maximum photon flux is achievable. If a source of high-energy photons i.e. bremsstrahlung, is conveniently directed to a suitable D2O target, a novel approach for production of an acceptable flux of filterable photoneturons for boron neutron capture therapy (BNCT) application is possible. This study consists of two parts. 1. Comparison and assessment of deuterium photonuclear cross section data. 2. Evaluation of the heavy water photonuclear source.

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy.

PubMed

Kawasaki, Riku; Sasaki, Yoshihiro; Akiyoshi, Kazunari

2017-01-29

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and, consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 μg/mL and 400 μg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating Hypnosis with Other Therapies for Treating Specific Phobias: A Case Series.

PubMed

Hirsch, Joseph A

2018-04-01

There is a high prevalence of anxiety disorders including specific phobias and panic disorder in the United States and Europe. A variety of therapeutic modalities including pharmacotherapy, cognitive behavioral therapy, systematic desensitization, hypnosis, in vivo exposure, and virtual reality exposure therapy have been applied. No one modality has been entirely successful. There has been only a limited attempt to combine psychological therapies in the treatment of specific phobias and panic disorder and what has been done has been primarily with systematic desensitization or cognitive behavioral therapy along with hypnotherapy. I present two cases of multiple specific phobias that were successfully treated with hypnotherapy combined with virtual reality exposure therapy or in vivo exposure therapy. The rationale for this integrative therapy and the neurobiological constructs are considered.

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer.

PubMed

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-Ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-Ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

2014-01-01

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10-12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7-40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted.

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer

PubMed Central

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

2014-01-01

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10–12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7–40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted. PMID:23955053

Single step synthesis of nanostructured boron nitride for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Singh, Bikramjeet; Singh, Paviter; Kumar, Manjeet; Thakur, Anup; Kumar, Akshay

2015-05-01

Nanostructured Boron Nitride (BN) has been successfully synthesized by carbo-thermic reduction of Boric Acid (H3BO3). This method is a relatively low temperature synthesis route and it can be used for large scale production of nanostructured BN. The synthesized nanoparticles have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential thermal analyzer (DTA). XRD analysis confirmed the formation of single phase nanostructured Boron Nitride. SEM analysis showed that the particles are spherical in shape. DTA analysis showed that the phase is stable upto 900 °C and the material can be used for high temperature applications as well boron neutron capture therapy (BNCT).

Treating Gastrointestinal and Autism Symptoms in Adults with Autism Using Microbiota Transfer Therapy (MTT)

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-16-1-0492 TITLE: Treating Gastrointestinal and Autism Symptoms in Adults with Autism Using Microbiota Transfer Therapy (MTT...DATES COVERED (From - To) Sept 1 2016 to Aug 31, 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Treating Gastrointestinal and Autism Symptoms in...Adults with Autism Using Microbiota Transfer Therapy (MTT) 5b. GRANT NUMBER W81XWH-16-1-0492 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawasaki, Riku; JST-ERATO, Japan Science and Technology Agency; Sasaki, Yoshihiro

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and,more » consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 μg/mL and 400 μg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic. - Highlights: • A carborane-bearing pullulan nanogel is developed as a boron delivery agent. • The nanogels are cell-friendly and show effective cell uptake for drug delivery. • The nanogels show passive tumor targeting by enhanced permeation and retention.« less

Studying infrared light therapy for treating Alzheimer's disease

NASA Astrophysics Data System (ADS)

Han, Mengmeng; Wang, Qiyan; Zeng, Yuhui; Meng, Qingqiang; Zhang, Jun; Wei, Xunbin

2016-03-01

Alzheimer's disease (AD) is an extensive neurodegenerative disease. It is generally believed that there are some connections between AD and amyloid protein plaques in the brain. AD is a chronic disease that usually starts slowly and gets worse over time. The typical symptoms are memory loss, language disorders, mood swings and behavioral issues. Gradual losses of somatic functions eventually lead patients to death. Currently, the main therapeutic method is pharmacotherapy, which may temporarily reduce symptoms, but has many side effects. No current treatment can reverse AD's deterioration. Infrared (IR) light therapy has been studied in a range of single and multiple irradiation protocols in previous studies and was found beneficial for neuropathology. In our research, we have verified the effect of infrared light on AD through Alzheimer's disease mouse model. This transgenic mouse model is made by co-injecting two vectors encoding mutant amyloid precursor protein (APP) and mutant presenilin-1 (PSEN1). We designed an experimental apparatus for treating mice, which primarily includes a therapeutic box and a LED array, which emits infrared light. After the treatment, we assessed the effects of infrared light by testing cognitive performance of the mice in Morris water maze. Our results show that infra-red therapy is able to improve cognitive performance in the mouse model. It might provide a novel and safe way to treat Alzheimer's disease.

Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

PubMed

Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

2015-03-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

PubMed Central

HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

2015-01-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC’s applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37–43 days). PMID:25546823

The accelerator neutron source for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Kasatov, D.; Koshkarev, A.; Kuznetsov, A.; Makarov, A.; Ostreinov, Yu; Shchudlo, I.; Sorokin, I.; Sycheva, T.; Taskaev, S.; Zaidi, L.

2016-11-01

The accelerator based epithermal neutron source for Boron Neutron Capture Therapy (BNCT) is proposed, created and used in the Budker Institute of Nuclear Physics. In 2014, with the support of the Russian Science Foundation created the BNCT laboratory for the purpose to the end of 2016 get the neutron flux, suitable for BNCT. For getting 3 mA 2.3 MeV proton beam, was created a new type accelerator - tandem accelerator with vacuum isolation. On this moment, we have a stationary proton beam with 2.3 MeV and current 1.75 mA. Generation of neutrons is carried out by dropping proton beam on to lithium target as a result of threshold reaction 7Li(p,n)7Be. Established facility is a unique scientific installation. It provides a generating of neutron flux, including a monochromatic energy neutrons, gamma radiation, alpha-particles and positrons, and may be used by other research groups for carrying out scientific researches. The article describes an accelerator neutron source, presents and discusses the result of experiments and declares future plans.

Catatonia after deep brain stimulation successfully treated with lorazepam and right unilateral electroconvulsive therapy: a case report.

PubMed

Quinn, Davin K; Rees, Caleb; Brodsky, Aaron; Deligtisch, Amanda; Evans, Daniel; Khafaja, Mohamad; Abbott, Christopher C

2014-09-01

The presence of a deep brain stimulator (DBS) in a patient who develops neuropsychiatric symptoms poses unique diagnostic challenges and questions for the treating psychiatrist. Catatonia has been described only once, during DBS implantation, but has not been reported in a successfully implanted DBS patient. We present a case of a patient with bipolar disorder and renal transplant who developed catatonia after DBS for essential tremor. The patient was successfully treated for catatonia with lorazepam and electroconvulsive therapy after careful diagnostic workup. Electroconvulsive therapy has been successfully used with DBS in a handful of cases, and certain precautions may help reduce potential risk. Catatonia is a rare occurrence after DBS but when present may be safely treated with standard therapies such as lorazepam and electroconvulsive therapy.

Radiobiological response of U251MG, CHO-K1 and V79 cell lines to accelerator-based boron neutron capture therapy

PubMed Central

Sato, Eisuke; Zaboronok, Alexander; Yamamoto, Tetsuya; Nakai, Kei; Taskaev, Sergey; Volkova, Olga; Mechetina, Ludmila; Taranin, Alexander; Kanygin, Vladimir; Isobe, Tomonori; Mathis, Bryan J; Matsumura, Akira

2018-01-01

Abstract In the current article, we provide in vitro efficacy evaluation of a unique accelerator-based neutron source, constructed at the Budker Institute of Nuclear Physics (Novosibirsk, Russian Federation), for boron neutron capture therapy (BNCT), which is particularly effective in the case of invasive cancers. U251MG, CHO-K1 and V79 cells were incubated and irradiated in various concentrations of boric acid with epithermal neutrons for 2–3 h in a plexiglass phantom, using 2.0 MeV proton energy and 1.5–3.0 mA proton current, resulting in a neutron fluence of 2.16 × 1012 cm−2. The survival curves of cells loaded with boron were normalized to those irradiated without boron (to exclude the influence of the fast neutron and gamma dose components) and fit to the linear–quadratic (LQ) model. Colony formation assays showed the following cell survival rates (means ± SDs): CHO-K1: 0.348 ± 0.069 (10 ppm), 0.058 ± 0.017 (20 ppm), 0.018 ± 0.005 (40 ppm); V79: 0.476 ± 0.160 (10 ppm), 0.346 ± 0.053 (20 ppm), 0.078 ± 0.015 (40 ppm); and U251MG: 0.311 ± 0.061 (10 ppm), 0.131 ± 0.022 (20 ppm), 0.020 ± 0.010 (40 ppm). The difference between treated cells and controls was significant in all cases (P < 0.01) and confirmed that the neutron source and irradiation regimen were sufficient for control over cell colony formation. We believe our study will serve as a model for ongoing in vitro experiments on neutron capture therapy to advance in this area for further development of accelerator-based BNCT into the clinical phase. PMID:29281044

Single step synthesis of nanostructured boron nitride for boron neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Bikramjeet; Singh, Paviter; Kumar, Akshay, E-mail: akshaykumar.tiet@gmail.com

2015-05-15

Nanostructured Boron Nitride (BN) has been successfully synthesized by carbo-thermic reduction of Boric Acid (H{sub 3}BO{sub 3}). This method is a relatively low temperature synthesis route and it can be used for large scale production of nanostructured BN. The synthesized nanoparticles have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential thermal analyzer (DTA). XRD analysis confirmed the formation of single phase nanostructured Boron Nitride. SEM analysis showed that the particles are spherical in shape. DTA analysis showed that the phase is stable upto 900 °C and the material can be used for high temperature applications asmore » well boron neutron capture therapy (BNCT)« less

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a monte carlo study.

PubMed

Jung, Joo-Young; Yoon, Do-Kun; Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-06-13

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a Monte Carlo study

PubMed Central

Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-01-01

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy. PMID:28427153

Using Acceptance and Commitment Therapy to Treat Distressed Couples: A Case Study With Two Couples

ERIC Educational Resources Information Center

Peterson, Brennan D.; Eifert, Georg H.; Feingold, Tal; Davidson, Sarah

2009-01-01

Although the field of couple therapy has made significant strides in recent years, there continues to be a need for theoretically sound and empirically supported treatments. The current case study examines whether Acceptance and Commitment Therapy (ACT), an experiential acceptance-based behavior therapy, can be effective in treating distressed…

Treating cerebral palsy with aculaser therapy

NASA Astrophysics Data System (ADS)

Anwar, Shahzad; Nazir Khan, Malik M.; Nadeem Khan, Malik M.; Qazi, Faiza M.; Awan, Abid H.; Dar, Irfan

2008-03-01

A single, open and non comparative study was conducted at Anwar Shah Trust for C.P. & Paralysis in collaboration with the Departments of Neurology and Neurosurgery, Children Hospital Lahore, Pakistan to evaluate the effects of ACULASER THERAPY in childern suffering from Cerebral Palsy (C.P.) and associated Neurological Disorders like epilepsy, cortical blindness, spasticity, hemiplegia, paraplegia, diplegia, quadriplegia, monoplegia, sensory-neural deafness and speech disorders. In all 250 childern were treated and the data was gathered during a period of 3 years from December 2003 till December 2006. These children were further classified according to the type of C.P. (spastic, athetoid, mixed) they suffered from and associated Neurological Disorders. This article shows results in C.P. childern who were treated with ACULASER THERAPY for minimum 6 weeks and more or had minimum of 15 treatment sessions and more. This article also shows that those childern who were given a break in the treatment for 1 month to 1 year did not show any reversal of the signs and symptoms. Analysis of the data showed that out of 171 children with Spasticity and Stiffness 147 showed marked improvement showing 87% success rate, out of 126 children with Epileptic fits, there was a significant reduction in the intensity, frequency and duration of Epileptic fits in 91 children showing 72% success rate, out of 48 children with Cortical Blindness 30 children showed improvement accounting for 63% efficacy rate, out of 105 children with Hearing Difficulties, 63 showed marked improvement accounting for 60% improvement rate, out of 190 children with Speech Disorders 122 showed improvement reflecting 64% improvement rate, out of 96 children with Hemiplegia 71 showed improvement in movement, tone and power accounting for 74% improvement rate, out of 76 children with Quadriplegia 52 showed improvement in gross and fine motor functions showing 69% success rate and out of 58 children with Paraplegia of

Multi-Family Pediatric Pain Group Therapy: Capturing Acceptance and Cultivating Change.

PubMed

Huestis, Samantha E; Kao, Grace; Dunn, Ashley; Hilliard, Austin T; Yoon, Isabel A; Golianu, Brenda; Bhandari, Rashmi P

2017-12-07

Behavioral health interventions for pediatric chronic pain include cognitive-behavioral (CBT), acceptance and commitment (ACT), and family-based therapies, though literature regarding multi-family therapy (MFT) is sparse. This investigation examined the utility and outcomes of the Courage to Act with Pain: Teens Identifying Values, Acceptance, and Treatment Effects (CAPTIVATE) program, which included all three modalities (CBT, ACT, MFT) for youth with chronic pain and their parents. Program utility, engagement, and satisfaction were evaluated via quantitative and qualitative feedback. Pain-specific psychological, behavioral, and interpersonal processes were examined along with outcomes related to disability, quality of life, pain interference, fatigue, anxiety, and depressive symptoms. Participants indicated that CAPTIVATE was constructive, engaging, and helpful for social and family systems. Clinical and statistical improvements with large effect sizes were captured for pain catastrophizing, acceptance, and protective parenting but not family functioning. Similar effects were found for functional disability, pain interference, fatigue, anxiety, and depression. Given the importance of targeting multiple systems in the management of pediatric chronic pain, preliminary findings suggest a potential new group-based treatment option for youth and families. Next steps involve evaluating the differential effect of the program over treatment as usual, as well as specific CBT, ACT, and MFT components and processes that may affect outcomes.

Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

PubMed

Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

2015-12-01

Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorge E. Cardoso; Elisa M. Heber; David W. Nigg

2007-10-01

The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis ismore » that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.« less

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model.

PubMed

Monti Hughes, A M; Pozzi, E C C; Thorp, S; Garabalino, M A; Farías, R O; González, S J; Heber, E M; Itoiz, M E; Aromando, R F; Molinari, A J; Miller, M; Nigg, D W; Curotto, P; Trivillin, V A; Schwint, A E

2013-11-01

Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model. Groups of cancerized hamsters were locally exposed to single or double (2 or 4 weeks apart) applications of BNCT at different dose levels, mediated by the boron compounds boronophenylalanine (BPA) or BPA and decahydrodecaborate (GB-10) administered jointly. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumour development from field-cancerized tissue and mucositis were followed for 8 months. A double application (4 weeks apart) of BNCT mediated by GB-10+ BPA at a total dose of 10 Gy in two 5-Gy doses rendered the best therapeutic advantage (63-100% inhibition of tumour development from field-cancerized tissue), minimizing dose-limiting mucositis. BNCT can be optimized for the integral treatment for head and neck cancer, considering the implications for field-cancerized tissue. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low-level laser therapy to treat fibromyalgia.

PubMed

Ruaro, J A; Fréz, A R; Ruaro, M B; Nicolau, R A

2014-11-01

Several clinical treatments have been proposed to manage symptoms of fibromyalgia. Low-level laser therapy (LLLT) may be a useful tool to treat this dysfunction. The aim of this study was to evaluate the effects of LLLT in patients with fibromyalgia. A placebo-controlled, randomized clinical trial was carried out with 20 patients divided randomly into either an LLLT group (n = 10) or a placebo group (n = 10). The LLLT group was treated with a GaAlAs laser (670 nm, 4 J/cm(2) on 18 tender points) three times a week over 4 weeks. Before and after treatment, patients were evaluated with the Fibromyalgia Impact Questionnaire (FIQ), McGill Pain Questionnaire, and visual analog scale (VAS). Data from the FIQ and McGill questionnaire for the treated and control groups were analyzed by paired t tests, and Wilcoxon tests were used to analyze data from the VAS. After LLLT or sham treatment, the number of tender points was significantly reduced in both groups (LLLT, p < 0.0001; placebo, p = 0.0001). However, all other fibromyalgia symptoms showed significant improvements after LLLT compared to placebo (FIQ, p = 0.0003; McGill, p = 0.0078; and VAS, p = 0.0020). LLLT provided relief from fibromyalgia symptoms in patients and should be further investigated as a therapeutic tool for management in fibromyalgia.

A Case Study Using Child-Centered Play Therapy Approach to Treat Enuresis and Encopresis.

ERIC Educational Resources Information Center

Cuddy-Casey, Maria

1997-01-01

Demonstrates an alternative method (nondirective child-centered therapy) in treating enuresis and encopresis resulting from emotional disturbances. Examines various etiologies and approaches to treating these conditions. Provides a case study example. Claims that professionals must differentiate between primary and secondary occurrences of these…

Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease.

PubMed

Fox, Ira J; Daley, George Q; Goldman, Steven A; Huard, Johnny; Kamp, Timothy J; Trucco, Massimo

2014-08-22

Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity, as well as a number of other challenges. Collaboration among scientists, clinicians, and industry is critical for generating new stem cell-based therapies. Copyright © 2014, American Association for the Advancement of Science.

Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lingos, T.I.; Recht, A.; Vicini, F.

1991-07-01

The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, the authors retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocentermore » from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002).« less

Final Stage in the Design of a Boron Neutron Capture Therapy facility at CEADEN, Cuba

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cabal, F. Padilla; Martin, G.

A neutron beam simulation study is carried out to determine the most suitable neutron energy for treatment of shallow and deep-seated brain tumors in the context of Boron Neutron Capture Therapy (BNCT). Two figures-of-merit, the therapeutic gain and the neutron fluence are utilized as beam assessment parameters. An irradiation cavity is used instead of a parallel beam port for the therapy. Calculations are performed using the MCNP5 code. After the optimization of our beam-shaper a study of the dose distribution in the head, neck, tyroids, lungs and upper and middle spine had been made. The therapeutic gain is increased whilemore » the current required for one hour treatment is decreased in comparison with the trading prototypes of NG used for BNCT.« less

Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

PubMed

Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

2016-10-01

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections.

PubMed

Bodier-Montagutelli, Elsa; Morello, Eric; L'Hostis, Guillaume; Guillon, Antoine; Dalloneau, Emilie; Respaud, Renaud; Pallaoro, Nikita; Blois, Hélène; Vecellio, Laurent; Gabard, Jérôme; Heuzé-Vourc'h, Nathalie

2017-08-01

Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation. Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy's clinical positioning in the antimicrobial arsenal against RTIs.

Outcomes of Pediatric Low-grade Gliomas Treated With Radiation Therapy: A Single-institution Study

PubMed Central

Raikar, Sunil S.; Halloran, Donna R.; Elliot, Michael; McHugh, Michele; Patel, Shaun; Gauvain, Karen M.

2014-01-01

Summary Radiation therapy is often considered the treatment of choice for low-grade gliomas. However, given the long-term effects of radiation on the developing brain, the appropriate use of radiation therapy in pediatric patients remains controversial. The purpose of this study was to evaluate progression-free survival (PFS) of pediatric low-grade glioma patients treated with radiation therapy. Data were obtained through a retrospective chart review of patients treated between 1991 and 2008 from a single tertiary care center in the midwest. The study population consisted of 17 patients, of whom 8 (47%) had tumor recurrence after radiation therapy. The median follow-up time was 8.2 years, with a range of 2.3 to 17.2 years. The median age at diagnosis was 5.4 years, and the median age at radiation therapy was 9.4 years. The 3- and the 10-year PFS were 69% ± 11.7% and 46% ± 13.3%, respectively. A significant difference in PFS was seen when comparing brainstem tumors with hypothalamic/optic pathway tumors (P = 0.019). Differences in PFS based on the age at diagnosis, the extent of initial surgery, and indication for radiation therapy were not significant. A larger multicenter study is needed to better assess PFS in these patients. PMID:24714505

High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents.

PubMed

Kaniowski, Damian; Ebenryter-Olbińska, Katarzyna; Sobczak, Milena; Wojtczak, Błażej; Janczak, Sławomir; Leśnikowski, Zbigniew J; Nawrot, Barbara

2017-08-23

Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted "click" conjugation of alkyne-modified DNA-oligonucleotides with a boron cluster alkyl azide component. The obtained oligomers exhibited increased lipophilicity compared to their non-modified precursors, while their binding affinity to complementary DNA and RNA strands was slightly decreased. Multiple metallacarborane residues present in the oligonucleotide chain, each containing 18 B-H groups, enabled the use of IR spectroscopy as a convenient analytical method for these oligomers based on the diagnostic B-H signal at 2400-2650 cm -1 . The silencing activity of boron cluster-modified ASOs used at higher concentrations was similar to that of unmodified oligonucleotides. The screened ASOs, when used in low concentrations (up to 50 μM), exhibited pro-oxidative properties by inducing ROS production and an increase in mitochondrial activities in HeLa cells. In contrast, when used at higher concentrations, the ASOs exhibited anti-oxidative properties by lowering ROS species levels. In the HeLa cells (tested in the MTT assay) treated (without lipofectamine) or transfected with the screened compounds, the mitochondrial activity remained equal to the control level or only slightly changed (±30%). These findings may be useful in the design of dual-action boron cluster-modified therapeutic nucleic acids with combined antisense and anti-oxidant properties.

A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

PubMed

Alberti, Diego; Protti, Nicoletta; Toppino, Antonio; Deagostino, Annamaria; Lanzardo, Stefania; Bortolussi, Silva; Altieri, Saverio; Voena, Claudia; Chiarle, Roberto; Geninatti Crich, Simonetta; Aime, Silvio

2015-04-01

This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of MCNP simulated gamma spectra of CdTe detectors for boron neutron capture therapy.

PubMed

Winkler, Alexander; Koivunoro, Hanna; Savolainen, Sauli

2017-06-01

The next step in the boron neutron capture therapy (BNCT) is the real time imaging of the boron concentration in healthy and tumor tissue. Monte Carlo simulations are employed to predict the detector response required to realize single-photon emission computed tomography in BNCT, but have failed to correctly resemble measured data for cadmium telluride detectors. In this study we have tested the gamma production cross-section data tables of commonly used libraries in the Monte Carlo code MCNP in comparison to measurements. The cross section data table TENDL-2008-ACE is reproducing measured data best, whilst the commonly used ENDL92 and other studied libraries do not include correct tables for the gamma production from the cadmium neutron capture reaction that is occurring inside the detector. Furthermore, we have discussed the size of the annihilation peaks of spectra obtained by cadmium telluride and germanium detectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

PubMed

Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

2006-12-11

In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection.

Biocompatibility of functionalized boron phosphate (BPO4) nanoparticles for boron neutron capture therapy (BNCT) application.

PubMed

Achilli, Cesare; Grandi, Stefania; Ciana, Annarita; Guidetti, Gianni F; Malara, Alessandro; Abbonante, Vittorio; Cansolino, Laura; Tomasi, Corrado; Balduini, Alessandra; Fagnoni, Maurizio; Merli, Daniele; Mustarelli, Piercarlo; Canobbio, Ilaria; Balduini, Cesare; Minetti, Giampaolo

2014-04-01

Boron neutron capture therapy (BNCT) is a radiotherapy treatment based on the accumulation in the tumor of a (10)B-containing drug and subsequent irradiation with low energy neutrons, which bring about the decay of (10)B to (7)Li and an α particle, causing the death of the neoplastic cell. The effectiveness of BNCT is limited by the low delivery and accumulation of the used boron-containing compounds. Here we report the development and the characterization of BPO4 nanoparticles (NPs) as a novel possible alternative drug for BNCT. An extensive analysis of BPO4 NP biocompatibility was performed using both mature blood cells (erythrocytes, neutrophils and platelets) and a model of hematopoietic progenitor cells. A time- and concentration-dependent cytotoxicity study was performed on neoplastic coloncarcinoma and osteosarcoma cell lines. BPO4 functionalization with folic acid, introduced to improve the uptake by tumor cells, appeared to effectively limit the unwanted effects of NPs on the analyzed blood components. Boron neutron capture therapy (BNCT) is a radiotherapy treatment modality based on the accumulation of a (10)B-containing drug and subsequent irradiation with low energy neutrons, inducing the decay of (10)B to (7)Li and an α particle, causing neoplastic cell death. This team of authors reports on a folic acid functionalized BPO4 nanoparticle with improved characteristics compared with conventional BNCT approaches, as demonstrated in tumor cell lines, and hopefully to be followed by translational human studies. © 2014.

Clinical efficiency of applying low-intensity laser therapy in treating dyscirculatory encephalopathy

NASA Astrophysics Data System (ADS)

Putilina, M. V.; Kozlov, V. I.; Vakhtin, V. I.

2001-04-01

An investigation was made of applying laser therapy combined with drug preparations in treating 300 patients affected by dyscirculatory encephalopathy. Neurological and neuropsychological examinations together with electroencephalography, rheoencephalography, computerized tomography, and magnetic resonance imaging were used to assess the patients' states prior to and after the treatment. It was found that the combined application of laser therapy and drug preparations produced a more pronounced therapeutic effect as compared with that produced by the separate application of laser therapy and drug preparations. The results obtained allowed us to conclude that the 0.89 micrometers laser infrared radiation increased patients' susceptibility to drugs. Moreover, the combined laser therapy improved the cerebral bloodflow and activated the metabolic and plastic functions of neurons. This decreased or eliminated late complications provoked by the cerebral blood circulation insufficiency.

Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: a boron neutron capture therapy study.

PubMed

Gifford, Ian; Vreeland, Wyatt; Grdanovska, Slavica; Burgett, Eric; Kalinich, John; Vergara, Vernieda; Wang, C-K Chris; Maimon, Eric; Poster, Dianne; Al-Sheikhly, Mohamad

2014-06-01

The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined. Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from (10)B thermal neutron capture. BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 μg/10(9) cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 10(11) n/cm(2) thermal neutron fluence yielded a 20-25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and (7)Li nuclei that deposit energy in densely ionizing radiation tracks. Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and (7)Li nuclei generated from (10)B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.

Medium voltage therapy for preventing and treating asystole and PEA in ICDs.

PubMed

Gilman, Byron L; Brewer, James E; Kroll, Kai; Kroll, Mark W

2009-01-01

Sudden cardiac death (SCD) takes up to 500,000 lives each year before a victim can even be treated. To address this the implantable cardioverter defibrillator (ICD) was developed to treat those identified at high risk of SCD. Unfortunately, there are a significant number of cases in which the ICD does not successfully return a victim to normal rhythm and effective perfusion of the blood. The vast majority of cases that are not responsive to the ICD therapy require cardio-pulmonary resuscitation (CPR) according to current resuscitation guidelines. A novel electrical stimulus called medium voltage therapy (MVT) has shown efficacy in producing coronary and carotid blood flow during ventricular fibrillation. This report presents the case that the same stimulus may be effective and feasible for use in ICD patients that do not respond to their ICD therapy, or do not have a rhythm in which, an ICD shock is indicated. The inclusion of MVT technology in implantable devices may be effective in preparing the heart for successful defibrillation or in improving the metabolic condition of the heart to the extent that a pulsatile rhythm may spontaneously develop.

Boron analysis for neutron capture therapy using particle-induced gamma-ray emission.

PubMed

Nakai, Kei; Yamamoto, Yohei; Okamoto, Emiko; Yamamoto, Tetsuya; Yoshida, Fumiyo; Matsumura, Akira; Yamada, Naoto; Kitamura, Akane; Koka, Masashi; Satoh, Takahiro

2015-12-01

The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18 μgB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20 min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness of low level laser therapy for treating male infertility

PubMed Central

Vladimirovich Moskvin, Sergey; Ivanovich Apolikhin, Oleg

2018-01-01

In half of the cases, the infertility of the couple is due to the disorder of the male fertility. The leading factors that cause male infertility are urogenital infections, disorders of the immune system, testicular and prostate pathology, as well as endocrine disorders. Low level laser therapy (LLLT) is a very effective physical therapy method, used in many areas of medicine, including obstetrics and gynaecology, andrology and urology; and it is recommended as an integral part of the complex treatment of infertility. The literature review showed that LLLT is beneficial in treating male infertility. Laser can significantly improve the survival, motility and speed of movement of spermatozoa. Laser therapy of patients with prostatitis and vesiculitis can eliminate infiltrative-exudative changes, improve reproductive and copulatory functions. Local illumination of red (635 nm) and infrared (904 nm) spectra should be combined with intravenous laser blood illumination (ILBI) of red (635 nm) and ultraviolet (UV) (365 nm) spectra. PMID:29806585

Rehabilitation outcomes of stroke patients treated with multi-modal endovascular reperfusion therapy.

PubMed

Meiner, Z; Cohen, J E; Gomori, J M; Sajin, A; Schwartz, I; Tsenter, J; Yovchev, I; Eichel, R; Ben-Hur, T; Leker, R R

2012-03-01

The aim of this study was to investigate the influence of multi-modal endovascular reperfusion therapy (MMRT) on functional outcomes following rehabilitation. Data from 14 MMRT-treated patients were analyzed and compared to MMRT-ineligible, age and stroke severity-matched patients treated at the same Neurological and Rehabilitation departments. Neurological evaluation was assessed with the NIH stroke scale (NIHSS). Activity of daily living was measured using the FIMTM instrument. Functional outcome was measured using the modified Rankin scale (mRS). The baseline characteristics of both groups were similar. NIHSS scores were lower in the MMRT group and they had slightly better functional and rehabilitation scores on admission to rehabilitation. At the end of rehabilitation, more MMRT-treated patients reached functional independence (mRS≤2; 50% vs. 7% respectively P=0.03). FIM scores were also higher in the MMRT group (mean score 93.3 vs. 87.7, respectively) but the difference did not reach significance. The delta in FIM and NIHSS scores obtained during rehabilitation did not significantly differ between the groups. MMRT remained a significant modifier of good outcome after regression analysis (OR 21.5 95% CI 1.1-410). MMRT-treated patients have better chances of attaining independence after rehabilitation therapy. However, the additional improvements gained while in active rehabilitation were independent of reperfusion status.

The effects of fractional microablative CO2 laser therapy on sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy.

PubMed

Gittens, Paul; Mullen, Gregory

2018-06-08

To examine the outcomes of sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy who were experiencing the symptoms of GSM for which they were treated with fractional microablative CO 2 laser. From July 2015 to October 2016, a retrospective chart review of women who underwent fractional microablative CO 2 laser therapy (MonaLisa Touch, DEKA) for GSM was conducted. Several validated questionnaires were used to assess changes in symptoms and sexual function including the Female Sexual Function Index (FSFI), the Wong-Baker Faces Scale (WBFS), and the Female Sexual Distress Scale-Revised (FSDSR). Comparisons of mean symptom scores were described at baseline and six weeks after each treatment. There was a statistically significant improvement in every domain of FSFI, WBFS, and FSDS-R when comparing baseline symptom scores to after treatment three symptom scores for all patients. The secondary outcome was to evaluate the differences, if any, in outcomes of sexual function between postmenopausal women and women with a history of breast cancer treated with endocrine therapy. Both groups had statistically significant improvements in many domains studied. Fractional microablative CO 2 laser therapy (MonaLisa Touch, DEKA) is an effective modality in treating the symptoms of GSM in postmenopausal women and women with a history of breast cancer treated with endocrine therapy.

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

2012-01-01

Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by usemore » of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent

Innovative Use of Cr(VI) Plume Depictions and Pump-and-Treat Capture Analysis to Estimate Risks of Contaminant Discharge to Surface Water at Hanford Reactor Areas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Chuck W.; Hanson, James P.; Ivarson, Kristine A.

2015-01-14

The Hanford Site nuclear reactor operations required large quantities of high-quality cooling water, which was treated with chemicals including sodium dichromate dihydrate for corrosion control. Cooling water leakage, as well as intentional discharge of cooling water to ground during upset conditions, produced extensive groundwater recharge mounds consisting largely of contaminated cooling water and resulted in wide distribution of hexavalent chromium (Cr[VI]) contamination in the unconfined aquifer. The 2013 Cr(VI) groundwater plumes in the 100 Areas cover approximately 6 km2 (1500 acres), primarily in the 100-HR-3 and 100-KR-4 groundwater operable units (OUs). The Columbia River is a groundwater discharge boundary; wheremore » the plumes are adjacent to the Columbia River there remains a potential to discharge Cr(VI) to the river at concentrations above water quality criteria. The pump-and-treat systems along the River Corridor are operating with two main goals: 1) protection of the Columbia River, and 2) recovery of contaminant mass. An evaluation of the effectiveness of the pump-and-treat systems was needed to determine if the Columbia River was protected from contamination, and also to determine where additional system modifications may be needed. In response to this need, a technique for assessing the river protection was developed which takes into consideration seasonal migration of the plume and hydraulic performance of the operating well fields. Groundwater contaminant plume maps are generated across the Hanford Site on an annual basis. The assessment technique overlays the annual plume and the capture efficiency maps for the various pump and treat systems. The river protection analysis technique was prepared for use at the Hanford site and is described in detail in M.J. Tonkin, 2013. Interpolated capture frequency maps, based on mapping dynamic water level observed in observation wells and derived water levels in the vicinity of extraction and injection

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience.

PubMed

Bortolussi, Silva; Postuma, Ian; Protti, Nicoletta; Provenzano, Lucas; Ferrari, Cinzia; Cansolino, Laura; Dionigi, Paolo; Galasso, Olimpio; Gasparini, Giorgio; Altieri, Saverio; Miyatake, Shin-Ichi; González, Sara J

2017-08-15

Osteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1 h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator. The therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison. The results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is

Basic requirements and parameter optimization for boron neutron capture therapy of extracorporeal irradiated and auto-transplanted organs.

PubMed

Wortmann, Birgit; Knorr, Jürgen

2012-08-01

In 2001 and 2003, at the University of Pavia, Italy, boron neutron capture therapy (BNCT) has been successfully used in the treatment of hepatic colorectal metastases (Pinelli et al., 2002; Zonta et al., 2006). The treatment procedure (TAOrMINA protocol) is characterised by the auto-transplantation and extracorporeal irradiation of the liver using a thermal neutron beam. The clinical use of this approach requires well founded data and an optimized irradiation facility. In order to start with this work and to decide upon its feasibility at the research reactor TRIGA Mainz, basic data and requirements have been considered (Wortmann, 2008). Computer calculations using the ATTILA (Transpire Inc. 2006) and MCNP (LANL, 2005) codes have been performed, including data from conventional radiation therapy, from the TAOrMINA approach, resulting in reasonable estimations. Basic data and requirements and optimal parameters have been worked out, especially for use at an optimized TRIGA irradiation facility (Wortmann, 2008). Advantages of the extracorporeal irradiation with auto-transplantation and the potential of an optimized irradiation facility could be identified. Within the requirements, turning the explanted organ over by 180° appears preferable to a whole side source, similar to a permanent rotation of the organ. The design study and the parameter optimization confirm the potential of this approach to treat metastases in explanted organs. The results do not represent actual treatment data but a first estimation. Although all specific values refer to the TRIGA Mainz, they may act as a useful guide for other types of neutron sources. The recommended modifications (Wortmann, 2008) show the suitability of TRIGA reactors as a radiation source for BNCT of extracorporeal irradiated and auto-transplanted organs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Boron Neutron Capture Therapy (BNCT) Dose Calculation using Geometrical Factors Spherical Interface for Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zasneda, Sabriani; Widita, Rena

2010-06-22

Boron Neutron Capture Therapy (BNCT) is a cancer therapy by utilizing thermal neutron to produce alpha particles and lithium nuclei. The superiority of BNCT is that the radiation effects could be limited only for the tumor cells. BNCT radiation dose depends on the distribution of boron in the tumor. Absorbed dose to the cells from the reaction 10B (n, {alpha}) 7Li was calculated near interface medium containing boron and boron-free region. The method considers the contribution of the alpha particle and recoiled lithium particle to the absorbed dose and the variation of Linear Energy Transfer (LET) charged particles energy. Geometricalmore » factor data of boron distribution for the spherical surface is used to calculate the energy absorbed in the tumor cells, brain and scalp for case Glioblastoma Multiforme. The result shows that the optimal dose in tumor is obtained for boron concentrations of 22.1 mg {sup 10}B/g blood.« less

Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II.

PubMed

Tumlin, James A; Murugan, Raghavan; Deane, Adam M; Ostermann, Marlies; Busse, Laurence W; Ham, Kealy R; Kashani, Kianoush; Szerlip, Harold M; Prowle, John R; Bihorac, Azra; Finkel, Kevin W; Zarbock, Alexander; Forni, Lui G; Lynch, Shannan J; Jensen, Jeff; Kroll, Stew; Chawla, Lakhmir S; Tidmarsh, George F; Bellomo, Rinaldo

2018-06-01

Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. ICUs. Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). IV angiotensin II or placebo. Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

A versatile nanoplatform for synergistic combination therapy to treat human esophageal cancer.

PubMed

Wang, Xin-Shuai; Kong, De-Jiu; Lin, Tzu-Yin; Li, Xiao-Cen; Izumiya, Yoshihiro; Ding, Xue-Zhen; Zhang, Li; Hu, Xiao-Chen; Yang, Jun-Qiang; Gao, She-Gan; Lam, Kit S; Li, Yuan-Pei

2017-06-01

One of the major goals of precision oncology is to promote combination therapy to improve efficacy and reduce side effects of anti-cancer drugs based on their molecular mechanisms. In this study, we aimed to develop and validate new nanoformulations of docetaxel (DTX) and bortezomib (BTZ) for targeted combination therapy to treat human esophageal cancer. By leveraging our versatile disulfide cross-linked micelles (DCMs) platform, we developed nanoformulations of DTX and BTZ (named DTX-DCMs and BTZ-DCMs). Their physical properties were characterized; their anti-cancer efficacies and mechanisms of action were investigated in a human esophageal cancer cell line in vitro. Furthermore, the in vitro anti-tumor activities of combination therapies (concurrent drug treatment, sequential drug treatment, and treatment using different ratios of the drugs) were examined in comparison with the single drug treatment and free drug strategies. These drug-loaded nanoparticles were spherical in shape and relatively small in size of approximately 20-22 nm. The entrapment efficiencies of DTX and BTZ into nanoparticles were 82.4% and 84.1%, respectively. The drug release rates of DTX-DCMs and BTZ-DCMs were sustained, and greatly increased in the presence of GSH. These nanodrugs were effectively internalized by KYSE30 esophageal cancer cells, and dose-dependently induced cell apoptosis. We further revealed a strong synergistic effect between DTX-DCMs and BTZ-DCMs against KYSE30 esophageal cancer cells. Sequential combination therapy with DTX-DCMs followed by BTZ-DCMs exhibited the best anti-tumor efficacy in vitro. This study demonstrates that DTX and BTZ could be successfully nanoformulated into disulfide cross-linked micelles. The nanoformulations of DTX and BTZ demonstrate an immense potential for synergistic combination therapy to treat human esophageal cancer.

Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients: four cases

PubMed Central

2014-01-01

Background and importance Recurrent malignant gliomas (RMGs) are very difficult to control, and no standard treatments have been established for them. We performed boron neutron capture therapy (BNCT) for patients with RMG. BNCT enables high-dose particle radiation to be applied selectively to tumor cells. However, RMG cases generally receive nearly 60 Gy X-ray irradiation prior to re-irradiation by BNCT. Therefore, even with tumor-selective particle radiation BNCT, radiation necrosis in the brain and symptomatic pseudoprogression may develop. In four of our recent patients with RMG after BNCT, we applied the anti-VEGF antibody bevacizumab to treat two pathological entities. This approach appeared to prolong survival. Here we present the case reports of these four consecutive patients with RMG and discuss the novel use of bevacizumab in this context. Clinical presentation Four patients with RMGs were treated with BNCT at our institutes. Upon the referral for BNCT, they were assessed as belonging to the recursive partitioning analysis (RPA) class 3 (n = 3 patients) or RPA class 4 (n = 1 patient) (the RPA classification for RMG was advocated by Carson et al. in 2007). The estimated median survival times for RPA classes 3 and 4 were 3.8 and 10.8 months, respectively, after some treatment at the recurrence. We applied BNCT for these four patients and administered bevacizumab when the lesions were considered radiation necrosis or symptomatic pseudoprogression. The class 3 patients survived after the BNCT for 14, 16.5 and > 23 months, and the class 4 patient survived > 26 months, with favorable improvements in clinical symptoms. Conclusion BNCT with the addition of bevacizumab for radiation necrosis or symptomatic pseudoprogression improved the clinical symptoms and prolonged the survival in RMG patients. PMID:24387301

Biological activity of N(4)-boronated derivatives of 2'-deoxycytidine, potential agents for boron-neutron capture therapy.

PubMed

Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

2015-10-01

Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system. Copyright © 2015 Elsevier Ltd. All rights reserved.

A critical assessment of boron target compounds for boron neutron capture therapy.

PubMed

Hawthorne, M Frederick; Lee, Mark W

2003-01-01

Boron neutron capture therapy (BNCT) has undergone dramatic developments since its inception by Locher in 1936 and the development of nuclear energy during World War II. The ensuing Cold War spawned the entirely new field of polyhedral borane chemistry, rapid advances in nuclear reactor technology and a corresponding increase in the number to reactors potentially available for BNCT. This effort has been largely oriented toward the eradication of glioblastoma multiforme (GBM) and melanoma with reduced interest in other types of malignancies. The design and synthesis of boron-10 target compounds needed for BNCT was not channeled to those types of compounds specifically required for GBM or melanoma. Consequently, a number of potentially useful boron agents are known which have not been biologically evaluated beyond a cursory examination and only three boron-10 enriched target species are approved for human use following their Investigational New Drug classification by the US Food and Drug Administration; BSH, BPA and GB-10. All ongoing clinical trials with GBM and melanoma are necessarily conducted with one of these three species and most often with BPA. The further development of BNCT is presently stalled by the absence of strong support for advanced compound evaluation and compound discovery driven by recent advances in biology and chemistry. A rigorous demonstration of BNCT efficacy surpassing that of currently available protocols has yet to be achieved. This article discusses the past history of compound development, contemporary problems such as compound classification and those problems which impede future advances. The latter include means for biological evaluation of new (and existing) boron target candidates at all stages of their development and the large-scale synthesis of boron target species for clinical trials and beyond. The future of BNCT is bright if latitude is given to the choice of clinical disease to be treated and if a recognized study

Clinical outcome in dogs with nasal tumors treated with intensity-modulated radiation therapy.

PubMed

Hunley, David W; Mauldin, G Neal; Shiomitsu, Keijiro; Mauldin, Glenna E

2010-03-01

Intensity-modulated radiation therapy (IMRT) is a valuable tool in human radiation oncology, but information on its use in veterinary medicine is lacking. In this study, 12 dogs with nasal tumors were treated with IMRT at a median radiation dose of 54 Gy. Patient survival times and frequency and severity of side effects on ocular structures, oral mucosa, and skin were recorded. Eight dogs (67%) had resolution of clinical signs during radiation therapy. Median overall survival time was 446 d with a 50% 1-year and a 25% 2-year survival rate. Minimal grade 2 or 3 acute skin toxicity, no grade 2 or 3 late skin toxicity, and no grade 2 or 3 toxicity to oral mucosa or the eye opposite the tumor were identified in the dogs treated with IMRT in this study. The ipsilateral eye could not be routinely spared due to its proximity to the tumor.

Chelation therapy to treat atherosclerosis, particularly in diabetes: Is it time to reconsider?

PubMed Central

Lamas, Gervasio A; Ergui, Ian

2016-01-01

Summary Reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years. These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. PMID:27149141

Multivariate analysis of prognostic factors for idiopathic sudden sensorineural hearing loss treated with adjuvant hyperbaric oxygen therapy.

PubMed

Xie, Shaobing; Qiang, Qingfen; Mei, Lingyun; He, Chufeng; Feng, Yong; Sun, Hong; Wu, Xuewen

2018-01-01

The objective of this study is to evaluate possible prognostic factors of idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT) using univariate and multivariate analyses. From January 2008 to October 2016, records of 178 ISSNHL patients treated with auxiliary hyperbaric oxygen therapy were reviewed to assess hearing recovery and evaluate associated prognostic factors (gender, age, localization, initial hearing threshold, presence of tinnitus, vertigo, ear fullness, hypertension, diabetes, onset of HBOT, number of HBOT, and audiogram), by using univariate and multivariate analyses. The overall recovery rate was 37.1%, including complete recovery (19.7%) and partial recovery (17.4%). According to multivariate analysis, later onset of HBOT and higher initial hearing threshold were associated with a poor prognosis in ISSNHL patients treated with HBOT. HBOT is a safe and beneficial adjuvant therapy for ISSNHL patients. 20 sessions of HBOT is possibly enough to show its therapeutic effect. Earlier HBOT onset and lower initial hearing threshold is associated with favorable hearing recovery.

Does Proton Therapy Offer Demonstrable Clinical Advantages for Treating Thoracic Tumors?

PubMed

Liao, Zhongxing; Gandhi, Saumil J; Lin, Steven H; Bradley, Jeffrey

2018-04-01

The finite range of proton beams in tissues offers unique dosimetric advantages that theoretically allow dose to the target to be escalated while minimizing exposure of surrounding tissues and thus minimizing radiation-induced toxicity. This theoretical advantage has led to widespread adoption of proton therapy around the world for a wide variety of tumors at different anatomical sites. Many treatment-planning comparisons have shown that proton therapy has substantial dosimetric advantages over conventional radiotherapy. However, given the significant difference in cost for proton vs conventional photon therapy, thorough investigation of the evidence of proton therapy's clinical benefits in terms of toxicity and survival is warranted. Some data from retrospective studies, single-arm prospective studies, and a very few randomized clinical trials comparing these modalities are beginning to emerge. In this review, we examine the available data with regard to proton therapy for thoracic malignancies. We begin by discussing the unique challenges involved in treating moving targets with significant tissue heterogeneity and the technologic efforts underway to overcome these challenges. We then discuss the rationale for minimizing normal tissue toxicity, particularly pulmonary, cardiac, and hematologic toxicity, within the context of previously unsuccessful attempts at dose escalation for lung and esophageal cancer. Finally, we explore strategies for accelerating the development of trials aimed at measuring meaningful clinical endpoints and for maximizing the value of proton therapy by personalizing its use for individual patients. Copyright © 2018 Elsevier Inc. All rights reserved.

MAGIC polymer gel for dosimetric verification in boron neutron capture therapy

PubMed Central

Heikkinen, Sami; Kotiluoto, Petri; Serén, Tom; Seppälä, Tiina; Auterinen, Iiro; Savolainen, Sauli

2007-01-01

Radiation‐sensitive polymer gels are among the most promising three‐dimensional dose verification tools developed to date. We tested the normoxic polymer gel dosimeter known by the acronym MAGIC (methacrylic and ascorbic acid in gelatin initiated by copper) to evaluate its use in boron neutron capture therapy (BNCT) dosimetry. We irradiated a large cylindrical gel phantom (diameter: 10 cm; length: 20 cm) in the epithermal neutron beam of the Finnish BNCT facility at the FiR 1 nuclear reactor. Neutron irradiation was simulated with a Monte Carlo radiation transport code MCNP. To compare dose–response, gel samples from the same production batch were also irradiated with 6 MV photons from a medical linear accelerator. Irradiated gel phantoms then underwent magnetic resonance imaging to determine their R2 relaxation rate maps. The measured and normalized dose distribution in the epithermal neutron beam was compared with the dose distribution calculated by computer simulation. The results support the feasibility of using MAGIC gel in BNCT dosimetry. PACS numbers: 87.53.Qc, 87.53.Wz, 87.66.Ff PMID:17592463

Cognitive Behavioural Therapy for Insomnia (CBT-I) to treat depression: A systematic review.

PubMed

Cunningham, Jasmyn E A; Shapiro, Colin M

2018-03-01

Major depressive disorder is one of the most commonly diagnosed psychiatric illnesses, and it has a profound negative impact on an individual's ability to function. Up to 90% of individuals suffering from depression also report sleep and circadian disruptions. If these disruptions are not effectively resolved over the course of treatment, the likelihood of relapse into depression is greatly increased. Cognitive Behavioural Therapy for Insomnia (CBT-I) has shown promise in treating these sleep and circadian disturbances associated with depression, and may be effective as a stand-alone treatment for depression. This may be particularly relevant in cases where antidepressant medications are not ideal (e.g. due to contraindications, cost, or treatment resistance). A systematic literature review was conducted of trials investigating the use of CBT-I to treat depression in adults. Therapy included in-person CBT-I, as well as telehealth and group CBT-I. CBT-I presents a promising treatment for depression comorbid with insomnia. In-person therapy has the most supporting evidence for its efficacy, though treatment effects may not be additive with those of antidepressant medications. Insomnia improvement due to CBT-I may mediate the improvement in depressive symptoms. There is less evidence for the use of telehealth, though a stepped-care approach is indicated based on baseline depressive severity. More research on group therapy and telehealth modalities of delivering CBT-I are required before making recommendations. Copyright © 2018 Elsevier Inc. All rights reserved.

Construction of a model for predicting creatinine clearance in Japanese patients treated with Cisplatin therapy.

PubMed

Yajima, Airi; Uesawa, Yoshihiro; Ogawa, Chiaki; Yatabe, Megumi; Kondo, Naoki; Saito, Shinichiro; Suzuki, Yoshihiko; Atsuda, Kouichiro; Kagaya, Hajime

2015-05-01

There exist various useful predictive models, such as the Cockcroft-Gault model, for estimating creatinine clearance (CLcr). However, the prediction of renal function is difficult in patients with cancer treated with cisplatin. Therefore, we attempted to construct a new model for predicting CLcr in such patients. Japanese patients with head and neck cancer who had received cisplatin-based chemotherapy were used as subjects. A multiple regression equation was constructed as a model for predicting CLcr values based on background and laboratory data. A model for predicting CLcr, which included body surface area, serum creatinine and albumin, was constructed. The model exhibited good performance prior to cisplatin therapy. In addition, it performed better than previously reported models after cisplatin therapy. The predictive model constructed in the present study displayed excellent potential and was useful for estimating the renal function of patients treated with cisplatin therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The TOPSHOCK study: Effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial

PubMed Central

2011-01-01

Background Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. Methods/design The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. Discussion The TOPSHOCK study is the

Local oxygen therapy for treating acute necrotizing periodontal disease in smokers.

PubMed

Gaggl, Alexander J; Rainer, Heribert; Grund, Eveline; Chiari, Friedrich M

2006-01-01

The main aim of treatment for acute necrotizing periodontal disease is fast and effective reduction of anaerobic destructive microorganisms to avoid periodontal damage. The effect of adjunctive local oxygen therapy in the treatment of necrotizing periodontal disease was examined in this study. Thirty patients with acute necrotizing periodontal disease were treated with the systemic antibiotics amoxicillin, clavulanic acid, and metronidazole. In 15 out of 30 patients, adjunctive local oxygen therapy was administered. The patients were followed from the first to 10th day of treatment with clinical and bacteriological examinations. The clinical examination registered gingival bleeding, periodontal probing depth, and attachment loss; to follow up microbiological colonization of the periodontal sulcus, five representative bacteria were registered by a semiquantitative DNA polymerase chain reaction test. In both groups of patients, colonization with Prevotella intermedia, Tannerella forsythensis, and Treponema denticola was initially positive. None of these three microorganisms were completely eradicated in any of the patients in the group without oxygen therapy within the first 10 days of treatment. In the group with adjunctive oxygen therapy, all patients either showed a reduction in or complete eradication of the microorganisms, resulting in more rapid clinical restitution with less periodontal destruction. Adjunctive oxygen therapy results in early eradication of pathogenic anaerobic microorganisms in cases of acute necrotizing periodontal disease. The damage to periodontal tissue is reduced.

Evaluation of patients with hepatic portal venous gas who can be treated with conservative therapy.

PubMed

Higashi, Takaaki; Hayashi, Hiromitsu; Takeyama, Hideaki; Arima, Kota; Taki, Katsunobu; Takamori, Hiroshi; Baba, Hideo

2016-01-01

Hepatic portal venous gas is an indication for emergency surgery and reportedly has a high mortality rate. However, these days, cases of hepatic portal venous gas associated with milder disease are increasing. In this report, we compared two groups to investigate whether there were any objective indicators for selecting conservative therapy. From July 2007 to August 2011, 19 patients with hepatic portal venous gas were evaluated at our hospital. The condition was diagnosed by computed tomography imaging. Vital signs, laboratory test results, and physical examination findings were compared. The A group included 12 patients who could be treated with conservative therapy. The B group included 7 patients who could not be treated with conservative therapy. The combined mortality rate was 31.5% (6/19 patients). There was a significant difference in the pulse rate and shock index. In the A group, none of the patients had signs of peritoneal irritation. However, in the B group, physical examination revealed signs of peritoneal irritation in all patients. Conservative therapy may be possible in patients with hepatic portal venous gas, depending on the cause. Evaluation of vital signs and serial changes on physical examination are important.

Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

PubMed

Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

2014-03-01

New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were investigated in tumor-bearing mice. The time to maximum accumulation of compound 13 in tumor tissue was one-fourth of that of compound 9, and compound 13 showed rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 13 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 13. Tumor growth was significantly inhibited by PDT using 13. These results suggested that 13 might be a good candidate for both PDT and BNCT of cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical outcome in dogs with nasal tumors treated with intensity-modulated radiation therapy

PubMed Central

Hunley, David W.; Mauldin, G. Neal; Shiomitsu, Keijiro; Mauldin, Glenna E.

2010-01-01

Intensity-modulated radiation therapy (IMRT) is a valuable tool in human radiation oncology, but information on its use in veterinary medicine is lacking. In this study, 12 dogs with nasal tumors were treated with IMRT at a median radiation dose of 54 Gy. Patient survival times and frequency and severity of side effects on ocular structures, oral mucosa, and skin were recorded. Eight dogs (67%) had resolution of clinical signs during radiation therapy. Median overall survival time was 446 d with a 50% 1-year and a 25% 2-year survival rate. Minimal grade 2 or 3 acute skin toxicity, no grade 2 or 3 late skin toxicity, and no grade 2 or 3 toxicity to oral mucosa or the eye opposite the tumor were identified in the dogs treated with IMRT in this study. The ipsilateral eye could not be routinely spared due to its proximity to the tumor. PMID:20514254

The basics of cell therapy to treat cardiovascular disease: one cell does not fit all.

PubMed

Taylor, Doris A; Robertson, Matthew J

2009-09-01

Cardiovascular disease represents a continuum of disease entities whose medical treatments differ. Cell therapy is a 21st century approach to treating cardiovascular disease and is being applied worldwide. However, no concerted approach exists for defining the best cell population(s) to use, or the best treatment conditions. It is naïve to believe that a single treatment -even a stem cell- can be found to treat the entire spectrum of cardiovascular disease. We describe the continuum of ischemic heart disease, the potential uses of cells for treating this continuum, and the basic issues that must be considered when contemplating cardiovascular cell therapy. The clinical goal is cardiac and vascular regeneration. Whether cells can deliver this remains to be determined. The correct cell, the ideal therapeutic window, and the patient likewise are open to debate. This article is designed to provide insights into the early, middle, and later stages of cardiovascular disease and how cells might be used differently for treatment at each stage.

Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

PubMed

Xiong, Hejian; Wei, Xing; Zhou, Dongfang; Qi, Yanxin; Xie, Zhigang; Chen, Xuesi; Jing, Xiabin; Huang, Yubin

2016-09-21

Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT.

Experiments to increase the parameters of the vacuum insulation tandem accelerator for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Kasatov, D. A.; Kolesnikov, J. A.; Koshkarev, A. M.; Kuznetsov, A. S.; Makarov, A. N.; Sokolova, E. O.; Sorokin, I. N.; Sycheva, T. V.; Taskaev, S. Yu.; Shchudlo, I. M.

2016-12-01

An epithermal neutron source that is based on a vacuum insulation tandem accelerator (VITA) and lithium target was created in the Budker Institute of Nuclear Physics for the development of boron neutron capture therapy (BNCT). A stationary proton beam with 2 MeV energy and 1.6 mA current has been obtained. To carry out BNCT, it is necessary to increase the beam parameters up to 2.3 MeV and 3 mA. Ways to increase the parameters of the proton beam have been proposed and discussed in this paper. The results of the experiments are presented.

Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus.

PubMed

Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

2016-09-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors. Stem cell therapy with assistance of cellular reprogramming and β-cell regeneration can open up new therapeutic modalities. The present review describes the history and current knowledge of T1DM, evolution of cell therapies and different cellular therapies to cure this condition. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Application of an ultraminiature thermal neutron monitor for irradiation field study of accelerator-based neutron capture therapy

PubMed Central

Ishikawa, Masayori; Tanaka, Kenichi; Endo, Satrou; Hoshi, Masaharu

2015-01-01

Abstract Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 105 n/cm2/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources. PMID:25589504

DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.

PubMed

Kondo, Natsuko; Sakurai, Yoshinori; Hirota, Yuki; Tanaka, Hiroki; Watanabe, Tsubasa; Nakagawa, Yosuke; Narabayashi, Masaru; Kinashi, Yuko; Miyatake, Shin-ichi; Hasegawa, Masatoshi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ohnishi, Takeo; Ono, Koji

2016-03-01

Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

Boron Neutron Capture Therapy for HER2+ breast cancers: A feasibility study evaluating BNCT for potential role in breast conservation therapies

NASA Astrophysics Data System (ADS)

Jenkins, Peter Anthony

A novel Boron Neutron Capture Therapy (BNCT) regimen for the treatment of HER2+ breast cancers has been proposed as an alternative to whole breast irradiation for breast conservation therapy patients. The proposed therapy regimen is based on the assumed production of boron delivery agents that would be synthesized from compounds of Trastuzumab (Herceptin ®) and oligomeric phosphate diesters (OPDs). The combination of the anti-HER2 monoclonal antibody and the high boron loading capability of OPDs has led to the assumption that boron could be delivered to the HER2+ cancer cells at Tumor to Healthy Tissue ratios (T:H) of up to 35:1 and boron concentrations above 50 μg/g. This significantly increased boron delivery efficiency has opened new BNCT possibilities. This proof of concept study examined treatment parameters derived as the results in previous efforts in the context of patient-specific geometry and compared calculated dose results to those observed during actual patient therapy. These results were based on dose calculations performed with a set of calculated Kerma coefficients derived from tissues specific to the regions of interest for breast cancer. A comparison was made of the dose to the tumor region, the patient's skin, and the peripheral organs. The results of this study demonstrated that, given the performance of the proposed boron delivery agent, the BNCT treatment regimen is feasible. The feasibility is based on the findings that the equivalent dose could be delivered to the treatment volume with less dose to the skin and peripheral organs. This is anticipated to improve the treatment outcomes by maintaining local control of tumor cells while reducing dose to healthy tissues.

Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

PubMed

Lamas, Gervasio A; Ergui, Ian

2016-08-01

Case reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. We discuss results and future research. Expert commentary: Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. We are seeking participating sites for TACT2.

Impact of attention deficit hyperactivity disorder therapy on fracture risk in children treated in German pediatric practices.

PubMed

Jacob, L; Kostev, K

2017-04-01

Two thousand eight hundred ninety-four children and adolescents treated by 243 pediatricians were analyzed. Patients receiving attention deficit hyperactivity disorder (ADHD) medications were at a lower risk of fractures than patients without ADHD medications. The strongest impact was in the age group of 6-9 years. Finally, there was a significant association between therapy duration and fracture risk. The aim of this study was to analyze the impact of ADHD therapy on fracture risk in children treated by German pediatricians. Children and adolescents initially diagnosed with ADHD and fractures between 2010 and 2015 were identified by 243 pediatricians. In this nested case-control study, each ADHD case with a fracture was matched (1:1) to an ADHD control without a fracture for age, gender, index year, and physician. In total, 2894 individuals were available for analysis. The main outcome of the study was the risk of fracture as a function of ADHD therapy. Multivariate logistic regression models were created to determine the effect of ADHD therapy on the risk of fracture in the entire population and in three age-specific subgroups. Patients receiving ADHD medications were at a lower risk of fracture than patients without ADHD medications (OR = 0.61). The impact of ADHD therapy on the risk of fracture was stronger in the age group of 6-9 years (OR = 0.41) than in the age groups of 10-13 years (OR = 0.68) and 14-17 years (OR = 0.74). Finally, a significant correlation was found between therapy duration and fracture risk (OR = 0.71 per month). ADHD therapy was associated with a decrease in the risk of fracture in children and adolescents treated by German pediatricians.

Electrostatic design and beam transport for a folded tandem electrostatic quadrupole accelerator facility for accelerator-based boron neutron capture therapy.

PubMed

Vento, V Thatar; Bergueiro, J; Cartelli, D; Valda, A A; Kreiner, A J

2011-12-01

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT), we discuss here the electrostatic design of the machine, including the accelerator tubes with electrostatic quadrupoles and the simulations for the transport and acceleration of a high intensity beam. Copyright © 2011 Elsevier Ltd. All rights reserved.

Photodynamic Therapy Effectively Treats Actinic Keratoses Without Pre-Illumination Incubation Time.

PubMed

Gandy, Jessica; Labadie, Brian; Bierman, Dina; Zachary, Christopher

2017-03-01

BACKGROUND: Actinic keratoses (AKs) are dysplastic lesions of the epidermis that have the potential to progress to non-melanoma skin cancers (NMSC). Traditional photodynamic therapy (PDT) requires a pre-illumination incubation time, which adds to overall in-office time and has been linked to pain. Our group has found a novel protocol to effectively treat AKs with PDT that eliminates the pre-illumination incubation period and uses 2 back-to-back cycles of 16 minute 40 seconds.

METHODS: The patient was prepped with soapy water and isopropyl alcohol, and thick AKs were descaled with a curette. Next, 5-aminolevulinic acid (ALA) was applied to the treatment areas and the patient was immediately placed under the blue light for 33 minutes and 20 seconds (two cycles of 16m/40s).

RESULTS: During therapy, the patient reported no pain. At one week, treated areas revealed a good reaction. The procedure was repeated at one month to treat residual AKs. At a 4-month follow-up, the patient's face and scalp showed near clearance of any AKs.

CONCLUSION: During PDT, the photosensitizer aminolevulinic acid (ALA), or in Europe methyl aminolevulinate (MAL), is utilized as a synthetic precursor that preferentially accumulates in dysplastic cells. The precursor then converts to PpIX via the heme pathway and causes apoptosis of the cells when excited, most commonly by either blue-violet (400-430 nm) or red (630-635 nm) light. Shorter incubation times are associated with reduced pain because less PpIX will have accumulated in the treated tissue by the start of the exposure to the light. The doubling of the light exposure time allows comparable levels of the photosensitizing molecule to accumulate and be activated so as to produce an equivalent reaction. The associated reduction in pain along with a more convenient treatment schedule makes this PDT protocol more tolerable and convenient to some patients.

J Drugs Dermatol. 2017;16(3):275-278.

Late recurrence of nonseminomatous germ cell tumor successfully treated with intensity-modulated radiation therapy.

PubMed

Kita, Yuki; Imamura, Masaaki; Mizowaki, Takashi; Norihisa, Yoshiki; Yoshimura, Koji; Hiraoka, Masahiro; Ogawa, Osamu

2013-08-01

We report the case of a 41-year-old man with a late recurrence of nonseminomatous germ cell tumor, which was successfully treated with intensity-modulated radiation therapy. For the residual retrocrural tumor invading the 11th and 12th thoracic vertebrae with an abnormal level of tumor marker (α-fetoprotein: 23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due to its neurotoxicity, and surgery could not be performed due to the location. In this situation, intensity-modulated radiation therapy achieved a complete response of tumor marker. The patient remained in complete clinical remission after 3 years. The efficacy of radiotherapy, especially intensity-modulated radiation therapy, for a nonseminomatous germ cell tumor is discussed.

Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy

PubMed Central

Dewi, Novriana; Higashi, Syushi; Ikushima, Ichiro; Seguchi, Koji; Mizumachi, Ryoji; Murata, Yuji; Morishita, Yasuyuki; Shinohara, Atsuko; Mikado, Shoji; Yasuda, Nakahiro; Fujihara, Mitsuteru; Sakurai, Yuriko; Mouri, Kikue; Yanagawa, Masashi; Iizuka, Tomoya; Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shin-ichiro; Tanaka, Hiroki; Matsukawa, Takehisa; Yokoyama, Kazuhito; Fujino, Takashi; Ogura, Koichi; Nonaka, Yasumasa; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Yui, Sho; Nishimura, Ryohei; Ono, Koji; Takamoto, Sinichi; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Hasumi, Kenichiro; Takahashi, Hiroyuki

2017-01-01

Objective: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. Methods: We prepared the 10BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 1012 n cm−2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. Results: Biodistribution results have revealed that 10B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. Conclusion: Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure. PMID:28406315

An objective assessment of melanin in vitiligo skin treated with Balneo PUVA therapy.

PubMed

Hegyi, V; Petrovajová, M; Novotný, M

2014-02-01

Visual clinical methods of skin color evaluation for diagnostic purposes are so far mostly subjective and thus inaccurate. We present a modified method of melanin amount measurement based on diffuse reflectance spectroscopy (DRS). This method is non-invasive and objective, and allows easy quantification and comparison of melanin levels. Skin pigmentation was measured by DRS method in 0-18 year old patients at the Department of Pediatric Dermatovenerology, School of Medicine Comenius University Bratislava. Patients were treated for their vitiligo by Balneo PUVA treatment twice weekly. Each patient had measured his remittance spectra from the treated vitiliginous skin before the treatment was started, after 10 irradiations of Balneo PUVA and at the end of the treatment after 25 irradiations of Balneo PUVA. In our study as a reference skin for spectroscopic assessment of melanin in vivo was used the averaged remittance spectra (measured on the inner arm) from the sample of 10 albino patients. The remittance spectra obtained from the vitiligo patients were ratioed against the newly described remittance reference albino skin. We exploited the linear behavior of the spectral curve in the 620-720 nm interval (significant for melanin absorption) and used the slope of the regression line to compute the quantification index α. By clinical examination before the Balneo PUVA therapy, after the 10th dose of Balneo PUVA therapy as well as at the end of the complete course of Balneo PUVA therapy (after 25 irradiations) we recorded a marked increase of pigmentation in all treated patients for their vitiligo. In each patient the values of melanin quantification angle α were calculated. Statistically we found a significant difference between the melanin quantification angle α in vitiliginous skin before, during the 10th dose of treatment and after the treatment. Similar significant difference was also observed between treated and non-involved skin. We could confirm a clear

Therapeutic efficacy for hepatocellular carcinoma by boric acid-mediated boron neutron capture therapy in a rat model.

PubMed

Lin, Sy-Yu; Lin, Chen-Jou; Liao, Jiunn-Wang; Peir, Jinn-Jer; Chen, Wei-Lin; Chi, Chin-Wen; Lin, Yung-Chang; Liu, Yu-Ming; Chou, Fong-In

2013-11-01

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model. The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses. HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded. BA-mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT.

Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dagrosa, Maria Alejandra; Thomasz, Lisa M.Sc.; Longhino, Juan

Purpose: To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. Methods and Materials: Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60more » mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10{sup 8} n/cm{sup 2}/sec for 83.4 min. Results: Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm{sup 3} or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p < 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. Conclusions: Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.« less

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

NASA Astrophysics Data System (ADS)

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

2014-11-01

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

Comparison of cost of immune globulin intravenous therapy to conventional immunosuppressive therapy in treating patients with autoimmune mucocutaneous blistering diseases.

PubMed

Daoud, Yassine J; Amin, Ketan G

2006-04-01

Autoimmune mucocutaneous blistering diseases (AMBD) are a group of potentially fatal diseases that affect the skin and mucous membranes. AMBD have different target antigens as well as variable clinical presentation, course, and prognosis. The mainstay of conventional immunosuppressive therapy (CIST) for AMBD is long-term high-dose systemic corticosteroids and immunosuppressive agents. Such therapy has proven effective in many patients; however, in some patients, the disease continues to progress with significant sequelae such as blindness, loss of voice, anal, and vaginal stenosis which causes poor quality of life. Furthermore, the CIST may have some serious side effects including opportunistic infections which may cause death. Immune globulin intravenous (IGIV) therapy has been reportedly used in the management of patients with AMBD refractory to CIST. IGIV has shown to be more clinically beneficial than CIST by bringing about long-term clinical remission and less recurrence. The high cost of the IGIV is of concern to patients, physicians, and insurance companies. In this report, we compare the cost of IGIV to that of CIST in treating a cohort of 15 mucous membrane pemphigoid (MMP), 10 ocular cicatricial pemphigoid (OCP), 15 bullous pemphigoid (BP), and 32 pemphigus vulgaris (PV) patients. In each cohort of patients, CIST had significant side effects, many of which were hazardous and required prolonged and frequent hospitalizations. Some of these side effects were severe enough to require discontinuation of the treatment. We consider the total cost of CIST to be the actual cost of the drug, plus the cost of management of the side effects produced by CIST. In the same patient cohort, no significant side effects to IGIV were observed. None of the IGIV treated patients required physician visits, laboratory tests, or hospitalizations specifically related to IGIV therapy. Hence, the total cost of the IGIV therapy is the actual cost of the IGIV only. The mean total cost

Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study.

PubMed

Kang, Weirong; Svirskis, Darren; Sarojini, Vijayalekshmi; McGregor, Ailsa L; Bevitt, Joseph; Wu, Zimei

2017-05-30

The efficacy of boron neutron capture therapy depends on the selective delivery of 10B to the target. Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. In conclusion, this study has demonstrated the potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron neutron capture therapy for glioblastoma.

Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study

PubMed Central

Kang, Weirong; Svirskis, Darren; Sarojini, Vijayalekshmi; McGregor, Ailsa L.; Bevitt, Joseph; Wu, Zimei

2017-01-01

The efficacy of boron neutron capture therapy depends on the selective delivery of 10B to the target. Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. In conclusion, this study has demonstrated the potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron neutron capture therapy for glioblastoma. PMID:28402271

Survival and selected outcomes of older adults with locally advanced head/neck cancer treated with chemoradiation therapy.

PubMed

Maggiore, Ronald J; Curran, Emily K; Witt, Mary Ellyn; Haraf, Daniel J; Vokes, Everett E; Cohen, Ezra E W

2013-10-01

Chemoradiation therapy (CRT) remains a potentially curative treatment in patients with locally advanced head/neck cancer (LA-HNC). However, survival and other outcomes in older patients with head/neck cancer receiving chemoradiotherapy are not well established. This study was performed to elucidate selected outcomes in this patient population. Retrospective study of LA-HNC patients ≥ 70 years of age who had received 5-fluorouracil-hydoxyurea-based CRT with a minimum of 3 years of follow up after therapy initiation was performed. Pre-treatment patient- and cancer-related characteristics were recorded. Survival data in addition to gastrostomy tube utilization, swallowing function, and hematologic toxicity were captured. Eighty-nine patients treated between 1997 and 2009 were eligible for analysis (median age, 76 years; range, 70-94; male, 61%; ECOG PS, 0-1 43%; stage IVA/B, 71%). 86 were evaluable for survival analysis. 5-year overall and event-free survival were both at 32% with a median follow-up time of 39.2 months. The majority (86.5%) were able to complete all planned treatment cycles. A significant proportion of patients, however, required gastrostomy tube during CRT (62%) and developed aspiration during swallowing evaluation post-treatment (44%). Several patients required hospice (9%) or skilled nursing facility (13%) referrals during treatment. Select older adults with LA-HNC can still experience long-term benefits despite 5-year survival rates lower than those historically reported in younger patients undergoing identical CRT regimens although potentially at higher risk for acute toxicities. Assessment and selection of those who can tolerate more intense combined-modality strategies and their long-term outcomes merit further larger, prospective studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis and biological evaluation of new BSH-conjugated chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

PubMed

Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

2014-11-01

New disodium mercaptoundecahydro-closo-dodecaborate (BSH)-conjugated chlorin derivatives 11, 12, 16 and 20 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized. The in vivo biodistribution and clearance of 11, 12, 16 and 20 were investigated in tumor-bearing mice. Compounds 12 and 16 showed good tumor-selective accumulation among the four derivatives. The time to maximum accumulation of compound 16 in tumor tissue was one-fourth of that of compound 12, and clearance from normal tissues of compound 16 was similar to that of compound 12. The in vivo therapeutic efficacy of PDT using 16, which has twice as many boron atoms as 12, was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 6h after injection of 16. Tumor growth was significantly inhibited by PDT using 16. These results suggested that 16 is a good candidate for both PDT and BNCT of cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

PubMed

Bussmann, Hermann; Wester, C William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G

2006-02-01

Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care.

Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

PubMed Central

Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.

2006-01-01

Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730

Spa therapy and balneotherapy for treating low back pain: meta-analysis of randomized trials.

PubMed

Pittler, M H; Karagülle, M Z; Karagülle, M; Ernst, E

2006-07-01

Low back pain is a major public health concern and complementary treatments are frequently used for this condition. The objective of this systematic review and meta-analysis was to assess the evidence for or against the effectiveness of spa therapy and balneotherapy for treating low back pain. Systematic searches were conducted on Medline, Embase, Amed Cochrane Central, the UK National Research Register and ClincalTrials.gov (all until July 2005). Hand searches were performed and experts contacted. Methodological quality was assessed using a standard scale. Five randomized clinical trials met all inclusion criteria. Quantitative data synthesis was performed. The data for spa therapy, assessed on a 100 mm visual analogue scale (VAS), suggest significant beneficial effects compared with waiting list control groups (weighted mean difference 26.6 mm, 95% confidence interval 20.4-32.8, n=442) for patients with chronic low back pain. For balneotherapy the data, assessed on a 100 mm VAS, also suggest beneficial effects compared with control groups (weighted mean difference 18.8 mm, 95% confidence interval 10.3-27.3, n=138). Even though the data are scarce, there is encouraging evidence suggesting that spa therapy and balneotherapy may be effective for treating patients with low back pain. These data are not compelling but warrant rigorous large-scale trials.

Carcinoma of penis. Review of cases treated by surgery and radiation therapy 1960-1977

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krieg, R.M.; Luk, K.H.

1981-08-01

Cases of squamous cell carcinoma of the penis treated by surgery and radiation therapy at Moffitt Hospital, University of California, and Mount Zion Hospital and Medical Center are reviewed. Only cases followed for more than three years or with autopsy findings are presented. For the primary lesion, over-all surgical control rate locally was 15/17 or 88 per cent. Over-all control rate with radiation therapy alone was 9/12 (75 per cent), and with surgical salvage 11/12 (92 per cent). Radiation therapy appears to be the treatment of choice for early stage lesions, reserving surgery for salvage. Prophylactic ilioinguinal lymph node dissectionmore » for N0 lesions is not warranted. The role of chemotherapy needs further investigation.« less

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

PubMed Central

Barth, Rolf F.; Miyatake, Shin-Ichi; Kawabata, Shinji; Suzuki, Minoru; Ono, Koji

2017-01-01

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients’ tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event. PMID:28534152

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma.

PubMed

Kondo, Natsuko; Barth, Rolf F; Miyatake, Shin-Ichi; Kawabata, Shinji; Suzuki, Minoru; Ono, Koji; Lehman, Norman L

2017-05-01

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1 R132H , were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1 R132H -positive and 1 control IDH1 R132H -negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients' tumors were IDH1 R132H -negative small cell GBMs. The remaining patients had tumors consisting of other IDH1 R132H -negative GBM variants, an IDH1 R132H -positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1 R132H -negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

"Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Santa Cruz, Gustavo A; Trivillin, Verónica A; Schwint, Amanda E

2011-04-01

In the present study the therapeutic effect and potential toxicity of the novel "Sequential" boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential" BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential" BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ± 2% and 91 ± 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ± 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ± 12% and 60 ± 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential" BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue. © 2011 by Radiation Research Society

Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases.

PubMed

Miyatake, Shin-Ichi; Furuse, Motomasa; Kawabata, Shinji; Maruyama, Takashi; Kumabe, Toshihiro; Kuroiwa, Toshihiko; Ono, Koji

2013-06-01

Bevacizumab, an anti-vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas. Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression. The first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT. Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas.

Clinical trials of boron neutron capture therapy [in humans] [at Beth Israel Deaconess Medical Center][at Brookhaven National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallace, Christine

2001-05-29

Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected from subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports.

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

PubMed

Yokoyama, Yoshihito; Shigeto, Tatsuhiko; Miura, Rie; Kobayashi, Asami; Mizunuma, Makito; Yamauchi, Aisa; Futagami, Masayuki; Mizunuma, Hideki

2016-01-01

The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at the Heidelberg Ion Therapy Center Using the Raster Scanning Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna

2011-12-01

Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed,more » in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.« less

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

PubMed

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra; Haberer, Thomas; Jäkel, Oliver; Münter, Marc W; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2011-12-01

PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility. Copyright © 2011 Elsevier Inc. All rights reserved.

The Effect of Deep Brain Stimulation Therapy on Fear-Related Capture of Attention in Parkinson's Disease and Essential Tremor: A Comparison to Healthy Individuals.

PubMed

Camalier, Corrie R; McHugo, Maureen; Zald, David H; Neimat, Joseph S

2018-01-01

In addition to motor symptoms, Parkinson's disease (PD) involves significant non-motor sequelae, including disruptions in cognitive and emotional processing. Fear recognition appears to be affected both by the course of the disease and by a common interventional therapy, deep brain stimulation of the subthalamic nucleus (STN-DBS). Here, we examined if these effects extend to other aspects of emotional processing, such as attentional capture by negative emotional stimuli. Performance on an emotional attentional blink (EAB) paradigm, a common paradigm used to study emotional capture of attention, was examined in a cohort of individuals with PD, both on and off STN-DBS therapy (n=20). To contrast effects of healthy aging and other movement disorder and DBS targets, we also examined performance in a healthy elderly (n=20) and young (n=18) sample on the same task, and a sample diagnosed with Essential Tremor (ET) undergoing therapeutic deep brain stimulation of the ventral-intermediate nucleus (VIM-DBS, n=18). All four groups showed a robust attentional capture of emotional stimuli, irrespective of aging processes, movement disorder diagnosis, or stimulation. PD patients on average had overall worse performance, but this decrement in performance was not related to the emotional capture of attention. PD patients exhibited a robust EAB, indicating that the ability of emotion to direct attention remains intact in PD. Congruent with other recent data, these findings suggest that fear recognition deficits in PD may instead reflect a highly specific problem in recognition, rather than a general deficit in emotional processing of fearful stimuli.

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

PubMed

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

2018-01-01

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

Photodynamic therapy to treat periimplantitis.

PubMed

Bombeccari, Gian Paolo; Guzzi, Gianpaolo; Gualini, Federico; Gualini, Sara; Santoro, Franco; Spadari, Francesco

2013-12-01

: Periimplantitis is a bacterial complication after dental implants implantation. Photodynamic therapy (PDT) implies the use of low-power laser in combination with appropriate photosensitizer to increase the detoxification of the implant surfaces. Little information exists about PDT in the treatment of periimplantitis. A randomized comparative case-control study has been conducted with 20 patients and 20 controls to compare the efficacy of antimicrobial PDT versus surgical therapy in patients with periimplantitis, who have received dental implants with rough surfaces. In the surgery group, mucoperiosteal flap surgery was used with scaling on implant surfaces and debridement of granulation tissue. Microbiologic testing was evaluated before and after intervention treatment, at 12 and 24 weeks in the study subjects. Total anaerobic counts of bacteria did not differ significantly between patients assigned to receive PDT and those assigned to receive surgical therapy (mean, 95.2% and 80.85%, respectively). PDT was associated with a significant decrease in bleeding scores (P = 0.02) as well as inflammatory exudation (P = 0.001). Treatment with PDT in patients with periimplantitis was not associated with major reduction of total anaerobic bacteria on the rough surfaces of dental implants as compared with surgical therapy. A significantly lower proinflammatory index of periimplantitis was observed in the PDT group at 24 weeks of follow-up.

Cotard's syndrome with schizophreniform disorder can be successfully treated with electroconvulsive therapy: case report

PubMed Central

Caliyurt, Okan; Vardar, Erdal; Tuglu, Cengiz

2004-01-01

We report a case of Cotard's syndrome associated with psychotic symptoms. A 27-year-old man was admitted to hospital with the diagnosis of schizophreniform disorder. His presenting symptoms, which had started 1 month before hospital admission, were somatic delusions of gastrointestinal and cardiovascular malfunction and the absence of a stomach, which resulted in a decrease in weight from 75 kg to 63 kg in 1 month. Cranial computed tomographic images showed dilatation of the lateral and third ventricles, whereas magnetic resonance imaging revealed central atrophy and lateral ventricle dilatation. Single- photon emission computed tomography demonstrated left temporal, left frontal and left parietal hypoperfusion. The patient did not respond to antipsychotic therapies, but he was successfully treated with electroconvulsive therapy. This report emphasizes that Cotard's syndrome may be accompanied by lesions of the left hemisphere and that electroconvulsive therapy could be the first-line therapy in such patients with psychotic disorder. PMID:15069468

Spinal interleukin-10 therapy to treat peripheral neuropathic pain.

PubMed

Milligan, Erin D; Penzkover, Kathryn R; Soderquist, Ryan G; Mahoney, Melissa J

2012-01-01

  Current research indicates that chronic peripheral neuropathic pain includes a role for glia and the actions of proinflammatory factors. This review briefly discusses the glial and cytokine responses that occur following peripheral nerve damage in support of utilizing anti-inflammatory cytokine interleukin-10 (IL-10) therapy to suppress chronic peripheral neuropathic pain. SPINAL NONVIRAL INTERLEUKIN-10 GENE THERAPY:  IL-10 is one of the most powerful endogenous counter-regulators of proinflammatory cytokine function that acts in the nervous system. Subarachnoid (intrathecal) spinal injection of the gene encoding IL-10 delivered by nonviral vectors has several advantages over virally mediated gene transfer methods and leads to profound pain relief in several animal models. NONVIRAL GENE DELIVERY:  Lastly, data are reviewed that nonviral deoxyribonucleic acid (DNA) encapsulated by a biologically safe copolymer, poly(lactic-co-glycolic) acid (PLGA), thought to protect DNA, leads to significantly improved therapeutic gene transfer in animal models, which additionally and significantly extends pain relief.   The impact of these early studies exploring anti-inflammatory genes emphasizes the exceptional therapeutic potential of new biocompatible intrathecal nonviral gene delivery approaches such as PLGA microparticles. Ultimately, ongoing expression of therapeutic genes is a viable option to treat chronic neuropathic pain in the clinic. © 2012 International Neuromodulation Society.

A Feedback Control Model of Comprehensive Therapy for Treating Immunogenic Tumours

NASA Astrophysics Data System (ADS)

Tang, Biao; Xiao, Yanni; Tang, Sanyi; Cheke, Robert A.

Surgery is the traditional method for treating cancers, but it often fails to cure patients for complex reasons so new therapeutic approaches that include both surgery and immunotherapy have recently been proposed. These have been shown to be effective, clinically, in inhibiting cancer cells while allowing retention of immunologic memory. This comprehensive strategy is guided by whether a population of tumour cells has or has not exceeded a threshold density. Conditions for successful control of tumours in an immune tumour system were modeled and the related dynamics were addressed. A mathematical model with state-dependent impulsive interventions is formulated to describe combinations of surgery with immunotherapy. By analyzing the properties of the Poincaré map, we examine the global dynamics of the immune tumour system with state-dependent feedback control, including the existence and stability of the semi-trivial order-1 periodic solution and the positive order-k periodic solution. The main results showed that surgery alone can only control the tumour size below a certain level while there is no immunologic memory. If comprehensive therapy involving combining surgery with immunotherapy is considered, then not only can the cancers be controlled below a certain level, but the immune system can also retain its activity. The existence of positive order-k periodic solutions implies that periodical therapy is needed to control the cancers. However, choosing the treatment frequency and the strength of the therapy remains challenging, and hence a strategy of individual-based therapy is suggested.

GPU-based prompt gamma ray imaging from boron neutron capture therapy.

PubMed

Yoon, Do-Kun; Jung, Joo-Young; Jo Hong, Key; Sil Lee, Keum; Suk Suh, Tae

2015-01-01

The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU). Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray image reconstruction using the GPU computation for BNCT simulations.

A Case of Refractory Pulmonary Coccidioidomycosis Successfully Treated with Posaconazole Therapy

PubMed Central

Patel, RH; Pandya, S; Nanjappa, S; Greene, JN

2018-01-01

Coccidioidomycosis is an endemic fungal infection caused by the inhalation of the spores of Coccidioides species. Patients with underlying immunosuppressive illness can contract chronic or disseminated disease which requires prolonged systemic therapy. Pulmonary coccidioidomycosis remains as an illusory and abstruse disease, with increased prevalence that poses as a challenge for clinicians in developing an effective strategy for treatment. Here, we report successful treatment of a refractory case of chronic relapsing pulmonary coccidioidomycosis in a 50-year old woman with a thin-walled cavitary lung lesion who was ultimately treated with posaconazole.

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

PubMed

Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

2012-02-07

Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

Study on High Speed Lithium Jet For Neutron Source of Boron Neutron Capture Therapy (BNCT)

NASA Astrophysics Data System (ADS)

Takahashi, Minoru; Kobayashi, Tooru; Zhang, Mingguang; Mák, Michael; Štefanica, Jirí; Dostál, Václav; Zhao, Wei

The feasibility study of a liquid lithium type proton beam target was performed for the neutron source of the boron neutron capture therapy (BNCT). As the candidates of the liquid lithium target, a thin sheet jet and a thin film flow on a concave wall were chosen, and a lithium flow experiment was conducted to investigate the hydrodynamic stability of the targets. The surfaces of the jets and film flows with a thickness of 0.5 mm and a width of 50 mm were observed by means of photography. It has been found that a stable sheet jet and a stable film flow on a concave wall can be formed up to certain velocities by using a straight nozzle and a curved nozzle with the concave wall, respectively.

Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis.

PubMed

Cangiano, B; Cacciatore, C; Persani, L; Bonomi, M

2017-01-01

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal

Successful treatment of capture myopathy in three wild greater sandhill cranes (Grus canadensis tabida).

PubMed

Businga, Nancy K; Langenberg, Julie; Carlson, LaVinda

2007-12-01

Two adult and 1 juvenile free-flying greater sandhill cranes (Grus canadensis tabida) were diagnosed with capture myopathy after alpha-chloralose baiting and physical capture during a banding and feeding ecologic study. Blood samples were collected for serum biochemical analysis at the time of capture for the 2 adults, and at 24 hours postcapture, at various intervals during treatment, and at the time of release for all 3 birds. Concentrations of creatine kinase, aspartate transaminase, and lactate dehydrogenase were high within 1 hour of capture and peaked approximately 3 days after capture. By days 10-17 after capture, creatine kinase and lactate dehydrogenase concentrations both decreased to within the reference range measured for cranes at capture, but aspartate transaminase concentrations remained 2-5 times higher than the measured reference range. Treatment consisted of corticosteroids, selenium/vitamin E, parenteral fluids, and gavage feedings. Physical therapy consisted of assisting the cranes to stand and walk 2-8 times a day, massaging leg muscles, and moving limbs manually through the range of motion. The adults were released when they were able to stand up independently and were pacing in the pen. The juvenile was released 12 hours after it was able to stand independently but was returned to the pen when it fell and could not rise. It was treated supportively for an additional 3 days and then successfully released. Both adult cranes were observed on their territories with their original mates after release and returned to their territories for the subsequent 8 years, raising chicks most years. After release, the juvenile was observed in a flock of cranes near its natal territory for the next 2 days.

A Pilot Study to Test the Efficacy of Psychologically Based Physical Therapy Training for Treating Deployed U.S. Sailors and Marines with Musculoskeletal Injuries

DTIC Science & Technology

2017-10-01

Department of Population Health , NYU Langone Medical Center, New York, NY. ****Department of Physical Therapy, Naval Medical Center Portsmouth...AWARD NUMBER: W81XWH-14-2-0146 TITLE: A Pilot Study to Test the Efficacy of Psychologically Based Physical Therapy Training for Treating...Test the Efficacy of Psychologically Based Physical Therapy Training for Treating Deployed U.S. Sailors and Marines with Musculoskeletal Injuries 5b

Non-convulsive status epilepticus in a patient with carbon-monoxide poisoning treated with hyperbaric oxygen therapy.

PubMed

Marziali, Simone; Di Giuliano, Francesca; Picchi, Eliseo; Natoli, Silvia; Leonardis, Carlo; Leonardis, Francesca; Garaci, Francesco; Floris, Roberto

2016-12-01

The presentation of carbon monoxide poisoning is non-specific and highly variable. Hyperbaric oxygen therapy is used for the treatment of this condition. Various reports show the occurrence of self-limiting seizures after carbon monoxide poisoning and as a consequence of hyperbaric oxygen therapy. Contrary to the seizures, status epilepticus has been rarely observed in these conditions. The exact pathophysiology underlying seizures and status epilepticus associated with carbon monoxide poisoning and hyperbaric oxygen therapy is not really clear, and some elements appear to be common to both conditions. We describe a case of non-convulsive status epilepticus in a patient with carbon monoxide poisoning treated with hyperbaric oxygen therapy. The mechanism, MRI findings and implications are discussed. © The Author(s) 2016.

“Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ana J. Molinari; Emiliano C. C. Pozzi; Andrea Monti Hughes

In the present study we evaluated the therapeutic effect and/or potential radiotoxicity of the novel “Tandem” Boron Neutron Capture Therapy (T-BNCT) for the treatment of oral cancer in the hamster cheek pouch model at RA-3 Nuclear Reactor. Two groups of animals were treated with “Tandem BNCT”, i.e. BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (T-24h-BNCT) or 48 h (T-48h-BNCT) later. A total tumor dose-matched single application of BNCT mediated by BPA and GB-10 administered jointly [(BPA + GB-10)-BNCT] was administered to an additional group of animals. At 28 days post-treatment, T-24h-BNCTmore » and T-48h-BNCT induced, respectively, overall tumor control (OTC) of 95% and 91%, with no statistically significant differences between protocols. Tumor response for the single application of (BPA + GB-10)-BNCT was 75%, significantly lower than for T-BNCT. The T-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47% and 60% of the animals respectively. No normal tissue radiotoxicity was associated to tumor control for any of the protocols. “Tandem” BNCT enhances tumor control in oral cancer and reduces or, at worst, does not increase, mucositis in dose-limiting precancerous tissue.« less

Subcellular SIMS imaging of gadolinium isotopes in human glioblastoma cells treated with a gadolinium containing MRI agent

NASA Astrophysics Data System (ADS)

Smith, Duane R.; Lorey, Daniel R.; Chandra, Subhash

2004-06-01

Neutron capture therapy is an experimental binary radiotherapeutic modality for the treatment of brain tumors such as glioblastoma multiforme. Recently, neutron capture therapy with gadolinium-157 has gained attention, and techniques for studying the subcellular distribution of gadolinium-157 are needed. In this preliminary study, we have been able to image the subcellular distribution of gadolinium-157, as well as the other six naturally abundant isotopes of gadolinium, with SIMS ion microscopy. T98G human glioblastoma cells were treated for 24 h with 25 mg/ml of the metal ion complex diethylenetriaminepentaacetic acid Gd(III) dihydrogen salt hydrate (Gd-DTPA). Gd-DTPA is a contrast enhancing agent used for MRI of brain tumors, blood-brain barrier impairment, diseases of the central nervous system, etc. A highly heterogeneous subcellular distribution was observed for gadolinium-157. The nuclei in each cell were distinctly lower in gadolinium-157 than in the cytoplasm. Even within the cytoplasm the gadolinium-157 was heterogeneously distributed. The other six naturally abundant isotopes of gadolinium were imaged from the same cells and exhibited a subcellular distribution consistent with that observed for gadolinium-157. These observations indicate that SIMS ion microscopy may be a viable approach for subcellular studies of gadolinium containing neutron capture therapy drugs and may even play a major role in the development and validation of new gadolinium contrast enhancing agents for diagnostic MRI applications.

Men Who Have Sex With Men in Peru: Acceptability of Medication-Assisted Therapy for Treating Alcohol Use Disorders.

PubMed

Brown, Shan-Estelle; Vagenas, Panagiotis; Konda, Kelika A; Clark, Jesse L; Lama, Javier R; Gonzales, Pedro; Sanchez, Jorge; Duerr, Ann C; Altice, Frederick L

2017-07-01

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs and improve antiretroviral therapy (ART) adherence among MSM/TGW in Peru. Three focus groups involving HIV-infected or HIV-uninfected MSM/TGW ( n = 26) with AUDs (AUDIT ≥ 8) were transcribed, translated from Spanish into English, and analyzed using thematic content analysis. Despite having an AUD, participants considered themselves "social" drinkers, minimized their drinking behaviors, and differed about whether or not alcohol problems could be treated. Participants expressed skepticism about medication for treating AUDs. Three concepts emerged as necessary components of a treatment program for alcohol problems: cost, family support, and the potential to drink less alcohol without attaining total abstinence. This study reveals important areas of education to increase potential acceptability of a medication for treating AUDs among MSM/TGW. Given the social conditions and knowledge base of the participants, medication-assisted therapies using naltrexone may be a beneficial strategy for MSM with AUDs.

A theoretical model for the production of Ac-225 for cancer therapy by neutron capture transmutation of Ra-226.

PubMed

Melville, G; Melville, P

2013-02-01

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation by bombarding Ra-226 with high-energy neutrons from a neutron source to produce Ra-225 and hence Ac-225, which can be used as a generator to produce Bi-213 for use in 'Targeted Alpha Therapy' for cancer. This paper examines the possibility of producing Ac-225 by neutron capture using a theoretical model in which neutron energy is convoluted with the corresponding neutron cross sections of Ra-226. The total integrated yield can then be obtained. This study shows that an intense beam of high-energy neutrons could initiate neutron capture on Ra-226 to produce Ra-225 and hence practical amounts of Ac-225 and a useful reduction of Ra-226. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Project of Boron Neutron Capture Therapy System based on a Proton Linac Neutron Source

NASA Astrophysics Data System (ADS)

Kiyanagi, Yoshikai; Asano, Kenji; Arakawa, Akihiro; Fukuchi, Shin; Hiraga, Fujio; Kimura, Kenju; Kobayashi, Hitoshi; Kubota, Michio; Kumada, Hiroaki; Matsumoto, Hiroshi; Matsumoto, Akira; Sakae, Takeji; Saitoh, Kimiaki; Shibata, Tokushi; Yoshioka, Masakazu

At present, the clinical trials of Boron Neutron Capture Therapy (BNCT) are being performed at research reactor facilities. However, an accelerator based BNCT has a merit that it can be built in a hospital. So, we just launched a development project for the BNCT based on an accelerator in order to establish and to spread the BNCT as an effective therapy in the near future. In the project, a compact proton linac installed in a hospital will be applied as a neutron source, and energy of the proton beam is planned to be less than about 10 MeV to reduce the radioactivity. The BNCT requires epithermal neutron beam with an intensity of around 1x109 (n/cm2/sec) to deliver the therapeutic dose to a deeper region in a body and to complete the irradiation within an hour. From this condition, the current of the proton beam required is estimated to be a few mA on average. Enormous heat deposition in the target is a big issue. We are aiming at total optimization of the accelerator based BNCT from the linac to the irradiation position. Here, the outline of the project is introduced and the moderator design is presented.

Molecular Medicine: Synthesis and In Vivo Detection of Agents for use in Boron Neutron Capture Therapy. Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabalka, G. W.

2005-06-28

The primary objective of the project was the development of in vivo methods for the detection and evaluation of tumors in humans. The project was focused on utilizing positron emission tomography (PET) to monitor the distribution and pharamacokinetics of a current boron neutron capture therapy (BNCT) agent, p-boronophenylalanine (BPA) by labeling it with a fluorine-18, a positron emitting isotope. The PET data was then used to develop enhanced treatment planning protocols. The study also involved the synthesis of new tumor selective BNCTagents that could be labeled with radioactive nuclides for the in vivo detection of boron.

Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

PubMed Central

Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

2016-01-01

Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT. PMID:27759052

Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

2016-10-01

Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT.

Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

DOEpatents

Yoon, W.Y.; Jones, J.L.; Nigg, D.W.; Harker, Y.D.

1999-05-11

A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0{times}10{sup 9} neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use. 3 figs.

Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

DOEpatents

Yoon, Woo Y.; Jones, James L.; Nigg, David W.; Harker, Yale D.

1999-01-01

A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0.times.10.sup.9 neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use.

Acupuncture in Treating Dry Mouth Caused By Radiation Therapy in Patients With Head and Neck Cancer | Division of Cancer Prevention

Cancer.gov

RATIONALE: Acupuncture may help relieve dry mouth caused by radiation therapy. PURPOSE: This randomized phase III trial is studying to see how well one set of acupuncture points work in comparison to a different set of acupuncture points or standard therapy in treating dry mouth caused by radiation therapy in patients with head and neck cancer. |

Advances in boron neutron capture therapy (BNCT) at kyoto university - From reactor-based BNCT to accelerator-based BNCT

NASA Astrophysics Data System (ADS)

Sakurai, Yoshinori; Tanaka, Hiroki; Takata, Takushi; Fujimoto, Nozomi; Suzuki, Minoru; Masunaga, Shinichiro; Kinashi, Yuko; Kondo, Natsuko; Narabayashi, Masaru; Nakagawa, Yosuke; Watanabe, Tsubasa; Ono, Koji; Maruhashi, Akira

2015-07-01

At the Kyoto University Research Reactor Institute (KURRI), a clinical study of boron neutron capture therapy (BNCT) using a neutron irradiation facility installed at the research nuclear reactor has been regularly performed since February 1990. As of November 2014, 510 clinical irradiations were carried out using the reactor-based system. The world's first accelerator-based neutron irradiation system for BNCT clinical irradiation was completed at this institute in early 2009, and the clinical trial using this system was started in 2012. A shift of BCNT from special particle therapy to a general one is now in progress. To promote and support this shift, improvements to the irradiation system, as well as its preparation, and improvements in the physical engineering and the medical physics processes, such as dosimetry systems and quality assurance programs, must be considered. The recent advances in BNCT at KURRI are reported here with a focus on physical engineering and medical physics topics.

Treating Internet Addiction with Cognitive-Behavioral Therapy: A Thematic Analysis of the Experiences of Therapists

ERIC Educational Resources Information Center

van Rooij, Antonius J.; Zinn, Mieke F.; Schoenmakers, Tim M.; van de Mheen, Dike

2012-01-01

In 2009, one of the major Dutch addiction care organizations initiated a pilot program to explore the possibility of using an existing Cognitive Behavioral Therapy and Motivational Interviewing based treatment program ("Lifestyle Training") to treat internet addiction. The current study evaluates this pilot treatment program by providing…

Treating angina pectoris by acupuncture therapy.

PubMed

Xu, Lixian; Xu, Hao; Gao, Wei; Wang, Wei; Zhang, Hui; Lu, Dominic P

2013-01-01

Acupuncture therapy on PC 6 (Neiguan) has a therapeutic effect on cardiac and chest ailments including angina pectoris. Additional beneficial acupuncture points are PC 4 (Ximen), HT 7 (Shenmen point), PC 7 (Daling point), PC 5 (Jianshi point), PC 3 (Quze point), CV 17 (Danzhong point), CV 6 (Qihai point), BL 15 (Xinshu point), L 20 (Pishu point), BL 17 (Geshu point), BL23 (Shenshu point), BL18 (Ganshu point), HT 5 (Tongli point), and ST36 (Zusanli point). Acupuncture not only quickly relieve the symptoms of acute angina pectoris, but also improve nitroglycerine's therapeutic effects. Therefore, it is an efficient simple therapeutic method used for emergency and for regular angina treatment. Review of studies on acupuncture therapy has shown effectiveness were between 80% to 96.2% that are almost as effective as conventional drug regimen. When compared with conventional medical treatment, the acupuncture therapy shows the obvious advantage of lacking, adverse side effects commonly associated with the Western anti-anginal drugs such as 1) Nitroglycerine (headache--63% with nitroglycerine patch and 50% with spray; syncope--4%; and dizziness--8% with patch; hypotension--4% with patch; and increased angina 2% with patch). 2) Isosorbide mononitrate (dizziness--3 to 5%; nausea/vomiting--2 to 4% and other reactions including hypotension, and syncope even with small doses). 3) Propranolol (bradycardia, chest pain, hypotension, worsening of AV conduction disturbance, Raynaud's syndrome, mental depression, hyperglycemia, etc.). Many conventional anti-anginal medications cause inter-drug reactions with other medications the patients taking for other diseases. Whereas, acupuncture therapy does not pose such an interference with patient's medications. Nevertheless, surgery is still the treatment of choice when acupuncture or conventional drug therapy fails. Combination of conventional drug therapy and acupuncture would considerably decrease the frequency and the required dosage

Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

PubMed

Bergueiro, J; Igarzabal, M; Sandin, J C Suarez; Somacal, H R; Vento, V Thatar; Huck, H; Valda, A A; Repetto, M; Kreiner, A J

2011-12-01

Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stem Cell Therapy to Treat Diabetes Mellitus

PubMed Central

Liew, Chee Gee; Andrews, Peter W.

2008-01-01

Transplantation of pancreatic islets offers a direct treatment for type 1 diabetes and in some cases, insulin-dependent type 2 diabetes. However, its widespread use is hampered by a shortage of donor organs. Many extant studies have focused on deriving β-cell progenitors from pancreas and pluripotent stem cells. Efforts to generate β-cells in vitro will help elucidate the mechanisms of β-cell formation and thus provide a versatile in vivo system to evaluate the therapeutic potential of these cells to treat diabetes. Various successful experiments using β-cells in animal models have generated extensive interest in using human embryonic stem cells to restore normoglycemia in diabetic patients. While new techniques are continually unveiled, the success of β-cell generation rests upon successful manipulation of culture conditions and the induction of key regulatory genes implicated in pancreas development. In this review, we compare successfully conducted protocols, highlight essential steps and identify some of the remarkable shortfalls common to these methods. In addition, we discuss recent advancements in the derivation of patient-specific pluripotent stem cells that may facilitate the use of autologous β-cells in stem cell therapy. PMID:19290381

Geant4 beam model for boron neutron capture therapy: investigation of neutron dose components.

PubMed

Moghaddasi, Leyla; Bezak, Eva

2018-03-01

Boron neutron capture therapy (BNCT) is a biochemically-targeted type of radiotherapy, selectively delivering localized dose to tumour cells diffused in normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal neutron capture by stable [Formula: see text]B nuclei resulting in emission of short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose of the current work was to develop and validate a Monte Carlo BNCT beam model and to investigate contribution of individual dose components resulting of neutron interactions. A neutron beam model was developed in Geant4 and validated against published data. The neutron beam spectrum, obtained from literature for a cyclotron-produced beam, was irradiated to a water phantom with boron concentrations of 100 μg/g. The calculated percentage depth dose curves (PDDs) in the phantom were compared with published data to validate the beam model in terms of total and boron depth dose deposition. Subsequently, two sensitivity studies were conducted to quantify the impact of: (1) neutron beam spectrum, and (2) various boron concentrations on the boron dose component. Good agreement was achieved between the calculated and measured neutron beam PDDs (within 1%). The resulting boron depth dose deposition was also in agreement with measured data. The sensitivity study of several boron concentrations showed that the calculated boron dose gradually converged beyond 100 μg/g boron concentration. This results suggest that 100μg/g tumour boron concentration may be optimal and above this value limited increase in boron dose is expected for a given neutron flux.

Dosimetry and radiobiology at the new RA-3 reactor boron neutron capture therapy (BNCT) facility: application to the treatment of experimental oral cancer.

PubMed

Pozzi, E; Nigg, D W; Miller, M; Thorp, S I; Heber, E M; Zarza, L; Estryk, G; Monti Hughes, A; Molinari, A J; Garabalino, M; Itoiz, M E; Aromando, R F; Quintana, J; Trivillin, V A; Schwint, A E

2009-07-01

The National Atomic Energy Commission of Argentina (CNEA) constructed a novel thermal neutron source for use in boron neutron capture therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The aim of the present study was to perform a dosimetric characterization of the facility and undertake radiobiological studies of BNCT in an experimental model of oral cancer in the hamster cheek pouch. The free-field thermal flux was 7.1 x 10(9) n cm(-2)s(-1) and the fast neutron flux was 2.5 x 10(6) n cm(-2)s(-1), indicating a very well-thermalized neutron field with negligible fast neutron dose. For radiobiological studies it was necessary to shield the body of the hamster from the neutron flux while exposing the everted cheek pouch bearing the tumors. To that end we developed a lithium (enriched to 95% in (6)Li) carbonate enclosure. Groups of tumor-bearing hamsters were submitted to BPA-BNCT, GB-10-BNCT, (GB-10+BPA)-BNCT or beam only treatments. Normal (non-cancerized) hamsters were treated similarly to evaluate normal tissue radiotoxicity. The total physical dose delivered to tumor with the BNCT treatments ranged from 6 to 8.5 Gy. Tumor control at 30 days ranged from 73% to 85%, with no normal tissue radiotoxicity. Significant but reversible mucositis in precancerous tissue surrounding tumors was associated to BPA-BNCT. The therapeutic success of different BNCT protocols in treating experimental oral cancer at this novel facility was unequivocally demonstrated.

Cardiac allograft prolongation in mice treated with combined posttransplantation total-lymphoid irradiation and anti-L3T4 antibody therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trager, D.K.; Banks, B.A.; Rosenbaum, G.E.

1989-04-01

Neonatal cardiac allograft survival was examined in mice treated with anti-L3T4 antibody, posttransplantation total lymphoid irradiation (TLI) or a combination of both therapies. Independently, both posttransplantation TLI and short-course antibody treatment allowed minimal prolongation. However, synergistic prolongation in graft survival was observed with the combination (synergistic) therapy. Fluorescence-activated cell sorter analysis of peripheral blood lymphocytes from animals treated with combined anti-L3T4 and posttransplantation TLI additionally revealed ''synergy'' with respect to the degree of peripheral lymphocyte depletion.

Impact of hormonal therapy on intermediate risk prostate cancer treated with combination brachytherapy and external beam irradiation.

PubMed

Stock, Richard G; Yalamanchi, Swati; Yamalachi, Swati; Hall, Simon J; Stone, Nelson N

2010-02-01

We assessed the impact of androgen suppressive therapy on biochemical failure in patients with intermediate risk prostate cancer treated with brachytherapy and external beam irradiation. From 1994 to 2006, 432 patients with intermediate risk prostate cancer as defined by the National Comprehensive Cancer Network were treated with low dose rate brachytherapy and external beam irradiation with or without 9 months of androgen suppressive therapy. Gleason score was 7 in 76% of cases and prostate specific antigen was 1.4 to 20 ng/ml (median 7.6). Of the patients 350 received androgen suppressive therapy and 82 did not. The biologically effective dose was 142 to 280 Gy2 (median 206). Followup was 23 to 155 months (median 56). The overall 8-year biochemical failure-free rate using the Phoenix definition in patients with vs without androgen suppressive therapy was 92% vs 92% (p = 0.4). The therapy had no significant impact on the biochemical failure-free rate in patients with Gleason score 7 (92% vs 90.5%, p = 0.55), prostate specific antigen 10 to 20 ng/ml (92% vs 100%, p = 0.32), T2b-T2c disease (89.5% vs 97%, p = 0.27) and more than 1 intermediate risk feature (90% vs 100%, p = 0.2). We addressed the relative importance of radiation dose vs hormonal therapy for intermediate risk prostate cancer. With high biologically effective dose combination treatment androgen suppressive therapy did not have a significant impact on the 8-year biochemical failure-free rate. We question its routine use in this setting. Copyright 2010 American Urological Association. Published by Elsevier Inc. All rights reserved.

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy

PubMed Central

Sun, Ting; Li, Yanyan; Huang, Yulun; Zhang, Zizhu; Yang, Weilian; Du, Ziwei; Zhou, Youxin

2016-01-01

The uptake of (10)boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10)boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo. Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133-expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT. PMID:27191269

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy.

PubMed

Sun, Ting; Li, Yanyan; Huang, Yulun; Zhang, Zizhu; Yang, Weilian; Du, Ziwei; Zhou, Youxin

2016-07-12

The uptake of (10)boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10)boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo. Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133-expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT.

Supervised physical therapy in women treated with radiotherapy for breast cancer 1

PubMed Central

Leal, Nara Fernanda Braz da Silva; de Oliveira, Harley Francisco; Carrara, Hélio Humberto Angotti

2016-01-01

ABSTRACT Objective: to evaluate the effect of physical therapy on the range of motion of the shoulders and perimetry of the upper limbs in women treated with radiotherapy for breast cancer. Methods: a total of 35 participants were randomized into two groups, with 18 in the control group (CG) and 17 in the study group (SG). Both of the groups underwent three evaluations to assess the range of motion of the shoulders and perimetry of the upper limbs, and the study group underwent supervised physical therapy for the upper limbs. Results: the CG had deficits in external rotation in evaluations 1, 2, and 3, whereas the SG had deficits in flexion, abduction, and external rotation in evaluation 1. The deficit in abduction was recovered in evaluation 2, whereas the deficits in all movements were recovered in evaluation 3. No significant differences in perimetry were observed between the groups. Conclusion: the applied supervised physical therapy was effective in recovering the deficit in abduction after radiotherapy, and the deficits in flexion and external rotation were recovered within two months after the end of radiotherapy. Registration number of the clinical trial: NCT02198118. PMID:27533265

Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy.

PubMed

Joseph, Richard W; Cappel, Mark; Goedjen, Brent; Gordon, Matthew; Kirsch, Brandon; Gilstrap, Cheryl; Bagaria, Sanjay; Jambusaria-Pahlajani, Anokhi

2015-01-01

Therapies that activate the immune system through blocking the binding of programmed death ligand 1 (PD-L1) present on tumors and PD-1 (programmed death 1) present on activated immune cells are revolutionizing the care for patients with cancer. These therapies work by inhibiting negative regulators of the immune system, thereby decreasing a tumor's ability to evade the immune system. The side effects of anti-PD-1/PD-L1 therapies are generally mild and as expected are related to autoimmune reactions. Two of the most common side effects of anti-PD-1/PD-L1 therapies are rash and pruritus occurring in approximately 20% of patients. Although the rash is generally recognized to be immune mediated, the exact mechanisms of the rash remain unclear. Herein, we report three cases of lichenoid dermatitis in three patients treated with MK-3475 (anti-PD-1) that were characterized with marked T-cell infiltrates with few PD-1-positive cells. The rashes in all three patients were relatively mild, allowing treatment to continue despite the rashes. ©2014 American Association for Cancer Research.

Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases

PubMed Central

Miyatake, Shin-Ichi; Furuse, Motomasa; Kawabata, Shinji; Maruyama, Takashi; Kumabe, Toshihiro; Kuroiwa, Toshihiko; Ono, Koji

2013-01-01

Background Bevacizumab, an anti–vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas. Methods Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression. Results The first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT. Conclusions Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas. PMID:23460324

GPU-based prompt gamma ray imaging from boron neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Do-Kun; Jung, Joo-Young; Suk Suh, Tae, E-mail: suhsanta@catholic.ac.kr

Purpose: The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. Methods: To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU).more » Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. Results: The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). Conclusions: The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray image reconstruction using the GPU computation for BNCT simulations.« less

Occurrence of simultaneous cathodal-anodal capture with left ventricular quadripolar leads for cardiac resynchronization therapy: an electrocardiogram evaluation.

PubMed

Occhetta, Eraldo; Dell'Era, Gabriele; Giubertoni, Ailia; Magnani, Andrea; Rametta, Francesco; Blandino, Alessandro; Magnano, Vincenzo; Malacrida, Maurizio; Marino, Paolo

2017-04-01

The occurrence of left ventricular (LV) anodal activation during pacing with modern multipolar cardiac resynchronization therapy (CRT) systems has never been reported. The aim of our study was to demonstrate, by means of electrocardiogram (ECG) analysis, the occurrence of simultaneous cathodal-anodal LV capture with quadripolar LV leads. We studied 10 first-time recipients of a CRT device equipped with a quadripolar LV lead. During follow-up, standard supine 12-lead ECGs were obtained in available cathode-to-anode LV pacing configurations with a pulse amplitude equal to twice the pacing threshold. The occurrence of simultaneous cathodal-anodal LV capture was defined as the presence of variations in electrocardiographic ventricular activation (EVA) when the distal tip (cathode)-to-device can (anode) pacing configuration was compared with the distal tip (cathode)-to-proximal ring (anode) configuration. In eight patients, we found differences in EVA when different LV sites were paced through the unipolar LV tip and unipolar LV ring configurations. In these patients, a difference in EVA was detected in 61.5% (59 of 96) of the ECG leads (marked difference in 31.3%, slight difference in 30.2%). Changes in EVA between unipolar tip-to-can and bipolar tip-to-ring pacing that were suggestive of cathodal-anodal LV capture were found in six patients. In these patients, a total of 30 (41.7%) ECG leads showed a difference in EVA (marked difference in 20.8%, slight difference in 20.8%). In our experience, additional anodal capture by the proximal LV ring during LV pacing is provable in most recipients of a resynchronization device equipped with a multipolar LV lead. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Altered Blood Flow Response to Small Muscle Mass Exercise in Cancer Survivors Treated With Adjuvant Therapy.

PubMed

Didier, Kaylin D; Ederer, Austin K; Reiter, Landon K; Brown, Michael; Hardy, Rachel; Caldwell, Jacob; Black, Christopher; Bemben, Michael G; Ade, Carl J

2017-02-07

Adjuvant cancer treatments have been shown to decrease cardiac function. In addition to changes in cardiovascular risk, there are several additional functional consequences including decreases in exercise capacity and increased incidence of cancer-related fatigue. However, the effects of adjuvant cancer treatment on peripheral vascular function during exercise in cancer survivors have not been well documented. We investigated the vascular responses to exercise in cancer survivors previously treated with adjuvant cancer therapies. Peripheral vascular responses were investigated in 11 cancer survivors previously treated with adjuvant cancer therapies (age 58±6 years, 34±30 months from diagnosis) and 9 healthy controls group matched for age, sex, and maximal voluntary contraction. A dynamic handgrip exercise test at 20% maximal voluntary contraction was performed with simultaneous measurements of forearm blood flow and mean arterial pressure. Forearm vascular conductance was calculated from forearm blood flow and mean arterial pressure. Left ventricular ejection time index (LVETi) was derived from the arterial pressure wave form. Forearm blood flow was attenuated in cancer therapies compared to control at 20% maximal voluntary contraction (189.8±53.8 vs 247.9±80.3 mL·min -1 , respectively). Forearm vascular conductance was not different between groups at rest or during exercise. Mean arterial pressure response to exercise was attenuated in cancer therapies compared to controls (107.8±10.8 vs 119.2±16.2 mm Hg). LEVTi was lower in cancer therapies compared to controls. These data suggest an attenuated exercise blood flow response in cancer survivors ≈34 months following adjuvant cancer therapy that may be attributed to an attenuated increase in mean arterial pressure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Men Who Have Sex With Men in Peru: Acceptability of Medication-Assisted Therapy for Treating Alcohol Use Disorders

PubMed Central

Brown, Shan-Estelle; Vagenas, Panagiotis; Konda, Kelika A.; Clark, Jesse L.; Lama, Javier R.; Gonzales, Pedro; Sanchez, Jorge; Duerr, Ann C.; Altice, Frederick L.

2015-01-01

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs and improve antiretroviral therapy (ART) adherence among MSM/TGW in Peru. Three focus groups involving HIV-infected or HIV-uninfected MSM/TGW (n = 26) with AUDs (AUDIT ≥ 8) were transcribed, translated from Spanish into English, and analyzed using thematic content analysis. Despite having an AUD, participants considered themselves “social” drinkers, minimized their drinking behaviors, and differed about whether or not alcohol problems could be treated. Participants expressed skepticism about medication for treating AUDs. Three concepts emerged as necessary components of a treatment program for alcohol problems: cost, family support, and the potential to drink less alcohol without attaining total abstinence. This study reveals important areas of education to increase potential acceptability of a medication for treating AUDs among MSM/TGW. Given the social conditions and knowledge base of the participants, medication-assisted therapies using naltrexone may be a beneficial strategy for MSM with AUDs. PMID:25787988

Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

PubMed

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

2005-06-01

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

Quality of Life in Patients with Noninfectious Uveitis Treated with or without Systemic Anti-inflammatory Therapy.

PubMed

Gui, Wei; Dombrow, Matthew; Marcus, Inna; Stowe, Meredith H; Tessier-Sherman, Baylah; Yang, Elizabeth; Huang, John J

2015-04-01

To compare vision-related (VR-QOL) and health-related quality of life (HR-QOL) in patients with noninfectious uveitis treated with systemic anti-inflammatory therapy versus nonsystemic therapy. A prospective, cross-sectional study design was employed. VR-QOL and HR-QOL were assessed by the 25-Item Visual Function Questionnaire (VFQ-25) and the Short Form 12-Item Health Survey (SF-12), respectively. Multivariate regression analysis was performed to assess the VR-QOL and HR-QOL based on treatment. Among the 80 patients, the median age was 51 years with 28 males (35%). The adjusted effect of treatment modality on VR-QOL or HR-QOL showed no statistically significant difference in all subscores of VFQ-25 or physical component score (PCS) and mental component score (MCS) of SF-12. Systemic therapy did not compromise VR-QOL or HR-QOL compared to nonsystemic therapy. Systemic therapy can be effectively used to control serious cases of noninfectious uveitis without significant relative adverse impact on quality of life.

Metastatic adenocarcinoma of mammary-like glands of the vulva successfully treated with surgery and hormonal therapy.

PubMed

Benito, Virginia; Arribas, Sara; Martínez, David; Medina, Norberto; Lubrano, Amina; Arencibia, Octavio

2013-01-01

Vulvar cancer is a rare malignancy; most tumors are squamous cell type while adenocarcinomas are rare. Primary adenocarcinomas of the vulva predominantly include extramammary Paget's disease and sweat gland carcinomas. Greene first described a rare form of adenocarcinoma in 1936, which was called adenocarcinoma of mammary-like glands of the vulva because of its morphologic and immunohistochemical resemblance to breast adenocarcinomas. In the management of this entity, varying combinations of surgery, radiation therapy, systemic chemotherapy and/or hormonal therapy may be used, as in patients with orthotopic breast carcinoma. However, hormonal therapy leads the way in patients with positive hormonal receptors, where other therapies cannot be used due to comorbidities or advanced age. We present the first reported case of an elderly patient with metastatic vulvar adenocarcinoma arising from mammary-like glands, successfully treated with a combination of surgery and hormonal therapy. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Apoptotic cell infusion treats ongoing collagen-induced arthritis, even in the presence of methotrexate, and is synergic with anti-TNF therapy.

PubMed

Bonnefoy, Francis; Daoui, Anna; Valmary-Degano, Séverine; Toussirot, Eric; Saas, Philippe; Perruche, Sylvain

2016-08-11

Apoptotic cell-based therapies have been proposed to treat chronic inflammatory diseases. The aim of this study was to investigate the effect of intravenous (i.v.) apoptotic cell infusion in ongoing collagen-induced arthritis (CIA) and the interaction of this therapy with other treatments used in rheumatoid arthritis (RA), including methotrexate (MTX) or anti-TNF therapy. The effects of i.v. apoptotic cell infusion were evaluated in a CIA mouse model in DBA/1 mice immunized with bovine type II collagen. The number and functions of antigen-presenting cells (APC), regulatory CD4(+) T cells (Treg), and circulating anti-collagen auto-antibodies were analyzed in CIA mice. Treatment of arthritic mice with i.v. apoptotic cell infusion significantly reduced the arthritis clinical score. This therapeutic approach modified T cell responses against the collagen auto-antigen with selective induction of collagen-specific Treg. In addition, we observed that APC from apoptotic-cell-treated animals were resistant to toll-like receptor ligand activation and favored ex vivo Treg induction, indicating APC reprogramming. Apoptotic cell injection-induced arthritis modulation was dependent on transforming growth factor (TGF)-β, as neutralizing anti-TGF-β antibody prevented the effects of apoptotic cells. Methotrexate did not interfere, while anti-TNF therapy was synergic with apoptotic-cell-based therapy. Overall, our data demonstrate that apoptotic-cell-based therapy is efficient in treating ongoing CIA, compatible with current RA treatments, and needs to be evaluated in humans in the treatment of RA.

Cognitive Behavioral Therapy vs. Eye Movement Desensitization and Reprocessing for Treating Panic Disorder: A Randomized Controlled Trial

PubMed Central

Horst, Ferdinand; Den Oudsten, Brenda; Zijlstra, Wobbe; de Jongh, Ad; Lobbestael, Jill; De Vries, Jolanda

2017-01-01

Objective: Cognitive Behavioral Therapy (CBT) is an effective intervention for patients with panic disorder (PD). From a theoretical perspective, Eye Movement Desensitization and Reprocessing (EMDR) therapy could also be useful in the treatment of PD because: (1) panic attacks can be experienced as life threatening; (2) panic memories specific to PD resemble traumatic memories as seen in posttraumatic stress disorder (PTSD); and (3) PD often develops following a distressing life event. The primary objective of this Randomized Controlled Trial (RCT), was to compare EMDR therapy with CBT for PD and determine whether EMDR is not worse than CBT in reducing panic symptoms and improving Quality Of Life (QOL). Methods: Two-arm (CBT and EMDR) parallel RCT in patients with PD (N = 84). Patients were measured at baseline (T1), directly after the last therapy session (T2), and 3 months after ending therapy (T3). Non-inferiority testing (linear mixed model with intention-to-treat analysis) was applied. Patients were randomly assigned to 13 weekly 60-min sessions of CBT (N = 42) or EMDR therapy (N = 42). Standard protocols were used. The primary outcome measure was severity of PD at T3, as measured with the Agoraphobic Cognitions Questionnaire (ACQ), the Body Sensations Questionnaire (BSQ), and the Mobility Inventory (MI). The secondary outcome measure was QOL, as measured with the World Health Organization Quality of Life short version (WHOQOL-Bref), at T3. Results: The severity of PD variables ACQ and BSQ showed non-inferiority of EMDR to CBT, while MI was inconclusive (adjusted analyses). Overall QOL and general health, Psychological health, Social relationships, and Environment showed non-inferiority of EMDR to CBT, while Physical health was inconclusive. Conclusion: EMDR therapy proved to be as effective as CBT for treating PD patients. Trial Registration: Dutch Trial Register, Nr. 3134 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3134 PMID:28868042

Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy.

PubMed

Hattori, Yoshihide; Kusaka, Shintaro; Mukumoto, Mari; Ishimura, Miki; Ohta, Yoichiro; Takenaka, Hiroshi; Uehara, Kouki; Asano, Tomoyuki; Suzuki, Minoru; Masunaga, Shin-Ichiro; Ono, Koji; Tanimori, Shinji; Kirihata, Mitsunori

2014-12-01

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

A randomized, comparative study of dual therapy (doxycycline-rifampin) versus triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis.

PubMed

Hasanain, Ahmad; Mahdy, Reem; Mohamed, Asmaa; Ali, Mostafa

2016-01-01

The aim of this study was to compare both the efficacy and safety profile of the WHO-recommended, dual therapy (doxycycline-rifampin) to a quinolone-based, triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis. We studied 107 consecutive, naïve patients with acute/subacute brucellosis admitted to Assiut University Hospital. Patients were randomly allocated to receive the dual therapy of doxycycline-rifampin (group-A) or to receive the triple therapy of doxycycline-rifampin-levofloxacin (group-B). Acute/subacute brucellosis was diagnosed based on the presence of: (1) contact with animals or fresh animal products, (2) suggestive clinical manifestations of less than one-year duration, and (3) positive antibody titer (1:160) by standard tube agglutination test. There was no significant difference between the two groups regarding their demographic data. Fever was the most frequent manifestation (96.3%). Epigastric pain was the most frequent adverse effect of treatment (12.1%). Group-A patients had a significantly higher relapse rate compared to group-B patients (22.6% versus 9.3%, p-value=0.01). The rate of treatment adverse effects was higher among group-B patients, although not reaching statistical significance (20.4% versus 11.3%, p-value=0.059). Adding levofloxacin to the dual therapy for acute/subacute brucellosis (doxycycline-rifampin) may increase its efficacy in terms of lowering the relapse rate of the disease. Further, larger scale studies are needed before considering modifying the standard, dual therapy for brucellosis. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Measurement of in-phantom neutron flux and gamma dose in Tehran research reactor boron neutron capture therapy beam line.

PubMed

Bavarnegin, Elham; Sadremomtaz, Alireza; Khalafi, Hossein; Kasesaz, Yaser

2016-01-01

Determination of in-phantom quality factors of Tehran research reactor (TRR) boron neutron capture therapy (BNCT) beam. The doses from thermal neutron reactions with 14N and 10B are calculated by kinetic energy released per unit mass approach, after measuring thermal neutron flux using neutron activation technique. Gamma dose is measured using TLD-700 dosimeter. Different dose components have been measured in a head phantom which has been designed and constructed for BNCT purpose in TRR. Different in-phantom beam quality factors have also been determined. This study demonstrates that the TRR BNCT beam line has potential for treatment of superficial tumors.

Patients with advanced and metastatic renal cell carcinoma treated with targeted therapy in the Czech Republic: twenty cancer centres, six agents, one database.

PubMed

Poprach, Alexandr; Bortlíček, Zbyněk; Büchler, Tomáš; Melichar, Bohuslav; Lakomý, Radek; Vyzula, Rostislav; Brabec, Petr; Svoboda, Marek; Dušek, Ladislav; Gregor, Jakub

2012-12-01

The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

Noninvasive extramammary Paget's disease treated with photodynamic therapy: case series from the Roswell Park Cancer Institute.

PubMed

Housel, Joseph P; Izikson, Leonid; Zeitouni, Nathalie C

2010-11-01

Extramammary Paget's disease (EMPD) is a rare low-grade cutaneous malignancy that affects apocrine gland-bearing areas and most commonly occurs on the perineal skin. Photodynamic therapy (PDT) may represent a useful treatment option for extensive, noninvasive EMPD, alone or as part of multimodal therapy. To analyze the clinical outcomes of PDT for noninvasive EMPD with topical aminolevulinic acid (ALA) or intravenous porfimer sodium as photosensitizing agents and argon laser as the photoactivator. Retrospective case series of patients with noninvasive EMPD treated at Roswell Park Cancer Institute with PDT from April 20, 1995, to December 4, 2008. Identified patients included five men and three women aged 50 to 80 (mean age 67) with a total of 24 distinct lesions of noninvasive EMPD without distant metastases. Four patients received topical ALA only as a photosensitizer, three received intravenous porfimer sodium only, and one received both. All patients were treated using a 632.8-nm argon-pumped dye laser, and some were also treated using a red lamp (590-729 nm). Seven of nine lesions (78%) treated with PDT using intravenous porfimer sodium showed a complete response (CR) and were disease free at 12 to 96 months. Eight of 16 lesions (50%) treated with PDT using topical ALA showed a CR, and 38% were disease free at 9 to 88 months. None of the treated patients developed any serious cosmetic or functional impairments, such as loss of sphincter control or dysesthesias. PDT with intravenous porfimer sodium or topical ALA and argon laser may represent a useful, surgery-sparing therapeutic option for management of noninvasive EMPD in selected patients. Prospective, randomized clinical trials are necessary to compare the effectiveness of PDT with that of surgery for noninvasive EMPD. © 2010 by the American Society for Dermatologic Surgery, Inc.

Intranasal melanoma treated with radiation therapy in three dogs.

PubMed

Davies, Owen; Spencer, Sarah; Necova, Slavomira; Holmes, Emma; Taylor, Angela; Blackwood, Laura; Lara-Garcia, Ana

2017-12-01

Three dogs were investigated for chronic unilateral nasal discharge. In all cases CT imaging showed an intranasal mass causing turbinate lysis and no evidence of metastasis. Cytology in cases 1 (a 14-year-old neutered male crossbreed dog) and 2 (a five-year-old neutered male German Shepherd dog) demonstrated a pleomorphic cell population with variable intracellular pigment suspicious of melanocytic neoplasia. Histopathology with immunohistochemistry (Melan-A and vimentin, plus PNL-2 in one case) confirmed the diagnosis of melanoma in all dogs. All dogs were treated with megavoltage radiotherapy using linear accelerators. Cases 1 and 3 (a nine-year-old neutered female beagle dog) received a hypofractionated (4 × 8 Gy) protocol and case 2 received a definitive (12 × 4 Gy) protocol. Complete remission was demonstrated on repeat CT scan five months after diagnosis in case 1 and seven months in case 2. Stable disease was documented on CT at four months for case 3; however, clinical signs in this dog remained controlled for 10 months in total. Case 1 died of unrelated causes five months after diagnosis, case 2 was euthanased due to the development of seizures 13 months after diagnosis, and case 3 was lost to follow-up 12 months after diagnosis. Melanoma should be considered as a rare differential diagnosis for primary nasal neoplasia in the dog and radiation therapy can be used as effective local therapy.

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

PubMed Central

Curtin, James F.; King, Gwendalyn D.; Candolfi, Marianela; Greeno, Remy B.; Kroeger, Kurt M.; Lowenstein, Pedro R.; Castro, Maria G.

2006-01-01

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as ‘immune privileged’, brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another

The Effectiveness of Eye Movement Desensitization and Reprocessing Therapy to Treat Symptoms Following Trauma in Timor Leste.

PubMed

Schubert, Sarah J; Lee, Christopher W; de Araujo, Guilhermina; Butler, Susan R; Taylor, Graham; Drummond, Peter D

2016-04-01

The effectiveness of eye movement desensitization and reprocessing (EMDR) therapy for treating trauma symptoms was examined in a postwar/conflict, developing nation, Timor Leste. Participants were 21 Timorese adults with symptoms of posttraumatic stress disorder (PTSD), assessed as those who scored ≥2 on the Harvard Trauma Questionnaire (HTQ). Participants were treated with EMDR therapy. Depression and anxiety symptoms were assessed using the Hopkins Symptom Checklist. Symptom changes post-EMDR treatment were compared to a stabilization control intervention period in which participants served as their own waitlist control. Sessions were 60-90 mins. The average number of sessions was 4.15 (SD = 2.06). Despite difficulties providing treatment cross-culturally (i.e., language barriers), EMDR therapy was followed by significant and large reductions in trauma symptoms (Cohen's d = 2.48), depression (d = 2.09), and anxiety (d = 1.77). At posttreatment, 20 (95.2%) participants scored below the HTQ PTSD cutoff of 2. Reliable reductions in trauma symptoms were reported by 18 participants (85.7%) posttreatment and 16 (76.2%) at 3-month follow-up. Symptoms did not improve during the control period. Findings support the use of EMDR therapy for treatment of adults with PTSD in a cross-cultural, postwar/conflict setting, and suggest that structured trauma treatments can be applied in Timor Leste. Copyright © 2016 International Society for Traumatic Stress Studies.

Neutron therapy of cancer

NASA Technical Reports Server (NTRS)

Frigerio, N. A.; Nellans, H. N.; Shaw, M. J.

1969-01-01

Reports relate applications of neutrons to the problem of cancer therapy. The biochemical and biophysical aspects of fast-neutron therapy, neutron-capture and neutron-conversion therapy with intermediate-range neutrons are presented. Also included is a computer program for neutron-gamma radiobiology.

Application of laser therapy in treating inherited forms of psychoverbal retardation in children

NASA Astrophysics Data System (ADS)

Ulas, V. Y.; Voinova, V. M.; Il'in, L. B.; Troitskaya, L. A.; Dobrynina, E. V.; Kazantseva, L. Z.

2001-04-01

An investigation was made of applying combined laser therapy in the treatment of 619 children (422 children constituted the experimental group and 197 children composed the control group) affected by inherited forms of psychoverbal retardation. It was found that low-intensity He-Ne laser radiation with the wavelength of 632.8 nm and the output power of 2 mW made it possible to improve the children's mental development. Moreover, it effectively increased their mental activities, such as speech, communication, arbitrary behavior regulation, and locomotory functions. Laser therapy applied in treating children affected by the arrested mental development aggravated by obesity additionally decreased their body weight, increased their field of vision, and eliminated dyslipidemia. It was also found that contraindications to He-Ne laser acupuncture included phenylketonuria-related noncorrected metabolic defects, convulsive syndromes, epileptic activities, convulsive readiness, and cerebrolysine intramuscular injections.

Therapies for Musculoskeletal Disease: Can we Treat Two Birds with One Stone?

PubMed Central

Girgis, Christian M.; Mokbel, Nancy; DiGirolamo, Douglas J.

2014-01-01

Musculoskeletal diseases are highly prevalent with staggering annual health care costs across the globe. The combined wasting of muscle (sarcopenia) and bone (osteoporosis)— both in normal aging and pathologic states—can lead to vastly compounded risk for fracture in patients. Until now, our therapeutic approach to the prevention of such fractures has focused solely on bone, but our increasing understanding of the interconnected biology of muscle and bone has begun to shift our treatment paradigm for musculoskeletal disease. Targeting pathways that centrally regulate both bone and muscle (eg, GH/IGF-1, sex steroids, etc.) and newly emerging pathways that might facilitate communication between these 2 tissues (eg, activin/myostatin) might allow a greater therapeutic benefit and/or previously unanticipated means by which to treat these frail patients and prevent fracture. In this review, we will discuss a number of therapies currently under development that aim to treat musculoskeletal disease in precisely such a holistic fashion. PMID:24633910

[A Case Report of Disappearance of Gastric Metastasis of Breast Cancer Treated with Combination Therapy Consisting of Paclitaxel and Cisplatin].

PubMed

Nakajima, Tooru; Taniwaka, Koichi; Goto, Hideki; Kawamura, Shunji

2017-04-01

A 63-year-old postmenopausal woman was treated with combination therapy consisting of paclitaxel(PTX)and cisplatin (CDDP)for gastric metastasis of breast cancer; she achieved a complete response as revealed by pathological examination. Combination therapy with PTX and CDDP seems to be an optional treatment for gastric metastasis of breast cancer.

Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuaron, John J.; Chon, Brian; Tsai, Henry

Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered wasmore » 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and

Experimental and Simulated Characterization of a Beam Shaping Assembly for Accelerator- Based Boron Neutron Capture Therapy (AB-BNCT)

NASA Astrophysics Data System (ADS)

Burlon, Alejandro A.; Girola, Santiago; Valda, Alejandro A.; Minsky, Daniel M.; Kreiner, Andrés J.

2010-08-01

In the frame of the construction of a Tandem Electrostatic Quadrupole Accelerator facility devoted to the Accelerator-Based Boron Neutron Capture Therapy, a Beam Shaping Assembly has been characterized by means of Monte-Carlo simulations and measurements. The neutrons were generated via the 7Li(p, n)7Be reaction by irradiating a thick LiF target with a 2.3 MeV proton beam delivered by the TANDAR accelerator at CNEA. The emerging neutron flux was measured by means of activation foils while the beam quality and directionality was evaluated by means of Monte Carlo simulations. The parameters show compliance with those suggested by IAEA. Finally, an improvement adding a beam collimator has been evaluated.

Gyrotron-driven high current ECR ion source for boron-neutron capture therapy neutron generator

NASA Astrophysics Data System (ADS)

Skalyga, V.; Izotov, I.; Golubev, S.; Razin, S.; Sidorov, A.; Maslennikova, A.; Volovecky, A.; Kalvas, T.; Koivisto, H.; Tarvainen, O.

2014-12-01

Boron-neutron capture therapy (BNCT) is a perspective treatment method for radiation resistant tumors. Unfortunately its development is strongly held back by a several physical and medical problems. Neutron sources for BNCT currently are limited to nuclear reactors and accelerators. For wide spread of BNCT investigations more compact and cheap neutron source would be much more preferable. In present paper an approach for compact D-D neutron generator creation based on a high current ECR ion source is suggested. Results on dense proton beams production are presented. A possibility of ion beams formation with current density up to 600 mA/cm2 is demonstrated. Estimations based on obtained experimental results show that neutron target bombarded by such deuteron beams would theoretically yield a neutron flux density up to 6·1010 cm-2/s. Thus, neutron generator based on a high-current deuteron ECR source with a powerful plasma heating by gyrotron radiation could fulfill the BNCT requirements significantly lower price, smaller size and ease of operation in comparison with existing reactors and accelerators.

Estimating Incidence Rate of Hospital-Treated Self-Harm in Hong Kong Using Capture-Recapture Approach.

PubMed

Leung Kwok, Chi; Yip, Paul S F

2018-05-01

A surveillance system for self-harm has not been established in Hong Kong. The existing data source has an unknown degree of underreporting, and therefore a capture-recapture method has been proposed to correct for the incompleteness. To assess the underestimation of the incidence of self-harm cases presenting to hospital in Hong Kong using a capture and recapture method. Two different yet overlapping hospital administrative datasets of self-harm were obtained from all public hospitals in Hong Kong. From 2002 to 2011, 59,473 distinct episodes involving 36,411 patients were identified. A capture-recapture model considering heterogeneous capture probabilities was applied to estimate the number of self-harm episodes. The estimated number of self-harm incidence was 79,923, equally shared by females and males. Cases of self-harm by females were more likely to be ascertained than those by males. The estimated annual incidence rate of self-harm in Hong Kong from 2002 to 2011 ranged from 96.4 in 2010 to 132.7 in 2002. The proposed method does not include patients who required no medical attention and those where the patient consulted private doctors. The capture-recapture model is a useful method for adjusting the underestimation of self-harm cases from existing databases when surveillance system is not available and to reveal some hidden patterns.

Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Tae Hyun; Park, Sook Ryun; Ryu, Keun Won

2012-12-01

Purpose: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Methods and Materials: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Results: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiationmore » therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Conclusions: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.« less

Stochastic modelling of wall stresses in abdominal aortic aneurysms treated by a gene therapy.

PubMed

Mohand-Kaci, Faïza; Ouni, Anissa Eddhahak; Dai, Jianping; Allaire, Eric; Zidi, Mustapha

2012-01-01

A stochastic mechanical model using the membrane theory was used to simulate the in vivo mechanical behaviour of abdominal aortic aneurysms (AAAs) in order to compute the wall stresses after stabilisation by gene therapy. For that, both length and diameter of AAAs rats were measured during their expansion. Four groups of animals, control and treated by an endovascular gene therapy during 3 or 28 days were included. The mechanical problem was solved analytically using the geometric parameters and assuming the shape of aneurysms by a 'parabolic-exponential curve'. When compared to controls, stress variations in the wall of AAAs for treated arteries during 28 days decreased, while they were nearly constant at day 3. The measured geometric parameters of AAAs were then investigated using probability density functions (pdf) attributed to every random variable. Different trials were useful to define a reliable confidence region in which the probability to have a realisation is equal to 99%. The results demonstrated that the error in the estimation of the stresses can be greater than 28% when parameters uncertainties are not considered in the modelling. The relevance of the proposed approach for the study of AAA growth may be studied further and extended to other treatments aimed at stabilisation AAAs, using biotherapies and pharmacological approaches.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease.

PubMed

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days' treatment. after 30 days' treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function.

Long-term coital behaviour in women treated with cognitive behaviour therapy for superficial coital pain and vaginismus.

PubMed

Engman, Maria; Wijma, Klaas; Wijma, Barbro

2010-01-01

The purpose of the present study was to investigate long-term coital behaviour in women treated with cognitive behaviour therapy (CBT) for superficial coital pain and vaginismus. Data were taken from a questionnaire concerning long-term coital behaviour sent to 59 women who presented to Linköping University Hospital because of superficial coital pain, had been diagnosed with vaginismus, and had been treated with CBT. Data were also traced from therapy records: mean follow-up time was 39 months, the women had suffered for an average of almost 4 years, and required a mean of 14 treatment sessions. Forty-four of the 59 women returned the questionnaire, for a response rate of 74.6%. At follow-up, 81% of the treated women had had intercourse. A majority (61%) rated their ability to have intercourse without pain as 6 or higher (on a scale from 0-10), and 61% rated their ability to enjoy intercourse as 6 or higher (on a scale from 0-10). The proportion of women with positive treatment outcome at follow-up ranged from 81% (able to have intercourse) to 6% (able to have pain-free intercourse). An ability to have intercourse at end of therapy was maintained at follow-up. Two-thirds of the women reported high fulfillment of individual treatment goals. At follow-up, the women estimated a significantly higher self-worth as sex partners, and as women and human beings, than before treatment. Twelve per cent of the original sample had healed after a few assessment sessions and without treatment.

Chronic catatonic schizophrenia treated successfully with right unilateral ultrabrief pulse electroconvulsive therapy: case report.

PubMed

Cupina, Denise; Patil, Sachin; Loo, Colleen

2013-06-01

Catatonia is a syndrome with prominent motor and behavioral symptoms commonly seen in acutely ill psychiatric patients. Catatonic symptoms have been considered as positive predictors of response to electroconvulsive therapy (ECT); however, few studies so far have addressed the role of ECT treatment technique in schizophrenia. We present the case of a 41-year-old woman with chronic catatonic schizophrenia who was treated successfully with a course of ultrabrief right unilateral ECT.

Adjunct Antimicrobial Therapy and Periodontal Surgery to Treat Generalized Aggressive Periodontitis: A Case Report.

PubMed

Irokawa, Daisuke; Makino-Oi, Asako; Fujita, Takahisa; Yamamoto, Shigeki; Tomita, Sachiyo; Saito, Atsushi

2016-01-01

Here we report a case of generalized aggressive periodontitis treated with periodontal therapy including adjunct antimicrobial therapy and periodontal surgery. The patient was a 22-year-old woman who presented with the chief complaint of gingival recession. Baseline examination revealed generalized plaque deposition and gingival inflammation. Thirty-nine percent of the sites had a probing depth (PD) of 4-6 mm and 2% a PD of ≥7 mm; 63% exhibited bleeding on probing (BOP). Radiographic examination revealed vertical bone loss in the molars and horizontal bone loss in other teeth. Microbiological examination of subgingival plaque revealed the presence of Aggregatibacter actinomycetemcomitans and Tannerella forsythia. Oral health-related quality of life was assessed as a measure of patient-reported outcome. Based on a clinical diagnosis of generalized aggressive periodontitis, initial periodontal therapy and adjunct antimicrobial therapy were implemented. After reducing inflammation and subgingival bacteria, open flap debridement was performed for teeth with a PD of ≥4 mm. Reevaluation showed no sites with a PD of ≥5 mm, a minimal level of BOP, and a marked reduction in the level of the targeted periodontal pathogens. The patient's oral health-related quality of life was slightly worsened during supportive periodontal therapy (SPT). Implementation of adjunct antimicrobial therapy targeting periodontal pathogens and subsequent periodontal surgery resulted in improvement in periodontal and microbiological parameters. This improvement has been adequately maintained over a 2-year period. However, additional care is necessary to further improve the patient's oral health-related quality of life during SPT.

Simple technique to treat pupillary capture after transscleral fixation of intraocular lens.

PubMed

Jürgens, Ignasi; Rey, Amanda

2015-01-01

We describe a simple surgical technique to manage pupillary capture after previous transscleral fixation of an intraocular lens. Neither author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Gastric and enteric anisakiasis successfully treated with Gastrografin therapy: A case report.

PubMed

Fujikawa, Hiroki; Kuwai, Toshio; Yamaguchi, Toshiki; Miura, Ryoichi; Sumida, Yuki; Takasago, Takeshi; Miyasako, Yuki; Nishimura, Tomoyuki; Iio, Sumio; Imagawa, Hiroki; Yamaguchi, Atsushi; Kouno, Hirotaka; Kohno, Hiroshi

2018-03-16

We report a case of a 59-year-old woman who was diagnosed with gastric and small intestinal anisakiasis, which was successfully treated with endoscopic extraction and Gastrografin therapy. She was admitted to our hospital with epigastric pain and vomiting one day after eating raw fish. She exhibited tenderness in the epigastrium without obvious rebound tenderness or guarding. Computed tomography (CT) demonstrated segmental edema of the intestinal wall with proximal dilatation and a small number of ascites. Because enteric anisakiasis was suspected based on the patient's history of recent raw fish consumption and abdominal CT, we performed gastroscopy and confirmed that nine Anisakis larvae were attached to the gastric mucosa. All of the Anisakis larvae were extracted via endoscopy, and the patient was diagnosed with gastric and enteric anisakiasis. Additionally, in the hospital, we performed ileography twice using Gastrografin, which led to shortened hospital stay. Based on the clinical results of this case, we suggest that Gastrografin therapy is a safe, convenient, and useful method to extract enteric Anisakis larvae.

Normal carboxyhaemoglobin level in carbon monoxide poisoning treated with hyperbaric oxygen therapy.

PubMed

Helgeson, Scott A; Wilson, Michael E; Guru, Pramod K

2017-07-24

Throughout the world both intentional and inadvertent exposure to carbon monoxide (CO) remains an important public health issue. While CO poisoning can be lethal, the morbidity is predominantly due to nervous system injury. A previously healthy 22-year-old woman was found unconscious at home by her sister. Her parents were found dead in the house with a recent history of a dysfunctional furnace. She was presumed to have CO poisoning despite an initial carboxyhaemoglobin level of 2.5%. Patient had both clinical and radiological evidence of neurological damage. However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered to a near normal functional status. There is no consensus that exists among treating physicians about the role of hyperbaric oxygen in management of neurological injury. The case described here has significant neurological damage related to CO exposure but improved after HBO therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Treating Posttraumatic Stress Disorder in Female Victims of Trafficking Using Narrative Exposure Therapy: A Retrospective Audit.

PubMed

Robjant, Katy; Roberts, Jackie; Katona, Cornelius

2017-01-01

Human trafficking is a form of modern slavery that involves the forced movement of people internally within countries, or externally across borders. Victims who are trafficked for sexual exploitation are subject to repeated, multiple trauma, and high rates of mental health problems including posttraumatic stress disorder (PTSD) have been found. Narrative exposure therapy (NET) is an evidence-based treatment for PTSD. In this retrospective audit, we record the results of NET to treat 10 women who had been trafficked for sexual exploitation who were diagnosed with PTSD. All 10 women completed the therapy and experienced a reduction in PTSD severity scores at posttreatment, with improvements that were maintained or further improved at 3-month follow-up. General distress was also significantly reduced following treatment. Although limited by sample size and retrospective design, this audit demonstrates that NET is a feasible treatment for PTSD in this population and warrants further evaluation in a randomized controlled trial. Further adjunctive interventions may also be necessary to treat the additional psychological problems experienced by this population.

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sher, David J., E-mail: david_sher@rush.edu; Fidler, Mary Jo; Seder, Christopher W.

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gymore » (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not

A Chaperone Enhances Blood α-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy

PubMed Central

Parenti, Giancarlo; Fecarotta, Simona; la Marca, Giancarlo; Rossi, Barbara; Ascione, Serena; Donati, Maria Alice; Morandi, Lucia Ovidia; Ravaglia, Sabrina; Pichiecchio, Anna; Ombrone, Daniela; Sacchini, Michele; Pasanisi, Maria Barbara; De Filippi, Paola; Danesino, Cesare; Della Casa, Roberto; Romano, Alfonso; Mollica, Carmine; Rosa, Margherita; Agovino, Teresa; Nusco, Edoardo; Porto, Caterina; Andria, Generoso

2014-01-01

Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone. PMID:25052852

Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

PubMed Central

Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

2012-01-01

Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults.

PubMed

Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A

2015-11-01

There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

PubMed Central

Sköld, K; Gorlia, T; Pellettieri, L; Giusti, V; H-Stenstam, B; Hopewell, J W

2010-01-01

The purpose of this study was to assess the potential of boron neutron capture therapy (BNCT), with a 6-h infusion of the boron carrier l-boronophenylalanine as a fructose preparation (BPA-f), as first-line radiotherapy for newly diagnosed glioblastoma multiforme (GBM). Patient survival data from a Phase II study using BNCT were compared with retrospective data from the two arms of a Phase III study using conventional radiotherapy (RT) in the reference arm and using RT plus concomitant and adjuvant medication with temozolomide (TMZ) in the experimental arm, and were also compared with small subgroups of these patients for whom the methylation status of the MGMT (O6-methylguanine–DNA methyltransferase) DNA repair gene was known. Differences in the baseline characteristics, salvage therapy after recurrence and levels of severe adverse events were also considered. The results indicate that BNCT offers a treatment that is at least as effective as conventional RT alone. For patients with an unmethylated MGMT DNA repair gene, a possible clinical advantage of BNCT over RT/TMZ was suggested. BNCT is a single-day treatment, which is of convenience to patients, with mild side effects, which would offer an initial 6 weeks of good-quality life during the time when patients would otherwise be undergoing daily treatments with RT and TMZ. It is suggested that the use of BNCT with a 6-h infusion of BPA-f should be explored in a stratified randomised Phase II trial in which patients with the unmethylated MGMT DNA repair gene are offered BNCT in the experimental arm and RT plus TMZ in the reference arm. PMID:20603410

Unorthodox Alternative Therapies Marketed to Treat Lyme Disease

PubMed Central

Lantos, Paul M.; Shapiro, Eugene D.; Auwaerter, Paul G.; Baker, Phillip J.; Halperin, John J.; McSweegan, Edward; Wormser, Gary P.

2015-01-01

Background. Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. Methods. Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. Results. More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. Conclusions. Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful. PMID:25852124

Acupuncture therapy in treating migraine: results of a magnetic resonance spectroscopy imaging study.

PubMed

Gu, Tao; Lin, Lei; Jiang, Yun; Chen, Juan; D'Arcy, Ryan Cn; Chen, Min; Song, Xiaowei

2018-01-01

Acupuncture has been proven to be effective as an alternative therapy in treating migraine, but the pathophysiological mechanisms of the treatment remain unclear. This study investigated possible neurochemical responses to acupuncture treatment. Proton magnetic resonance spectroscopy imaging was used to investigate biochemical levels pre- and post-acupuncture treatment. Participants (N=45) included subjects diagnosed with: 1) migraine without aura; 2) cervicogenic headache; and 3) healthy controls. Participants in the two patient groups received verum acupuncture using acupoints that target migraine without aura but not cervicogenic headache, while the healthy controls received a sham treatment. All participants had magnetic resonance spectroscopy scans before and after the acupuncture therapy. Levels of brain metabolites were examined in relation to clinical headache assessment scores. A significant increase in N -acetylaspartate/creatine was observed in bilateral thalamus in migraine without aura after the acupuncture treatment, which was significantly correlated with the headache intensity score. The data demonstrate brain biochemical changes underlying the effect of acupuncture treatment of migraine.

The power of combining adoptive cell therapy (ACT) and pathogen-boosted vaccination to treat solid tumors.

PubMed

Zander, Ryan; Cui, Weiguo

2017-10-03

Recent advancements in adoptive cell therapy (ACT) are opening up new frontiers for cancer immunotherapy. CAR T cells targeting CD19 have emerged as a remarkable T cell-based therapy for the successful treatment of certain types of leukemia and lymphomas. Despite these clinical successes, as well as significant breakthroughs in T cell engineering, the treatment of solid tumors with ACT remains a relentless challenge. Thus, the current consensus of the field is that an urgent need exists for the design of innovative approaches that can improve the efficacy of ACT in treating solid cancers while maintaining a high degree of reliability and safety.

Treating bulimia with hypnosis and low-level light therapy: a case report

NASA Astrophysics Data System (ADS)

Laser, Eleanor; Sassack, Michael

2012-03-01

This case report describes an effort to control bulimia nervosa by combining low-level laser therapy (LLLT)-the application of red and near-infrared light to specific body points-and hypnosis. A 29-year old female with a 14-year history of bulimia received one session of LLLT combined with hypnosis. Two weeks later, following a measurable decrease in bulimic episodes (purging), a session of psychotherapy and hypnosis was administered. Six months post-treatment, the patient has experienced a complete cessation of purging activities without recurrence. LLLT, when used in conjunction with hypnosis and psychotherapy, was effective in managing bulimia and may prove useful in treating other eating disorders.

Epithermal neutron formation for boron neutron capture therapy by adiabatic resonance crossing concept

NASA Astrophysics Data System (ADS)

Khorshidi, A.; Ghafoori-Fard, H.; Sadeghi, M.

2014-05-01

Low-energy protons from the cyclotron in the range of 15-30 MeV and low current have been simulated on beryllium (Be) target with a lead moderator around the target. This research was accomplished to design an epithermal neutron beam for Boron Neutron Capture Therapy (BNCT) using the moderated neutron on the average produced from 9Be target via (p, xn) reaction in Adiabatic Resonance Crossing (ARC) concept. Generation of neutron to proton ratio, energy distribution, flux and dose components in head phantom have been simulated by MCNP5 code. The reflector and collimator were designed in prevention and collimation of derivation neutrons from proton bombarding. The scalp-skull-brain phantom consisting of bone and brain equivalent material has been simulated in order to evaluate the dosimetric effect on the brain. Results of this analysis demonstrated while the proton energy decreased, the dose factor altered according to filters thickness. The maximum epithermal flux revealed using fluental, Fe and bismuth (Bi) filters with thicknesses of 9.4, 3 and 2 cm, respectively and also the epithermal to thermal neutron flux ratio was 103.85. The potential of the ARC method to replace or complement the current reactor-based supply sources of BNCT purposes.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma.

PubMed

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-10-01

Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

Feasibility of the Utilization of BNCT in the Fast Neutron Therapy Beam at Fermilab

DOE R&D Accomplishments Database

Langen, Katja; Lennox, Arlene J.; Kroc, Thomas K.; DeLuca, Jr., Paul M.

2000-06-01

The Neutron Therapy Facility at Fermilab has treated cancer patients since 1976. Since then more than 2,300 patients have been treated and a wealth of clinical information accumulated. The therapeutic neutron beam at Fermilab is produced by bombarding a beryllium target with 66 MeV protons. The resulting continuous neutron spectrum ranges from thermal to 66 MeV in neutron energy. It is clear that this spectrum is not well suited for the treatment of tumors with boron neutron capture therapy (BNCT) only However, since this spectrum contains thermal and epithermal components the authors are investigating whether BNCT can be used in this beam to boost the tumor dose. There are clinical scenarios in which a selective tumor dose boost of 10 - 15% could be clinically significant. For these cases the principal treatment would still be fast neutron therapy but a tumor boost could be used either to deliver a higher dose to the tumor tissue or to reduce the dose to the normal healthy tissue while maintaining the absorbed dose level in the tumor tissue.

Prognostic Utility of Apoptosis Index, Ki-67 and Survivin Expression in Dogs with Nasal Carcinoma Treated with Orthovoltage Radiation Therapy

PubMed Central

FU, Dah-Renn; KATO, Daiki; WATABE, Ai; ENDO, Yoshifumi; KADOSAWA, Tsuyoshi

2014-01-01

ABSTRACT Apoptosis, Ki-67 and survivin expression have been reported as prognostic values in human cancer treated with radiation therapy. The aim of this study was to evaluate the correlation between the outcome of canine nasal carcinomas treated with radiation therapy and these cancer markers. The apoptotic index (AI) was evaluated with TUNEL assays, and an immunohistochemical evaluation was performed on Ki-67 and survivin in 33 biopsy samples taken before treatment. Median survival times were estimated using Kaplan-Meier curves and the log-rank method. The AI ranged from 0 to 0.7%, and the percentage of Ki-67-positive cells defined as the proliferative index (PI) ranged from 0.8 to 77% in all samples. Neither the AI nor the PI had a significant relationship with survival time (P=0.056 and 0.211). Survivin expression was detected in 84.9% of samples of canine nasal carcinoma. Dogs with high survivin expression were associated with poorer response to treatment and had shorter survival times (P=0.017 and 0.031). Advanced-stage tumors were also significantly associated with a high level of survivin (P=0.026). Overexpression of survivin was shown to be an unfavorable prognostic factor in dogs with nasal carcinomas treated with radiation therapy. PMID:25452259

Prognostic utility of apoptosis index, Ki-67 and survivin expression in dogs with nasal carcinoma treated with orthovoltage radiation therapy.

PubMed

Fu, Dah-Renn; Kato, Daiki; Watabe, Ai; Endo, Yoshifumi; Kadosawa, Tsuyoshi

2014-11-01

Apoptosis, Ki-67 and survivin expression have been reported as prognostic values in human cancer treated with radiation therapy. The aim of this study was to evaluate the correlation between the outcome of canine nasal carcinomas treated with radiation therapy and these cancer markers. The apoptotic index (AI) was evaluated with TUNEL assays, and an immunohistochemical evaluation was performed on Ki-67 and survivin in 33 biopsy samples taken before treatment. Median survival times were estimated using Kaplan-Meier curves and the log-rank method. The AI ranged from 0 to 0.7%, and the percentage of Ki-67-positive cells defined as the proliferative index (PI) ranged from 0.8 to 77% in all samples. Neither the AI nor the PI had a significant relationship with survival time (P=0.056 and 0.211). Survivin expression was detected in 84.9% of samples of canine nasal carcinoma. Dogs with high survivin expression were associated with poorer response to treatment and had shorter survival times (P=0.017 and 0.031). Advanced-stage tumors were also significantly associated with a high level of survivin (P=0.026). Overexpression of survivin was shown to be an unfavorable prognostic factor in dogs with nasal carcinomas treated with radiation therapy.

Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.

PubMed

Futamura, Gen; Kawabata, Shinji; Nonoguchi, Naosuke; Hiramatsu, Ryo; Toho, Taichiro; Tanaka, Hiroki; Masunaga, Shin-Ichiro; Hattori, Yoshihide; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi

2017-01-23

Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma. We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED. In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant. Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.

Unorthodox alternative therapies marketed to treat Lyme disease.

PubMed

Lantos, Paul M; Shapiro, Eugene D; Auwaerter, Paul G; Baker, Phillip J; Halperin, John J; McSweegan, Edward; Wormser, Gary P

2015-06-15

Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease

PubMed Central

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Objective: Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. Methods: 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days’ treatment. Results: after 30 days’ treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). Conclusion: patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function. PMID:26309664

Erythropoiesis-stimulating agent use among non-dialysis-dependent CKD patients before and after the trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) using a large US health plan database.

PubMed

Thamer, Mae; Zhang, Yi; Kshirsagar, Onkar; Cotter, Dennis J; Kaufman, James S

2014-11-01

In a landmark study, TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) examined the use of erythropoiesis-stimulating agent (ESA) therapy to treat anemia among patients with chronic kidney disease (CKD) and found no benefit compared to placebo. A retrospective observational design was used to determine the impact of TREAT on clinical practice. A large US health plan database with more than 1.2 million claims for patients with non-dialysis-dependent CKD stages 3 and 4. ESA prescribing 2 years before and after publication of TREAT. Rate of ESA prescribing for ESA-naive and -prevalent cohorts. (1) Monthly ESA prescribing in the 2 years before and after publication of TREAT (ordinary least squares regression), (2) adjusted likelihood of prescribing ESA after TREAT (clustered logistic regression), and (3) probability of receiving ESA therapy based on anemia status (χ(2) test). For patients with CKD stage 3, the proportion prescribed ESA therapy declined from 17% pre-TREAT to 11% post-TREAT (a 38% decline), and for those with CKD stage 4, from 34% to 27% (a 22% decline). Prescribing of ESA therapy was declining even before TREAT, but the decline accelerated in the post-TREAT period (stage 3: change of slope, -0.08 [P<0.001]; stage 4: change of slope, -0.16 [P<0.001]). ESA prescribing declined after TREAT regardless of anemia status; among patients with hemoglobin levels <10g/dL, only 25% of patients with CKD stage 3 and 33% of patients with stage 4 were prescribed ESAs 2 years after TREAT, a notable 50% decline. After adjusting for all covariates, the probability of prescribing ESAs was 35% lower during the 2-year period after versus before publication of TREAT (OR, 0.65; 95% CI, 0.63-0.67). The cumulative effect of adverse safety concerns in the period before TREAT also influenced physician prescribing of ESA therapy and could not be separated from the influence of TREAT. TREAT appears to be a watershed study that was followed by a marked

Effectiveness of Physical Therapy in Treating Atraumatic Full Thickness Rotator Cuff Tears. A Multicenter Prospective Cohort Study

PubMed Central

Kuhn, John E.; Dunn, Warren R.; Sanders, Rosemary; An, Qi; Baumgarten, Keith M.; Bishop, Julie Y.; Brophy, Robert H.; Carey, James L.; Holloway, Brian G.; Jones, Grant L.; Ma, C. Benjamin; Marx, Robert G.; McCarty, Eric C.; Poddar, Sourav K.; Smith, Matthew V.; Spencer, Edwin E.; Vidal, Armando F.; Wolf, Brian R.; Wright, Rick W.

2013-01-01

Purpose To assess the effectiveness of a specific non-operative physical therapy program in treating atraumatic full thickness rotator cuff tears using a multicenter prospective cohort study design. Methods Patients with atraumatic full thickness rotator cuff tears who consented to enroll provided data via questionnaire on demographics, symptom characteristics, co-morbidities, willingness to undergo surgery, and patient related outcome assessments (SF-12, ASES, WORC, SANE score, Shoulder Activity Scale). Physicians recorded physical examination and imaging data. Patients began a physical therapy program developed from a systematic review of the literature and returned for evaluation at 6 and 12 weeks. At those visits patients could chose one of three courses: 1.) Cured (no formal follow up scheduled), 2.) Improved (continue therapy with scheduled reassessment in 6 weeks), or 3.) No better (offered surgery). Patients were contacted by telephone at 1 and 2 years to determine if they had undergone surgery since their last visit. A Wilcoxon signed rank test with continuity correction was used to compare initial, 6 week, and 12 week outcome scores. Results The cohort consists of 452 patients. Patient reported outcomes improved significantly at 6 and 12 weeks. Patients elected to undergo surgery less than 25% of the time. Patients who decided to have surgery generally did so between 6 and 12 weeks, and few had surgery between 3 and 24 months. Conclusion Non-operative treatment using this physical therapy protocol is effective for treating atraumatic full thickness rotator cuff tears in approximately 75% of patients followed for two years. Level of evidence Level IV, Case Series, Treatment Study PMID:23540577

Protein C deficiency related obscure gastrointestinal bleeding treated by enteroscopy and anticoagulant therapy.

PubMed

Hsu, Wei-Fan; Tsang, Yuk-Ming; Teng, Chung-Jen; Chung, Chen-Shuan

2015-01-21

Obscure gastrointestinal bleeding is an uncommonly encountered and difficult-to-treat clinical problem in gastroenterology, but advancements in endoscopic and radiologic imaging modalities allow for greater accuracy in diagnosing obscure gastrointestinal bleeding. Ectopic varices account for less than 5% of all variceal bleeding cases, and jejunal variceal bleeding due to extrahepatic portal hypertension is rare. We present a 47-year-old man suffering from obscure gastrointestinal bleeding. Computed tomography of the abdomen revealed multiple vascular tufts around the proximal jejunum but no evidence of cirrhosis, and a visible hypodense filling defect suggestive of thrombus was visible in the superior mesenteric vein. Enteroscopy revealed several serpiginous varices in the proximal jejunum. Serologic data disclosed protein C deficiency (33.6%). The patient was successfully treated by therapeutic balloon-assisted enteroscopy and long-term anticoagulant therapy, which is normally contraindicated in patients with gastrointestinal bleeding. Diagnostic modalities for obscure gastrointestinal bleeding, such as capsule endoscopy, computed tomography enterography, magnetic resonance enterography, and enteroscopy, were also reviewed in this article.

Circulating endothelial progenitor cells are inversely correlated with in-stent restenosis in patients with non-ST-segment elevation acute coronary syndromes treated with EPC-capture stents (JACK-EPC trial).

PubMed

Wojakowski, W; Pyrlik, A; Król, M; Buszman, P; Ochała, A; Milewski, K; Smolka, G; Kawecki, D; Rudnik, A; Pawłowski, T; Jadczyk, T; Wyderka, R; Cybulski, W; Dworowy, S; Tendera, M

2013-06-01

Aim of the study was to evaluate the association between circulating endothelial progenitor cells (EPCs) and angiographic outcomes after implantation of GenousTM stent in patients with non-ST-segment elevation acute coronary syndromes (ACS) (NSTE-ACS) undergoing urgent percutaneous coronary intervention (PCI). Sixty patients treated with EPC-capture stent (N.=30) or bare metal stents (BMS) (N.=30) receiving 80 mg atorvastatin and dual antiplatelet therapy (DAT) for 12 months. Restenosis was assessed after 6 months by quantitative coronary angiography (QCA) and major acute coronary events (MACE) evaluated after 6 and 12 months. de novo lesion >70% in native vessel, diameter 2.5-4 mm, lesion length <30 mm. diabetes, previous revascularization, significant left main stenosis, chronic total occlusions (CTO) and multivessel disease. Majority of patients in EPC-capture stent and BMS groups presented with NSTEMI (73.3% and 70%, respectively). Mean stent length was 20.1±8 and 19.9±10 mm, diameter 3±0.97 and 3.1±0.88 mm in respective groups. The binary restenosis was significantly lower in GenousTM (13 vs. 26.6%, P=0.04). Risk of MACE after 6 and 12 months were comparable in both groups. There was no stent thrombosis. Numbers of circulating EPCs were significantly approximately 2-fold higher during the ACS than after 6 months. Mobilization of EPCs during acute ischemia was significantly lower in patients who developed restenosis after 6 months (3 vs. 4.5 cells/μL, P=0.002) and it was negatively correlated with late-loss after 6 months (R=-0.42; P<0.03). Use of GenousTM stents in NSTE-ACS is associated with lower restenosis rate than BMS at 6 months. There was no ST through 1 year. The number of circulating EPCs is inversely correlated with in-stent late loss (LL).

Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

PubMed

Andoh, T; Fujimoto, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Kawabata, S; Kirihata, M; Akisue, T; Yayama, K; Kurosaka, M; Miyatake, S; Fukumori, Y; Ichikawa, H

2011-12-01

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg). Copyright © 2011 Elsevier Ltd. All rights reserved.

Characteristics of newly diagnosed COPD patients treated with triple inhaled therapy by general practitioners: a real world Italian study.

PubMed

Di Marco, Fabiano; Santus, Pierachille; Terraneo, Silvia; Peruzzi, Elena; Muscianisi, Elisa; Ripellino, Claudio; Pegoraro, Valeria

2017-09-07

Factors predicting prescriptions of triple therapy were investigated in a large group of general practitioners in Italy. In the population treated by identified general practitioners, a cohort of newly diagnosed chronic obstructive pulmonary disease patients was extracted from IMS Health Longitudinal Database during the period 2010-2013. From the diagnosis, 1-year follow-up was evaluated. Thirty-two thousand forty-six newly diagnosed chronic obstructive pulmonary disease patients were evaluated (57.7% male, mean age 67 years). During 2 years prior to diagnosis less than 13% of patients were requested with a pulmonology evaluation and less than 5% with a spirometry; 65.1% cases were prescribed with a respiratory drug, which in 9.6% of cases was inhaled corticosteroid/long-acting β 2 -agonist fixed-dose combination. Two thousand and twenty eight patients (6.3% of the newly diagnosed chronic obstructive pulmonary disease patients) were treated with triple therapy during the first year of follow-up, whose 858 (42.3%) starting immediately, and 762 (37.6%) following an initial treatment with inhaled corticosteroid/long-acting β 2 -agonist fixed-dose combination. Being older, being requested with pulmonologist evaluation or spirometry, being prescribed with a inhaled corticosteroid/long-acting β 2 -agonist fixed-dose combination at diagnosis resulted independent predictors of triple therapy use. ENSURING CORRECT PRESCRIPTIONS FOR EARLY-STAGE DISEASE: An improved education program for doctors promoting correct use of medication for chronic lung disease is needed in Italy. Current guidelines state that inhaled corticosteroids (ICSs) should be reserved for patients with severe chronic obstructive pulmonary disease (COPD), but it appears that doctors do not always follow this advice. Fabiano Di Marco, at San Paolo Hospital-Università degli Studi di Milano, and co-workers analyzed data from 32,046 COPD patients newly-diagnosed by family doctors in Italy between 2010 and

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

PubMed

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

2015-06-23

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

Influence of p53 status on the effects of boron neutron capture therapy in glioblastoma.

PubMed

Seki, Keiko; Kinashi, Yuko; Takahashi, Sentaro

2015-01-01

The tumor suppressor gene p53 is mutated in glioblastoma. We studied the relationship between the p53 gene and the biological effects of boron neutron capture therapy (BNCT). The human glioblastoma cells; A172, expressing wild-type p53, and T98G, with mutant p53, were irradiated by the Kyoto University Research Reactor (KUR). The biological effects after neutron irradiation were evaluated by the cell killing effect, 53BP1 foci assay and apoptosis induction. The survival-fraction data revealed that A172 was more radiosensitive than T98G, but the difference was reduced when boronophenylalanine (BPA) was present. Both cell lines exhibited similar numbers of foci, suggesting that the initial levels of DNA damage did not depend on p53 function. Detection of apoptosis revealed a lower rate of apoptosis in the T98G. BNCT causes cell death in glioblastoma cells, regardless of p53 mutation status. In T98G cells, cell killing and apoptosis occurred effectively following BNCT. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

PubMed Central

Xia, Feifei; Li, Xin; Wang, Bin; Gong, Pengjuan; Xiao, Feng; Yang, Mei; Zhang, Lei; Song, Jun; Hu, Liyuan; Cheng, Mengjun; Sun, Changjiang; Feng, Xin; Lei, Liancheng; Ouyang, Songying; Liu, Zhi-Jie; Li, Xinwei

2015-01-01

Pneumonia is one of the most prevalent Staphylococcus aureus-mediated diseases, and the treatment of this infection is becoming challenging due to the emergence of multidrug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA) strains. It has been reported that LysGH15, the lysin derived from phage GH15, displays high efficiency and a broad lytic spectrum against MRSA and that apigenin can markedly diminish the alpha-hemolysin of S. aureus. In this study, the combination therapy of LysGH15 and apigenin was evaluated in vitro and in a mouse S. aureus pneumonia model. No mutual adverse influence was detected between LysGH15 and apigenin in vitro. In animal experiments, the combination therapy showed a more effective treatment effect than LysGH15 or apigenin monotherapy (P < 0.05). The bacterial load in the lungs of mice administered the combination therapy was 1.5 log units within 24 h after challenge, whereas the loads in unprotected mice or mice treated with apigenin or LysGH15 alone were 10.2, 4.7, and 2.6 log units, respectively. The combination therapy group showed the best health status, the lowest ratio of wet tissue to dry tissue of the lungs, the smallest amount of total protein and cells in the lung, the fewest pathological manifestations, and the lowest cytokine level compared with the other groups (P < 0.05). With regard to its better protective efficacy, the combination therapy of LysGH15 and apigenin exhibits therapeutic potential for treating pneumonia caused by MRSA. This paper reports the combination therapy of lysin and natural products derived from traditional Chinese medicine. PMID:26475103

A Retrospective Chart Review of Chronic Wound Patients Treated with Topical Oxygen Therapy.

PubMed

Copeland, Karen; Purvis, Angie R

2017-05-01

Objective: Topical oxygen devices are Food and Drug Administration (FDA) cleared for the following indications for use of various etiologies: skin ulcerations due to diabetes, venous stasis, postsurgical infections and gangrenous lesions, decubitus ulcers; amputations/infected stumps; skin grafts; burns; and frostbite. The goal of this study was to understand the impact of topical oxygen therapy (TOT) on patient outcomes, including amputation and healing rates. Approach: This retrospective chart review included records collected between January 1, 2007, and July 18, 2016, from male and female patients ranging in age from 4 years to 105 years. All wounds were at least 1 cm 2 and were treated with at least one separate modality before treatment with TOT and then treated with TOT for a minimum of 2 weeks in compliance with the FDA-approved indications. All records were from wounds that were no longer being treated with TOT. Results: In this study, TOT was associated with an overall rate of 59.4% for a reduction in chronic wound size, while 41.6% of wounds had no healing. The overall amputation rate was 2.4% for wounds in this study. Innovation: To our knowledge, this retrospective chart review represents one of the largest data sets (4,127 total wounds) collected over one of the longest time periods (9.5 years) to evaluate patient outcomes following TOT. Conclusion: This study revealed healing and amputation rates similar to those reported in controlled clinical studies using TOT to treat chronic wounds.

A rationale for treating leg length discrepancy using photodynamic therapy

NASA Astrophysics Data System (ADS)

Bisland, Stuart K.; Johnson, Crystal; Diab, Mohammed; Wilson, Brian C.; Burch, Shane

2005-09-01

This study investigates the use of photodynamic therapy (PDT) in regulating bone development with a view to its potential role in treating Juvenile leg length discrepancy (LLD). Transgenic mice expressing the luciferase firefly gene upon activation of a promoter sequence specific to the vascular endothelial growth factor (VEGF) gene were subject to benzoporphyrin derivative monoacid (BPD-MA)-mediated PDT in the right, tibial epiphyseal growth plate at the age of 3 weeks. BPD-MA was administered intracardially (2mg/kg) followed 10 mins later by a laser light (690 +/- 5 nm) at a range of doses (5-27J, 50 mW output) delivered either as a single or repeat regimen (x2-3). Contra-lateral legs served as no-light controls. Further controls included animals that received light treatment in the absence of photosensitizer or no treatment. Mice were imaged for VEGF related bioluminescence (photons/sec/steradian) at t= 0, 24, 48, 72 h and 1-4 weeks post PDT. FaxitronTM x-ray images provided accurate assessment of bone morphometry. Upon sacrifice, the tibia and femur of the treated and untreated limbs were harvested, imaged and measured again and prepared for histology. A number of animals were sacrificed at 24 h post PDT to allow immunohistochemical staining for CD31, VEGF and hypoxia-inducible factor (HIF-1 alpha) within the bone. PDT-treated (10 J, x2) mice displayed enhanced bioluminescence at the treatment site (and ear nick) for up to 4 weeks post treatment while control mice were bioluminescent at the ear-nick site only. Repeat regimens provided greater shortening of the limb than the corresponding single treatment. PDT-treated limbs were shorter by 3-4 mm on average as compared to the contra lateral and light only controls (10 J, x2). Immunohistochemistry confirmed the enhanced expression VEGF and CD31 at 4 weeks post-treatment although no increase in HIF-1α was evident at either 24 h or 4 weeks post PDT treatment. Results confirm the utility of PDT to provide localized

Mucoepidermoid carcinoma of the parotid gland treated by surgery and postoperative radiation therapy: clinicopathologic correlates of outcome.

PubMed

Chen, Allen M; Lau, Valerie H; Farwell, D Gregory; Luu, Quang; Donald, Paul J

2013-12-01

To determine clinical and pathological correlates of outcome among patients treated by surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Retrospective review. The medical records of 61 patients treated by surgery and postoperative radiation therapy for localized mucoepidermoid carcinoma of the parotid gland were retrospectively reviewed in an attempt to identify clinicopathologic correlates of overall survival. Secondary endpoints included local-regional control, distant metastasis-free survival, and complications. The 3- and 5-year estimates of overall survival were 85% and 79%, respectively. Multivariate analysis identified high tumor grade (hazard ratio [HR] = 7.92) and T4 disease (HR = 3.35) as independent predictors of decreased survival, with the former also predicting for distant metastasis and the latter predicting for local-regional recurrence. The 5-year estimate of overall survival was 83% for patients with non-high-grade tumors, compared to 52% for those with high-grade histology (P = 0.001). Late complications included trismus (2 patients), osteoradionecrosis (1 patient), and hearing loss (1 patient). Patients with high-grade tumors and T4 disease are at increased risk for treatment failure after surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Investigative strategies to improve outcome should be considered for these particular patients in the future. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Micromachined fragment capturer for biomedical applications.

PubMed

Choi, Young-Soo; Lee, Dong-Weon

2011-11-01

Due to changes in modern diet, a form of heart disease called chronic total occlusion has become a serious disease to be treated as an emergency. In this study, we propose a micromachined capturer that is designed and fabricated to collect plaque fragments generated during surgery to remove the thrombus. The fragment capturer consists of a plastic body made by rapid prototyping, SU-8 mesh structures using MEMS techniques, and ionic polymer metal composite (IPMC) actuators. An array of IPMC actuators combined with the SU-8 net structure was optimized to effectively collect plaque fragments. The evaporation of solvent through the actuator's surface was prevented using a coating of SU-8 and polydimethylsiloxane thin film on the actuator. This approach improved the available operating time of the IPMC, which primarily depends on solvent loss. Our preliminary results demonstrate the possibility of using the capturer for biomedical applications. © 2011 American Institute of Physics

Effectiveness of Transactional Analysis Group Therapy on Addiction Intensity of Woman Patients Treated with Methadone.

PubMed

Etemadi-Chardah, Niloofar; Matinpour, Bahman; Heshmati, Rasoul

2017-07-01

Addiction brings about severe and profound physical, psychological and social damages such as divorce, crime, and unemployment. The present study was to investigate the effectiveness of transactional analysis (TA) therapy on addiction intensity of woman patients treated with methadone. The research design was quasi-experimental with a pretest-posttest and a control group. The statistical population consisted of all the addicted women who referred to any drug rehabilitation center of Tehran, Iran, in 2016. They were selected using available sampling. Forty addicted patients were placed randomly in both the experimental and control groups. Addiction severity index (ASI) and demographic questionnaires were used. Group therapy using TA approach was executed on the experimental group for 10 sessions, each session for 2 hours (one session per week). The results of covariance analysis after controlling pretest showed that the difference between test and control group was significant for three subscales of psychological, drug abuse and alcohol consumption status (P < 0.001). The difference between test and control groups was significant considering the seven-variable centroid (P < 0.001). The difference in dimensions of addiction intensity between the two groups was significant (P < 0.001). Also, analysis of the variables separately showed significant differences in psychiatric condition, drug and alcohol use dimensions (P < 0.001). Based on these findings, it seems that group therapy using TA approach is effective in reducing addiction intensity of woman patients treated with methadone. Therefore, it can be concluded that TA group interventions account for 76% of the changes in psychological status, 43% of the changes in drug abuse status, and 49% of the changes in alcohol consumption status in woman patients under methadone treatment.

A proton therapy model using discrete difference equations with an example of treating hepatocellular carcinoma.

PubMed

Bodine, Erin N; Monia, K Lars

2017-08-01

Proton therapy is a type of radiation therapy used to treat cancer. It provides more localized particle exposure than other types of radiotherapy (e.g., x-ray and electron) thus reducing damage to tissue surrounding a tumor and reducing unwanted side effects. We have developed a novel discrete difference equation model of the spatial and temporal dynamics of cancer and healthy cells before, during, and after the application of a proton therapy treatment course. Specifically, the model simulates the growth and diffusion of the cancer and healthy cells in and surrounding a tumor over one spatial dimension (tissue depth) and the treatment of the tumor with discrete bursts of proton radiation. We demonstrate how to use data from in vitro and clinical studies to parameterize the model. Specifically, we use data from studies of Hepatocellular carcinoma, a common form of liver cancer. Using the parameterized model we compare the ability of different clinically used treatment courses to control the tumor. Our results show that treatment courses which use conformal proton therapy (targeting the tumor from multiple angles) provides better control of the tumor while using lower treatment doses than a non-conformal treatment course, and thus should be recommend for use when feasible.

Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves' ophthalmopathy treated successfully with glucocorticoids themselves.

PubMed

Marinò, M; Morabito, E; Altea, M A; Ambrogini, E; Oliveri, F; Brunetto, M R; Pollina, L E; Campani, D; Vitti, P; Bartalena, L; Pincheral, A; Marcocci, C

2005-03-01

We report a case of acute hepatitis of autoimmune origin which occurred in a 43-yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves' ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no previous history of liver disorders or conditions predisposing to GC-associated liver damage. After the administration of a 4.7-g cumulative dose of methylprednisolone acetate, there was a marked increase of liver enzymes, prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes increased further, reaching a peak 45 days later, with values 30- to 50-fold greater than those prior to therapy, associated with evidence of impaired liver function. Liver biopsy showed a marked lymphocytic infiltration, likely indicating an autoimmune hepatitis. Based on the assumption that following GC-induced immune suppression, autoimmune hepatitis might have been precipitated by sudden re-activation of the immune system during interpulse periods, we treated the patient with im and then oral GC, in order to re-induce immune suppression. Within three days from re-institution of GC therapy, there was a marked reduction of liver enzymes and amelioration of liver function. Complete normalization was achieved two months later, while the patient was still receiving a low maintenance dose of oral prednisone.

A catheter-related bloodstream infection caused by Chryseobacterium indologenes successfully treated with antibiotic-lock rescue therapy.

PubMed

Corbella, Marta; Brandolini, Micaela; Cambieri, Patrizia; Decembrino, Nunzia; Pagani, Michele; Bottazzi, Andrea; Muzzi, Alba; Zecca, Marco; Mariani, Bianca; Marone, Piero

2017-07-01

We report the case of a catheter-related bloodstream infection caused by Chryseobacterium indologenes, an uncommon and multi-resistant pathogen, in a pediatric patient with a long-term vascular access device placed for chemotherapy treatment. The infection was successfully treated with ciprofloxacin antibiotic-lock therapy. This is the first report on successful salvage of a long-term device colonized by multi-resistant Chryseobacterium indologenes.

Clinical activity of fulvestrant in metastatic breast cancer previously treated with endocrine therapy and/or chemotherapy.

PubMed

Heo, Mi Hwa; Kim, Hee Kyung; Lee, Hansang; Kim, Ji-Yeon; Ahn, Jin-Seok; Im, Young-Hyuck; Park, Yeon Hee

2018-03-16

We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy. We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016). Tumor responses were assessed every 8 weeks and at the end of treatment, as well as when disease progression was suspected. A total of 84 patients were included in this study. A median of two previous endocrine treatments had been performed; 79% of the patients had received two or more endocrine treatments. Forty-five patients (54%) had been treated with chemotherapy for MBC before the fulvestrant treatment course. Visceral metastasis was found in 49 patients (58%). The estimated median progression-free survival and overall survival were 4.4 months (95% confidence interval [CI], 3.4 to 5.5) and 32.5 months (95% CI, 17.6 to 47.4), respectively. The disease control rate was 40.5% (95% CI, 30.5 to 51.5); partial response was observed in 16% of the patients and stable disease was observed in 25% of the patients. The most frequently reported adverse reactions were mild-to-moderate grade myalgia (10.5% of the patients), injection site pain (7%), and fatigue (7%). Fulvestrant was generally well tolerated. Fulvestrant showed encouraging clinical activity and favorable feasibility in postmenopausal women with MBC who had been treated with multiple endocrine therapies and/or cytotoxic chemotherapies.

Bogolon-mediated electron capture by impurities in hybrid Bose-Fermi systems

NASA Astrophysics Data System (ADS)

Boev, M. V.; Kovalev, V. M.; Savenko, I. G.

2018-04-01

We investigate the processes of electron capture by a Coulomb impurity center residing in a hybrid system consisting of spatially separated two-dimensional layers of electron and Bose-condensed dipolar exciton gases coupled via the Coulomb forces. We calculate the probability of the electron capture accompanied by the emission of a single Bogoliubov excitation (bogolon), similar to regular phonon-mediated scattering in solids. Furthermore, we study the electron capture mediated by the emission of a pair of bogolons in a single capture event and show that these processes not only should be treated in the same order of the perturbation theory, but also they give a more important contribution than single-bogolon-mediated capture, in contrast with regular phonon scattering.

The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orman, Amber; Koru-Sengul, Tulay; Miao, Feng

2014-12-01

Purpose/Objective(s): To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. Methods and Materials: This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. Results: Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT inmore » 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. Conclusions: External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.« less

Towards boron neutron capture therapy: the formulation and preliminary in vitro evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium salt of bis-nido-carborane.

PubMed

Theodoropoulos, Dimitrios; Rova, Aikaterini; Smith, James R; Barbu, Eugen; Calabrese, Gianpiero; Vizirianakis, Ioannis S; Tsibouklis, John; Fatouros, Dimitrios G

2013-11-15

Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that incorporate bis-nido-carborane dequalinium salt are stable in physiologically relevant media and have in vitro toxicity profiles that appear to be compatible with potential therapeutic applications. These features render the structures suitable candidate boron-delivery vehicles for evaluation in the boron neutron capture therapy of cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro.

PubMed

Sun, Ting; Zhang, Zizhu; Li, Bin; Chen, Guilin; Xie, Xueshun; Wei, Yongxin; Wu, Jie; Zhou, Youxin; Du, Ziwei

2013-08-06

Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma.

Treating Individuals With Intellectual Disabilities and Challenging Behaviors With Adapted Dialectical Behavior Therapy

PubMed Central

Brown, Julie F.; Brown, Milton Z.; Dibiasio, Paige

2013-01-01

Approximately one third of adults with intellectual and developmental disabilities have emotion dysregulation and challenging behaviors (CBs). Although research has not yet confirmed that existing treatments adequately reduce CBs in this population, dialectical behavior therapy (DBT) holds promise, as it has been shown to effectively reduce CBs in other emotionally dysregulated populations. This longitudinal single-group pilot study examined whether individuals with impaired intellectual functioning would show reductions in CBs while receiving standard DBT individual therapy used in conjunction with the Skills System (DBT-SS), a DBT emotion regulation skills curriculum adapted for individuals with cognitive impairment. Forty adults with developmental disabilities (most of whom also had intellectual disabilities) and CBs, including histories of aggression, self-injury, sexual offending, or other CBs, participated in this study. Changes in their behaviors were monitored over 4 years while in DBT-SS. Large reductions in CBs were observed during the 4 years. These findings suggest that modified DBT holds promise for effectively treating individuals with intellectual and developmental disabilities. PMID:23914278

Acupuncture therapy in treating migraine: results of a magnetic resonance spectroscopy imaging study

PubMed Central

Gu, Tao; Lin, Lei; Jiang, Yun; Chen, Juan; D’Arcy, Ryan CN; Chen, Min; Song, Xiaowei

2018-01-01

Background Acupuncture has been proven to be effective as an alternative therapy in treating migraine, but the pathophysiological mechanisms of the treatment remain unclear. This study investigated possible neurochemical responses to acupuncture treatment. Patients and methods Proton magnetic resonance spectroscopy imaging was used to investigate biochemical levels pre- and post-acupuncture treatment. Participants (N=45) included subjects diagnosed with: 1) migraine without aura; 2) cervicogenic headache; and 3) healthy controls. Participants in the two patient groups received verum acupuncture using acupoints that target migraine without aura but not cervicogenic headache, while the healthy controls received a sham treatment. All participants had magnetic resonance spectroscopy scans before and after the acupuncture therapy. Levels of brain metabolites were examined in relation to clinical headache assessment scores. Results A significant increase in N-acetylaspartate/creatine was observed in bilateral thalamus in migraine without aura after the acupuncture treatment, which was significantly correlated with the headache intensity score. Conclusion The data demonstrate brain biochemical changes underlying the effect of acupuncture treatment of migraine. PMID:29740217

Incorporating Physical Activity with Dialectical Behavior Therapy to Treat Non Suicidal Self Injury in Freshman Female University Students

ERIC Educational Resources Information Center

Lovelady, Tiffany T.

2016-01-01

As Non-Suicidal Self Injury (NSSI) is increasing in prevalence among adolescents and young adults, College Counseling Centers (CCC's) are tasked with treating this population of students. CCC's are designed to provide counseling services to all students seeking assistance and therapy is typically relegated to short term psychotherapy with…

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

PubMed

Hall, Matthew D; Schultheiss, Timothy E; Smith, David D; Fakih, Marwan G; Wong, Jeffrey Y C; Chen, Yi-Jen

2016-12-01

Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

PubMed Central

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-01-01

Purpose Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. Methods B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. Results B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. Conclusions B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on tumor hypoxic metabolism, and further studies are warranted to evaluate this compound and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma. PMID:27401411

Anal fistula with foot extension—Treated by kshara sutra (medicated seton) therapy: A rare case report

PubMed Central

Ramesh, P. Bhat

2013-01-01

INTRODUCTION An ‘anal’ fistula is a track which communicates anal canal or rectum and usually is in continuity with one or more external openings. Distant communication from rectum is rare. It is a challenging disease because of its recurrence especially, with high level and distant communications. Ksharasutra (medicated seton) therapy is being practiced in India with high success rate (recurrence of 3.33%) in the management of complicated anal fistula. PRESENTATION OF CASE A 56 year old man presented with recurrent boils in the left lower limb at different places from thigh to foot. He underwent repeated incision and drainage at different hospitals. Examination revealed sinus with discharge and multiple scars on left lower limb from thigh up to foot. Suspecting anal fistula, MRI was advised which revealed a long cutaneous fistula from rectum to left lower limb. Patient was treated with Ksharasutra therapy. Within 6 months of treatment whole tract was healed completely. DISCUSSION Sushrutha (500BC) was the first to explain the role of surgical excision and use of kshara sutra for the management of anal fistula. Ksharasutra therapy showed least recurrence. Fistula from rectum to foot is of extremely rare variety. Surgical treatment of anal fistula requires hospitalization, regular post-operative care, is associated with a significant risk of recurrence (0.7–26.5%) and a high risk of impaired continence (5–40%). CONCLUSION Rectal fistula communicating till foot may be a very rare presentation in proctology practice. Kshara sutra treatment was useful in treating this condition, with minimal surgical intervention with no recurrence. PMID:23702360

[Morita Therapy to Treat Depression: When and How to Encourage Patients to Join Activities].

PubMed

Nakamura, Kei

2015-01-01

The author discusses how Morita therapy is used to treat depression, illustrated with a clinical case, and makes comparisons between Morita therapy and behavioral activation (BA). The author further examines the issue of when and how to encourage patients to join activities in clinical practice in Japan. Both Morita therapy and BA share at least a common view that it is effective to activate patients' constructive behavior at a certain point in depression treatment. However, BA therapists, compared to Morita therapists, seem to pay less attention to the necessity of resting and the appropriate timing for introducing behavioral activation. There may be some contextual differences between depressive patients in Japan and those in North America. In the case of Japanese patients, exhaustion from overwork is often considered a factor triggering the development of depression. At the same time, the Morita-based pathogenic model of depression seems different from BA's model of the same disorder. BA's approach to understanding depression may be considered a psychological (behavioristic) model. In this model, the cause of depression lies in: (a) a lack of positive reinforcement, and (b) negative reinforcement resulting from avoidance of the experience of discomfort. Therefore, the basic strategy of BA is to release depressive patients from an avoidant lifestyle, which serves as a basis for negative reinforcement, and to redirect the patients toward activities which offer the experience of positive reinforcement BA is primarily practiced by clinical psychologists in the U. S. while psychiatrists prescribe medication as a medical service. On the other hand, the clinical practice of treating depression in Japan is based primarily on medical models of depression. This is also true of Morita therapy, but in a broad sense. While those who follow medical models in a narrow sense try to identify the cause of illness and then remove it, Morita therapists pay more attention to the

Periodontal Therapy Reduces the Severity of Active Rheumatoid Arthritis in Patients Treated With or Without Tumor Necrosis Factor Inhibitors

PubMed Central

Ortiz, P; Bissada, NF; Palomo, L; Han, YW; Al-Zahrani, MS; Panneerselvam, A; Askari, A

2010-01-01

Background Rheumatoid arthritis (RA) and periodontitis (PD) are common chronic inflammatory conditions. Recent studies have shown a beneficial effect of periodontal treatment on reducing the severity of active RA. This study was undertaken to further examine the effect of non-surgical periodontal treatment on signs and symptoms of RA in patients treated with or without anti-Tumor Necrosis Factor (TNF)-α medications. The effect of anti-TNF-α therapy on periodontitis also was assessed. Methods Forty participants diagnosed with moderate/severe RA (under treatment for RA) and severe periodontitis were randomly assigned to receive initial non-surgical periodontal therapy with scaling/root planing and oral hygiene instructions (n=20) or no periodontal therapy (n=20). To control RA, all participants had been using disease-modifying anti-rheumatic drugs (DMARDs), and 20 had been using anti-TNF-α in addition to DMARDs before randomization. Periodontal probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival (GI) and plaque (PI) indices, RA disease activity score (DAS-28) and erythrocyte sedimentation rate (ESR) were measured at baseline and six weeks afterwards. Linear mixed models were used to identify significant differences between subjects receiving periodontal treatment and those who did not. Results Patients receiving periodontal treatment showed a significant decrease in the mean DAS28, ESR (p < 0.001) and serum TNF-α (p < 0.05). There was no statistically significant decrease in these parameters in those patients not receiving periodontal treatment. Anti- TNF-α therapy resulted in a significant improvement in CAL, PD, BOP and GI. Conclusions Non-surgical periodontal therapy had a beneficial effect on signs and symptoms of RA regardless of the medications used to treat this condition. Anti-TNF-α therapy without periodontal treatment has no significant effect on the periodontal condition. PMID:19335072

Incidence of anaemia among HIV-infected patients treated with highly active antiretroviral therapy.

PubMed

Curkendall, S M; Richardson, J T; Emons, M F; Fisher, A E; Everhard, F

2007-11-01

The aim of the study was to compare the incidence of anaemia in patients treated with zidovudine (ZDV) with that in patients treated with highly active antiretroviral therapy (HAART) not including ZDV. Using HIV Insight, a database of abstracted US HIV care centre medical charts, ZDV-naïve patients starting ZDV-containing HAART were compared with those starting non-ZDV, nucleoside reverse transcriptase inhibitor-containing HAART. Cohorts were divided as follows: group 1: without baseline anaemia [haemoglobin (Hb) >or=11 g/dL]; group 2: with baseline anaemia (Hb <11 g/dL). The incidence of anaemia (anaemia diagnosis, Hb <11 g/dL, erythropoietic therapy or blood transfusion) was computed for group 1. The anaemia hazard ratio (HR) was adjusted using Cox regression. The rate of worsening anaemia (Hb decrease >or=1.0 g/dL) was computed for group 2. In group 1, the incidence of anaemia was 24.3 and 8.1 per 100 person-years in the ZDV and non-ZDV cohorts, respectively, after 6 months of follow-up, and 12.5 and 5.3 per 100 person-years after 24 months. Significant predictors of anaemia were ZDV, low initial Hb, injecting drug use, CD4 count <200 cells/microL and AIDS. The adjusted HR for ZDV was 1.6 (P=0.005). In group 2, the ZDV/non-ZDV risk ratio for worsening anaemia was 2.2 (95% confidence interval 1.1-4.3). Patients initiating ZDV-containing HAART are at greater risk of developing new anaemia or worsening anaemia than patients initiating non-ZDV-containing HAART.

Evaluating the Usefulness of a Novel 10B-Carrier Conjugated With Cyclic RGD Peptide in Boron Neutron Capture Therapy

PubMed Central

Masunaga, Shin-ichiro; Kimura, Sadaaki; Harada, Tomohiro; Okuda, Kensuke; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Maruhashi, Akira; Nagasawa, Hideko; Ono, Koji

2012-01-01

Background To evaluate the usefulness of a novel 10B-carrier conjugated with an integrin-binding cyclic RGD peptide (GPU-201) in boron neutron capture therapy (BNCT). Methods GPU-201 was synthesized from integrin-binding Arg-Gly-Asp (RGD) consensus sequence of matrix proteins and a 10B cluster 1, 2-dicarba-closo-dodecaborane-10B. Mercaptododecaborate-10B (BSH) dissolved in physiological saline and BSH and GPU-201 dissolved with cyclodextrin (CD) as a solubilizing and dispersing agent were intraperitoneally administered to SCC VII tumor-bearing mice. Then, the 10B concentrations in the tumors and normal tissues were measured by γ-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with GPU-201, BSH-CD, or BSH. Immediately after reactor neutron beam or γ-ray irradiation, during which intratumor 10B concentrations were kept at levels similar to each other, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. Results The 10B from BSH was washed away rapidly in all these tissues and the retention of 10B from BSH-CD and GPU-201 was similar except in blood where the 10B concentration from GPU-201 was higher for longer. GPU-201 showed a significantly stronger radio-sensitizing effect under neutron beam irradiation on both total and Q cell populations than any other 10B-carrier. Conclusion A novel 10B-carrier conjugated with an integrin-binding RGD peptide (GPU-201) that sensitized tumor cells more markedly than conventional 10B-carriers may be a promising candidate for use in BNCT. However, its toxicity needs to be tested further. PMID:29147290

Ultra-fast electron capture by electrosterically-stabilized gold nanoparticles.

PubMed

Ghandi, Khashayar; Findlater, Alexander D; Mahimwalla, Zahid; MacNeil, Connor S; Awoonor-Williams, Ernest; Zahariev, Federico; Gordon, Mark S

2015-07-21

Ultra-fast pre-solvated electron capture has been observed for aqueous solutions of room-temperature ionic liquid (RTIL) surface-stabilized gold nanoparticles (AuNPs; ∼9 nm). The extraordinarily large inverse temperature dependent rate constants (k(e)∼ 5 × 10(14) M(-1) s(-1)) measured for the capture of electrons in solution suggest electron capture by the AuNP surface that is on the timescale of, and therefore in competition with, electron solvation and electron-cation recombination reactions. The observed electron transfer rates challenge the conventional notion that radiation induced biological damage would be enhanced in the presence of AuNPs. On the contrary, AuNPs stabilized by non-covalently bonded ligands demonstrate the potential to quench radiation-induced electrons, indicating potential applications in fields ranging from radiation therapy to heterogeneous catalysis.

Neuroplastic Sensorimotor Resting State Network Reorganization in Children With Hemiplegic Cerebral Palsy Treated With Constraint-Induced Movement Therapy.

PubMed

Manning, Kathryn Y; Menon, Ravi S; Gorter, Jan Willem; Mesterman, Ronit; Campbell, Craig; Switzer, Lauren; Fehlings, Darcy

2016-02-01

Using resting state functional magnetic resonance imaging (MRI), we aim to understand the neurologic basis of improved function in children with hemiplegic cerebral palsy treated with constraint-induced movement therapy. Eleven children including 4 untreated comparison subjects diagnosed with hemiplegic cerebral palsy were recruited from 3 clinical centers. MRI and clinical data were gathered at baseline and 1 month for both groups, and 6 months later for the case group only. After constraint therapy, the sensorimotor resting state network became more bilateral, with balanced contributions from each hemisphere, which was sustained 6 months later. Sensorimotor resting state network reorganization after therapy was correlated with a change in the Quality of Upper Extremity Skills Test score at 1 month (r = 0.79, P = .06), and Canadian Occupational Performance Measure scores at 6 months (r = 0.82, P = .05). This clinically correlated resting state network reorganization provides further evidence of the neuroplastic mechanisms underlying constraint-induced movement therapy. © The Author(s) 2015.

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma.

PubMed

Aguiar, João P; Cardoso Borges, Fábio; Murteira, Rodrigo; Ramos, Catarina; Gouveia, Emanuel; Passos, Maria José; Miranda, Ana; da Costa, Filipa Alves

2018-06-02

Background Toxicity of oncology treatments in real-life patients is frequently disregarded and hence underreported. Objective To characterize adverse events (AEs) of immunotherapy and targeted therapy reported in patients with locally advanced or metastatic melanoma. Setting District Hospital for Cancer treatment (Instituto Português de Oncologia de Lisboa Francisco Gentil). Method A retrospective cohort of melanoma patients was established, comprising adult patients diagnosed with malignant melanoma treated with immunotherapy or targeted therapy. Exposure was characterized by nature, time and intensity of exposure. To account for different exposure periods, person-time was used as unit of analysis. Main outcomes measure Occurrence of AEs. Results Data from 111 patients included in the cohort indicates the majority received immunotherapy regimens (CTLA-4, anti-PD-1 and combination therapy; (n = 70; 63.1%), among which anti-PD-1 were the predominant treatment. Pembrolizumab was the most frequently prescribed drug (n = 30; 45.7%). Three hundred and seventy-one AEs were extracted. The incidence of AEs was lower in the anti-PD-1 mAc group (54 AEs per 1000 person.months) and the number of AEs/patient was also lower (3.1 ± 2.0). Grade 3 to 4 AEs occurred in 15.3% (n = 17) of the cohort, being more common in the targeted therapy group. Forty-two (11.6%) of the extracted AEs were not described in the Summary of Product Characteristics of the drugs under study. Conclusion This study suggests various known and unknown AEs of immunotherapy and targeted therapy may be identified using the Cancer Registry database. These events should be considered as signals worth further investigation for assessment of causality as the underreporting of AEs in cancer may have potential implications for the patient's quality of life.

Contributions of microtubule rotation and dynamic instability to kinetochore capture

NASA Astrophysics Data System (ADS)

Sweezy-Schindler, Oliver; Edelmaier, Christopher; Blackwell, Robert; Glaser, Matt; Betterton, Meredith

2014-03-01

The capture of lost kinetochores (KCs) by microtubules (MTs) is a crucial part of prometaphase during mitosis. Microtubule dynamic instability has been considered the primary mechanism of KC capture, but recent work discovered that lateral KC attachment to pivoting MTs enabled rapid capture even with significantly reduced MT dynamics. We aim to understand the relative contributions of MT rotational diffusion and dynamic instability to KC capture, as well as KC capture through end-on and/or lateral attachment. Our model consists of rigid MTs and a spherical KC, which are allowed to diffuse inside a spherical nuclear envelope consistent with the geometry of fission yeast. For simplicity, we include a single spindle pole body, which is anchored to the nuclear membrane, and its associated polar MTs. Brownian dynamics treats the diffusion of the MTs and KC and kinetic Monte Carlo models stochastic processes such as dynamic instability. NSF 1546021.

Single institution experience treating 104 vestibular schwannomas with fractionated stereotactic radiation therapy or stereotactic radiosurgery.

PubMed

Anderson, Bethany M; Khuntia, Deepak; Bentzen, Søren M; Geye, Heather M; Hayes, Lori L; Kuo, John S; Baskaya, Mustafa K; Badie, Behnam; Basavatia, Amar; Pyle, G Mark; Tomé, Wolfgang A; Mehta, Minesh P

2014-01-01

The pupose of this study is to assess the long-term outcome and toxicity of fractionated stereotactic radiation therapy (FSRT) and stereotactic radiosurgery (SRS) for 100 vestibular schwannomas treated at a single institution. From 1993 to 2007, 104 patients underwent were treated with radiation therapy for vestibular schwannoma. Forty-eight patients received SRS, with a median prescription dose of 12.5 Gy for SRS (range 9.7-16 Gy). For FSRT, two different fraction schedules were employed: a conventional schedule (ConFSRT) of 1.8 Gy per fraction (Gy/F) for 25 or 28 fractions to a total dose of 45 or 50.4 Gy (n = 19); and a once weekly hypofractionated course (HypoFSRT) consisting of 4 Gy/F for 5 fractions to a total dose of 20 Gy (n = 37). Patients treated with FSRT had better baseline hearing, facial, and trigeminal nerve function, and were more likely to have a diagnosis of NF2. The 5-year progression free rate (PFR) was 97.0 after SRS, 90.5% after HypoFSRT, and 100.0% after ConFSRT (p = NS). Univariate analysis demonstrated that NF2 and larger tumor size (greater than the median) correlated with poorer local control, but prior surgical resection did not. Serviceable hearing was preserved in 60.0% of SRS patients, 63.2% of HypoFSRT patients, and 44.4% of ConFSRT patients (p = 0.6). Similarly, there were no significant differences in 5-year rates of trigeminal toxicity facial nerve toxicity, vestibular dysfunction, or tinnitus. Equivalent 5-year PFR and toxicity rates are shown for patients with vestibular schwanoma selected for SRS, HypoFSRT, and ConFSRT after multidisciplinary evaluation. Factors correlating with tumor progression included NF2 and larger tumor size.

The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide.

PubMed

Michiue, Hiroyuki; Sakurai, Yoshinori; Kondo, Natsuko; Kitamatsu, Mizuki; Bin, Feng; Nakajima, Kiichiro; Hirota, Yuki; Kawabata, Shinji; Nishiki, Tei-ichi; Ohmori, Iori; Tomizawa, Kazuhito; Miyatake, Shin-ichi; Ono, Koji; Matsui, Hideki

2014-03-01

New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the nuclear reaction of boron-10 with neutron irradiation. The median survival of BNCT patients with glioblastoma was almost twice as long as those receiving standard therapy in a Japanese BNCT clinical trial. In this clinical trial, two boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were used for BNCT. BPA is taken up into cells through amino acid transporters that are expressed highly in almost all malignant cells, but BSH cannot pass through the cell membrane and remains outside the cell. We simulated the energy transfer against the nucleus at different locations of boron from outside the cell to the nuclear region with neutron irradiation and concluded that there was a marked difference between inside and outside the cell in boron localization. To overcome this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for transduction of BSH. CPP (cell-membrane penetrating peptide) is very common peptide domains that transduce many physiologically active substances into cells in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize inside a cell. To increase the boron ratio in one BSH-peptide molecule, 8BSH fused to 11R with a dendritic lysine structure was synthesized and administrated to malignant glioma cells and a brain tumor mouse model. 8BSH-11R localized at the cell nucleus and showed a very high boron value in ICP results. With neutron irradiation, the 8BSH-11R administrated group showed a significant cancer killing effect compared to the 100 times higher concentration of BSH-administrated group. We concluded that BSH-fused CPPs were one of the most improved and potential boron compounds in the next-stage BNCT trial and 8BSH-11R may be applied in the clinical setting. Copyright © 2013 Elsevier Ltd. All rights reserved.

A case of pulmonary carcinoid tumour in a pregnant woman successfully treated with bronchoscopic (electrocautery) therapy

PubMed Central

Binesh, Fariba; Samet, Mohammad; Bovanlu, Taghi Roshan

2013-01-01

We present an uncommon case of a carcinoid tumour of the bronchus that was diagnosed during pregnancy in a 28-year-old woman. The patient was admitted at the emergency department with massive haemoptysis. Owing to the patient's critical condition, she underwent urgent flexible bronchoscopy. Bleeding was controlled by local injection of 500 mg tranexamic acid and electrocautery. After the bleeding has stopped, multiple specimens were taken. Histological examination confirmed typical carcinoid tumour. Owing to repeated haemoptysis, she was treated with bronchoscopic (electrocautery) therapy, and, after delivery, she underwent pulmonary lobectomy. Only a few similar cases were found in the literature reporting bronchopulmonary carcinoid tumour during pregnancy and we could not find any similar case which was treated by electrocautery. PMID:23608865

Nuclear magnetic resonance study of Gd-based nanoparticles to tag boron compounds in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Corti, M.; Bonora, M.; Borsa, F.; Bortolussi, S.; Protti, N.; Santoro, D.; Stella, S.; Altieri, S.; Zonta, C.; Clerici, A. M.; Cansolino, L.; Ferrari, C.; Dionigi, P.; Porta, A.; Zanoni, G.; Vidari, G.

2011-04-01

We report the investigation of new organic complexes containing a magnetic moment (Gd-based molecular nanomagnets), which can serve the double purpose of acting as boron neutron capture therapy (BNCT) agents, and at the same time act as contrast agents to detect the molecule in the tissue by a proton magnetic resonance imaging (MRI). We also explore the possibility of monitoring the concentration of the BNCT agent directly via proton and boron NMR relaxation. The absorption of 10B-enriched molecules inside tumoral liver tissues has been shown by NMR measurements and confirmed by α spectroscopy. A new molecular Gd-tagged nanomagnet and BNCT agent (GdBPA) has been synthesized and characterized measuring its relaxivity R1 between 10 kHz and 66 MHz, and its use as a contrast agent in MRI has been demonstrated. The NMR-based evidence of the absorption of GdBPA into living tumoral cells is also shown.

The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma.

PubMed

Bernard-Arnoux, F; Lamure, M; Ducray, F; Aulagner, G; Honnorat, J; Armoiry, X

2016-08-01

There is strong concern about the costs associated with adding tumor-treating fields (TTF) therapy to standard first-line treatment for glioblastoma (GBM). Hence, we aimed to determine the cost-effectiveness of TTF therapy for the treatment of newly diagnosed patients with GBM. We developed a 3-health-state Markov model. The perspective was that of the French Health Insurance, and the horizon was lifetime. We calculated the transition probabilities from the survival parameters reported in the EF-14 trial. The main outcome measure was incremental effectiveness expressed as life-years gained (LYG). Input costs were derived from the literature. We calculated the incremental cost-effectiveness ratio (ICER) expressed as cost/LYG. We used 1-way deterministic and probabilistic sensitivity analysis to evaluate the model uncertainty. In the base-case analysis, adding TTF therapy to standard of care resulted in increases of life expectancy of 4.08 months (0.34 LYG) and €185 476 per patient. The ICER was €549 909/LYG. The discounted ICER was €596 411/LYG. Parameters with the most influence on ICER were the cost of TTF therapy, followed equally by overall survival and progression-free survival in both arms. The probabilistic sensitivity analysis showed a 95% confidence interval of the ICER of €447 017/LYG to €745 805/LYG with 0% chance to be cost-effective at a threshold of €100 000/LYG. The ICER of TTF therapy at first-line treatment is far beyond conventional thresholds due to the prohibitive announced cost of the device. Strong price regulation by health authorities could make this technology more affordable and consequently accessible to patients. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identification of a putative protein profile associating with tamoxifen therapy resistance in breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Umar, Arzu; Kang, Hyuk; Timmermans, A. M.

2009-06-01

Tamoxifen-resistance is a major cause of death in patients with recurrent breast cancer. Current clinical factors can correctly predict therapy response in only half of the treated patients. Identification of proteins that associate with tamoxifen-resistance is a first step towards better response prediction and tailored treatment of patients. In the present study we intended to identify putative protein biomarkers indicative of tamoxifen therapy-resistance in breast cancer, using nanoLC coupled with FTICR MS. Comparative proteome analysis was performed on ~5,500 pooled tumor cells (corresponding to ~550 ng protein lysate/analysis) obtained through laser capture microdissection (LCM) from two independently processed data setsmore » (n=24 and n=27) containing both tamoxifen therapy-sensitive and therapy-resistant tumors. Peptides and proteins were identified by matching mass and elution time of newly acquired LC-MS features to information in previously generated accurate mass and time tag (AMT) reference databases.« less

A retrospective cohort study of patients treated with anti-tuberculous therapy for presumed ocular tuberculosis.

PubMed

Damato, Erika Marie; Dawson, Sarah; Liu, Xiaoxuan; Mukherjee, Chandoshi; Horsburgh, John; Denniston, Alastair K; Moran, Edward; Dedicoat, Martin; Murray, Philip Ian

2017-12-04

Uveitis involving the posterior segment is a significant and potentially blinding condition. The diagnosis and treatment of patients with uveitis associated with tuberculosis remains controversial, and commonly, patients are systemically well. Use of the interferon-gamma release assays has added to the controversy, as the significance of a positive test may be uncertain. We aim to report the outcomes of anti-tuberculous treatment in a cohort of patients treated in Birmingham, for presumed "ocular tuberculosis", based on clinical findings, systemic assessment and specific testing for tuberculosis. We found that in our cohort of 41 patients treated between 2010 and 2014, the majority achieved disease-free remission, even in cases where anti-tuberculous treatment was delayed. Despite controversy, this study strongly supports the use of anti-tuberculous therapy in such patients and highlights the need for formal prospective trials and treatment protocols.

[Stopping secondary prevention in AIDS patients with inactive CMV retinitis treated with HAART (highly active antiretroviral therapy)].

PubMed

Best, J; Althaus, C; Kersten, A; Theisen, A; Gantke, B

2000-08-01

Immune recovery of AIDS patients with cytomegalovirus (CMV) retinitis treated and healed by highly active antiretroviral therapy (HAART) is reflected by increased CD4 cell count and decreased virus load. Due to partial reconstitution of the immune status the risk of opportunistic infections decreases, as well as the risk of reactivating inactive CMV retinitis. It may therefore be possible to stop anti-CMV maintenance therapy may after HAART-induced immune recovery. We present six patients (nine eyes) with a follow-up of 9.5 months (range 7-12 months) after cessation of the CMV-specific maintenance therapy (five orally, one intravenously). There was no reactivation of retinal CMV infection during the follow-up period. The virus load (< 50 Eq/ml; a single value of one patient was 2047 Eq/ml) and CD4 cell counts (range 207-454/microliter; mean: 313/microliter) remained stable during the follow-up period, reflecting immune recovery. Our findings confirm the expected low risk of retinal CMV reactivation after immune recovery in AIDS patients receiving HAART without secondary prophylaxis with an anti-CMV maintenance therapy. Regular ophthalmic and medical follow-up is mandatory in these patients. Cessation of maintenance therapy represents a major improvement in quality of live in AIDS patients.

Lithium Nitride Synthesized by in situ Lithium Deposition and Ion Implantation for Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Ishitama, Shintaro; Baba, Yuji; Fujii, Ryo; Nakamura, Masaru; Imahori, Yoshio

Li3N synthesis on Li deposition layer was conducted without H2O and O2 by in situ lithium deposition in high vacuum chamber of 10-6 Pa and ion implantation techniques and the thermo-chemical stability of the Li3N/Li/Cu tri-layered target for Boron Neutron Capture Therapy (BNCT) under laser heating and air exposure was characterized by X-ray photoelectron spectroscopy (XPS). Following conclusions were derived; (1) Li3N/Li/Cu tri-layered target with very low oxide and carbon contamination was synthesized by in situ lithium vacuum deposition and N2+ ion implantation without H2O and O2 additions, (2) The starting temperature of evaporation of Li3N/Li/Cu tri-layered target increased by 120K compared to that of the Li/Cu target and (3) Remarkable oxidation and carbon contamination were observed on the surface of Li3N/Li/Cu after air exposure and these contaminated compositions was not removed by Ar+ heavy sputtering.

A Framework for Treating Cumulative Trauma with Art Therapy

ERIC Educational Resources Information Center

Naff, Kristina

2014-01-01

Cumulative trauma is relatively undocumented in art therapy practice, although there is growing evidence that art therapy provides distinct benefits for resolving various traumas. This qualitative study proposes an art therapy treatment framework for cumulative trauma derived from semi-structured interviews with three art therapists and artistic…

Anal fistula with foot extension-Treated by kshara sutra (medicated seton) therapy: A rare case report.

PubMed

Ramesh, P Bhat

2013-01-01

An 'anal' fistula is a track which communicates anal canal or rectum and usually is in continuity with one or more external openings. Distant communication from rectum is rare. It is a challenging disease because of its recurrence especially, with high level and distant communications. Ksharasutra (medicated seton) therapy is being practiced in India with high success rate (recurrence of 3.33%) in the management of complicated anal fistula. A 56 year old man presented with recurrent boils in the left lower limb at different places from thigh to foot. He underwent repeated incision and drainage at different hospitals. Examination revealed sinus with discharge and multiple scars on left lower limb from thigh up to foot. Suspecting anal fistula, MRI was advised which revealed a long cutaneous fistula from rectum to left lower limb. Patient was treated with Ksharasutra therapy. Within 6 months of treatment whole tract was healed completely. Sushrutha (500BC) was the first to explain the role of surgical excision and use of kshara sutra for the management of anal fistula. Ksharasutra therapy showed least recurrence. Fistula from rectum to foot is of extremely rare variety. Surgical treatment of anal fistula requires hospitalization, regular post-operative care, is associated with a significant risk of recurrence (0.7-26.5%) and a high risk of impaired continence (5-40%). Rectal fistula communicating till foot may be a very rare presentation in proctology practice. Kshara sutra treatment was useful in treating this condition, with minimal surgical intervention with no recurrence. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Refractory major depression successfully treated with electroconvulsive therapy in a patient with Addison disease.

PubMed

Heijnen, Willemijn T C J; Pluijms, Esther M; Birkenhager, Tom K

2013-06-01

This report describes a 55-year-old woman who had 1 previous episode of major depression that responded favorably to treatment with tricyclic antidepressants. After the development of Addison disease, she experienced a new episode of major depression that failed to respond to adequate treatment with imipramine and was subsequently successfully treated with electroconvulsive therapy (ECT) with steroid cover. The patient did not experience adrenal crisis or adverse effects. After 9 ECT sessions, she attained full remission. These findings support the suggestion that ECT treatment is safe in patients with Addison disease when using 100 mg intravenous hydrocortisone as prophylaxis.

Incidence of retinopathy in chronic hepatitis C patients treated with pegylated interferon alpha 2a and ribavirin combination therapy.

PubMed

Kashif, Muhammad; Saleem, Muhammad Khurram; Farooka, Imran Khan; Husnain, Amina; Siddiqui, Arif Mahmood

2015-01-01

The objective of this study was to determine the incidence of retinopathy in chronic hepatitis C patients treated with Pegylated interferon alpha 2a and Ribavirin. This descriptive case series study was conducted in Medical Unit II of the Jinnah Hospital Lahore from September 2012 to February 2013. One hundred chronic hepatitis C patients visiting Medical Unit II outpatient department fulfilling inclusion criteria were selected for this study via non probability purposive sampling. Patients were started on pegylated interferon and ribavirin combination therapy. Subjects were subjected to dilated eye fundoscopic examination at the start of therapy and then after three months of the therapy. One hundred patients were included in this study. Out of these 100 patients 5% developed retinopathy whereas fundus examination was normal in rest of the patients. Interferon therapy can lead to retinopathy. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss.

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

PubMed

Takahara, Kiyoshi; Inamoto, Teruo; Minami, Koichiro; Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model

PubMed Central

Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Purpose Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa. PMID:26325195

Development of real-time thermal neutron monitor using boron-loaded plastic scintillator with optical fiber for boron neutron capture therapy.

PubMed

Ishikawa, M; Ono, K; Sakurai, Y; Unesaki, H; Uritani, A; Bengua, G; Kobayashi, T; Tanaka, K; Kosako, T

2004-11-01

A new thermal neutron monitor for boron neutron capture therapy was developed in this study. We called this monitor equipped boron-loaded plastic scintillator that uses optical fiber for signal transmission as an [scintillator with optical fiber] SOF detector. A water phantom experiment was performed to verify how the SOF detector compared with conventional method of measuring thermal neutron fluence. Measurements with a single SOF detector yielded indistinguishable signals for thermal neutrons and gamma rays. To account for the gamma ray contribution in the signal recorded by the SOF detector, a paired SOF detector system was employed. This was composed of an SOF detector with boron-loaded scintillator and an SOF detector with a boron-free scintillator. The difference between the recorded counts of these paired SOF detectors was used as the measure of the gamma ray contribution in the measured neutron fluence. The paired SOF detectors were ascertained to be effective in measuring thermal neutron flux in the range above 10(6)(n/cm(2)/s). Clinical trials using paired SOF to measure thermal neutron flux during therapy confirmed that paired SOF detectors were effective as a real-time thermal neutron flux monitor.

Using Music Therapy Techniques To Treat Teacher Burnout.

ERIC Educational Resources Information Center

Cheek, James R.; Bradley, Loretta J.; Parr, Gerald; Lan, William

2003-01-01

This study was conducted to determine the effectiveness of music therapy techniques as an intervention for teacher burnout. Results of the study indicated that teachers who participated in school-based counseling groups, using music therapy techniques in conjunction with cognitive behavioral interventions, reported lower levels of burnout symptoms…

Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

PubMed Central

2013-01-01

Background Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. Methods The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. Results The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Conclusions Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma. PMID:23915425

Keratomycosis due to Tintelnotia destructans refractory to common therapy treated successfully with systemic and local terbinafine in combination with polyhexamethylene biguanide.

PubMed

Behrens-Baumann, Wolfgang J; Hofmüller, Wolfram; Tammer, Ina; Tintelnot, Kathrin

2018-04-28

To report on a wearer of rigid gas-permeable contact lenses with a keratomycosis due to Tintelnotia-a new genus of Phaeosphaeriaceae-treated with terbinafine and polyhexamethylene biguanide. Chart review of a patient with fungal keratitis treated additionally with systemic and topical terbinafine 0.25% after symptoms increased under conventional antimycotic therapy with voriconazole. Antifungal susceptibility had been tested in vitro. After starting an additional treatment with systemic and topical terbinafine, the severe corneal infection was sufficiently resolved. The drug was well tolerated without any neurological, dermatological or gastroenterological problems. Terbinafine revealed a marked in vitro antifungal activity of 0.12 µg/ml. The fungus was identified as Tintelnotia destructans. Terbinafine might be considered as a therapeutic option in severe cases of fungal keratitis refractory to common antifungal therapy.

Analysis on the emission and potential application of Cherenkov radiation in boron neutron capture therapy: A Monte Carlo simulation study.

PubMed

Shu, Di-Yun; Geng, Chang-Ran; Tang, Xiao-Bin; Gong, Chun-Hui; Shao, Wen-Cheng; Ai, Yao

2018-07-01

This paper was aimed to explore the physics of Cherenkov radiation and its potential application in boron neutron capture therapy (BNCT). The Monte Carlo toolkit Geant4 was used to simulate the interaction between the epithermal neutron beam and the phantom containing boron-10. Results showed that Cherenkov photons can only be generated from secondary charged particles of gamma rays in BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The number of Cherenkov photons per unit mass generated in the measurement region decreases linearly with the increase of boron concentration in both water and tissue phantom. The work presented the fundamental basis for applications of Cherenkov radiation in BNCT. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sex Therapy

MedlinePlus

Sex therapy Overview Sex therapy is a type of psychotherapy — a general term for treating mental health problems by talking with a mental health professional. Through sex therapy, you can address concerns about sexual function, ...

Dynamic infrared imaging for biological and medical applications in Boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Santa Cruz, Gustavo A.; González, Sara J.; Dagrosa, Alejandra; Schwint, Amanda E.; Carpano, Marina; Trivillin, Verónica A.; Boggio, Esteban F.; Bertotti, José; Marín, Julio; Monti Hughes, Andrea; Molinari, Ana J.; Albero, Miguel

2011-05-01

Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment of cancer, which involves a tumor selective 10B compound and a specially tuned neutron beam to produce a lethal nuclear reaction. BNCT kills target cells with microscopic selectivity while sparing normal tissues from potentially lethal doses of radiation. In the context of the Argentine clinical and research BNCT projects at the National Atomic Energy Commission and in a strong collaboration with INVAP SE, we successfully implemented Dynamic Infrared Imaging (DIRI) in the clinical setting for the observation of cutaneous melanoma patients and included DIRI as a non invasive methodology in several research protocols involving small animals. We were able to characterize melanoma lesions in terms of temperature and temperature rate-of-recovery after applying a mild cold thermal stress, distinguishing melanoma from other skin pigmented lesions. We observed a spatial and temporal correlation between skin acute reactions after irradiation, the temperature pattern and the dose distribution. We studied temperature distribution as a function of tumor growth in mouse xenografts, observing a significant correlation between tumor temperature and drug uptake; we investigated temperature evolution in the limbs of Wistar rats for a protocol of induced rheumatoid arthritis (RA), DIRI being especially sensitive to RA induction even before the development of clinical signs and studied surface characteristics of tumors, precancerous and normal tissues in a model of oral cancer in the hamster cheek pouch.

Radiative capture reactions via indirect methods

NASA Astrophysics Data System (ADS)

Mukhamedzhanov, A. M.; Rogachev, G. V.

2017-10-01

Many radiative capture reactions of astrophysical interest occur at such low energies that their direct measurement is hardly possible. Until now the only indirect method, which was used to determine the astrophysical factor of the astrophysical radiative capture process, was the Coulomb dissociation. In this paper we address another indirect method, which can provide information about resonant radiative capture reactions at astrophysically relevant energies. This method can be considered an extension of the Trojan horse method for resonant radiative capture reactions. The idea of the suggested indirect method is to use the indirect reaction A (a ,s γ )F to obtain information about the radiative capture reaction A (x ,γ )F , where a =(s x ) and F =(x A ) . The main advantage of using the indirect reactions is the absence of the penetrability factor in the channel x +A , which suppresses the low-energy cross sections of the A (x ,γ )F reactions and does not allow one to measure these reactions at astrophysical energies. A general formalism to treat indirect resonant radiative capture reactions is developed when only a few intermediate states contribute and a statistical approach cannot be applied. The indirect method requires coincidence measurements of the triple differential cross section, which is a function of the photon scattering angle, energy, and the scattering angle of the outgoing spectator particle s . Angular dependence of the triple differential cross section at fixed scattering angle of the spectator s is the angular γ -s correlation function. Using indirect resonant radiative capture reactions, one can obtain information about important astrophysical resonant radiative capture reactions such as (p ,γ ) , (α ,γ ) , and (n ,γ ) on stable and unstable isotopes. The indirect technique makes accessible low-lying resonances, which are close to the threshold, and even subthreshold bound states located at negative energies. In this paper, after

A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

PubMed

Braun, Dominique L; Rauch, Andri; Aouri, Manel; Durisch, Nina; Eberhard, Nadia; Anagnostopoulos, Alexia; Ledergerber, Bruno; Müllhaupt, Beat; Metzner, Karin J; Decosterd, Laurent; Böni, Jürg; Weber, Rainer; Fehr, Jan

2015-01-01

The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group. Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin. We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No serious

Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Lai, Chian-Hui; Lai, Nien-Chu; Chuang, Yung-Jen; Chou, Fong-In; Yang, Chia-Min; Lin, Chun-Cheng

2013-09-01

A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use.A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

PubMed

Trivillin, Verónica A; Pozzi, Emiliano C C; Colombo, Lucas L; Thorp, Silvia I; Garabalino, Marcela A; Monti Hughes, Andrea; González, Sara J; Farías, Rubén O; Curotto, Paula; Santa Cruz, Gustavo A; Carando, Daniel G; Schwint, Amanda E

2017-11-01

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 6 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 6 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm 3 . In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm 3 . The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA).

PubMed

Henriksson, Roger; Capala, Jacek; Michanek, Annika; Lindahl, Sten-Ake; Salford, Leif G; Franzén, Lars; Blomquist, Erik; Westlin, Jan-Erik; Bergenheim, A Tommy

2008-08-01

To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.

Pharmacotherapeutic approaches for treating psoriasis in difficult-to-treat areas.

PubMed

Kivelevitch, Dario; Frieder, Jillian; Watson, Ian; Paek, So Yeon; Menter, M Alan

2018-04-01

Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients' quality of life and requires an adequate selection of treatments. Areas covered: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature. Expert opinion: Clinical trials assessing therapies for the difficult-to-treat areas have been inadequate. With the first biological clinical trial for genital psoriasis pending publication, it is with hope that other biological agents will be evaluated for region-specific psoriasis. A greater understanding of the genetic and immunologic aspects of regional psoriasis, as well as identification of unique biomarkers, will further guide management decisions. For example, the recent discovery of the IL-36 receptor gene for generalized pustular psoriasis may prove valuable for other forms of psoriasis. Ultimately, identification of the most beneficial treatments for each psoriasis subtype and difficult-to-treat area will provide patients with maximal quality of life.

Uric acid therapy improves the outcomes of stroke patients treated with intravenous tissue plasminogen activator and mechanical thrombectomy.

PubMed

Chamorro, Ángel; Amaro, Sergio; Castellanos, Mar; Gomis, Meritxell; Urra, Xabier; Blasco, Jordi; Arenillas, Juan F; Román, Luis S; Muñoz, Roberto; Macho, Juan; Cánovas, David; Marti-Fabregas, Joan; Leira, Enrique C; Planas, Anna M

2017-06-01

Background Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0-2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08-34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06-226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.

Incidence of retinopathy in chronic hepatitis C patients treated with pegylated interferon alpha 2a and ribavirin combination therapy

PubMed Central

Kashif, Muhammad; Saleem, Muhammad Khurram; Farooka, Imran Khan; Husnain, Amina; Siddiqui, Arif Mahmood

2015-01-01

Objectives: The objective of this study was to determine the incidence of retinopathy in chronic hepatitis C patients treated with Pegylated interferon alpha 2a and Ribavirin. Methods: This descriptive case series study was conducted in Medical Unit II of the Jinnah Hospital Lahore from September 2012 to February 2013. One hundred chronic hepatitis C patients visiting Medical Unit II outpatient department fulfilling inclusion criteria were selected for this study via non probability purposive sampling. Patients were started on pegylated interferon and ribavirin combination therapy. Subjects were subjected to dilated eye fundoscopic examination at the start of therapy and then after three months of the therapy. Results: One hundred patients were included in this study. Out of these 100 patients 5% developed retinopathy whereas fundus examination was normal in rest of the patients. Conclusion: Interferon therapy can lead to retinopathy. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss. PMID:25878638

Thermal Propulsion Capture System Heat Exchanger Design

NASA Technical Reports Server (NTRS)

Richard, Evan M.

2016-01-01

One of the biggest challenges of manned spaceflight beyond low earth orbit and the moon is harmful radiation that astronauts would be exposed to on their long journey to Mars and further destinations. Using nuclear energy has the potential to be a more effective means of propulsion compared to traditional chemical engines (higher specific impulse). An upper stage nuclear engine would allow astronauts to reach their destination faster and more fuel efficiently. Testing these engines poses engineering challenges due to the need to totally capture the engine exhaust. The Thermal Propulsion Capture System is a concept for cost effectively and safely testing Nuclear Thermal Engines. Nominally, hydrogen exhausted from the engine is not radioactive, but is treated as such in case of fuel element failure. The Thermal Propulsion Capture System involves injecting liquid oxygen to convert the hydrogen exhaust into steam. The steam is then cooled and condensed into liquid water to allow for storage. The Thermal Propulsion Capture System concept for ground testing of a nuclear powered engine involves capturing the engine exhaust to be cooled and condensed before being stored. The hydrogen exhaust is injected with liquid oxygen and burned to form steam. That steam must be cooled to saturation temperatures before being condensed into liquid water. A crossflow heat exchanger using water as a working fluid will be designed to accomplish this goal. Design a cross flow heat exchanger for the Thermal Propulsion Capture System testing which: Eliminates the need for water injection cooling, Cools steam from 5800 F to saturation temperature, and Is efficient and minimizes water requirement.

Description of Patients Treated with Biologic Drugs as First-Line Systemic Therapy in the BIOBADADERM Registry Between 2008 and 2016.

PubMed

Carretero Hernández, G; Ferrándiz, C; Rivera Díaz, R; Daudén Tello, E; de la Cueva-Dobao, P; Gómez-García, F J; Herrera-Ceballos, E; Belinchón Romero, I; López-Estebaranz, J L; Alsina Gibert, M; Sánchez-Carazo, J L; Ferrán Farrés, M; González Quesada, A; Carrascosa Carrillo, J M; Llamas-Velasco, M; Mendiola Fernández, M V; Ruiz Genao, D; Muñoz Santos, C; García-Doval, I; Descalzo, M A

2018-06-07

Biologic drugs are usually prescribed as second-line treatment for psoriasis, that is, after the patient has first been treated with a conventional psoriasis drug. There are, however, cases where, depending on the characteristics of the patient or the judgement of the physician, biologics may be chosen as first-line therapy. No studies to date have analyzed the demographics or clinical characteristics of patients in this setting or the safety profile of the agents used. The main aim of this study was to characterize these aspects of first-line biologic therapy and compare them to those observed for patients receiving biologics as second-line therapy. We conducted an observational study of 181 patients treated in various centers with a systemic biologic drug as first-line treatment for moderate to severe psoriasis between January 2008 and November 2016. All the patients were registered in the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology. The characteristics of the first- and second-line groups were very similar, although the patients receiving a biologic as first-line treatment for their psoriasis were older. No differences were observed for disease severity (assessed using the PASI) or time to diagnosis. Hypertension, diabetes, and liver disease were all more common in the first-line group. There were no differences between the groups in terms of reasons for drug withdrawal or occurrence of adverse effects. No major differences were found between patients with psoriasis receiving biologic drugs as first- or second-line therapy, a finding that provides further evidence of the safety of biologic therapy in patients with psoriasis. Publicado por Elsevier España, S.L.U.

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model.

PubMed

Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Thorp, Silvia; Monti Hughes, Andrea; Molinari, Ana J; Garabalino, Marcela A; Heber, Elisa M; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Trivillin, Verónica A; Schwint, Amanda E

2012-08-01

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT, boronophenylalanine (BPA) + neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA-BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks post-treatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA-BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mg fell significantly to 19 ± 16 mg for BPA-BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA-BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA-BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model

DOE Office of Scientific and Technical Information (OSTI.GOV)

David W. Nigg

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA–BNCT, boronophenylalanine (BPA) ? neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA–BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks posttreatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA–BNCT, 2.7 ± 1.8more » for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mgfell significantly to 19 ± 16 mg for BPA–BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA–BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA– BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.« less

Manual vs. automatic capture management in implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators.

PubMed

Murgatroyd, Francis D; Helmling, Erhard; Lemke, Bernd; Eber, Bernd; Mewis, Christian; van der Meer-Hensgens, Judith; Chang, Yanping; Khalameizer, Vladimir; Katz, Amos

2010-06-01

The Secura ICD and Consulta CRT-D are the first defibrillators to have automatic right atrial (RA), right ventricular (RV), and left ventricular (LV) capture management (CM). Complete CM was evaluated in an implantable cardioverter defibrillator (ICD) population. Two prospective clinical studies were conducted in 28 centres in Europe and Israel. Automatic CM data were compared with manual threshold measurements, the CM applicability was determined, and adjustments to pacing outputs were analysed. In total, 160 patients [age 64.6 +/- 10.4 years, 77% male, 80 ICD and 80 cardiac resynchronization therapy defibrillator (CRT-D)] were included. The differences between automatic and manual measurements were 2.5 V) due to raised RA threshold in seven (4.4%), high RV threshold in nine (5.6%), and high LV threshold in three patients (3.8%). All high threshold detections and all automatic modulations of pacing output were adjudicated appropriate. Complete CM adjusts pacing output appropriately, permitting a reduction in office visits while it may maximize device longevity. The study was registered at ClinicalTrials.gov identifiers: NCT00526227 and NCT00526162.

Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis

PubMed Central

Qi, Guo-Yan; Liu, Peng

2013-01-01

Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P < 0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P < 0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P < 0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy. PMID:24348721

Attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy.

PubMed

Antonini, Tanya N; Ris, M Douglas; Grosshans, David R; Mahajan, Anita; Okcu, M Fatih; Chintagumpala, Murali; Paulino, Arnold; Child, Amanda E; Orobio, Jessica; Stancel, Heather H; Kahalley, Lisa S

2017-07-01

This study examines attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy (PBRT). We examined 39 survivors (age 6-19years) who were 3.61years post-PBRT on average. Craniospinal (CSI; n=21) and focal (n=18) subgroups were analyzed. Attention, processing speed, and executive functioning scores were compared to population norms, and clinical/demographic risk factors were examined. As a group, survivors treated with focal PBRT exhibited attention, processing speed, and executive functioning that did not differ from population norms (all p>0.05). Performance in the CSI group across attention scales was normative (all p>0.05), but areas of relative weakness were identified on one executive functioning subtest and several processing speed subtests (all p<0.01). Survivors treated with PBRT may exhibit relative resilience in cognitive domains traditionally associated with radiation late effects. Attention, processing speed, and executive functioning remained intact and within normal limits for survivors treated with focal PBRT. Among survivors treated with CSI, a score pattern emerged that was suggestive of difficulties in underlying component skills (i.e., processing speed) rather than true executive dysfunction. No evidence of profound cognitive impairment was found in either group. Copyright © 2017 Elsevier B.V. All rights reserved.

Dermatofibrosarcoma Protuberans: Long-term Outcomes of 53 Patients Treated With Conservative Surgery and Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castle, Katherine O.; Guadagnolo, B. Ashleigh, E-mail: aguadagn@mdanderson.org; Tsai, C. Jillian

Purpose: To evaluate outcomes of conservative surgery and radiation therapy (RT) treatment in patients with dermatofibrosarcoma protuberans. Methods and Materials: We retrospectively reviewed the medical records of 53 consecutive dermatofibrosarcoma protuberans patients treated with surgery and preoperative or postoperative radiation therapy between 1972 and 2010. Median tumor size was 4 cm (range, 1-25 cm). Seven patients (13%) were treated with preoperative RT (50-50.4 Gy) and 46 patients (87%) with postoperative RT (60-66 Gy). Of the 46 patients receiving postoperative radiation, 3 (7%) had gross disease, 14 (30%) positive margins, 26 (57%) negative margins, and 3 (7%) uncertain margin status. Radiationmore » dose ranged from 50 to 66 Gy (median dose, 60 Gy). Results: At a median follow-up time of 6.5 years (range, 0.5 months-23.5 years), 2 patients (4%) had disease recurrence, and 3 patients (6%) had died. Actuarial overall survival was 98% at both 5 and 10 years. Local control was 98% and 93% at 5 and 10 years, respectively. Disease-free survival was 98% and 93% at 5 and 10 years, respectively. The presence of fibrosarcomatous change was not associated with increased risk of local or distant relapse (P=.43). One of the patients with a local recurrence had gross residual disease at the time of RT and despite RT to 65 Gy developed both an in-field recurrence and a nodal and distant recurrence 3 months after RT. The other patient with local recurrence was found to have in-field recurrence 10 years after initial treatment. Thirteen percent of patients had an RT complication at 5 and 10 years, and 9% had a moderate or severe complication at 5 and 10 years. Conclusions: Dermatofibrosarcoma protuberans is a radioresponsive disease with excellent local control after conservative surgery and radiation therapy. Adjuvant RT should be considered for patients with large or recurrent tumors or when attempts at wide surgical margins would result in significant morbidity.« less

Role of Comorbid Depression and Co-Occurring Depressive Symptoms in Outcomes for Anxiety-Disordered Youth Treated with Cognitive-Behavioral Therapy

ERIC Educational Resources Information Center

O'Neil, Kelly A.; Kendall, Philip C.

2012-01-01

This study examined the role of comorbid depressive disorders (major depressive disorder or dysthymic disorder) and co-occurring depressive symptoms in treatment outcome and maintenance for youth (N = 72, aged 7-14) treated with cognitive-behavioral therapy for a principal anxiety disorder (generalized anxiety disorder, separation anxiety…

Tumoral cavitation in patients with non-small-cell lung cancer treated with antiangiogenic therapy using bevacizumab

PubMed Central

Nishino, Mizuki; Cryer, Sarah K.; Okajima, Yuka; Sholl, Lynette M.; Hatabu, Hiroto; Rabin, Michael S.; Jackman, David M.; Johnson, Bruce E.

2012-01-01

Abstract Rationale and objectives: To investigate the frequency and radiographic patterns of tumoral cavitation in patients with non-small cell lung cancer (NSCLC) treated with bevacizumab, and correlate the imaging findings with the pathology, clinical characteristics and outcome. Materials and methods: Seventy-two patients with NSCLC treated with bevacizumab therapy were identified retrospectively. Baseline and follow-up chest computed tomography scan were reviewed to identify tumoral cavitation and subsequent filling in of cavitation. Radiographic cavitation patterns were classified into 3 groups. The clinical and outcome data were correlated with cavity formation and patterns. Results: Out of 72 patients, 14 patients developed cavitation after the initiation of bevacizumab therapy (19%; median time to event, 1.5 months; range 1.0–24.8 months). Three radiographic patterns of tumoral cavitation were noted: (1) development of cavity within the dominant lung tumor (n = 8); (2) development of non-dominant cavitary nodules (n = 3); and (3) development of non-dominant cavitary nodules with adjacent interstitial abnormalities (n = 3). Eleven patients (79%) demonstrated subsequent filling in of cavitation (the time from the cavity formation to filling in; median 3.7 months; range 1.9–22.7 months). No significant difference was observed in the clinical characteristics, including smoking history, or in the survival between patients who developed cavitation and those who did not. Smoking history demonstrated a significant difference across 3 radiographic cavitation patterns (P = 0.006). Hemoptysis was noted in 1 patient with cavity formation and 4 patients without, with no significant difference between the 2 groups. Conclusion: Tumoral cavitation occurred in 19% in patients with NSCLC treated with bevacizumab and demonstrated 3 radiographic patterns. Subsequent filling in of cavitation was noted in the majority of cases. PMID:22743083

Evaluation of a Gait Assessment Module Using 3D Motion Capture Technology

PubMed Central

Baskwill, Amanda J.; Belli, Patricia; Kelleher, Leila

2017-01-01

Background Gait analysis is the study of human locomotion. In massage therapy, this observation is part of an assessment process that informs treatment planning. Massage therapy students must apply the theory of gait assessment to simulated patients. At Humber College, the gait assessment module traditionally consists of a textbook reading and a three-hour, in-class session in which students perform gait assessment on each other. In 2015, Humber College acquired a three-dimensional motion capture system. Purpose The purpose was to evaluate the use of 3D motion capture in a gait assessment module compared to the traditional gait assessment module. Participants Semester 2 massage therapy students who were enrolled in Massage Theory 2 (n = 38). Research Design Quasi-experimental, wait-list comparison study. Intervention The intervention group participated in an in-class session with a Qualisys motion capture system. Main Outcome Measure(s) The outcomes included knowledge and application of gait assessment theory as measured by quizzes, and students’ satisfaction as measured through a questionnaire. Results There were no statistically significant differences in baseline and post-module knowledge between both groups (pre-module: p = .46; post-module: p = .63). There was also no difference between groups on the final application question (p = .13). The intervention group enjoyed the in-class session because they could visualize the content, whereas the comparison group enjoyed the interactivity of the session. The intervention group recommended adding the assessment of gait on their classmates to their experience. Both groups noted more time was needed for the gait assessment module. Conclusions Based on the results of this study, it is recommended that the gait assessment module combine both the traditional in-class session and the 3D motion capture system. PMID:28293329

An accelerator-based Boron Neutron Capture Therapy (BNCT) facility based on the 7Li(p,n)7Be

NASA Astrophysics Data System (ADS)

Musacchio González, Elizabeth; Martín Hernández, Guido

2017-09-01

BNCT (Boron Neutron Capture Therapy) is a therapeutic modality used to irradiate tumors cells previously loaded with the stable isotope 10B, with thermal or epithermal neutrons. This technique is capable of delivering a high dose to the tumor cells while the healthy surrounding tissue receive a much lower dose depending on the 10B biodistribution. In this study, therapeutic gain and tumor dose per target power, as parameters to evaluate the treatment quality, were calculated. The common neutron-producing reaction 7Li(p,n)7Be for accelerator-based BNCT, having a reaction threshold of 1880.4 keV, was considered as the primary source of neutrons. Energies near the reaction threshold for deep-seated brain tumors were employed. These calculations were performed with the Monte Carlo N-Particle (MCNP) code. A simple but effective beam shaping assembly (BSA) was calculated producing a high therapeutic gain compared to previously proposed facilities with the same nuclear reaction.

Combining group-based exposure therapy with prolonged exposure to treat U.S. Vietnam veterans with PTSD: a case study.

PubMed

Ready, David J; Vega, Edward M; Worley, Virginia; Bradley, Bekh

2012-10-01

Group-based exposure therapy (GBET) of 16-week duration was developed to treat combat-related posttraumatic stress disorder (PTSD) and decreased PTSD symptoms in 3 noncontrolled open trials with low attrition (0%-5%). Group-based exposure therapy has not produced as much PTSD symptom reduction as Prolonged Exposure (PE) within a U.S. Veterans Affairs PTSD treatment program, although PE had more dropouts (20%). This pilot study was of a model that combined key elements of GBET with components of PE in an effort to increase the effectiveness of a group-based treatment while reducing its length and maintaining low attrition. Twice per week, 8 Vietnam combat veterans with PTSD were treated for 12 weeks, with an intervention that included 2 within-group war trauma presentations per participant, 6 PE style individual imaginal exposure (IE) sessions per participant, daily listening to recorded IE sessions, and daily in vivo exposure exercises. All completed treatment and showed Significant reductions on all measures of PTSD with large effect sizes; 7 participants no longer met PTSD criteria on treating clinician administered interviews and a self-report measure at posttreatment. Significant reductions in depression with large effect sizes and moderate reductions in PTSD-related cognitions were also found. Most gains were maintained 6 months posttreatment. Published 2012. This article is a US Government work and is in the public domain in the USA.

Low-intensity laser therapy to treat dentin hypersensitivity: comparative clinical study using different light doses

NASA Astrophysics Data System (ADS)

Lizarelli, Rosane F. Z.; Mazzetto, Marcello O.; Bagnato, Vanderlei S.

2001-04-01

Dentin hypersensitivity is the most common patient's complain related to pain. In fact, this is a challenge to treat specially if conventional techniques are used. The possibility to treat pain through a low intensity laser gives us an opportunity to solve this important clinical problem without promote a discomfort to patient. The main point here is not if this kind of treatment is anti- inflammatory to pulp and/or biostimulatory to production of irregular secondary dentin. The most important point here is to understand how much energy is necessary to reach conditions where to tooth become insensible to external stimulus. Our double-blinded study compared a group without laser (Placebo) with five other groups where different doses at 660 nm low intensity laser were employed. The final conclusion is that for 660 nm laser therapy, the doses from 0.13 to 2.0 J/cm2 were more efficiency than the others. The follow up care in this study was of 45 days.

Rechallenge of oxaliplatin-containing regimens in the third- or later-line therapy for patients with heavily treated metastatic colorectal cancer

PubMed Central

Jiang, Zhimin; Wang, Huizhong; Li, Weiyu; Zhang, Bei; Xie, Derong

2018-01-01

Purpose The third- or later-line therapy available often yield poor survival benefit in patients metastatic colorectal cancer (mCRC). The retrospective study aimed to evaluate efficacy of rechallenge of oxaliplatin-containing regimens. Patients and methods Patients with mCRC who progressed from fluoropyrimidine, oxaliplatin, and irinotecan in the first- and second-line chemotherapy, were treated by reexposure to oxaliplatin-containing regimen. Patients treated by anti-epidermal growth factor receptor (EGFR) antibodies with irinotecan were included in the control arm. Results Ninety-five and 29 patients were treated with either oxaliplatin reexposure or anti-EGFR antibodies with irinotecan, respectively, as the third- or later-line therapy. The median time to treatment failure (TTF) and overall survival (OS) was 3.77 and 12.17 months in the oxaliplatin arm, with 4.77 months of TTF and 11.37 months of OS in the control arm; there was no significance between the 2 arms (p>0.05). Oxaliplatin reexposure resulted in 6.3% objective response rate with no complete response, 6 partial response, 39 stable disease, and 37 progressive disease. The disease control rate was 47.4% (45/95). The multivariate analysis found that patients who achieved disease control by oxaliplatin reexposure had a superior TTF (6.13 vs 1.7 months, p<0.001) and OS (15.73 vs 6.27 months, p<0.001) compared with those presenting with progressive disease. Conclusion This study showed that rechallenge of oxaliplatin-containing chemotherapy in the third- or later-line therapy may lead to tumor control and improved survival in mCRC patients, which was equivalent to that of anti-EGFR antibodies with irinotecan. Clinical significance Rechallenge of oxaliplatin-containing regimens in the third- or later-line of therapy is a common practice, despite few evidence available. The present study found that rechallenge of oxaliplatin-containing regimens produced equivalent tumor control and survival benefit to that of

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy

PubMed Central

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-01-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their 24Na and 38Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to 24Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive 24Na is mainly generated from 23Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood 24Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood 24Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood 24Na was determined using a germanium counter. The activity of 24Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood 24Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible. PMID:23392825

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy.

PubMed

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-07-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their (24)Na and (38)Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to (24)Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive (24)Na is mainly generated from (23)Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood (24)Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood (24)Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood (24)Na was determined using a germanium counter. The activity of (24)Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood (24)Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible.

Antiretroviral Therapy Outcomes of HIV-infected children in the TREAT Asia Pediatric HIV Observational Database

PubMed Central

Hansudewechakul, Rawiwan; Sirisanthana, Virat; Kurniati, Nia; Puthanakit, Thanyawee; Lumbiganon, Pagakrong; Yusoff, Nik Khairulddin Nik; Fong, Siew Moy; Nallusamy, Revathy; Srasuebkul, Preeyaporn; Law, Matthew; Sohn, Annette H.; Chokephaibulkit, Kulkanya

2010-01-01

Introduction We report responses to combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database. Methods Children included were those who had received cART (i.e., ≥3 antiretrovirals) at <18 years. The analysis was intention-to-treat by the first cART regimen. Median values are provided with interquartile ranges; hazard ratios (HR) with 95% confidence intervals. Results Of the 1655 children included, 50.4% were male, with a median age at cART of 7.0 (3.9, 9.8) years and CD4 of 8 (2.0, 15)%; 92.5% were started on an NNRTI; median duration of follow-up was 2.9 (1.4, 4.6) years. Loss-to-follow-up and death rates were 4.2 (3.7, 4.8) and 2.1 (1.7, 2.5) per 100 person-years, respectively. At 36 months, median CD4 was 26 (21, 31)%; 81% of those with viral load (N=302) were <400 copies/mL. Children who reached CD4 ≥25% within five years were more likely to be females (HR 1.4; 1.2, 1.7), start before 18 months old (HR 3.8; 2.4, 6.2), lack a history of mono/dual-therapy (HR 1.7; 1.4, 2.5), and have a higher baseline CD4 (per 10% increase: HR 2; 1.9, 2.2). Conclusion These data underscore the need for early diagnosis and cART initiation to preserve immune function. PMID:20842043

Procedures and rationale for marking sea otters captured and treated during the T/V Exxon Valdez oil spill

USGS Publications Warehouse

DeGange, A.R.; Williams, T.D.; Bayha, Keith; Kormendy, Jennifer

1990-01-01

Four methods were used for marking sea otters (Enhydra lutris) captured and treated during the response to the T/V Exxon Valdez oil spill. Colored and numbered flipper tags were placed on each sea otter that was brought to the otter treatment centers. These tags allowed individual recognition and permitted the tracking of individuals through the treatment and holding processes. Recovery of tagged carcasses may provide a crude measure of the fates of rehabilitated otters. Seven sea otters were instrumented with radio transmitters attached to flipper tags as part of a pilot release program. The results of that study were inconclusive. Forty-five sea otters were implanted with radio transmitters as part of a study to assess the fate of rehabilitated sea otters. Specific objectives of the study include estimating survived rates and monitoring the reproductive success of the sample of rehabilitated sea otters and comparing the results with similar variables in a control population. Transponder chips were injected in the perianal region of all but seven of the instrumented sea otters, and all were tagged with red flipper tags. The advantages and disadvantages of each type of tag are discussed.

Do different attention capture paradigms measure different types of capture?

PubMed

Roque, Nelson A; Wright, Timothy J; Boot, Walter R

2016-10-01

When something captures our attention, why does it do so? This topic has been hotly debated, with some arguing that attention is captured only by salient stimuli (bottom-up view) and others arguing capture is always due to a match between a stimulus and our goals (top-down view). Many different paradigms have provided evidence for 1 view or the other. If either of these strong views are correct, then capture represents a unitary phenomenon, and there should be a high correlation between capture in these paradigms. But if there are different types of capture (top-down, bottom-up), then some attention capture effects should be correlated and some should not. In 2 studies, we collected data from several paradigms used in support of claims of top-down and bottom-up capture in relatively large samples of participants. Contrary to either prediction, measures of capture were not strongly correlated. Results suggest that capture may in fact be strongly determined by idiosyncratic task demands and strategies. Relevant to this lack of relations among tasks, we observed that classic measures of attention capture demonstrated low reliability, especially among measures used to support bottom-up capture. Implications for the low reliability of capture measures are discussed. We also observed that the proportion of participants demonstrating a pattern of responses consistent with capture varied widely among classic measures of capture. Overall, results demonstrate that, even for relatively simple laboratory measures of attention, there are still important gaps in knowledge regarding what these paradigms measure and how they are related.

Successfully treated necrotizing fasciitis using extracorporeal life support combined with hemoadsorption device and continuous renal replacement therapy.

PubMed

Eid, Maroua; Fouquet, Olivier; Darreau, Cédric; Pierrot, Marc; Kouatchet, Achille; Mercat, Alain; Baufreton, Christophe

2018-03-01

Necrotizing fasciitis represents a life-threatening infectious condition that causes spreading necrotisis of superficial fascia and subcutaneous cellular tissues. We describe the case of a patient diagnosed with septic and toxic shocks leading to multiple organ failure successfully treated with a combination of extracorporeal life support, continuous renal replacement therapy, and a hemoadsorption device. A 41-year-old patient presented with necrotizing fasciitis and multi-organ failure. Initial extracorporeal life support therapy was implanted, compensating for systolic failure. Due to acute renal failure that persisted in time, continuous renal replacement therapy was added. Despite these treatments and as a last attempt to control the septic condition, a CytoSorb ® hemoadsorption device was installed in parallel to the extracorporeal life support circuit and two sessions were run. During the days following CytoSorb ® treatment, hemodynamic stabilization was observed, as well as normalization of lactic acidosis and blood parameters. This case describes the successful use of CytoSorb ® with continuous renal replacement therapy and extracorporeal life support in a combined way to overcome a critical phase of septic shock in a young adult patient. This combination of treatments turned out to be efficient for this patient in the context of necrotizing fasciitis.

Cupping therapy for treating knee osteoarthritis: The evidence from systematic review and meta-analysis.

PubMed

Li, Jin-Quan; Guo, Wen; Sun, Ze-Gan; Huang, Qing-Song; Lee, En Yeong; Wang, Ying; Yao, Xiao-Dong

2017-08-01

Cupping therapy is widely used in East Asia, the Middle East, or Central and North Europe to manage the symptom of knee osteoarthritis (KOA). The purpose of this systematic review was to evaluate the available evidence from randomized controlled trials (RCTs) of cupping therapy for treating patients with KOA. The following databases were searched from their inception until January 2017: PubMed, Embase, the Cochrane Central Register of Controlled Trials and four Chinese databases [WanFang Med Database, Chinese BioMedical Database, Chinese WeiPu Database, and China National Knowledge Infrastructure (CNKI)]. Only the RCTs related to the effects of cupping therapy on KOA were included in this systematic review. A quantitative synthesis of RCTs will be conducted using RevMan 5.3 software. Study selection, data extraction, and validation was performed independently by two reviewers. Cochrane criteria for risk-of-bias were used to assess the methodological quality of the trials. Seven RCTs met the inclusion criteria, and most were of low methodological quality. Study participants in the dry cupping therapy plus the Western medicine therapy group showed significantly greater improvements in the pain [MD = -1.01, 95%CI (-1.61, -0.41), p < 0.01], stiffness [MD = -0.81, 95%CI (-1.14, -0.48), p < 0.01] and physical function [MD = -5.53, 95%CI (-8.58, -2.47), p < 0.01] domains of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to participants in the Western medicine therapy group, with low heterogeneity (Chi 2  = 0.00 p = 1.00, I 2  = 0% in pain; Chi 2  = 0.45 p = 0.50, I 2  = 0% in stiffness; Chi 2  = 1.09 p = 0.30, I 2  = 9% in physical function). However, it failed to do so on a Visual Analog Scale (VAS) [MD = -0.32, 95%CI (-0.70, 0.05), p = 0.09]. In addition, when compared with Western medicine therapy alone, meta-analysis of four RCTs suggested favorable statistically significant effects of wet cupping

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

PubMed

Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research

Comprehensive evaluation of the revised international staging system in multiple myeloma patients treated with novel agents as a primary therapy.

PubMed

Cho, Hyungwoo; Yoon, Dok Hyun; Lee, Jung Bok; Kim, Sung-Yong; Moon, Joon Ho; Do, Young Rok; Lee, Jae Hoon; Park, Yong; Lee, Ho Sup; Eom, Hyeon Seok; Shin, Ho-Jin; Min, Chang-Ki; Kim, Jin Seok; Jo, Jae-Cheol; Kang, Hye Jin; Mun, Yeung-Chul; Lee, Won Sik; Lee, Je-Jung; Suh, Cheolwon; Kim, Kihyun

2017-12-01

The revised International Staging System (R-ISS) has recently been developed to improve the risk stratification of multiple myeloma (MM) patients over the ISS. We assessed the R-ISS in MM patients who were treated with novel agents as a primary therapy and evaluated its discriminative power and ability to reclassify patients from the ISS. A total of 514 newly diagnosed MM patients treated with novel agents including thalidomide, bortezomib, and lenalidomide as a primary therapy were included in this retrospective analysis. With a median follow-up duration of 42.3 months (range, 40.5-44.1), the median overall survival (OS) was 61.0 months. There was a significant difference in median OS (not reached, 60.9, and 50.1 months for stages 1, 2, and 3, respectively, P < 0.001) among the three stages of R-ISS. The C-statistic was significantly greater for R-ISS than for ISS (0.769 vs. 0.696, P < 0.001). The event NRI was -0.08 (95% confidence interval [CI], -0.18-0.01) and the non-event NRI was 0.05 (95% CI, -0.03-0.10), resulting in a total NRI of -0.03 (95% CI, -0.14-0.08, P = 0.602). The R-ISS performs well and has significantly better discriminative power than the ISS in MM patients treated with novel agents as a primary therapy. However, it does not better reclassify patients from the ISS, suggesting that there is still room to improve the staging system. Moreover, new statistical measures for assessing and quantifying the risk prediction of new prognostic models are necessary in future studies. © 2017 Wiley Periodicals, Inc.

Proton Radiation Therapy for Pediatric Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumors: Outcomes for Very Young Children Treated With Upfront Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimenez, Rachel B., E-mail: rbjimenez@partners.org; Sethi, Roshan; Depauw, Nicolas

Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients hadmore » medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity.« less

Treating uncomplicated malaria in children: comparing artemisinin-based combination therapies.

PubMed

Yeka, Adoke; Harris, Jamal C

2010-12-01

In response to increased resistance to conventional drugs, the WHO is promoting artemisinin-based combination therapy (ACT) for treating uncomplicated malaria. The objective of this report is to review the available evidence on the efficacy and effectiveness, acceptability, and deployment of ACT in resource-limited settings with a focus on sub-Saharan Africa. ACTs are very effective in the treatment of uncomplicated Plasmodium falciparum malaria in children. ACTs are relatively safe and tolerable with no reported resistance in sub-Saharan Africa despite indications of delayed clearance of infections in south-east Asia. The major challenges to the widespread use of ACT include its high cost, availability, and inefficient delivery due to, among other things, weak healthcare systems. ACTs are an essential tool in the fight to control and eliminate malaria. They are currently the most effective drugs against P. falciparum malaria. They should be deployed through programs that address availability, cost, adherence, and quality assurance. Initiatives including home-based management of malaria, improving public sector procurement and supply chains, and reducing private sector pricing should make ACTs more accessible for sub-Saharan African children who bear the brunt of the burden of malarial disease.

Esophageal Dose Tolerance in Patients Treated With Stereotactic Body Radiation Therapy.

PubMed

Nuyttens, Joost J; Moiseenko, Vitali; McLaughlin, Mark; Jain, Sheena; Herbert, Scott; Grimm, Jimm

2016-04-01

Mediastinal critical structures such as trachea, bronchus, esophagus, and heart are among the dose-limiting factors for stereotactic body radiation therapy (SBRT) to central lung lesions. The purpose of this study was to characterize the risk of esophagitis for patients treated with SBRT and to develop a statistical dose-response model to assess the equivalent uniform dose, D10%, D5cc, D1cc, and Dmax, to the esophagus and the risk of toxicity. Toxicity outcomes of a dose-escalation study of 56 patients who had taken CyberKnife treatment from 45-60Gy in 3-7 fractions at the Erasmus MC-Daniel den Hoed Cancer Center were utilized to create the dose-response model for esophagus. A total of 5 grade 2 esophageal complications were reported (Common Terminology Criteria for Adverse Events version 3.0); 4 complications were early effects and 1 complication was a late effect. All analyses were performed in terms of 5-fraction equivalent dosing. According to our study, D1cc at a dose of 32.9Gy and Dmax dose of 43.4Gy corresponded to a complication probability of 50% for grade 2 toxicity. In this series of 58 CyberKnife mediastinal lung cases, no grade 3 or higher esophageal toxicity occurred. Our estimates of esophageal toxicity are compared with the data in the literature. Further research needs to be performed to establish more reliable dose limits as longer follow-up and toxicity outcomes are reported in patients treated with SBRT for central lung lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of Neutron Sources and 10B Concentration on Boron Neutron Capture Therapy for Shallow and Deeper Non-small Cell Lung Cancer.

PubMed

Yu, Haiyan; Tang, Xiaobin; Shu, Diyun; Liu, Yuanhao; Geng, Changran; Gong, Chunhui; Hang, Shuang; Chen, Da

2017-03-01

Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high Linear Energy Transfer (LET). It is considered a potential therapeutic approach for non-small cell lung cancer (NSCLC). It could avoid the inaccurate treatment caused by the lung motion during radiotherapy, because the dose deposition mainly depends on the boron localization and neutron source. Thus, B concentration and neutron sources are both principal factors of BNCT, and they play significant roles in the curative effect of BNCT for different cases. The purpose was to explore the feasibility of BNCT treatment for NSCLC with either of two neutron sources (the epithermal reactor at the Massachusetts Institute of Technology named "MIT source" and the accelerator neutron source designed in Argentina named "MEC source") and various boron concentrations. Shallow and deeper lung tumors were defined in the Chinese hybrid radiation phantom, and the Monte Carlo method was used to calculate the dose to tumors and healthy organs. The MEC source was more appropriate to treat the shallow tumor (depth of 6 cm) with a shorter treatment time. However, the MIT source was more suitable for deep lung tumor (depth of 9 cm) treatment, as the MEC source is more likely to exceed the skin dose limit. Thus, a neutron source consisting of more fast neutrons is not necessarily suitable for deep treatment of lung tumors. Theoretical distribution of B in tumors and organs at risk (especially skin) was obtained to meet the treatable requirement of BNCT, which may provide the references to identify the feasibility of BNCT for the treatment of lung cancer using these two neutron sources in future clinical applications.

Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

PubMed

Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun; Ono, Minoru; Takahashi, Hiroyuki; Eriguchi, Masazumi

2014-06-01

A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that (10)BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca; Fortin, Andre; Wang, Chang Shu

2012-03-15

Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, andmore » the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting

Neutron capture therapy with deep tissue penetration using capillary neutron focusing

DOEpatents

Peurrung, Anthony J.

1997-01-01

An improved method for delivering thermal neutrons to a subsurface cancer or tumor which has been first doped with a dopant having a high cross section for neutron capture. The improvement is the use of a guide tube in cooperation with a capillary neutron focusing apparatus, or neutron focusing lens, for directing neutrons to the tumor, and thereby avoiding damage to surrounding tissue.

Proof of Principle of Ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy

PubMed Central

Lawrence, Jessica A.; Forrest, Lisa J.; Turek, Michelle M.; Miller, Paul E.; Mackie, T. Rockwell; Jaradat, Hazim A.; Vail, David M.; Dubielzig, Richard R.; Chappell, Richard; Mehta, Minesh P.

2010-01-01

Intensity modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared to a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT treated and 2D treated dogs was 420 days and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared to historical controls treated with 2D-RT. PMID:20973393

A creative therapy in treating cavernous hemangioma of penis with copper wire.

PubMed

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

2014-10-01

Cavernous hemangiomas of penis are rare benign lesions infrequently described in the literature. No completely satisfactory treatment has been found to correct the cosmetic deformities especially the extensive hemangiomas of corpus penis. In light of the promising application of copper wire/needle in vascular malformations, we began a clinical study to investigate the safety, feasibility, and cosmetic effect of copper wire therapy in treating cavernous hemangioma of penis. Seven patients ranging in age from 12 to 32 years with penile cavernous hemangiomas entered our study from 2005 to 2011. All patients received treatments with percutaneous copper wires. Perioperative data including mean operation time, estimated blood loss, length of copper wire retention, and length of hospital stay were analyzed. All possible complications were noted, and cosmetic result was evaluated. Patients were followed up after discharge from the hospital. All operations were successful, and no obvious complications were observed. The patients were satisfied with the aesthetic results. Follow-up time ranged from 1 to 5 years. Recurrence was discovered in a patient with the largest lesion of corpus penis 2 months after the treatment. Secondary procedure was carried out with the same technique, and no lesions were found later. The shortage of studies on this topic prevented us from defining a therapeutic reference standard. The results of our study confirmed that copper wire therapy was a simple, safe, and useful option for penile cavernous hemangioma. © 2013 International Society for Sexual Medicine.

Novel Approach to Treating Androgenetic Alopecia in Females With Photobiomodulation (Low-Level Laser Therapy).

PubMed

Friedman, Shelly; Schnoor, Patricia

2017-06-01

Photobiomodulation, also referred to as low-level laser therapy (LLLT), has been studied and used for (among other diseases) the promotion of hair regrowth. A clinical study was developed to define the physiologic effects that occur when the human hair follicle and surrounding tissue structures are exposed to laser light using a novel device that is fitted with an array of laser diode sources operating at 650 nm and placed inside a sports cap to promote discretion while in use. The study demonstrates that low-level laser treatment of the scalp every other day for 17 weeks using the HANDI-DOME LASER device is a safe and effective treatment for androgenetic alopecia in healthy females between the ages of 18 to 60 with Fitzpatrick skin Types I to IV and Ludwig-Savin Baldness Scale I-2 to II-2 baldness patterns. Subjects receiving LLLT at 650 nm achieved a 51% increase in hair counts as compared with sham-treated control patients in this multicenter randomized controlled trial. These results suggest that the emerging technology of low-level laser therapy may play a potentially significant role in health care providers' armamentarium for the disease androgenic alopecia.

A new low-cost negative-pressure wound therapy versus a commercially available therapy device widely used to treat complex traumatic injuries: a prospective, randomized, non-inferiority trial.

PubMed

Kamamoto, Fabio; Lima, Ana Lucia Munhoz; Rezende, Marcelo Rosa de; Mattar-Junior, Rames; Leonhardt, Marcos de Camargo; Kojima, Kodi Edson; Santos, Carla Chineze Dos

2017-12-01

Negative-pressure wound therapy has been widely adopted to reduce the complexity of treating a broad range of acute and chronic wounds. However, its cost is high. The objective of this study was to evaluate the following two different methods of negative-pressure wound therapy in terms of healing time: a low-cost method of negative-pressure wound therapy (a pressure stabilizer device connected to a hospital wall-vacuum system with a gauze-sealed dressing, USP) and the standard of care (vacuum-assisted closure, VAC). This is a randomized, controlled, non-inferiority, unblinded trial. Patients admitted with complex injuries to a trauma center in a public referral hospital who were indicated for orthopedic surgery were randomized to a USP or VAC group. The primary outcome was the time required to achieve a "ready for surgery condition", which was defined as a wound bed with healthy granulation tissue and without necrosis or purulent secretion. Wound bed area contraction, granulation tissue growth and the direct costs of the dressings were secondary outcomes. Variation in area and granulation tissue growth were essentially the same between the systems, and healing time was equal between the groups (p=0.379). In both systems, serial debridement increased wound area (p=0.934), and granulation tissue was also increased (p=0.408). The mean treatment cost was US$ 15.15 in the USP group and US$ 872.59 in the VAC group. For treating complex traumatic injuries, USP was non-inferior to and less expensive than VAC.

The Effect of Combination Antiviral Therapy in the Treatment of Hepatitis C on the Occurrence of Depressive Disorder in Patients Treated for Hepatitis C in the Republic of Srpska.

PubMed

Banjac, Visnja; Zivlak-Radulovic, Nera; Miskovic, Mirjana

2016-04-01

The current standard treatment of chronic hepatitis C in Bosnia and Herzegovina consists of pegylated interferon alpha in combination with ribavirin. Interferon therapy has many psychiatric side effects, with depressive symptomatology being most prominent. The aim of the study was to establish the frequency and severity of depression in patients with chronic hepatitis C during two months of the aforementioned therapy. The overall sample consisted of 46 subjects, divided into three subgroups, aged 18 to 65. The study population consisted of subjects treated for chronic hepatitis C (n = 15), subjects infected but not treated for chronic hepatitis C (n = 15), and healthy controls (n = 16). The assessment and level of depression were based on the Structural clinical interview (SCID), Montgomery-Asberg Depression Rating Scale and Zung Self-Rating Depression Scale. The assessments were conducted before interferon therapy (on the day 0), after 4 and 8 weeks of therapy. Regarding its frequency, MADRS scoring showed that the number of depressed subjects receiving therapy increased after 8 weeks (46.7%). There was statistical significance between the subgroups after 4 and 8 weeks. Likewise, the ZUNG scale showed that the number of depressed subjects receiving therapy increased after 8 weeks (73.3%). There was statistical significance between the subgroups on the day 0, after 4 and 8 weeks. Depression was significantly more frequent in chronic hepatitis C subjects treated with interferon alpha in combination with ribavirin than in subjects in the group without therapy. Mild depression was most prevalent.

Compromised breast flap treated with leech therapy, hyperbaric oxygen, pentoxifylline and topical nitroglycerin: A case report.

PubMed

Moffat, Andrew D; Weaver, Lindell K; Tettelbach, William H

2015-01-01

Hyperbaric oxygen (HBO2) is often indicated in compromised surgical flaps. Although limited to animal models and human case reports, the utilization of leech therapy (Hirudo medicinalis) with HBO2 provides better outcomes than each modality alone. Topical nitroglycerin and pentoxifylline are also frequently used adjunctively for compromised flaps. We present a case of successful breast flap salvage utilizing a combination of leech therapy, HBO2, topical nitroglycerin and pentoxifylline. A 34-year-old female, one day post-status cosmetic breast reduction mammoplasty developed a dusky discoloration of the left nipple areolar complex, indicating imminent flap failure. The patient was immediately treated with topical nitroglycerin, oral pentoxifylline, and referred for HBO2. After her first HBO2 treatment, there was clinical improvement to the superior portion of the areolar flap, with little improvement inferiorly where the discoloration had remained essentially unchanged. To address this, we added leech therapy and discontinued the topical nitroglycerin. Ceftriaxone for Aeromonas prophylaxis was started, and leeches were attached two at a time and removed from the area once feeding had ceased. These were applied three times per day for three days while receiving HBO2 twice per day for six days. The patient's flap improved and completely healed by Week 8 without need for further surgery. This is the first case to our knowledge of successful breast flap salvage using a combination of leech therapy, HBO2, topical nitroglycerin and pentoxifylline.

Baseline Serum Testosterone in Men Treated With Androgen Deprivation Therapy and Radiotherapy for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Mack, E-mail: mroach@radonc.ucsf.ed; Bae, Kyounghwa; Lawton, Colleen

Introduction: It is believed that men diagnosed with prostate cancer and a low baseline serum testosterone (BST) may have more aggressive disease, and it is frequently recommended they forgo testosterone replacement therapy. We used two large Phase III trials involving androgen deprivation therapy and external beam radiation therapy to assess the significance of a BST. Methods and Materials: All patients with a BST and complete data (n = 2,478) were included in this analysis and divided into four categories: 'Very Low BST' (VLBST) {<=}16.5th percentile of BST ({<=}248 ng/dL; n = 408); 'Low BST' (LBST) >16.5th percentile and {<=}33rd percentilemore » (>248 ng/dL but {<=}314 ng/dL; n = 415); 'Average BST' (ABST) >33rd percentile and {<=}67th percentile (314-437 ng/dL; n = 845); and 'High BST' (HBST) >67th percentile (>437 ng/dL; n = 810). Outcomes included overall survival, distant metastasis, biochemical failure, and cause-specific survival. All outcomes were adjusted for the following covariates: treatment arm, BST, age (<70 vs. {>=}70), prostate-specific antigen (PSA; <10 vs. 10 {<=} PSA <20 vs. 20 {<=}), Gleason score (2-6 vs. 7 vs. 8-10); T stage (T1-T2 vs. T3-T4), and Karnofsky Performance Status (60-90 vs. 100). Results: On multivariable analysis age, Gleason score, and PSA were independently associated with an increased risk of biochemical failure, distant metastasis and a reduced cause-specific and overall survival (p < 0.05), but BST was not. Conclusions: BST does not affect outcomes in men treated with external beam radiation therapy and androgen deprivation therapy for prostate cancer.« less

Amine enriched solid sorbents for carbon dioxide capture

DOEpatents

Gray, McMahan L.; Soong, Yee; Champagne, Kenneth J.

2003-04-15

A new method for making low-cost CO.sub.2 sorbents that can be used in large-scale gas-solid processes. The new method entails treating a solid substrate with acid or base and simultaneous or subsequent treatment with a substituted amine salt. The method eliminates the need for organic solvents and polymeric materials for the preparation of CO.sub.2 capture systems.

Neutron capture therapy with deep tissue penetration using capillary neutron focusing

DOEpatents

Peurrung, A.J.

1997-08-19

An improved method is disclosed for delivering thermal neutrons to a subsurface cancer or tumor which has been first doped with a dopant having a high cross section for neutron capture. The improvement is the use of a guide tube in cooperation with a capillary neutron focusing apparatus, or neutron focusing lens, for directing neutrons to the tumor, and thereby avoiding damage to surrounding tissue. 1 fig.

Population-Based Study of Cardiovascular Mortality Among Patients With Prostate Cancer Treated With Radical External Beam Radiation Therapy With and Without Adjuvant Androgen Deprivation Therapy at the British Columbia Cancer Agency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Julian; Vaid, Moninder; Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca

2011-07-01

Purpose: There are conflicting studies of the impact of androgen deprivation therapy (ADT) on cardiovascular (CV) mortality among prostate cancer patients receiving curative intent external beam radiation therapy (EBRT). We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Methods and Materials: Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by durationmore » of ADT using competing risk analysis and Fine and Gray multivariant analysis. A total of 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Results: Of 5,948 prostate cancer patients treated with radical intent EBRT, of whom 1,933 were treated without ADT, 674 received ADT for {<=}6 months and 3,341 received > 6 months of ADT. The cumulative CV mortality at 7 years was 2.6% (95% confidence interval [CI] 1.9-3.5%), 2.1% (95% CI = 1.2-3.5%), and 1.4 (95% CI = 1.0-2.0%) for patients with no ADT, {<=}6 months of ADT, and >6 months of ADT, respectively (Gray's p = 0.002). Baseline CV disease and risk factors were more prevalent in the no-ADT group compared with the >6-month ADT group. Conclusions: This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT rather than effect of ADT itself.« less

The effects of home oxygen therapy on energy metabolism in patients with COPD

PubMed Central

Kırıcı Berber, Nurcan; Yetkin, Özkan; Kılıç, Talat; Berber, Ilhami; Özgel, Mehmet

2018-01-01

Background COPD is preventable and treatable and is characterized by completely nonreversible airflow obstruction. In this study, we aimed to investigate the effect of long-term oxygen therapy on patients with stage 4 COPD who were followed up and treated at the polyclinic or clinic service. We evaluated the effects of oxygen therapy on energy metabolism and physical activity in patients with COPD. Methods Nineteen patients with COPD (16 male/3 female), treated with oxygen therapy for the first time, were included in this study. Analysis of arterial blood gases and pulmonary function test was performed. Metabolic Holter device (SenseWear® Armband) was placed pre- and post-oxygen therapy on the patients’ arm for at least 3 days. This device captures Holter data in a digitized electronic system, and the daily average value was calculated from the data. Results Post-oxygen treatment showed a significant increase in energy expenditure by patients with COPD (pretreatment, 1,497±596 joule; posttreatment, 2,977±5,985 joule; P=0.044). Moreover, number of steps during walking (pretreatment, 2,056±256; posttreatment, 2,120±195; P=0.03), resting (pretreatment, 6.36±3.31 hours; posttreatment, 3.47±2.19 hours; P<0.03), and sleeping (pretreatment, 4.23±2.13 hours; posttreatment, 2.33±1.42 hours; P<0.00) showed significant differences. Increased daily energy expenditure in patients with respiratory failure was detected with long-term oxygen therapy. In addition, the immobility of patients decreased and duration of physical activity increased in patients with COPD. Conclusion In this study, positive effects of long-term oxygen therapy have been demonstrated with respect to energy metabolism and physical activity of patients with COPD. Thus, we recommend that medication adherence and long-term oxygen therapy should begin early in patients with COPD.

[Efficacy on hemiplegic spasticity treated with plum blossom needle tapping therapy at the key points and Bobath therapy: a randomized controlled trial].

PubMed

Wang, Fei; Zhang, Lijuan; Wang, Jianhua; Shi, Yan; Zheng, Liya

2015-08-01

To evaluate the efficacy on hemiplegic spasticity after cerebral infarction treated with plum blossom needle tapping therapy at the key points and Bobath therapy. Eighty patients were collected, in compliance with the inclusive criteria of hemiplegic spasticity after cerebral infarction, and randomized into an observation group and a control group, 40 cases in each one. In the control group, Bobath manipulation therapy was adopted to relieve spasticity and the treatment of 8 weeks was required. In the observation group, on the basis of the treatment as the control group, the tapping therapy with plum blossom needle was applied to the key points, named Jianyu (LI 15), Jianliao (LI 14), Jianzhen (SI 9), Hegu (LI 4), Chengfu (BL 36), Zusanli (ST 36), Xiyangguan (GB 33), etc. The treatment was given for 15 min each time, once a day. Before treatment, after 4 and 8 weeks of treatment, the Fugl-Meyer assessment (FMA) and Barthel index (BI) were adopted to evaluate the motor function of the extremity and the activity of daily life in the patients of the two groups separately. The modified Ashworth scale was used to evaluate the effect of anti-spasticity. In 4 and 8 weeks of treatment, FMA: scores and BI scores were all significantly increased as compared with those before treatment in the two groups: (both P<0. 05). The results in 8 weeks of treatment in the observation group were significantly better than those in the control group (all P<0. 05). In 4 and 8 weeks of treatment, the scores of spasticity state were improved as compared with those before treatment in the patients of the two groups (all P<0. 05). The result in 8 weeks of treatment in the observation group was significantly better than that in the control group (P<0. 05). In 8 weeks of treatment, the total effective rate of anti-spasticity was 90. 0% (36/40) in the observation group, better than 75. 0% (30/40) in the control group (P<0. 05). The tapping therapy with plum blossom needle at the key points

Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy.

PubMed

Capuron, L; Ravaud, A; Gualde, N; Bosmans, E; Dantzer, R; Maes, M; Neveu, P J

2001-11-01

The relationship between immune activation and the development of early depressive symptoms were studied in 33 cancer patients undergoing cytokine therapy. Patients were treated either with subcutaneous IL-2 administered alone (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone administered subcutaneously at low doses (n=5) or intravenously at high doses (n=10). The intensity of depressive symptoms was assessed during a clinical interview carried out before the start of cytokine therapy and five days later using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same days, blood samples were collected for each patient to measure serum concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R, LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha displayed concomitant mood symptoms and increased serum cytokine levels during treatment. In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is produced in response to the production of pro-inflammatory cytokines, and thereby reflects an inflammatory response. These results support the hypothesis of close relationship between depressive symptoms and the activation of the cytokine network.

Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

2011-03-15

Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failuremore » (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT {<=}2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs ({<=} 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT {<=}2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.« less

The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria.

PubMed

Ambler, Michael T; Dubowitz, Lilly M; Arunjerdja, Ratree; Hla, Eh Paw; Thwai, Kyaw Lay; Viladpainguen, Jacher; Singhasivanon, Pratap; Luxemburger, Christine; Nosten, François; McGready, Rose

2009-09-02

Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children. Children, aged between three months and five years, with acute uncomplicated Plasmodium falciparum malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28. From December 1994 to July 1997, 91 children with uncomplicated P. falciparum, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033). In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.

Nonsurgical periodontal therapy to treat a case of severe periodontitis: A 12-year follow-up.

PubMed

Carnio, João; Moreira, Ana Karina; Jenny, Todd; Camargo, Paulo M; Pirih, Flavia Q

2015-08-01

This case report describes the successful treatment of a severe chronic periodontitis case by nonsurgical therapy and a strict maintenance program over a 12-year period. A 38-year-old man concerned about the protrusion of his maxillary incisors was referred for periodontal treatment. The teeth in the maxillary arch had generalized severe chronic periodontitis. Several treatment options were presented to the patient including the most aggressive, extraction of all maxillary teeth, and the most conservative, scaling and root planing. The patient opted to having the most conservative approach, even though the prognoses for the maxillary teeth were unfavorable. Therefore, he received nonsurgical therapy via scaling and root planing combined with systemic antibiotics before referral to an orthodontist to address the esthetic concerns. The maxillary dentition was treated with orthodontic therapy to retract and align the maxillary anterior segment. Periodontal maintenance (1-hour session), including subgingival instrumentation, was performed 4 times per year until the end of the 12-year follow-up period. The patient only missed 2 appointments in 12 years. Twelve years later, the results revealed that all but 1 maxillary tooth were maintained in a state of acceptable health, function, and esthetics. Although most would agree with the initial poor prognosis of this patient's case, nonsurgical periodontal therapy was utilized with a 3-month periodontal maintenance program and demonstrated long-term success. The outcome presented in this case report may only have been possible because of patient compliance, professional experience, skill, and supervision throughout the course of treatment. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

Topical herbal therapies for treating osteoarthritis

PubMed Central

Cameron, Melainie; Chrubasik, Sigrun

2014-01-01

Background Before extraction and synthetic chemistry were invented, musculoskeletal complaints were treated with preparations from medicinal plants. They were either administered orally or topically. In contrast to the oral medicinal plant products, topicals act in part as counterirritants or are toxic when given orally. Objectives To update the previous Cochrane review of herbal therapy for osteoarthritis from 2000 by evaluating the evidence on effectiveness for topical medicinal plant products. Search methods Databases for mainstream and complementary medicine were searched using terms to include all forms of arthritis combined with medicinal plant products. We searched electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, World Health Organization Clinical Trials Registry Platform) to February 2013, unrestricted by language. We also searched the reference lists from retrieved trials. Selection criteria Randomised controlled trials of herbal interventions used topically, compared with inert (placebo) or active controls, in people with osteoarthritis were included. Data collection and analysis Two review authors independently selected trials for inclusion, assessed the risk of bias of included studies and extracted data. Main results Seven studies (seven different medicinal plant interventions; 785 participants) were included. Single studies (five studies, six interventions) and non-comparable studies (two studies, one intervention) precluded pooling of results. Moderate evidence from a single study of 174 people with hand osteoarthritis indicated that treatment with Arnica extract gel probably results in similar benefits as treatment with ibuprofen (non-steroidal anti-inflammatory drug) with a similar number of adverse events. Mean pain in the ibuprofen group was 44.2 points on a 100 point scale; treatment with Arnica gel reduced the pain by 4 points after three weeks: mean difference (MD

Misdiagnosed zoophile tinea faciei and tinea corporis effectively treated with isoconazole nitrate and diflucortolone valerate combination therapy.

PubMed

Czaika, Viktor A

2013-05-01

There have been few published reports on the human transmission of Trichophyton mentagrophytes, a zoophilic fungus frequently occurring in pets. Here we report on 2 girls, living with a pet dwarf rabbit, who presented with inflammatory skin lesions positive for T. mentagrophytes and subsequently diagnosed as zoophile tinea faciei and tinea corporis. The patients were successfully treated with systemic terbinafine and 2-week therapy with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%. © 2013 Blackwell Verlag GmbH.

The roles of the Q (q) wave in lead I and QRS frontal axis for diagnosing loss of left ventricular capture during cardiac resynchronization therapy.

PubMed

Cao, Yuan-Yuan; Su, Yan-Gang; Bai, Jin; Wang, Wei; Wang, Jing-Feng; Qin, Sheng-Mei; Ge, Jun-Bo

2015-01-01

Loss of left ventricular (LV) capture may lead to deterioration of heart failure in patients with cardiac resynchronization therapy (CRT). Recognition of loss of LV capture in time is important in clinical practice. A total of 422 electrocardiograms were acquired and analyzed from 53 CRT patients at 8 different pacing settings (LV only, right ventricle [RV] only, biventricular [BV] pacing with LV preactivation of 60, 40, 20, and 0 milliseconds and RV preactivation of 20 and 40 milliseconds). A modified Ammann algorithm by adding a third step-presence of Q (q, or QS) wave-to the original 2-step Ammann algorithm and a QRS axis shift method were devised to identify the loss of LV capture. The accuracy of modified Ammann algorithm was significantly higher than that of Ammann algorithm (78.9% vs. 69.1%, P < 0.001). The accuracy of the axis shift method was 66.4%, which was significantly lower than the modified Ammann algorithm (P < 0.001) and similar to the original one (P = 0.412). However, in the ECGs with QRS axis shift, 96.8% were correctly classified. LV preactivation or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall could elevate the accuracies of the modified Ammann algorithm and the QRS axis shift method. The accuracy of the modified Ammann algorithm is greatly improved. The QRS axis shift method can help diagnose LV capture. The LV preactivation, or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall can increase the diagnostic power of the modified Ammann algorithm and QRS axis shift method. © 2014 Wiley Periodicals, Inc.

TU-FG-BRB-07: GPU-Based Prompt Gamma Ray Imaging From Boron Neutron Capture Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, S; Suh, T; Yoon, D

Purpose: The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. Methods: To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU).more » Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. Results: The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). Conclusion: The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray reconstruction using the GPU computation for BNCT simulations.« less

Mathematical modelling of prostate cancer growth and its application to hormone therapy.

PubMed

Tanaka, Gouhei; Hirata, Yoshito; Goldenberg, S Larry; Bruchovsky, Nicholas; Aihara, Kazuyuki

2010-11-13

Hormone therapy in the form of androgen deprivation is a major treatment for advanced prostate cancer. However, if such therapy is overly prolonged, tumour cells may become resistant to this treatment and result in recurrent fatal disease. Long-term hormone deprivation also is associated with side effects poorly tolerated by patients. In contrast, intermittent hormone therapy with alternating on- and off-treatment periods is a possible clinical strategy to delay progression to hormone-refractory disease with the advantage of reduced side effects during the off-treatment periods. In this paper, we first overview previous studies on mathematical modelling of prostate tumour growth under intermittent hormone therapy. The model is categorized into a hybrid dynamical system because switching between on-treatment and off-treatment intervals is treated in addition to continuous dynamics of tumour growth. Next, we present an extended model of stochastic differential equations and examine how well the model is able to capture the characteristics of authentic serum prostate-specific antigen (PSA) data. We also highlight recent advances in time-series analysis and prediction of changes in serum PSA concentrations. Finally, we discuss practical issues to be considered towards establishment of mathematical model-based tailor-made medicine, which defines how to realize personalized hormone therapy for individual patients based on monitored serum PSA levels.

Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice.

PubMed

Baldo, Guilherme; Mayer, Fabiana Q; Martinelli, Bárbara Z; de Carvalho, Talita G; Meyer, Fabiola S; de Oliveira, Patrícia G; Meurer, Luise; Tavares, Angela; Matte, Ursula; Giugliani, Roberto

2013-05-01

Since we previously observed that in patients with mucopolysaccharidosis (MPS) the storage of undegraded glycosaminoglycans (GAG) occurs from birth, in the present study we aimed to compare normal, untreated MPS I mice (knockout for alpha-l-iduronidase-IDUA), and MPS I mice treated with enzyme replacement therapy (ERT, Laronidase, 1.2mg/kg every 2 weeks) started from birth (ERT-neo) or from 2 months of age (ERT-ad). All mice were sacrificed at 6 months. Both treatments were equally effective in normalizing GAG levels in the viscera but had no detectable effect on the joint. Heart function was also improved with both treatments. On the other hand, mice treated from birth presented better outcomes in the difficult-to-treat aortas and heart valves. Surprisingly, both groups had improvements in behavior tests, and normalization of GAG levels in the brain and IDUA injection resulted in detectable levels of enzyme in the brain tissue 1h after administration. ERT-ad mice developed significantly more anti-IDUA-IgG antibodies, and mice that didn't develop antibodies had better performances in behavior tests, indicating that development of antibodies may reduce enzyme bioavailability. Our results suggest that ERT started from birth leads to better outcomes in the aorta and heart valves, as well as a reduction in antibody levels. Some poor vascularized organs, such as the joints, had partial or no benefit and ancillary therapies might be needed for patients. The results presented here support the idea that ERT started from birth leads to better treatment outcomes and should be considered whenever possible, a observation that gains relevance as newborn screening programs are being considered for MPS and other treatable lysosomal storage disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Exercise in Treating Hypertension: Tailoring Therapies for Active Patients.

ERIC Educational Resources Information Center

Chintanadilok, Jirayos

2002-01-01

Exercise can be definitive therapy for some, and adjunctive therapy for many, people with hypertension, though people with secondary hypertension may not derive as much benefit. Low-to- moderate-intensity aerobic exercise can help with mild hypertension and reduce drug dosages in more severe cases. For active patients requiring medication,…

Relationship Enhancement Therapy: A Case Study for Treating Vaginismus.

ERIC Educational Resources Information Center

Harman, Marsha J.; And Others

1994-01-01

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

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

PubMed Central

Morris, G M; Smith, D R; Patel, H; Chandra, S; Morrison, G H; Hopewell, J W; Rezvani, M; Micca, P L; Coderre, J A

2000-01-01

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,α)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as

Photodynamic therapy (PDT) to treat a chronic skin wound in a dog

NASA Astrophysics Data System (ADS)

Hage, Raduan; Plapler, Hélio; Bitar, Renata A.

2008-02-01

Photodynamic Therapy (PDT) is an emerging and promising therapeutic modality for treatment of a wide variety of malignant and nononcologic tumors, as well as in the treatment of infected skin ulcers. This study evaluated the effectiveness of the PDT to treat a chronic skin wound that had been already subjected to several clinical and surgical type treatments in a dog. The animal with an infected chronic skin wound with 8 cm diameter in the left leg received an injection of an aqueous solution of 1% methylene blue (MB) with 2% lidocaine into the lesion. After MB injection the wound was irradiated using a LED (LED-VET MMOptics(r)) with a wavelength between 600 and 700 nm, 2 cm diameter circular light beam, of 150 mW of power, light dose of 50 J/cm2. After 3 and 6 weeks PDT was repeated and the wound was re-evaluated. Complete healing was achieved 10 weeks after the first procedure.

Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR).

PubMed

Dixon, W G; Hyrich, K L; Watson, K D; Lunt, M; Galloway, J; Ustianowski, A; Symmons, D P M

2010-03-01

The risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF) therapy, with a proposed differential risk between the anti-TNF drugs etanercept (ETA), infliximab (INF) and adalimumab (ADA). To compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity. Data from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504 ADA) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs. To April 2008, 40 cases of TB were reported, all in the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA (144 events/100,000 person-years) and INF (136/100,000 person-years) than for ETA (39/100,000 person-years). After adjustment, the incidence rate ratio compared with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to 12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated. Patients of non-white ethnicity had a sixfold increased risk of TB compared with white patients treated with anti-TNF therapy. The rate of TB in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving INF and ADA than in those receiving ETA.

[The expression of thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) protein in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy].

PubMed

Ishibashi, Keiichiro; Okada, Norimichi; Ishiguro, Toru; Kuwabara, Kouki; Ohsawa, Tomonori; Yokoyama, Masaru; Kumamoto, Kensuke; Haga, Norihiro; Mori, Takashi; Yamada, Hirofumi; Miura, Ichiro; Tamaru, Junichi; Itoyama, Shinji; Ishida, Hideyuki

2010-11-01

Thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) were known to be important biomarkers to predict a tumor response to 5-fluorouracil (5-FU) and oxaliplatin, but the relationship between these expressions and tumor response were still unclear. The aim of this study was to determine whether the expression of TS and ERCC-1 protein predict a tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy as first-line treatment. Fifty patients with unresectable colorectal cancer treated with mFOLFOX6 therapy were enrolled in this study. The expression of TS and ERCC-1 protein in primary cancer cells were examined using immunohistochemistry. There were no significant differences between response rate and the expression of TS or ERCC-1 protein (TS: p>0.99, ERCC-1: p= 0.50). There were no significant differences between progression-free survival time and the expression of TS or ERCC-1 protein (TS: p=0.60, ERCC-1: p=0.60). In this study, the expression TS and ERCC-1 protein may not be useful for the prediction of tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy.

In-phantom two-dimensional thermal neutron distribution for intraoperative boron neutron capture therapy of brain tumours

NASA Astrophysics Data System (ADS)

Yamamoto, T.; Matsumura, A.; Yamamoto, K.; Kumada, H.; Shibata, Y.; Nose, T.

2002-07-01

The aim of this study was to determine the in-phantom thermal neutron distribution derived from neutron beams for intraoperative boron neutron capture therapy (IOBNCT). Gold activation wires arranged in a cylindrical water phantom with (void-in-phantom) or without (standard phantom) a cylinder styrene form placed inside were irradiated by using the epithermal beam (ENB) and the mixed thermal-epithermal beam (TNB-1) at the Japan Research Reactor No 4. With ENB, we observed a flattened distribution of thermal neutron flux and a significantly enhanced thermal flux delivery at a depth compared with the results of using TNB-1. The thermal neutron distribution derived from both the ENB and TNB-1 was significantly improved in the void-in-phantom, and a double high dose area was formed lateral to the void. The flattened distribution in the circumference of the void was observed with the combination of ENB and the void-in-phantom. The measurement data suggest that the ENB may provide a clinical advantage in the form of an enhanced and flattened dose delivery to the marginal tissue of a post-operative cavity in which a residual and/or microscopically infiltrating tumour often occurs. The combination of the epithermal neutron beam and IOBNCT will improve the clinical results of BNCT for brain tumours.

Treating Traumatized Offenders and Veterans by Means of Narrative Exposure Therapy

PubMed Central

Hecker, Tobias; Hermenau, Katharin; Crombach, Anselm; Elbert, Thomas

2015-01-01

Violent offenders and soldiers are at high risk of developing appetitive aggression and trauma-related disorders, which reduce successful integration into societies. Narrative exposure therapy (NET) for forensic offender rehabilitation (FORNET) aims at reducing symptoms of traumatic stress (e.g., posttraumatic stress disorder) and controlling readiness for aggressive behavior. It follows the logic of the evidence-based trauma-focused NET with special emphasis on violent acts in past and future behavior. In NET, the therapist guides the client by means of exposure through his traumatic experiences in chronological order linking the negative emotions, such as fear, shame, and disgust, to the past context and integrating the traumatic experiences into the autobiographical memory. During FORNET, we also encourage verbalization of any positive emotions and experiences linked to past violent and aggressive behaviors. This recall of positive emotions (linked to the there and then) is contrasted with feelings that emerge during the narration process (here and now). In this way, the therapist helps the client to anchor the whole range of sensory and bodily experiences, cognitions, and emotions to the contextual cues. Over the process of the therapy, we support the client to begin the role change from a violent offender to a citizen, who is capable of living a non-violent and socially adjusted life. Finally, the client develops visions and wishes for the future to support a successful integration into society. Several studies with veterans and violent youths have proven the feasibility of FORNET, found evidence of a positive outcome (recovered mental health, fewer offenses committed, less drug intake, and improved integration into civil society), and highlighted the importance of addressing the whole range of experiences while treating violent offenders or veterans. PMID:26157395

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lollert, André, E-mail: andre.lollert@unimedizin-mainz.de; Gies, Christina; Laudemann, Katharina

Purpose: The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Methods and Materials: Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations throughmore » 2014 (median follow-up time: 48 months). Results: A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Conclusions: Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy.« less

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood.

PubMed

Lollert, André; Gies, Christina; Laudemann, Katharina; Faber, Jörg; Jacob-Heutmann, Dorothee; König, Jochem; Düber, Christoph; Staatz, Gundula

2016-01-01

The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations through 2014 (median follow-up time: 48 months). A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy. Copyright © 2016. Published by Elsevier Inc.

The role of metabolic therapy in treating glioblastoma multiforme

PubMed Central

Maroon, Joseph C.; Seyfried, Thomas N.; Donohue, Joseph P.; Bost, Jeffrey

2015-01-01

Glioblastoma multiforme (GBM) is an aggressive and nearly uniformly fatal malignancy of the central nervous system. Despite extensive research and clinical trials over the past 50 years, very little progress has been made to significantly alter its lethal prognosis. The current standard of care (SOC) includes maximal surgical resection, radiation therapy and chemotherapy and temozolomide (TMZ), including the selective use of glucocorticoids for symptom control. These same treatments, however, have the potential to create an environment that may actually facilitate tumor growth and survival. Research investigating the unique metabolic needs of tumor cells has led to the proposal of a new metabolic treatment for various cancers including GBMs that may enhance the effectiveness of the SOC. The goal of metabolic cancer therapy is to restrict GBM cells of glucose, their main energy substrate. By recognizing the underlying energy production requirements of cancer cells, newly proposed metabolic therapy is being used as an adjunct to standard GBM therapies. This review will discuss the calorie restricted ketogenic diet (CR-KD) as a promising potential adjunctive metabolic therapy for patients with GBMs. The effectiveness of the CR-KD is based on the “Warburg Effect” of cancer metabolism and the microenvironment of GBM tumors. We will review recent case reports, clinical studies, review articles, and animal model research using the CR-KD and explain the principles of the Warburg Effect as it relates to CR-KD and GBMs. PMID:25949849

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

PubMed

Tang, Yu; Qu, Jintao; Wu, Juan; Li, Song; Zhou, Yue; Xiao, Jianru

2015-09-02

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Palliation of clinical signs in 48 dogs with nasal carcinomas treated with coarse-fraction radiation therapy.

PubMed

Gieger, Tracy; Rassnick, Kenneth; Siegel, Sheri; Proulx, David; Bergman, Philip; Anderson, Christine; LaDue, Tracy; Smith, Annette; Northrup, Nicole; Roberts, Royce

2008-01-01

Data from 48 dogs with nasal carcinomas treated with palliative radiation therapy (PRT) were retrospectively reviewed. Factors potentially influencing resolution of clinical signs and survival after PRT were evaluated. Clinical signs completely resolved in 66% of dogs for a median of 120 days. The overall median survival time was 146 days. Duration of response to PRT was shorter in dogs that had clinical signs for <90 days before PRT. Survival times were shorter in dogs that had partial or no resolution of clinical signs after PRT than in dogs that had complete resolution of clinical signs.

SU-F-J-122: Rectal Sparing Reproducibility in Prostate Cancer Patients Treated with Hydrogel Spacer and Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hedrick, S; Robison, B; Blakey, M

2016-06-15

Purpose: Rectal hydrogel spacer has been shown to improve rectal sparing in prostate radiotherapy. The purpose of this study was to determine the reproducibility of rectal sparing throughout treatment in patients undergoing proton therapy. Methods: At our facility, prostate cancer patients are treated with pencil beam scanning proton therapy, utilizing an endorectal balloon (ERB) or rectal spacer hydrogel (Gel) “SpaceOAR” implant. All patients were treated with a full bladder and empty rectum (low residue diet and stool softeners). A quality assurance CT (QACT) was performed periodically throughout treatment to ensure rectal filling consistency and sparing in 41 patients treated withmore » Gel. The treatment planning (TP) dose was calculated on each QACT and the rectum V90%, V75%, V65%, V50%, and V40% were recorded. QACT scans were acquired on day 0, week 1, week 3, and week 5. Results: 144 QACT scans were analyzed, each patient receiving 3–4 QACTs. Rectum V90% was within +/−1% of the TP dose in 70% of the QACTs and within +/−5% in 95% of scans. From previous data analyses, our ERB rectum V90% average is 6%. This value was used as an upper threshold for the Gel QACT analysis. 5 of the 41 patients (12%), corresponding to 7 QACTs, had a rectum V90% that exceeded 6% on one or more QACTs. However, the average rectal V90% measured over multiple QACTs never exceeded 6%. 55% of the QACTs had a rectum volume within 5cc of the TPCT volume, 68% were within 10cc. Conclusion: In this study, we have shown that a majority of our prostate patients can maintain consistent rectal sparing when treated with a hydrogel spacer. QACT rectal V90% exceeding our threshold was most often related to increased rectal filling and gas, which was addressed with improved dietary compliance and the intensification of stool softeners or laxatives.« less

Comorbidity and quality of life in childhood cancer survivors treated with proton beam therapy.

PubMed

Fukushima, Hiroko; Fukushima, Takashi; Suzuki, Ryoko; Iwabuchi, Atsushi; Hidaka, Kyoko; Shinkai, Toko; Masumoto, Kouji; Muroi, Ai; Yamamoto, Tetsuya; Nakao, Tomohei; Oshiro, Yoshiko; Mizumoto, Masashi; Sakurai, Hideyuki; Sumazaki, Ryo

2017-10-01

The rate of childhood cancer survival has recently reached >80%. Various adverse events among childhood cancer survivors (CCS) have been reported. Proton beams are able to avoid unnecessary irradiation to normal/vital organs. We conducted a quality of life (QOL) study for CCS who were treated with proton beam therapy (PBT). We included those patients treated with PBT to the brain, head, or neck and who were ≤15 years old at the University of Tsukuba Hospital between 1983 and 2011. Clinical information was collected from medical records. Questionnaires including the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (which assess health-related quality of life) were sent to the families/patients. Sixty patients were included. Median age at treatment was 6.2 years. The number of patients with status alive/dead/unknown was 32/24/4. Median follow-up period was 63.0 months (range, 48-340 months) for survivors. Questionnaires were sent to 25 families/patients and 19 were returned. PedsQL was assessed for 17 patients. Eleven of 32 living patients had at least one comorbidity grade 3/4. Average QOL score was above that for Japanese schoolchildren and adolescents. There was no correlation with comorbidity, and only longer time from treatment was correlated with a higher PedsQL score (P = 0.006). CCS who were treated with multimodal treatment using PBT had a higher QOL score. Higher score was related to longer time since treatment, regardless of comorbidity. © 2017 Japan Pediatric Society.

An international dosimetry exchange for boron neutron capture therapy. Part I: Absorbed dose measurements.

PubMed

Binns, P J; Riley, K J; Harling, O K; Kiger, W S; Munck af Rosenschöld, P M; Giusti, V; Capala, J; Sköld, K; Auterinen, I; Serén, T; Kotiluoto, P; Uusi-Simola, J; Marek, M; Viererbl, L; Spurny, F

2005-12-01

An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step (Part I) the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik (Sweden), VTT Espoo (Finland), and the Nuclear Research Institute (NRI) at Rez (Czech Republic). A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 microg g(-1) that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study.

A 13C(d,n)-based epithermal neutron source for Boron Neutron Capture Therapy.

PubMed

Capoulat, M E; Kreiner, A J

2017-01-01

Boron Neutron Capture Therapy (BNCT) requires neutron sources suitable for in-hospital siting. Low-energy particle accelerators working in conjunction with a neutron producing reaction are the most appropriate choice for this purpose. One of the possible nuclear reactions is 13 C(d,n) 14 N. The aim of this work is to evaluate the therapeutic capabilities of the neutron beam produced by this reaction, through a 30mA beam of deuterons of 1.45MeV. A Beam Shaping Assembly design was computationally optimized. Depth dose profiles in a Snyder head phantom were simulated with the MCNP code for a number of BSA configurations. In order to optimize the treatment capabilities, the BSA configuration was determined as the one that allows maximizing both the tumor dose and the penetration depth while keeping doses to healthy tissues under the tolerance limits. Significant doses to tumor tissues were achieved up to ∼6cm in depth. Peak doses up to 57Gy-Eq can be delivered in a fractionated scheme of 2 irradiations of approximately 1h each. In a single 1h irradiation, lower but still acceptable doses to tumor are also feasible. Treatment capabilities obtained here are comparable to those achieved with other accelerator-based neutron sources, making of the 13 C(d,n) 14 N reaction a realistic option for producing therapeutic neutron beams through a low-energy particle accelerator. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A computer vision-based system for monitoring Vojta therapy.

PubMed

Khan, Muhammad Hassan; Helsper, Julien; Farid, Muhammad Shahid; Grzegorzek, Marcin

2018-05-01

A neurological illness is t he disorder in human nervous system that can result in various diseases including the motor disabilities. Neurological disorders may affect the motor neurons, which are associated with skeletal muscles and control the body movement. Consequently, they introduce some diseases in the human e.g. cerebral palsy, spinal scoliosis, peripheral paralysis of arms/legs, hip joint dysplasia and various myopathies. Vojta therapy is considered a useful technique to treat the motor disabilities. In Vojta therapy, a specific stimulation is given to the patient's body to perform certain reflexive pattern movements which the patient is unable to perform in a normal manner. The repetition of stimulation ultimately brings forth the previously blocked connections between the spinal cord and the brain. After few therapy sessions, the patient can perform these movements without external stimulation. In this paper, we propose a computer vision-based system to monitor the correct movements of the patient during the therapy treatment using the RGBD data. The proposed framework works in three steps. In the first step, patient's body is automatically detected and segmented and two novel techniques are proposed for this purpose. In the second step, a multi-dimensional feature vector is computed to define various movements of patient's body during the therapy. In the final step, a multi-class support vector machine is used to classify these movements. The experimental evaluation carried out on the large captured dataset shows that the proposed system is highly useful in monitoring the patient's body movements during Vojta therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Pilot testing of a membrane system for postcombustion CO 2 capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merkel, Tim; Kniep, Jay; Wei, Xiaotong

2015-09-30

This final report summarizes work conducted for the U.S. Department of Energy, National Energy Technology Laboratory (DOE) to scale up an efficient post-combustion CO 2 capture membrane process to the small pilot test stage (award number DE-FE0005795). The primary goal of this research program was to design, fabricate, and operate a membrane CO 2 capture system to treat coal-derived flue gas containing 20 tonnes CO 2/day (20 TPD). Membrane Technology and Research (MTR) conducted this project in collaboration with Babcock and Wilcox (B&W), the Electric Power Research Institute (EPRI), WorleyParsons (WP), the Illinois Sustainable Technology Center (ISTC), Enerkem (EK), andmore » the National Carbon Capture Center (NCCC). In addition to the small pilot design, build and slipstream testing at NCCC, other project efforts included laboratory membrane and module development at MTR, validation field testing on a 1 TPD membrane system at NCCC, boiler modeling and testing at B&W, a techno-economic analysis (TEA) by EPRI/WP, a case study of the membrane technology applied to a ~20 MWe power plant by ISTC, and an industrial CO 2 capture test at an Enerkem waste-to-biofuel facility. The 20 TPD small pilot membrane system built in this project successfully completed over 1,000 hours of operation treating flue gas at NCCC. The Polaris™ membranes used on this system demonstrated stable performance, and when combined with over 10,000 hours of operation at NCCC on a 1 TPD system, the risk associated with uncertainty in the durability of postcombustion capture membranes has been greatly reduced. Moreover, next-generation Polaris membranes with higher performance and lower cost were validation tested on the 1 TPD system. The 20 TPD system also demonstrated successful operation of a new low-pressure-drop sweep module that will reduce parasitic energy losses at full scale by as much as 10 MWe. In modeling and pilot boiler testing, B&W confirmed the viability of CO 2 recycle to the

Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunther, Jillian R.; Sato, Mariko; Chintagumpala, Murali

Purpose: The clinical significance of magnetic resonance imaging (MRI) changes after radiation therapy (RT) in children with ependymoma is not well defined. We compared imaging changes following proton beam radiation therapy (PBRT) to those after photon-based intensity modulated RT (IMRT). Methods and Materials: Seventy-two patients with nonmetastatic intracranial ependymoma who received postoperative RT (37 PBRT, 35 IMRT) were analyzed retrospectively. MRI images were reviewed by 2 neuroradiologists. Results: Sixteen PBRT patients (43%) developed postradiation MRI changes at 3.8 months (median) with resolution by 6.1 months. Six IMRT patients (17%) developed changes at 5.3 months (median) with 8.3 months to resolution. Mean age at radiation wasmore » 4.4 and 6.9 years for PBRT and IMRT, respectively (P=.06). Age at diagnosis (>3 years) and time of radiation (≥3 years) was associated with fewer imaging changes on univariate analysis (odds ratio [OR]: 0.35, P=.048; OR: 0.36, P=.05). PBRT (compared to IMRT) was associated with more frequent imaging changes, both on univariate (OR: 3.68, P=.019) and multivariate (OR: 3.89, P=.024) analyses. Seven (3 IMRT, 4 PBRT) of 22 patients with changes had symptoms requiring intervention. Most patients were treated with steroids; some PBRT patients also received bevacizumab and hyperbaric oxygen therapy. None of the IMRT patients had lasting deficits, but 2 patients died from recurrent disease. Three PBRT patients had persistent neurological deficits, and 1 child died secondarily to complications from radiation necrosis. Conclusions: Postradiation MRI changes are more common with PBRT and in patients less than 3 years of age at diagnosis and treatment. It is difficult to predict causes for development of imaging changes that progress to clinical significance. These changes are usually self-limiting, but some require medical intervention, especially those involving the brainstem.« less

Co-Expression of Bmi-1 and Podoplanin Predicts Overall Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Radio(chemo)therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vormittag, Laurenz; Thurnher, Dietmar; Geleff, Silvana

2009-03-01

Purpose: This study was conducted to determine the expression of Bmi-1 and podoplanin in healthy oral mucosa and in untreated tumor tissues samples of patients with squamous cell carcinomas of the head and neck. All patients were treated by primary radio(chemo)therapy. Methods and Materials: The expression of Bmi-1 and podoplanin was immunohistochemically evaluated in 12 normal oral mucosa and 63 tumor specimens and correlated with patients' clinical data. Results: In healthy mucosa expression of Bmi-1 and podoplanin was restricted to the basal cell layer. Expression of both proteins was found in 79% and 86% of our tumor samples, respectively. Inmore » 17 and 8 samples, Bmi-1 and podoplanin were co-expressed at the invasive border or diffuse in the bulk of the tumor, respectively. Univariate analysis showed that the co-expression of Bmi-1 and podoplanin correlated to decreased overall survival (p = 0.044). Moreover, multivariate testing identified high expression of podoplanin (p = 0.044), co-expression of Bmi-1 and podoplanin (p = 0.007) and lack of response to therapy (p < 0.0001) as predictors of shortened overall survival in patients treated with primary radio(chemo)therapy. Conclusions: Bmi-1 and podoplanin are expressed at the invasive front of squamous cell carcinomas of the head and neck. Co-expression of Bmi-1 and podoplanin predicts significantly overall survival of patients treated with primary radio(chemo)therapy.« less

Optimizing topical therapies for treating psoriasis: a consensus conference.

PubMed

Zeichner, Joshua A; Lebwohl, Mark G; Menter, Alan; Bagel, Jerry; Del Rosso, James Q; Elewski, Boni E; Feldman, Steven R; Kircik, Leon H; Koo, John; Gold, Linda Stein; Tanghetti, Emil

2010-09-01

In 2010, an expert committee of physicians and researchers in the field of dermatology working together as the Psoriasis Process of Care Consensus Panel developed consensus guidelines for the treatment of psoriasis. As much as possible, the guidelines were evidence based but also included the extensive clinical experience of the dermatologists. Psoriasis is a lifelong disease that requires long-term treatment and 80% of psoriasis patients have mild to moderate disease. Topical therapies play an important role in the treatment of psoriasis, especially in patients with mild to moderate disease. Patients usually start with monotherapy; however, in more severe cases (> 10% body surface area [BSA], severely impaired quality of life [QOL], or recalcitrant psoriatic lesions), multiple treatment modalities may be used as part of combination, sequential, or rotational therapeutic regimens. Main treatment options include topical steroids, systemic therapies, topical vitamin D treatments such as vitamin D3 ointment, retinoids, phototherapy, and biologic therapies. Other topical therapies include the following steroid-sparing agents: coal tar, anthralin, calcineurin inhibitors, keratolytics, and emollients. Therapeutic considerations also should focus on adherence, improving QOL, and promoting a good patient-physician relationship.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giantsoudi, Drosoula; Sethi, Roshan V.; Yeap, Beow Y.

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imagingmore » (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.« less

Magnetizable stent-grafts enable endothelial cell capture

NASA Astrophysics Data System (ADS)

Tefft, Brandon J.; Uthamaraj, Susheil; Harburn, J. Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S.

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Magnetizable stent-grafts enable endothelial cell capture.

PubMed

Tefft, Brandon J; Uthamaraj, Susheil; Harburn, J Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Skin dose for head and neck cancer patients treated with intensity-modulated radiation therapy(IMRT)

NASA Astrophysics Data System (ADS)

Fu, Hsiao-Ju; Li, Chi-Wei; Tsai, Wei-Ta; Chang, Chih-Chia; Tsang, Yuk-Wah

2017-11-01

The reliability of thermoluminescent dosimeters (ultrathin TLD) and ISP Gafchromic EBT2 film to measure the surface dose in phantom and the skin dose in head-and-neck patients treated with intensity-modulated radiation therapy technique(IMRT) is the research focus. Seven-field treatment plans with prescribed dose of 180 cGy were performed on Eclipse treatment planning system which utilized pencil beam calculation algorithm(PBC). In calibration tests, the variance coefficient of the ultrathin TLDs were within 3%. The points on the calibration curve of the Gafchromic film was within 1% variation. Five measurements were taken on phantom using ultrathin TLD and EBT2 film respectively. The measured mean surface doses between ultrathin TLD or EBT2 film were within 5% deviation. Skin doses of 6 patients were measured for initial 5 fractions and the mean dose per-fraction was calculated. If the extrapolated doses for 30 fractions were below 4000 cGy, the skin reaction grading observed according to Radiation Therapy Oncology Group (RTOG) was either grade 1 or grade 2. If surface dose exceeded 5000 cGy in 32 fractions, then grade 3 skin reactions were observed.

Hyperadrenocorticism: treating dogs.

PubMed

Brown, Cassandra G; Graves, Thomas K

2007-03-01

This article is a complete review of all reported therapies for hyperadrenocorticism in dogs. Both medical and surgical options for treating pituitary-dependent hyperadrenocorticism and adrenal tumor-related disease are discussed, and the efficacy, safety, and use of these treatments are compared.

Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

PubMed

Polak, David; Martin, Conchita; Sanz-Sánchez, Ignacio; Beyth, Nurit; Shapira, Lior

2015-04-01

Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TREatment of ATopic eczema (TREAT) Registry Taskforce: An international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

PubMed

Gerbens, L A A; Apfelbacher, C J; Irvine, A D; Barbarot, S; de Booij, R J; Boyce, A E; Deleuran, M; Eichenfield, L F; Hof, M H; Middelkamp-Hup, M A; Roberts, A; Schmitt, J; Vestergaard, C; Wall, D; Weidinger, S; Williamson, P R; Flohr, C; Spuls, P I

2018-05-15

Evidence of immunomodulatory therapies to guide clinical management for atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real world conditions which can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and -dynamic research which cannot be adequately addressed in clinical trials. The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. Participants from six stakeholder groups were included: doctors, nurses, non-clinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised 3 sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. 479 participants from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2, and 3 respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). This core set of domains and items to be captured by national AE systemic therapy registries will standardise data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Synthesis and characterization of boron fenbufen and its F-18 labeled homolog for boron neutron capture therapy of COX-2 overexpressed cholangiocarcinoma.

PubMed

Yeh, Chun-Nan; Chang, Chi-Wei; Chung, Yi-Hsiu; Tien, Shi-Wei; Chen, Yong-Ren; Chen, Tsung-Wen; Huang, Ying-Cheng; Wang, Hsin-Ell; Chou, You-Cheng; Chen, Ming-Huang; Chiang, Kun-Chun; Huang, Wen-Sheng; Yu, Chung-Shan

2017-09-30

Boron neutron capture therapy (BNCT) is a binary therapy that employs neutron irradiation on the boron agents to release high-energy helium and alpha particles to kill cancer cells. An optimal response to BNCT depends critically on the time point of maximal 10 B accumulation and highest tumor to normal ratio (T/N) for performing the neutron irradiation. The aggressive cholangiocarcinoma (CCA) representing a liver cancer that overexpresses COX-2 enzyme is aimed to be targeted by COX-2 selective boron carrier, fenbufen boronopinacol (FBPin). Two main works were performed including: 1) chemical synthesis of FBPin as the boron carrier and 2) radiochemical labeling with F-18 to provide the radiofluoro congener, m-[ 18 F]fluorofenbufen ester boronopinacol (m-[ 18 F]FFBPin), to assess the binding affinity, cellular accumulation level and distribution profile in CCA rats. FBPin was prepared from bromofenbufen via 3 steps with 82% yield. The binding assay employed [ 18 F]FFBPin to compete FBPin for binding to COX-1 (IC 50 =0.91±0.68μM) and COX-2 (IC 50 =0.33±0.24μM). [ 18 F]FFBPin-derived 60-min dynamic PET scans predict the 10 B-accumulation of 0.8-1.2ppm in liver and 1.2-1.8ppm in tumor and tumor to normal ratio=1.38±0.12. BNCT was performed 40-55min post intravenous administration of FBPin (20-30mg) in the CCA rats. CCA rats treated with BNCT display more tumor reduction than that by NCT with respect of 2-[ 18 F]fluoro-2-deoxy glucose uptake in the tumor region of interest, 20.83±3.00% (n=12) vs. 12.83±3.79% (n=10), P=0.05. The visualizing agent [ 18 F]FFBPin resembles FBPin to generate the time-dependent boron concentration profile. Optimal neutron irradiation period is thus determinable for BNCT. A boron-substituted agent based on COX-2-binding features has been prepared. The moderate COX-2/COX-1 selectivity index of 2.78 allows a fair tumor selectivity index of 1.38 with a mild cardiovascular effect. The therapeutic effect from FBPin with BNCT warrants a proper

Accelerator driven neutron source design via beryllium target and 208Pb moderator for boron neutron capture therapy in alternative treatment strategy by Monte Carlo method.

PubMed

Khorshidi, Abdollah

2017-01-01

The reactor has increased its area of application into medicine especially boron neutron capture therapy (BNCT); however, accelerator-driven neutron sources can be used for therapy purposes. The present study aimed to discuss an alternative method in BNCT functions by a small cyclotron with low current protons based on Karaj cyclotron in Iran. An epithermal neutron spectrum generator was simulated with 30 MeV proton energy for BNCT purposes. A low current of 300 μA of the proton beam in spallation target concept via 9Be target was accomplished to model neutron spectrum using 208Pb moderator around the target. The graphite reflector and dual layer collimator were planned to prevent and collimate the neutrons produced from proton interactions. Neutron yield per proton, energy distribution, flux, and dose components in the simulated head phantom were estimated by MCNPX code. The neutron beam quality was investigated by diverse filters thicknesses. The maximum epithermal flux transpired using Fluental, Fe, Li, and Bi filters with thicknesses of 7.4, 3, 0.5, and 4 cm, respectively; as well as the epithermal to thermal neutron flux ratio was 161. Results demonstrated that the induced neutrons from a low energy and low current proton may be effective in tumor therapy using 208Pb moderator with average lethargy and also graphite reflector with low absorption cross section to keep the generated neutrons. Combination of spallation-based BNCT and proton therapy can be especially effective, if a high beam intensity cyclotron becomes available.

Video game therapy for emotional regulation and impulsivity control in a series of treated cases with bulimia nervosa.

PubMed

Fagundo, Ana B; Santamaría, Juan J; Forcano, Laura; Giner-Bartolomé, Cristina; Jiménez-Murcia, Susana; Sánchez, Isabel; Granero, Roser; Ben-Moussa, Maher; Magnenat-Thalmann, Nadia; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Bults, Richard G A; Tarrega, Salomé; Menchón, José M; de la Torre, Rafael; Cardi, Valentina; Treasure, Janet; Fernández-Aranda, Fernando

2013-11-01

Although standard psychological treatments have been successful in treating several core features in eating disorders (ED), other characteristics such as emotional regulation or impulsivity appear to be more resistant to change. There is a growing body of evidence to support the efficacy of cognitive remediation for cognitive and emotional difficulties in ED. Playmancer/ Islands is a video game (VG) designed to specifically treat mental disorders, characterized by problems in impulse control. The objective of the game is to increase self-control over emotions, decision making and behaviours. The aim of this study is to describe the results from a consecutive series of nine bulimia nervosa patients who were treated with the VG in addition to cognitive behaviour therapy (CBT). The outcomes included clinical and psychopathological questionnaires, and physiological measures were obtained during the VG. Emotional regulation improved, heart rate variability increased, and respiratory rate and impulsivity measures reduced after the treatment. These findings suggest that VG training may enhance treatment for ED. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

The Efficacy of Danshen Injection as Adjunctive Therapy in Treating Angina Pectoris: A Systematic Review and Meta-Analysis.

PubMed

Shao, Huikai; Li, Mengsi; Chen, Fuchao; Chen, Lianghua; Jiang, Zhengjin; Zhao, Lingguo

2018-04-01

During the last 40 years, Danshen injection has been widely used as an adjunctive therapy for angina pectoris in China, but its efficacy is not yet well defined. The objective of this study was to verify the efficacy of Danshen injection as adjunctive therapy in treating angina pectoris. The major databases including PubMed, Cochrane Library, Sino-Med, Medline, Embase, Google Scholar, China National Knowledge Infrastructure, Wanfang Databases, Chinese Scientific Journal Database, Chinese Biomedical Literature Database and the Chinese Science Citation Database were systematically searched for the published randomised controlled trials (RCTs) on Danshen injection until April 2016. Meta-analysis was conducted on the primary outcomes (i.e., the improvements in symptoms and electrocardiography (ECG)). The quality of the included RCTs was evaluated with the M scoring system (the refined Jadad scale). Based on the quality, year of publication and sample size of RCTs, sensitivity analysis and subgroup analysis were performed in this study. Ten RCTs, including 944 anginal patients, were identified in this meta-analysis. Compared with using antianginal agents (β-blockers, calcium antagonists, nitrates, etc.) alone, Danshen injection combined with antianginal agents had a better therapeutic effect in symptom improvement (odds ratio [OR], 3.66; 95% confidence interval [CI]: 2.50-5.36) and in ECG improvement (OR, 3.25; 95% CI: 1.74-6.08). This study showed that Danshen injection as adjunctive therapy seemed to be more effective than antianginal agents alone in treating angina pectoris. However, more evidence is needed to accurately evaluate the efficacy of Danshen injection because of the low methodological quality of the included RCTs. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

NASA Astrophysics Data System (ADS)

Sztejnberg Goncalves-Carralves, Manuel Leonardo

This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients' images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT

Enhanced Cell Capture on Functionalized Graphene Oxide Nanosheets through Oxygen Clustering.

PubMed

Bardhan, Neelkanth M; Kumar, Priyank V; Li, Zeyang; Ploegh, Hidde L; Grossman, Jeffrey C; Belcher, Angela M; Chen, Guan-Yu

2017-02-28

With the global rise in incidence of cancer and infectious diseases, there is a need for the development of techniques to diagnose, treat, and monitor these conditions. The ability to efficiently capture and isolate cells and other biomolecules from peripheral whole blood for downstream analyses is a necessary requirement. Graphene oxide (GO) is an attractive template nanomaterial for such biosensing applications. Favorable properties include its two-dimensional architecture and wide range of functionalization chemistries, offering significant potential to tailor affinity toward aromatic functional groups expressed in biomolecules of interest. However, a limitation of current techniques is that as-synthesized GO nanosheets are used directly in sensing applications, and the benefits of their structural modification on the device performance have remained unexplored. Here, we report a microfluidic-free, sensitive, planar device on treated GO substrates to enable quick and efficient capture of Class-II MHC-positive cells from murine whole blood. We achieve this by using a mild thermal annealing treatment on the GO substrates, which drives a phase transformation through oxygen clustering. Using a combination of experimental observations and MD simulations, we demonstrate that this process leads to improved reactivity and density of functionalization of cell capture agents, resulting in an enhanced cell capture efficiency of 92 ± 7% at room temperature, almost double the efficiency afforded by devices made using as-synthesized GO (54 ± 3%). Our work highlights a scalable, cost-effective, general approach to improve the functionalization of GO, which creates diverse opportunities for various next-generation device applications.

Family Mode Deactivation Therapy Results and Implications

ERIC Educational Resources Information Center

Apsche, Jack A.; Bass, Christopher K.

2006-01-01

This article highlights the inclusion of Mode Deactivation Therapy as a treatment modality for families in crisis. As an empirically validated treatment, Mode Deactivation Therapy has been effective in treating a wide variety of psychological issues. Mode Deactivation Therapy, (MDT) was developed to treat adolescents with disorders of conduct…

Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

PubMed

Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

2013-02-01

Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

Modeling association among demographic parameters in analysis of open population capture-recapture data.

PubMed

Link, William A; Barker, Richard J

2005-03-01

We present a hierarchical extension of the Cormack-Jolly-Seber (CJS) model for open population capture-recapture data. In addition to recaptures of marked animals, we model first captures of animals and losses on capture. The parameter set includes capture probabilities, survival rates, and birth rates. The survival rates and birth rates are treated as a random sample from a bivariate distribution, thus the model explicitly incorporates correlation in these demographic rates. A key feature of the model is that the likelihood function, which includes a CJS model factor, is expressed entirely in terms of identifiable parameters; losses on capture can be factored out of the model. Since the computational complexity of classical likelihood methods is prohibitive, we use Markov chain Monte Carlo in a Bayesian analysis. We describe an efficient candidate-generation scheme for Metropolis-Hastings sampling of CJS models and extensions. The procedure is illustrated using mark-recapture data for the moth Gonodontis bidentata.

Emerging genetic therapies to treat Duchenne muscular dystrophy

PubMed Central

Nelson, Stanley F.; Crosbie, Rachelle H.; Miceli, M. Carrie; Spencer, Melissa J.

2010-01-01

Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called `exon skipping' and `nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy. PMID:19745732

An algorithm for verifying biventricular capture based on evoked-response morphology.

PubMed

Diotallevi, Paolo; Ravazzi, Pier Antonio; Gostoli, Enrico; De Marchi, Giuseppe; Militello, Carmelo; Kraetschmer, Hannes

2005-01-01

Cardiac resynchronization therapy relies on consistent beat-by-beat myocardial capture in both ventricles. A pacemaker ensuring right (RV) and left ventricular (LV) capture through reliable capture verification and automatic output adjustment would contribute to patients' safety and quality of life. We studied the feasibility of an algorithm based on evoked-response (ER) morphology for capture verification in both the ventricles. RV and LV ER signals were recorded in 20 patients (mean age 72.5 years, range 64.3-80.4 years, 4 females and 16 males) during implantation of biventricular (BiV) pacing systems. Leads of several manufacturers were tested. Pacing and intracardiac electrogram (IEGM) recording were performed using an external pulse generator. IEGM and surface-lead electrocardiogram (ECG) signals were recorded under different pacing conditions for 10 seconds each: RV pacing only, LV pacing only, and BiV pacing with several interventricular delays. Based on morphology characteristics, ERs were classified manually for capture and failure to capture, and the validity of the classification was assessed by reference to the ECG. A total of 3,401 LV- and 3,345 RV-paced events were examined. In the RV and LV, the sensitivities of the algorithm were 95.6% and 96.1% in the RV and LV, respectively, and the corresponding specificities were 91.4% and 95.2%, respectively. The lower sensitivity in the RV was attributed to signal blanking in both channels during BiV pacing with a nonzero interventricular delay. The analysis revealed that the algorithm for identifying capture and failure to capture based on the ER-signal morphology was safe and effective in each ventricle with all leads tested in the study.

Clinical Application of Pluripotent Stem Cells: An Alternative Cell-Based Therapy for Treating Liver Diseases?

PubMed

Tolosa, Laia; Pareja, Eugenia; Gómez-Lechón, Maria José

2016-12-01

The worldwide shortage of donor livers for organ and hepatocyte transplantation has prompted the search for alternative therapies for intractable liver diseases. Cell-based therapy is envisaged as a useful therapeutic option to recover and stabilize the lost metabolic function for acute liver failure, end-stage and congenital liver diseases, or for those patients who are not considered eligible for organ transplantation. In recent years, research to identify alternative and reliable cell sources for transplantation that can be derived by reproducible methods has been encouraged. Human pluripotent stem cells (PSCs), which comprise both embryonic and induced PSCs, may offer many advantages as an alternative to hepatocytes for liver cell therapy. Their capacity for expansion, hepatic differentiation and self-renewal make them a promising source of unlimited numbers of hepatocyte-like cells for treating and repairing damaged livers. Immunogenicity and tumorigenicity of human PSCs remain the bottleneck for successful clinical application. However, recent advances made to develop disease-corrected hepatocyte-like cells from patients' human-induced PSCs by gene editing have opened up many potential gateways for the autologous treatment of hereditary liver diseases, which may likely reduce the risk of rejection and the need for lifelong immunosuppression. Well-defined methods to reduce the expression of oncogenic genes in induced PSCs, including protocols for their complete and safe hepatic differentiation, should be established to minimize the tumorigenicity of transplanted cells. On top of this, such new strategies are currently being rigorously tested and validated in preclinical studies before they can be safely transferred to clinical practice with patients.

Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabolizadeh, Peyman, E-mail: peyman.kabolizadeh@beaumont.org; Chen, Yen-Lin; Liebsch, Norbert

Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modifiedmore » Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

[Physical therapy for scars].

PubMed

Masanovic, Marguerite Guillot

2013-01-01

Physical therapy consists notably of hand or mechanical massages, pressure therapy using various fabrics or splints, cryotherapy, laser therapy, etc. It forms part of the range of therapies used to treat pathological scars, including medical and surgical treatment. While the results are often satisfactory for hypertrophic scars, they remain uncertain for major keloids.

The Perspectives of the Boron Neutron Capture Therapy-Clinical Applications Research and Development in Saudi Arabia

NASA Astrophysics Data System (ADS)

Badhrees, I.; Alrumayan, F.; Mahube, F.

Boron Neutron Capture Therapy (BNCT) is a binary form of experimental radiotherapy which is based on the administration of a drug able to concentrate the isotopes in a tumor cell that later are irradiated with a neutron beam. Even though the first evidence of the success of this treatment dates back many years ago, BNCT showed successful treatment results in malignant melanoma, and Glioblastoma. In order for BNCT to be successful, a sufficient amount of Boron (10B) must be selectively delivered to the tumor cell, and then irradiated by neutrons of sufficient enough. The CS-30 cyclotron at King Faisal Specialist Hospital & Research Center is a positive-ion machine capable of accelerating protons at 26MeV, and other isotopes as well. Although the peak beam intensity from the CS-30 is low, the key to success of using it for the BNCT is by using a high average beam current at low energy. This work is aimed at testing the capability of the CS-30 Cyclotron to produce a low-energy neutron beam to be used to activate the Boron atoms injected into the tumor cell, through simulation of a compatible moderator. We are also planning to measure the overall dosimetry of the energy dose as well as that for the boron in the tumor cell.

Clinical research on intelligence seven needle therapy treated infants with brain damage syndrome.

PubMed

Liu, Zhen-Huan; Li, Ye-Rong; Lu, Yong-Lin; Chen, Jie-Kui

2016-06-01

treating with the intelligence seven needle therapy. This approach can improve the brain blood supply and promote the growth of frontal and parietal lobes.

Impact of a Respiratory Therapy Assess-and-Treat Protocol on Adult Cardiothoracic ICU Readmissions.

PubMed

Dailey, Robert T; Malinowski, Thomas; Baugher, Mitchel; Rowley, Daniel D

2017-05-01

The purpose of this retrospective medical record review was to report on recidivism to the ICU among adult postoperative cardiac and thoracic patients managed with a respiratory therapy assess-and-treat (RTAT) protocol. Our primary null hypothesis was that there would be no difference in all-cause unexpected readmissions and escalations between the RTAT group and the physician-ordered respiratory care group. Our secondary null hypothesis was that there would be no difference in primary respiratory-related readmissions, ICU length of stay, or hospital length of stay. We reviewed 1,400 medical records of cardiac and thoracic postoperative subjects between January 2015 and October 2016. The RTAT is driven by a standardized patient assessment tool, which is completed by a registered respiratory therapist. The tool develops a respiratory severity score for each patient and directs interventions for bronchial hygiene, aerosol therapy, and lung inflation therapy based on an algorithm. The protocol period commenced on December 1, 2015, and continued through October 2016. Data relative to unplanned admissions to the ICU for all causes as well as respiratory-related causes were evaluated. There was a statistically significant difference in the all-cause unplanned ICU admission rate between the RTAT (5.8% [95% CI 4.3-7.9]) and the physician-ordered respiratory care (8.8% [95% CI 6.9-11.1]) groups ( P = .034). There was no statistically significant difference in respiratory-related unplanned ICU admissions with RTAT (36% [95% CI 22.7-51.6]) compared with the physician-ordered respiratory care (53% [95% CI 41.1-64.8]) group ( P = .09). The RTAT protocol group spent 1 d less in the ICU ( P < .001) and in the hospital ( P < .001). RTAT protocol implementation demonstrated a statistically significant reduction in all-cause ICU readmissions. The reduction in respiratory-related ICU readmissions did not reach statistical significance. Copyright © 2017 by Daedalus Enterprises.

SU-E-J-100: Reconstruction of Prompt Gamma Ray Three Dimensional SPECT Image From Boron Neutron Capture Therapy(BNCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, D; Jung, J; Suh, T

2014-06-01

Purpose: Purpose of paper is to confirm the feasibility of acquisition of three dimensional single photon emission computed tomography (SPECT) image from boron neutron capture therapy (BNCT) using Monte Carlo simulation. Methods: In case of simulation, the pixelated SPECT detector, collimator and phantom were simulated using Monte Carlo n particle extended (MCNPX) simulation tool. A thermal neutron source (<1 eV) was used to react with the boron uptake region (BUR) in the phantom. Each geometry had a spherical pattern, and three different BURs (A, B and C region, density: 2.08 g/cm3) were located in the middle of the brain phantom.more » The data from 128 projections for each sorting process were used to achieve image reconstruction. The ordered subset expectation maximization (OSEM) reconstruction algorithm was used to obtain a tomographic image with eight subsets and five iterations. The receiver operating characteristic (ROC) curve analysis was used to evaluate the geometric accuracy of reconstructed image. Results: The OSEM image was compared with the original phantom pattern image. The area under the curve (AUC) was calculated as the gross area under each ROC curve. The three calculated AUC values were 0.738 (A region), 0.623 (B region), and 0.817 (C region). The differences between length of centers of two boron regions and distance of maximum count points were 0.3 cm, 1.6 cm and 1.4 cm. Conclusion: The possibility of extracting a 3D BNCT SPECT image was confirmed using the Monte Carlo simulation and OSEM algorithm. The prospects for obtaining an actual BNCT SPECT image were estimated from the quality of the simulated image and the simulation conditions. When multiple tumor region should be treated using the BNCT, a reasonable model to determine how many useful images can be obtained from the SPECT could be provided to the BNCT facilities. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research

Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy.

PubMed

Reifschneider, Olga; Schütz, Christian L; Brochhausen, Christoph; Hampel, Gabriele; Ross, Tobias; Sperling, Michael; Karst, Uwe

2015-03-01

An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noticewala, Sonal S.; Li, Nan; Williamson, Casey W.

Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m{sup 2}) and 14 were treated with cisplatin (40 mg/m{sup 2}) plus gemcitabine (50-125 mg/m{sup 2}) (C/G). Patients underwent {sup 18}F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV ofmore » the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense

Salivary duct carcinoma treated with cetuximab-based targeted therapy: A case report.

PubMed

Kawahara, Kenta; Hiraki, Akimitsu; Yoshida, Ryoji; Arita, Hidetaka; Matsuoka, Yuichiro; Yamashita, Toshio; Koga, Kan-Ichi; Nagata, Masashi; Hirosue, Akiyuki; Fukuma, Daiki; Nakayama, Hideki

2017-06-01

Salivary duct carcinoma is a highly aggressive disease with a poor prognosis. Surgical resection is currently the only curative treatment, as there is no effective systemic therapy for this malignancy. Recently, trastuzumab has been shown to exhibit therapeutic efficacy in the treatment of salivary duct carcinoma; similarly, molecularly targeted agents, such as cetuximab, are expected to be useful for salivary duct carcinoma treatment. We herein describe the case of a 56-year-old man diagnosed with salivary duct carcinoma in the left submandibular region, with ipsilateral multiple metastases to the neck lymph nodes. Radical resection of the tumor and submandibular gland with neck dissection were performed. One month after radical surgery, computed tomography (CT) scans indicated metastasis in the lower lobe of the left lung. CT-guided transthoracic fine-needle aspiration biopsy revealed a single metastasis and lung metastasectomy was immediately performed. The tumor cells of the primary lesion and those of the lung metastasis were immunohistochemically positive for epidermal growth factor receptor. One month later, multiple right lung metastases appeared, and the patient was treated with cisplatin/5-fluorouracil (5-FU) chemotherapy plus cetuximab, achieving a complete radiographic response. However, multiple lung metastases developed during adjuvant weekly cetuximab monotherapy. Subsequently, treatment with S-1 and weekly cetuximab was initiated, and the multiple lung metastases have been maintained as stable disease for 5 months. To the best of our knowledge, this is the first report of cetuximab use for the treatment of salivary duct carcinoma. Although cisplatin/5-FU chemotherapy plus cetuximab was efficacious in treating the lung metastasis, cetuximab monotherapy was insufficient for controlling tumor growth.

Fatal hypermagnesemia in a child treated with megavitamin/megamineral therapy.

PubMed

McGuire, J K; Kulkarni, M S; Baden, H P

2000-02-01

We report a case of fatal hypermagnesemia resulting from the unsupervised use of high doses of magnesium oxide administered as part of a regimen of megavitamin and megamineral therapy to a child with mental retardation, spastic quadriplegia, and seizures. The treatment regimen was given at the recommendation of a dietician working as a private nutritional consultant without the involvement or notification of the child's pediatrician. Hypermagnesemia is an uncommon but serious side effect of the use of magnesium containing compounds. These compounds are widely used as laxatives and dietary supplements, and serious side effects are uncommon when used in appropriate dosages and with adequate supervision. The use of alternative medical therapies, including megavitamin/megamineral therapy, is widespread. Many patients use alternative medicine or seek care from alternative medicine practitioners without the recommendation or knowledge of their primary physicians. Despite unproved benefit, many alternative therapies may be safe. However, unsupervised use of generally safe treatments can result in serious side effects. This case report serves to illustrate the characteristic pathophysiologic changes of severe hypermagnesemia, an entity rarely seen in pediatric practice, and more importantly, it alerts primary care and subspecialty pediatricians to be aware of and monitor the use of alternative medical therapies in their patients.

Incomplete IgG response to HIV-1 proteins and low avidity levels in recently converted HIV patients treated with early antiretroviral therapy.

PubMed

Re, Maria Carla; Schiavone, Pasqua; Bon, Isabella; Vitone, Francesca; De Crignis, Elisa; Biagetti, Carlo; Gibellini, Davide

2010-11-01

To evaluate the evolution of antibody avidity and Western blot reactivity in recently infected HIV-1 subjects and to study the impact of highly active antiretroviral therapy (HAART) on avidity maturation of HIV-1-specific immunoglobulin G (IgG) in patients with recent HIV-1 infection. Thirty-six HIV-1 seroconverters were enrolled in this study and followed longitudinally over 24 months to evaluate if the administration of antiretroviral therapy during primary infection affects Western blot reactivity and the evolution of antibody avidity. The patients were divided into two groups; group A consisted of 19 HIV-1-untreated patients who did not receive any drug treatment during our follow-up period; group B consisted of 17 subjects who were treated early with an association of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) within 3 months after seroconversion. At diagnosis, Western blot analysis and avidity index (mean value) were exactly matched in untreated and treated patients; subsequently, however, a significantly lower reactivity to HIV-1 pol and gag proteins and a lower avidity index (mean values) were observed in HAART-treated patients up until the end of the follow-up period. The impaired production and maturation of the humoral immunological response in antiretroviral-treated patients might be related to a rapid suppression of HIV replication, driven by HAART. These results could have important implications in understanding the complex mechanism of the immune response during HIV infection. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

PubMed

Yang, Li-Juan; Liu, Ya-Li; Wang, Shu-Bin; Jin, Zhi-Gao

2014-04-01

To compare the difference of the clinical efficacy on common peroneal palsy between the comprehensive therapy of electroacupuncture, moxibustion and moving cupping method and western medication. Ninety cases of common peroneal nerve palsy were randomized into a comprehensive therapy group and a western medication group, 45 cases in each one. In the comprehensive therapy group, electroacupuncture was applied to Yanglingquan (GB 34), Zusanli (ST 36), Xuanzhong (GB 39), Jiexi (ST 41), Taichong (LR 3), Zulinqi (GB 41) and the others, combined with warm moxibustion and moving cupping on the lateral side of the affected leg. The comprehensive therapy was used once a day. In the western medication group, vitamin B1 , 10 mg each time, 3 times a day; and mecobalamine, 0. 5 mg each time, three times a day were prescribed for oral administration. In the two groups, 15 days made one session, and the efficacy was observed after 2 sessions treatment. The total effective rate of the improvement of sensory function and motor nerve function was 97. 8% (44/45) in the comprehensive therapy group and was 82. 2% (37/ 45) in the western medication. The efficacy in the comprehensive therapy group was better than that of the western medication (P<0. 01). The electrophysiological examination showed that the amplitude of motor conduction of deep peroneal nerve and that of sensory conduction of surficial peroneal nerve after treatment were improved remarkably as compared with those before treatment in the comprehensive therapy group (both P<0. 05). The amplitude of motor conduction of deep peroneal nerve was improved significantly in the comprehensive therapy group as compared with that in the western medication group (P<0. 05). The comprehensive therapy of electroacupuncture, moxibustion and moving cupping method achieves the significant efficacy on common peroneal nerve palsy as compared with western medication.

Experimental Studies of Boronophenylalanine ((10)BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment.

PubMed

Carpano, Marina; Perona, Marina; Rodriguez, Carla; Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A; Brandizzi, Daniel; Cabrini, Romulo; Pisarev, Mario; Juvenal, Guillermo Juan; Dagrosa, Maria Alejandra