Facilitating Occupational Therapy Student Learning to Enhance Cross-Cultural Effectiveness

ERIC Educational Resources Information Center

Gilbertson, Barbara Carol Hooper

2012-01-01

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

Improved animal models for testing gene therapy for atherosclerosis.

PubMed

Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

2014-04-01

Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long-term therapy from vascular endothelium without accelerating atherosclerotic disease.

Morphoproteomic-Guided Host-Directed Therapy for Tuberculosis.

PubMed

Brown, Robert E; Hunter, Robert L; Hwang, Shen-An

2017-01-01

In an effort to develop more effective therapy for tuberculosis (TB), research efforts are looking toward host-directed therapy, reprograming the body's natural defenses to better control the infection. While significant progress is being made, the efforts are limited by lack of understanding of the pathology and pathogenesis of adult type TB disease. We have recently published evidence that the developing lesions in human lungs are focal endogenous lipid pneumonia that constitutes a region of local susceptibility in a person with strong systemic immunity. Since most such lesions regress spontaneously, the ability to study them directly with immunohistochemistry provides means to investigate why some progress to clinical disease while others asymptomatically regress. Furthermore, this should enable us to develop more effective host-directed therapies. Morphoproteomics has proven to be an effective means of characterizing protein expression that can be used to identify metabolic pathways, which can lead to more effective therapies. The purpose of this perspective will argue that using morphoproteomics on human TB lung tissue is a particularly promising method to direct selection of host-directed therapeutics.

[Helicobacter pylori-related diseases].

PubMed

Gisbert, Javier P

2013-10-01

This article summarizes the main conclusions drawn from the presentations on Helicobacter pylori at Digestive Disease Week 2013. Knowledge of this infection among the general population continues to be extremely limited. H. pylori is the main cause of "aging" of the human stomach. In developed countries, the prevalence of H. pylori infection has decreased but continues to be considerable. In most countries, clarithromycin and metronidazole resistance rates are markedly high. H. pylori eradication improves the symptoms of functional dyspepsia, but only in a minority of patients. The frequency of idiopathic peptic ulcers seems to be rising and their prognosis is worse. Most patients with gastric cancer have, or have had, prior H. pylori infection. The risk of developing preneoplastic lesions depends on the type (strain) of the microorganism. To prevent the development of gastric cancer, eradication therapy should be administered early (before the development of intestinal metaplasia). Among H. pylori-infected patients, those who receive long-term treatment with proton pump inhibitors more frequently develop preneoplastic lesions. In patients who undergo endoscopic resection of early gastric cancer, H. pylori eradication reduces the incidence of metachronous tumors. Eradication therapy induces regression of MALT lymphoma in most patients and tumoral recurrence in the long term is exceptional; eradication is a reasonable option even when H. pylori infection has not been identified in patients with MALT lymphoma. Several diagnostic innovations were presented, such as some polymerase chain reaction techniques for use in gastric biopsy specimens or gastric juice. The efficacy of triple standard therapy is clearly inadequate. The superiority of "sequential" therapy over standard triple therapy has not been definitively established. "Concomitant" therapy is more effective and is simpler than "sequential" therapy. After failure of standard triple therapy, second-line levofloxacin-based schemes for 10 days are effective and are also simpler and better tolerated than bismuth-based quadruple therapy. Levofloxacin-based triple therapy is also a promising alternative after failure of "sequential" and "concomitant" therapies. New-generation quinolones, such as moxifloxacin, could be useful as eradication therapy, especially as rescue therapy. After failure of clarithromycin-based triple therapy, followed by that of levofloxacin-based triple therapy, a bismuth-based quadruple scheme is an acceptable alternative. Even after the failure of 3 eradication therapies, a fourth empirical rescue therapy (with rifabutin) can be effective. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Interleukin-2 therapy reverses some immunosuppressive effects of skeletal unloading

NASA Technical Reports Server (NTRS)

Armstrong, Jason W.; Balch, Signe; Chapes, Stephen K.

1994-01-01

Using antiorthostatic suspension, we characterized hematopoietic changes that may be responsible for the detrimental effect of skeletal unloading on macrophage development. Skeletally unloaded mice had suppressed macrophage development in unloaded and loaded bones, which indicated a systemic effect. Bone marrow cells from unloaded mice secreted less macrophage colony-stimulating factor and interleukin-6 than control mice. Additionally, T-lymphocyte proliferation was reduced after skeletal unloading. We show that polyethylene glycol-interleukin-2 therapy reversed the effects of skeletal unloading on macrophage development and cell proliferation.

Do the frequencies of adverse events increase, decrease, or stay the same with long-term use of statins?

PubMed

Huddy, Karlyn; Dhesi, Pavittarpaul; Thompson, Paul D

2013-02-01

Statins are widely used for their cholesterol-lowering properties and proven reduction of cardiovascular disease risk. Many patients take statins as long-term treatment for a variety of conditions without a clear-cut understanding of how treatment duration affects the frequency of adverse effects. We aimed to evaluate whether the frequencies of documented adverse events increase, decrease, or remain unchanged with long-term statin use. We reviewed the established literature to define the currently known adverse effects of statin therapy, including myopathy, central nervous system effects, and the appearance of diabetes, and the frequency of these events with long-term medication use. The frequency of adverse effects associated with long-term statin therapy appears to be low. Many patients who develop side effects from statin therapy do so relatively soon after initiation of therapy, so the frequency of side effects from statin therapy when expressed as a percentage of current users decreases over time. Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration. Also, clinical trials of statin therapy rarely exceed 5 years, so it is impossible to determine with certainty the frequency of long-term side effects with these drugs.

Vitamin Therapy and Children with Down's Syndrome: A Review of Research.

ERIC Educational Resources Information Center

Pruess, James B.; And Others

1989-01-01

Following a brief outline of vitamin therapy's effects on schizophrenia and learning disabilities, research is reviewed on vitamin therapy for children with Down's Syndrome, concluding with a discussion of critical responses to research endorsing vitamin therapy. It is concluded that vitamin therapy contributes nothing to the development of…

Curricular Integration and Measurement of Cultural Competence Development in a Group of Physical Therapy Students

ERIC Educational Resources Information Center

Palombaro, Kerstin M.; Dole, Robin L.; Black, Jill D.

2015-01-01

Introduction and Background: The link between cultural competence and effective physical therapy encounters is established. Physical therapist educational programs face the challenge of fostering the cultural competence of students in effective and meaningful ways within the curriculum. They also face the challenge of measuring the development of…

Effect of hyperbaric oxygen on the growth and development of medicinal maggots.

PubMed

Sherman, Ronald A; Khavari, Borna; Werner, Darryl

2013-01-01

Some wound care therapists use both maggot debridement therapy (MDT) and hyperbaric oxygen (HBO2) therapy to treat non-healing wounds. Some practitioners have reported success using both MDT and HBO2 therapy concurrently; others have not. To begin evaluating the utility of using MDT and HBO2 therapy concurrently, we assessed the effects of hyperbaric oxygen (HBO2) on maggot growth and development, as a surrogate for debridement capacity. Replicate sets of medical-grade blowfly larvae were placed on liver-agar wound models and exposed to HBO2 at 2.0 atmospheres absolute (atm abs) for 90 minutes on 0 (control), 1, 2 or 3 sequential days. The effects of HBO2 exposure were quantified by measuring the maggots' subsequent growth and development. Exposure to HBO2 was most lethal to young larvae (second instars), but not to older larvae (third instars). There was no dose-relationship between the number of HBO2 treatments and rate of larval survival. Our findings suggest that maggot therapy and HBO2 therapy may be administered concurrently, as long as the larvae are not too immature (that is, as long as they are beyond the second instar) by the time they take their first dive. A clinical trial evaluating the clinical benefits of concurrent HBO2 therapy and MDT is warranted.

Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT) and Photodynamic Therapy (PDT)

PubMed Central

Kushibiki, Toshihiro; Hirasawa, Takeshi; Okawa, Shinpei; Ishihara, Miya

2013-01-01

Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression. PMID:23807510

Regulation of miRNA expression by low-level laser therapy (LLLT) and photodynamic therapy (PDT).

PubMed

Kushibiki, Toshihiro; Hirasawa, Takeshi; Okawa, Shinpei; Ishihara, Miya

2013-06-27

Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression.

A controlled study of agoraphobia and the independent effect of virtual reality exposure therapy.

PubMed

Malbos, Eric; Rapee, Ronald M; Kavakli, Manolya

2013-02-01

Past controlled clinical trials centred on virtual reality exposure therapy (VRET) for agoraphobia mostly used multicomponent therapy with success. However, the present paper aimed to evaluate the independent effect of VRET for agoraphobia. A controlled study involving 18 agoraphobic participants assigned to two groups: VRET only and VRET with cognitive therapy. Nine specific virtual environments were developed using an affordable game level editor. Questionnaires, behavioural tests and physiological measures indicated a positive effect of VRET. Correlations supported the predictive value of presence towards treatment outcome. The addition of cognitive therapy did not provide significant additional benefit. Overall, the isolated effects of VRET did not seem to be significantly less than the effects of VRET combined with cognitive therapy. Future research should explore the use of other components in addition to cognitive therapy and VRET for agoraphobia as well as its possible use in patients' homes.

A literature review about effectiveness of massage therapy for cancer pain.

PubMed

Somani, Salima; Merchant, Samima; Lalani, Sharifa

2013-11-01

This literature review explores the effectiveness of massage therapy to reduce cancer pain. As part of the review, systematic literature search was carried out on various electronic databases and specialised journals. Included are 19 research-based articles and 8 review articles. The review suggests that cancer has become a common health problem in the world and most of the cancer patients are going through intense and unbearable pain. Studies have reported that most of the cancer patients' pain reduced with therapeutic massage. Seventy-three per cent of cancer patients use massage therapy in the USA. Few studies are available in the context of the developing world related to massage therapy and we could not find any study in the Pakistani context. There is a need to conduct an interventional study about the effectiveness of massage therapy to control cancer pain in developing countries such as Pakistan.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin.

PubMed

Suii, Hirokazu; Ozeki, Itaru; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Nakajima, Tomoaki; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2017-01-01

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was -3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only -1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin

PubMed Central

Ozeki, Itaru; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Nakajima, Tomoaki; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2017-01-01

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was −3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only −1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV. PMID:29375917

Developing an Integrative Play Therapy Group Model for Middle School Male Students to Address Bullying Behaviors

ERIC Educational Resources Information Center

Jordan, Jakarla

2016-01-01

This research examines the systematic process of developing an integrative play therapy group model for middle school male students, ages 11-15 who participate in bullying behaviors. Play therapy approaches and evidence-based practices are documented as effective measures for addressing bullying behaviors with children and adolescents. This group…

Effects of GH replacement therapy on thyroid volume and nodule development in GH deficient adults: a retrospective cohort study.

PubMed

Curtò, Lorenzo; Giovinazzo, Salvatore; Alibrandi, Angela; Campennì, Alfredo; Trimarchi, Francesco; Cannavò, Salvatore; Ruggeri, Rosaria Maddalena

2015-05-01

Despite the well-known effects of GH/IGF1 signaling on the thyroid, few data are available on the risk of developing nodular goiter in hypopituitary subjects during GH replacement therapy (GHRT). We aimed to define the effects of GH therapy on thyroid volume (TV) and nodular growth. The records of 96 subjects (47 males and 49 females, median age 48 years) with GH deficit (GHD) were investigated. Seventy also had central hypothyroidism (CH). At the time of our retrospective evaluation, median treatment duration was 5 years. Pre-treatment TV was smaller in GHD patients than in healthy subjects (P=0.030). During GH treatment, TV significantly increased (P=0.016 for the entire group and P=0.014 in euthyroid GHD patients). Before starting GH therapy, 17 patients harbored thyroid nodules. During GH therapy, nodule size increased slightly in seven patients, and new thyroid nodules occurred in nine patients. Among the 79 patients without pre-existing thyroid nodules, 17 developed one or more nodules. There was no difference in the prevalence of CH in GHD patients with or without thyroid nodules (P=0.915; P=0.841, when patients with pre-therapy nodular goiter were excluded), the main predictor for nodule development being serum IGF1 (P=0.038). GHRT is associated with TV's increase in GHD patients. Thyroid nodules developed in 27% of patients, mainly in relation to pre-therapy IGF1 levels, independently of normal or impaired TSH stimulation. © 2015 European Society of Endocrinology.

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

PubMed

Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

2016-05-26

The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

Therapeutics: Alpha-1 Antitrypsin Augmentation Therapy.

PubMed

Campos, Michael; Lascano, Jorge

2017-01-01

Subjects with alpha-1 antitrypsin deficiency who develop pulmonary disease are managed following general treatment guidelines, including disease management interventions. In addition, administration of intravenous infusions of alpha-1 proteinase inhibitor (augmentation therapy) at regular schedules is a specific therapy for individuals with AATD with pulmonary involvement.This chapter summarizes the manufacturing differences of commercially available formulations and the available evidence of the effects of augmentation therapy. Biologically, there is clear evidence of in vivo local antiprotease effects in the lung and systemic immunomodulatory effects. Clinically, there is cumulative evidence of slowing lung function decline and emphysema progression. The optimal dose of augmentation therapy is being revised as well as more individualized assessment of who needs this therapy.

Stress in multiple sclerosis: review of new developments and future directions.

PubMed

Lovera, Jesus; Reza, Tara

2013-11-01

In the experimental autoimmune encephalitis model of multiple sclerosis, the effects of stress on disease severity depend on multiple factors, including the animal's genetics and the type of stressor. The studies in humans relating stress to the risk of developing multiple sclerosis have found discordant results. The studies looking at the association of stress with relapses show a fairly consistent association, where higher stress is associated with a higher risk of relapse. Higher stress levels also appear to increase the risk of development of gadolinium-enhancing lesions. A recent randomized trial shows that reducing stress using stress management therapy (SMT), a cognitive-behavioral therapy approach, results in a statistically significant reduction in new magnetic resonance imaging lesions. The magnitude of this effect is large and comparable to the effects of existent disease-modifying therapies, but no data exist yet proving that SMT reduces relapses or clinical progression; the effect of SMT appears to be short-lived. Additional work is needed to improve the duration of this effect and make this therapy more widely accessible.

A review of research into the uses of low level ultrasound in cancer therapy.

PubMed

Yu, Tinghe; Wang, Zhibiao; Mason, Timothy J

2004-04-01

The use of low power ultrasound in therapeutic medicine is a developing field and this review will concentrate on the applications of this technology in cancer therapy. The effects of low power ultrasound have been evaluated in terms of the biological changes induced in the structure and function of tissue. The main fields of study have been in sonodynamic therapy, improving chemotherapy, gene therapy and apoptosis therapy. The range of ultrasonic power levels that can be effectively employed in therapy appears to be narrow and this may have hindered past research in the applications in cancer treatment.

[The optimization of an early rehabilitation program for cerebral stroke patients: the use of different methods of magneto- and laser therapy].

PubMed

Kochetkov, A V; Gorbunov, F E; Minenkov, A A; Strel'tsova, E N; Filina, T F; Krupennikov, A I

2000-01-01

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

Setting a research agenda for progressive multiple sclerosis: the International Collaborative on Progressive MS.

PubMed

Fox, Robert J; Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-11-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS.

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

PubMed Central

Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-01-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. PMID:22917690

Design and Implementation of an Interactive Website for Pediatric Voice Therapy-The Concept of In-Between Care: A Telehealth Model.

PubMed

Doarn, Charles R; Zacharias, Stephanie; Keck, Casey Stewart; Tabangin, Meredith; DeAlarcon, Alessandro; Kelchner, Lisa

2018-06-05

This article describes the design and implementation of a web-based portal developed to provide supported home practice between weekly voice therapy sessions delivered through telehealth to children with voice disorders. This in-between care consisted of supported home practice that was remotely monitored by speech-language pathologists (SLPs). A web-based voice therapy portal (VTP) was developed as a platform so participants could complete voice therapy home practice by an interdisciplinary team of SLPs (specialized in pediatric voice therapy), telehealth specialists, biomedical informaticians, and interface designers. The VTP was subsequently field tested in a group of children with voice disorders, participating in a larger telehealth study. Building the VTP for supported home practice for pediatric voice therapy was challenging, but successful. Key interactive features of the final site included 11 vocal hygiene questions, traditional voice therapy exercises grouped into levels, audio/visual voice therapy demonstrations, a store-and-retrieval system for voice samples, message/chat function, written guidelines for weekly therapy exercises, and questionnaires for parents to complete after each therapy session. Ten participants (9-14 years of age) diagnosed with a voice disorder were enrolled for eight weekly telehealth voice therapy sessions with follow-up in-between care provided using the VTP. The development and implementation of the VTP as a novel platform for the delivery of voice therapy home practice sessions were effective. We found that a versatile individual, who can work with all project staff (speak the language of both SLPs and information technologists), is essential to the development process. Once the website was established, participants and SLPs effectively utilized the web-based VTP. They found it feasible and useful for needed in-between care and reinforcement of therapeutic exercises.

Endocrine therapy toxicity: management options.

PubMed

Henry, N Lynn

2014-01-01

Treatment with adjuvant endocrine therapy, including tamoxifen and the aromatase inhibitors, has resulted in notable improvements in disease-free and overall survival for patients with hormone receptor-positive breast cancer. Despite their proven benefit, however, adherence to and persistence with the medications is poor in part because of bothersome side effects that can negatively affect quality of life. Retrospective analyses have identified possible predictors of development of toxicity. Reports have also suggested that development of toxicity may be a biomarker of better response to therapy. In addition, there has been considerable research investment into the management of these side effects, which may lead to improved adherence and persistence with therapy. However, although notable advances have been made, much more remains to be done to provide patients with truly personalized therapy for hormone receptor-positive breast cancer.

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…

Developing evaluation scales for horticultural therapy.

PubMed

Im, Eun-Ae; Park, Sin-Ae; Son, Ki-Cheol

2018-04-01

This study developed evaluation scales for measuring the effects of horticultural therapy in practical settings. Qualitative and quantitative research, including three preliminary studies and a main study, were conducted. In the first study, a total of 779 horticultural therapists answered an open-end questionnaire based on 58 items about elements of occupational therapy and seven factors about singularity of horticultural therapy. In the second study, 20 horticultural therapists participated in in-depth interviews. In the third study, a Delphi method was conducted with 24 horticultural therapists to build a model of assessment indexes and ensure the validity. In the final study, the reserve scales were tested by 121 horticultural therapists in their practical settings for 1045 clients, to verify their reliability and validity. Preliminary questions in the effects area of horticultural therapy were developed in the first study, and validity for the components in the second study. In the third study, an expert Delphi survey was conducted as part of content validity verification of the preliminary tool of horticultural therapy for physical, cognitive, psychological-emotional, and social areas. In the final study, the evaluation tool, which verified the construct, convergence, discriminant, and predictive validity and reliability test, was used to finalise the evaluation tool. The effects of horticultural therapy were classified as four different aspects, namely, physical, cognitive, psycho-emotional, and social, based on previous studies on the effects of horticultural therapy. 98 questions in the four aspects were selected as reserve scales. The reliability of each scale was calculated as 0.982 in physical, 0.980 in cognitive, 0.965 in psycho-emotional, and 0.972 in social aspects based on the Cronbach's test of intra-item internal consistency and half reliability of Spearman-Brown. This study was the first to demonstrate validity and reliability by simultaneously developing four measures of horticultural therapy effectiveness, namely, physical, cognitive, psychological-emotional, and social, both locally and externally. It is especially worthwhile in that it can be applied in common to people. Copyright © 2018 Elsevier Ltd. All rights reserved.

Treatment of uveal melanoma: where are we now?

PubMed Central

Yang, Jessica; Manson, Daniel K.; Marr, Brian P.; Carvajal, Richard D.

2018-01-01

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease. PMID:29497459

Combination therapeutics of Nilotinib and radiation in acute lymphoblastic leukemia as an effective method against drug-resistance.

PubMed

Kaveh, Kamran; Takahashi, Yutaka; Farrar, Michael A; Storme, Guy; Guido, Marcucci; Piepenburg, Jamie; Penning, Jackson; Foo, Jasmine; Leder, Kevin Z; Hui, Susanta K

2017-07-01

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI) therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR) in combination with TKI therapy overcome chemo-resistance. Additionally, we developed a mathematical model, parameterized by cell viability experiments under Nilotinib treatment and LDR, to explain the cellular response to combination therapy. The addition of LDR significantly reduced drug resistance both in vitro and in computational model. Decreased expression level of phosphorylated AKT suggests that the combination treatment plays an important role in overcoming resistance through the AKT pathway. Model-predicted cellular responses to the combined therapy provide good agreement with experimental results. Augmentation of LDR and Nilotinib therapy seems to be beneficial to control Ph+ leukemia resistance and the quantitative model can determine optimal dosing schedule to enhance the effectiveness of the combination therapy.

New Mouse Model May Aid in Developing Effective Therapies for Ovarian Cancer | Poster

Cancer.gov

By Frank Blanchard, Staff Writer A new genetically engineered mouse model appears promising as an effective tool for preclinical testing of novel therapies for ovarian cancer, which tends to be diagnosed in late stage. There are few effective treatments for the disease.

Music therapy in the assessment and treatment of autistic spectrum disorder: clinical application and research evidence.

PubMed

Wigram, T; Gold, C

2006-09-01

Children and adolescents with autistic spectrum disorder (ASD) presenting with significant limitations in conventional forms of verbal and non-verbal communication are found to respond positively to music therapy intervention involving both active, improvizational methods and receptive music therapy approaches. Improvizational musical activity with therapeutic objectives and outcomes has been found to facilitate motivation, communication skills and social interaction, as well as sustaining and developing attention. The structure and predictability found in music assist in reciprocal interaction, from which tolerance, flexibility and social engagement to build relationships emerge, relying on a systematic approach to promote appropriate and meaningful interpersonal responses. Published reports of the value and effectiveness of music therapy as an intervention for children with ASD range from controlled studies to clinical case reports. Further documentation has emphasized the role music therapy plays in diagnostic and clinical assessment. Music therapy assessment can identify limitations and weaknesses in children, as well as strengths and potentials. Research evidence from a systematic review found two randomized controlled trials that examined short-term effects of structured music therapy intervention. Significant effects were found in these studies even with extremely small samples, and the findings are important because they demonstrate the potential of the medium of music for autistic children. Case series studies were identified that examined the effects of improvizational music therapy where communicative behaviour, language development, emotional responsiveness, attention span and behavioural control improved over the course of an intervention of improvizational music therapy.

The psychophysiological effects of music therapy in intensive care units.

PubMed

Austin, Donna

2010-04-01

This article reviews the evidence for using music therapy with young people who are supported by mechanical ventilation. The author argues that music therapy is essential for developing a holistic approach focusing on the developmental level of a child or young person, as well as being an inexpensive, non-pharmacological, non-invasive therapy, with significant physiological and psychological benefits. She argues that more research is needed in this area to develop a sound evidence base on which guidelines to inform practice could be based.

Lentiviral vectors for gene therapy of heart disease.

PubMed

Higuchi, Koji; Medin, Jeffrey A

2007-01-01

Technological advances in genetic engineering developed over the past few years have been applied to the research and treatment of cardiovascular diseases. In many animal models, gene therapy has been shown to be an effective treatment schema. Some of these gene therapy treatments are now being applied in clinical trials. Also, as the science of gene therapy has progressed, alternative vector systems such as lentiviruses have been developed and implemented. Here we focus on the emerging role of lentiviral vectors in the treatment of cardiovascular disease.

Fallout: Its Characteristics and Management

DTIC Science & Technology

1983-12-01

subclinical ) 100-200 Excellent (clinical surveillance) 200-600 0-90% mortality (therapy effective) 600-1000 90%-100% mortality (therapy promising...the time of exposure (i 1954). Of those 28 persons with thyroid lesions, 3 developed malignancy, 2 suffered hypothyroidism , and all others developed

Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

PubMed Central

Raj, Ganesh V; Sareddy, Gangadhara Reddy; Ma, Shihong; Lee, Tae-Kyung; Viswanadhapalli, Suryavathi; Li, Rui; Liu, Xihui; Murakami, Shino; Chen, Chien-Cheng; Lee, Wan-Ru; Mann, Monica; Krishnan, Samaya Rajeshwari; Manandhar, Bikash; Gonugunta, Vijay K; Strand, Douglas; Tekmal, Rajeshwar Rao; Ahn, Jung-Mo; Vadlamudi, Ratna K

2017-01-01

The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly with ER and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers. DOI: http://dx.doi.org/10.7554/eLife.26857.001 PMID:28786813

[An assessment of tinnitus retraining therapy].

PubMed

von Wedel, H; von Wedel, U C

2000-12-01

Based on the neurophysiological model of tinnitus developed by Jastreboff and Hazell [39] there have been some important developments in understanding and therapy of tinnitus over the last decade. The clinical applications of this model are known as "tinnitus retraining therapy", which has the objective of reducing both the distress associated with tinnitus and the tinnitus perception itself. As a form of systematic, repeated and skilled counselling over a long period of up to 2 years supported by sound therapy (hearing aid or noise generator) the evidence for their high degree of effectiveness is overwhelming. On the basis of a "German concept" of tinnitus retraining therapy developed and proposed by the ADANO (Arbeitsgemeinschaft deutschsprachiger Audiologen und Neurootologen) the current status of this treatment will be briefly reviewed including some actual studies of Goebel et al. [14] that confirm the world wide critical comments on the recent developments in the management of tinnitus especially with regard to tinnitus retraining therapy [79].

Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

NASA Astrophysics Data System (ADS)

Yuan, Chenyan; An, Yanli; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng

2014-08-01

Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression.

Metacognitive therapy versus cognitive behavioural therapy for depression: a randomized pilot study.

PubMed

Jordan, Jennifer; Carter, Janet D; McIntosh, Virginia V W; Fernando, Kumari; Frampton, Christopher M A; Porter, Richard J; Mulder, Roger T; Lacey, Cameron; Joyce, Peter R

2014-10-01

Metacognitive therapy (MCT) is one of the newer developments within cognitive therapy. This randomized controlled pilot study compared independently applied MCT with cognitive behavioural therapy (CBT) in outpatients with depression to explore the relative speed and efficacy of MCT, ahead of a planned randomized controlled trial. A total of 48 participants referred for outpatient therapy were randomized to up to 12 weeks of MCT or CBT. Key outcomes were reduction in depressive symptoms at week 4 and week 12, measured using the independent-clinician-rated Quick Inventory of Depressive Symptomatology16. Intention-to-treat and completer analyses as well as additional methods of reporting outcome of depression are presented. Both therapies were effective in producing clinically significant change in depressive symptoms, with moderate-to-large effect sizes obtained. No differences were detected between therapies in overall outcome or early change on clinician-rated or self-reported measures. Post-hoc analyses suggest that MCT may have been adversely affected by greater comorbidity. In this large pilot study conducted independently of MCT's developers, MCT was an effective treatment for outpatients with depression, with similar results overall to CBT. Insufficient power and imbalanced comorbidity limit conclusions regarding comparative efficacy so further studies of MCT and CBT are required. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Current applications and future prospects of nanomaterials in tumor therapy.

PubMed

Huang, Yu; Fan, Chao-Qiang; Dong, Hui; Wang, Su-Min; Yang, Xiao-Chao; Yang, Shi-Ming

2017-01-01

Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed.

Delayed onset and prolonged interictal delirium following electroconvulsive therapy.

PubMed

Selvaraj, Arun G; Praharaj, Samir Kumar

2012-09-01

Electroconvulsive therapy is safe and effective in the treatment of depression in older individuals. Minor cognitive side effects of electroconvulsive therapy include acute postictal confusion and reversible short-term memory deficits. However, interictal delirium is uncommon in absence of risk factors. Herein, we report the case a depressed male patient without any known risk factors who developed interictal delirium 2 days after his sixth electroconvulsive therapy session. Interictal delirium improved with treatment within 1 week. © 2012 The Authors. Psychogeriatrics © 2012 Japanese Psychogeriatric Society.

Gene Therapy Targeting Glaucoma: Where Are We?

PubMed Central

Liu, Xuyang; Rasmussen, Carol A.; Gabelt, B’Ann T.; Brandt, Curtis R.; Kaufman, Paul L.

2010-01-01

In a chronic disease such as glaucoma, a therapy that provides a long lasting local effect, with minimal systemic side effects, while circumventing the issue of patient compliance, is very attractive. The field of gene therapy is growing rapidly and ocular applications are expanding. Our understanding of the molecular pathogenesis of glaucoma is leading to greater specificity in ocular tissue targeting. Improvements in gene delivery techniques, refinement of vector construction methods, and development of better animal models combine to bring this potential therapy closer to reality. PMID:19539835

[Dance/movement therapy in oncological rehabilitation].

PubMed

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

2013-01-01

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

Cancer Systems Biology: a peak into the future of patient care?

PubMed Central

Werner, Henrica M. J.; Mills, Gordon B.; Ram, Prahlad T.

2015-01-01

Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function or the effect of the manipulation of one protein on a biological phenotype. A range of technologies, combined with the ability to develop robust and predictive mathematical models, is beginning to provide information that will enable a holistic view of how the genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, at the organ and organism level. This systems biology process needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients most likely to benefit from targeted therapies as well as for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current (often short term) effects of targeted therapies into durable responses, ultimately to improve quality of life and provide a cure. PMID:24492837

Neurobiological mechanisms of exercise and psychotherapy in depression: The SPeED study-Rationale, design, and methodological issues.

PubMed

Heinzel, Stephan; Rapp, Michael A; Fydrich, Thomas; Ströhle, Andreas; Terán, Christina; Kallies, Gunnar; Schwefel, Melanie; Heissel, Andreas

2018-02-01

Even though cognitive behavioral therapy has become a relatively effective treatment for major depressive disorder and cognitive behavioral therapy-related changes of dysfunctional neural activations were shown in recent studies, remission rates still remain at an insufficient level. Therefore, the implementation of effective augmentation strategies is needed. In recent meta-analyses, exercise therapy (especially endurance exercise) was reported to be an effective intervention in major depressive disorder. Despite these findings, underlying mechanisms of the antidepressant effect of exercise especially in combination with cognitive behavioral therapy have rarely been studied to date and an investigation of its neural underpinnings is lacking. A better understanding of the psychological and neural mechanisms of exercise and cognitive behavioral therapy would be important for developing optimal treatment strategies in depression. The SPeED study (Sport/Exercise Therapy and Psychotherapy-evaluating treatment Effects in Depressive patients) is a randomized controlled trial to investigate underlying physiological, neurobiological, and psychological mechanisms of the augmentation of cognitive behavioral therapy with endurance exercise. It is investigated if a preceding endurance exercise program will enhance the effect of a subsequent cognitive behavioral therapy. This study will include 105 patients diagnosed with a mild or moderate depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.). The participants are randomized into one of three groups: a high-intensive or a low-intensive endurance exercise group or a waiting list control group. After the exercise program/waiting period, all patients receive an outpatient cognitive behavioral therapy treatment according to a standardized therapy manual. At four measurement points, major depressive disorder symptoms (Beck Depression Inventory, Hamilton Rating Scale for Depression), (neuro)biological measures (neural activations during working memory, monetary incentive delay task, and emotion regulation, as well as cortisol levels and brain-derived neurotrophic factor), neuropsychological test performance, and questionnaires (psychological needs, self-efficacy, and quality of life) are assessed. In this article, we report the design of the SPeED study and refer to important methodological issues such as including both high- and low-intensity endurance exercise groups to allow the investigation of dose-response effects and physiological components of the therapy effects. The main aims of this research project are to study effects of endurance exercise and cognitive behavioral therapy on depressive symptoms and to investigate underlying physiological and neurobiological mechanisms of these effects. Results may provide important implications for the development of effective treatment strategies in major depressive disorder, specifically concerning the augmentation of cognitive behavioral therapy by endurance exercise.

Development of the Clinical Teaching Effectiveness Questionnaire in the United States.

PubMed

Wormley, Michelle E; Romney, Wendy; Greer, Anna E

2017-01-01

The purpose of this study was to develop a valid measure for assessing clinical teaching effectiveness within the field of physical therapy. The Clinical Teaching Effectiveness Questionnaire (CTEQ) was developed via a 4-stage process, including (1) initial content development, (2) content analysis with 8 clinical instructors with over 5 years of clinical teaching experience, (3) pilot testing with 205 clinical instructors from 2 universities in the Northeast of the United States, and (4) psychometric evaluation, including principal component analysis. The scale development process resulted in a 30-item questionnaire with 4 sections that relate to clinical teaching: learning experiences, learning environment, communication, and evaluation. The CTEQ provides a preliminary valid measure for assessing clinical teaching effectiveness in physical therapy practice.

Cost-effectiveness analysis of adjunct VSL#3 therapy versus standard medical therapy in pediatric ulcerative colitis.

PubMed

Park, K T; Perez, Felipe; Tsai, Raymond; Honkanen, Anita; Bass, Dorsey; Garber, Alan

2011-11-01

Inflammatory bowel diseases (IBDs) are costly chronic gastrointestinal diseases, with pediatric IBD representing increased costs per patient compared to adult disease. Health care expenditures for ulcerative colitis (UC) are >$2 billion annually. It is not clear whether the addition of VSL#3 to standard medical therapy in UC induction and maintenance of remission is a cost-effective strategy. We performed a systematic review of the literature and created a Markov model simulating a cohort of 10-year-old patients with severe UC, studying them until 100 years of age or death. We compared 2 strategies: standard medical therapy versus medical therapy + VSL#3. For both strategies, we assumed that patients progressed through escalating therapies--mesalamine, azathioprine, and infliximab--before receiving a colectomy + ileal pouch anal anastamosis (IPAA) if the 3 medical therapy options were exhausted. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), defined as the difference of costs between strategies for each quality-adjusted life-year (QALY) gained. One-way sensitivity analyses were performed on variables to determine the key variables affecting cost-effectiveness. Standard medical care accrued a lifetime cost of $203,317 per patient, compared to $212,582 per patient for medical therapy + VSL#3. Lifetime QALYs gained was comparable for standard medical therapy and medical therapy + VSL#3 at 24.93 versus 25.05, respectively. Using the definition of ICER <50,000/QALY as a cost-effective intervention, medical therapy + VSL#3 produced an ICER of $79,910 per QALY gained, making this strategy cost-ineffective. Sensitivity analyses showed that 4 key parameters could affect the cost-effectiveness of the 2 strategies: cost of colectomy + IPAA, maintenance cost after surgery, probability of developing pouchitis after surgery, and the quality of life after a colectomy + IPAA. High surgical and postsurgical costs, a high probability of developing pouchitis, and a low quality of life after a colectomy + IPAA could make adjunct VSL#3 use a cost-effective strategy. Given present data, adjunct VSL#3 use for pediatric UC induction and maintenance of remission is not cost-effective, although several key parameters could make this strategy cost-effective. The quality of life after an IPAA is the single most important variable predicting whether this procedure benefits patients over escalating standard medical therapy.

Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine

PubMed Central

Hack, C. C.; Voiß, P.; Lange, S.; Paul, A. E.; Conrad, S.; Dobos, G. J.; Beckmann, M. W.; Kümmel, S.

2015-01-01

With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patientʼs quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patientsʼ wellbeing and quality of life, reducing stress, and improving patientsʼ mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle. PMID:26257404

Single dose treatment of malaria - current status and perspectives.

PubMed

Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

2016-07-01

Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

Safety, therapeutic effectiveness, and cost of parenteral iron therapy.

PubMed

Asma, Suheyl; Boga, Can; Ozdogu, Hakan

2009-07-01

Patients have to discontinue the use of oral iron therapy due to the development of side effects and lack of long-term adherence to medication for iron deficiency anemia. This study aimed to evaluate the therapeutic effectiveness, safety, and cost of intravenous iron sucrose therapy. The computerized database and medical records of 453 patients diagnosed with iron deficiency anemia who received intravenous iron sucrose therapy for iron deficiency anemia between 2004 and 2008 were reviewed. The improvement of hematologic parameters and cost of therapy were evaluated 4 weeks after therapy. 453 patients (443 females, 10 males; age: 44.2 +/- 12.3 years) received iron sucrose therapy. Mean hemoglobin, hematocrit, and mean corpuscular volume values were 8.2 +/- 1.4 g/dL, 26.9 +/- 3.8%, and 66.1 +/- 7.8 fL, respectively, before therapy and 11.5 +/- 1.0 g/dL, 35.8 +/- 2.5%, 76.5 +/- 6.1 fL, respectively, after therapy (P < 0.001). A mean ferritin level of 3.4 +/- 2.4 ng/mL before therapy increased to 65.9 +/- 40.6 ng/mL after therapy (P < 0.001). All patients responded to intravenous iron therapy (transferrin saturation values of the patients were >50%). The mean cost of therapy was 143.07 +/- 29.13 US dollars. The therapy was well tolerated. Although the cost of intravenous iron sucrose therapy may seem high, a lack of adherence to therapy and side effects including gastrointestinal irritation during oral iron therapy were not experienced during intravenous therapy.

Classification of complementary and alternative medical practices: Family physicians' ratings of effectiveness.

PubMed

Fries, Christopher J

2008-11-01

ABSTRACTOBJECTIVETo develop a classification of complementary and alternative medicine (CAM) practices widely available in Canada based on physicians' effectiveness ratings of the therapies.DESIGNA self-administered postal questionnaire asking family physicians to rate their "belief in the degree of therapeutic effectiveness" of 15 CAM therapies.SETTINGProvince of Alberta.PARTICIPANTSA total of 875 family physicians.MAIN OUTCOME MEASURESDescriptive statistics of physicians' awareness of and effectiveness ratings for each of the therapies; factor analysis was applied to the ratings of the 15 therapies in order to explore whether or not the data support the proposed classification of CAM practices into categories of accepted and rejected.RESULTSPhysicians believed that acupuncture, massage therapy, chiropractic care, relaxation therapy, biofeedback, and spiritual or religious healing were effective when used in conjunction with biomedicine to treat chronic or psychosomatic indications. Physicians attributed little effectiveness to homeopathy or naturopathy, Feldenkrais or Alexander technique, Rolfing, herbal medicine, traditional Chinese medicine, and reflexology. The factor analysis revealed an underlying dimensionality to physicians' effectiveness ratings of the CAM therapies that supports the classification of these practices as either accepted or rejected.CONCLUSIONThis study provides Canadian family physicians with information concerning which CAM therapies are generally accepted by their peers as effective and which are not.

The challenge and promise of anti-epileptic therapy development in animal models

PubMed Central

Simonato, Michele; Brooks-Kayal, Amy R; Engel, Jerome; Galanopoulou, Aristea S; Jensen, Frances E; Moshé, Solomon L; O’Brien, Terence J; Pitkanen, Asla; Wilcox, Karen S; French, Jacqueline A

2016-01-01

Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies—complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. Available treatments do not fully control seizures in a third of patients with epilepsy, and produce substantial side-effects. No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed. PMID:25127174

Advances in the medical treatment of juvenile rheumatoid arthritis.

PubMed

Onel, K B

2000-02-01

Juvenile rheumatoid arthritis (JRA) remains a challenge for clinicians. Nonsteroidal anti-inflammatory drugs and corticosteroids remain the mainstays of therapy, but concerns persist about side effects and the ability of these agents to prevent progression of bony disease. In recent years, novel treatments have been developed and quickly discarded because of unexpected toxicities or lack of efficacy. However, recent studies have shown that methotrexate and sulfasalazine are relatively safe and effective for JRA. Newly developed drugs, such as selective cyclooxygenase-2 inhibitors and soluble tumor necrosis factor receptor, whose development has stemmed from a more basic understanding of pathophysiology, may provide better disease control with fewer side effects. Finally, novel therapies, such as stem cell transplantation, may offer hope for children with JRA, especially systemic-onset JRA, whose disease has been refractory to conventional therapy.

Family therapy: critique from a feminist perspective.

PubMed

Penfold, P S

1989-05-01

Family therapy is a powerful modality which, all too often, is used without awareness of its possible constricting, or even crippling, effects. Textbooks and articles about family therapy focus soley or mainly on the family system alone, thus obscuring the influence of school, workplace, neighborhood, peer group, class, race and sex. Theorists, who are predominantly male, have developed rigid and mechanical concepts which encourage formulations encompassing the family system alone. Power inequalities between men and women are ignored and socially programmed sex roles are reflected and reinforced by theory and practice. Thus family therapy may function to locate and contain, within the family, difficulties and distress derived from stresses outside the family. The negative effects of traditional sex roles on emotional growth, sexuality and the development of mutually gratifying male-female relationships are never dealt with. As a result, family therapy may contribute to men's straitjacketing and women's oppression. To fulfill its promise, family therapy research and teaching must move beyond shortsighted and narrowly conceptualized theories which could damage, rather than heal, families who are suffering.

PubMed Central

Schneeweiss, Andreas; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin-Andrei; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Wöckel, Achim; Ettl, Johannes; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Beckmann, Matthias W.; Belleville, Erik; Wallwiener, Diethelm; Brucker, Sara Y.; Schütz, Florian; Fasching, Peter A.; Fehm, Tanja N.

2018-01-01

The treatment of metastatic breast cancer has become more complicated due to increasing numbers of new therapies which need to be tested. Therapies are now being developed to treat special clinical or molecular subgroups. Even though intrinsic molecular subtypes play a major role, more and more new therapies for subgroups and histological subtypes are being developed, such as the use of PARP inhibitors to treat patients with BRCA mutations (breast and ovarian cancer). Supportive therapies are also evolving, allowing problems such as alopecia or nausea and vomiting to be treated more effectively. Treatment-related side effects have a direct impact on the prognosis of patients with metastatic breast cancer, and supportive therapy can improve compliance. Digital tools could be useful to establish better patient management systems. This overview provides an insight into recent trials and how the findings could affect routine treatment. Current aspects of breast cancer prevention are also presented. PMID:29576630

Physical Therapy and Infants with Down's Syndrome: The Effects of Early Intervention.

ERIC Educational Resources Information Center

Harris, Susan R.

1981-01-01

The neuromotor development of Down's syndrome (DS) infants is reviewed, current physical therapy approaches are cited, a neurodevelopmental treatment (NDT) approach is described, and a study on the effects of NDT on motor performance in DS infants is reported. (SB)

New developments in psychosocial interventions for adults with unipolar depression.

PubMed

Lau, Mark A

2008-01-01

Depression treatment guidelines typically recommend cognitive behavioral therapy and/or interpersonal therapy for the acute treatment of mild-moderate depression. However, several new developments support an expanded role for psychotherapy in depression treatment. This article summarizes recent psychotherapy efficacy studies across the depression treatment continuum and the effectiveness of psychosocial interventions in community settings. New psychotherapies in the acute treatment of mild-moderate depression include emotion-focused therapy, self-system therapy, cognitive control training and positive psychotherapy. Furthermore, emerging evidence supports the use of psychotherapy for moderate-severe and treatment-resistant depression and for recurrent depression with a seasonal pattern. An important area of growth is the development and evaluation of continuation/maintenance treatments based on cognitive behavioral therapy and interpersonal therapy to reduce depressive relapse risk in recurrent and chronic depression. Finally, there is evidence supporting the effectiveness of stepped care, chronic disease management and collaborative care models in community settings. Emerging evidence supports an expanded role for the use of psychosocial interventions as acute and continuation/maintenance treatments for unipolar depression. Although further research is required to replicate these findings, a remaining challenge is to increase the availability of these treatments to the mental health consumer.

Sensorimotor plasticity after music-supported therapy in chronic stroke patients revealed by transcranial magnetic stimulation.

PubMed

Amengual, Julià L; Rojo, Nuria; Veciana de Las Heras, Misericordia; Marco-Pallarés, Josep; Grau-Sánchez, Jennifer; Schneider, Sabine; Vaquero, Lucía; Juncadella, Montserrat; Montero, Jordi; Mohammadi, Bahram; Rubio, Francisco; Rueda, Nohora; Duarte, Esther; Grau, Carles; Altenmüller, Eckart; Münte, Thomas F; Rodríguez-Fornells, Antoni

2013-01-01

Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

"Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy.

PubMed

Kemp, Jessica A; Shim, Min Suk; Heo, Chan Yeong; Kwon, Young Jik

2016-03-01

The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

Theranostics for cancer therapy.

PubMed

Palekar-Shanbhag, Pradnya; Jog, Sneha V; Chogale, Manasi M; Gaikwad, Sujata S

2013-06-01

With over 10 million new cases per year worldwide, Cancer remains one of the most urgent health concerns and a difficult disease to treat. For an effective treatment, improved diagnostic and therapeutic techniques with minimal side-effects are required. Research and development in the areas of nanoscience and nanotechnology promise to provide innovative and more effective approaches for early diagnosis, imaging and therapy. An emerging trend in this direction is Theranostics which represents a combinatorial diagnosis and therapeutic approach to cancer disease and aims to eliminate multi-step procedures, reduce delays in treatment and improves patient care. It offers various advantages like improved diagnosis, tumor specific delivery of drugs, reduced lethal effects to normal tissues etc. Theranostic nanomedicines like nanoshells, plasmonic nanobubbles, quantum dots etc. can be used effectively for achieving these goals. With the advances in nano-imaging and nano-therapy new avenues for the development of effective cancer treatment will be opened.

[New possibilities will open up in human gene therapy].

PubMed

Portin, Petter

2016-01-01

Gene therapy is divided into somatic and germ line therapy. The latter involves reproductive cells or their stem cells, and its results are heritable. The effects of somatic gene therapy are generally restricted to a single tissue of the patient in question. Until now, all gene therapies in the world have belonged to the regime of somatic therapy, germ line therapy having been a theoretical possibility only. Very recently, however, a method has been developed which is applicable to germ line therapy as well. In addition to technical challenges, severe ethical problems are associated with germ line therapy, demanding opinion statement.

Dissociative identity disorder and the process of couple therapy.

PubMed

Macintosh, Heather B

2013-01-01

Couple therapy in the context of dissociative identity disorder (DID) has been neglected as an area of exploration and development in the couple therapy and trauma literature. What little discussion exists focuses primarily on couple therapy as an adjunct to individual therapy rather than as a primary treatment for couple distress and trauma. Couple therapy researchers have begun to develop adaptations to provide effective support to couples dealing with the impact of childhood trauma in their relationships, but little attention has been paid to the specific and complex needs of DID patients in couple therapy (H. B. MacIntosh & S. Johnson, 2008 ). This review and case presentation explores the case of "Lisa," a woman diagnosed with DID, and "Don," her partner, and illustrates the themes of learning to communicate, handling conflicting needs, responding to child alters, and addressing sexuality and education through their therapy process. It is the hope of the author that this discussion will renew interest in the field of couple therapy in the context of DID, with the eventual goal of developing an empirically testable model of treatment for couples.

Microwave pumped high-efficient thermoacoustic tumor therapy with single wall carbon nanotubes.

PubMed

Wen, Liewei; Ding, Wenzheng; Yang, Sihua; Xing, Da

2016-01-01

The ultra-short pulse microwave could excite to the strong thermoacoustic (TA) shock wave and deeply penetrate in the biological tissues. Based on this, we developed a novel deep-seated tumor therapy modality with mitochondria-targeting single wall carbon nanotubes (SWNTs) as microwave absorbing agents, which act efficiently to convert ultra-short microwave energy into TA shock wave and selectively destroy the targeted mitochondria, thereby inducing apoptosis in cancer cells. After the treatment of SWNTs (40 μg/mL) and ultra-short microwave (40 Hz, 1 min), 77.5% of cancer cells were killed and the vast majority were caused by apoptosis that initiates from mitochondrial damage. The orthotopic liver cancer mice were established as deep-seated tumor model to investigate the anti-tumor effect of mitochondria-targeting TA therapy. The results suggested that TA therapy could effectively inhibit the tumor growth without any observable side effects, while it was difficult to achieve with photothermal or photoacoustic therapy. These discoveries implied the potential application of TA therapy in deep-seated tumor models and should be further tested for development into a promising therapeutic modality for cancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Equine-Assisted Occupational Therapy: Increasing Engagement for Children With Autism Spectrum Disorder.

PubMed

Llambias, Cecilia; Magill-Evans, Joyce; Smith, Veronica; Warren, Sharon

Engagement in meaningful activities is essential to development and is often reduced in children with autism spectrum disorder (ASD) who have limited engagement in activities or relationships. A multiple-baseline design was used with 7 children with ASD ages 4-8 yr to assess the effect of including a horse in occupational therapy intervention on task engagement. The children showed improvements in engagement. Including horses in occupational therapy sessions may be a valuable addition to conventional treatments to increase task engagement of children with ASD. Factors related to the environment, therapeutic strategies, and individual participation need to be considered in understanding why this intervention may be effective and developing a theoretical basis for implementation. Copyright © 2016 by the American Occupational Therapy Association, Inc.

Diabetes Mellitus and Its Effects on All-Cause Mortality After Radiopeptide Therapy for Neuroendocrine Tumors.

PubMed

Umlauft, Maria; Radojewski, Piotr; Spanjol, Petar-Marko; Dumont, Rebecca; Marincek, Nicolas; Kollar, Attila; Brunner, Philippe; Beyersmann, Jan; Müller-Brand, Jan; Maecke, Helmut R; Laimer, Markus; Walter, Martin A

2017-01-01

We aimed to assess the risk of developing diabetes mellitus and its effects on all-cause mortality after radiopeptide therapy for neuroendocrine tumors (NETs). NET patients received somatostatin radiopeptide therapy with 90 Y-DOTATOC or 177 Lu-DOTATOC. The incidence of diabetes mellitus and its mortality were assessed using univariate and multivariate regression. Overall, 1,535 NET patients were enrolled and received 3,807 treatment cycles. After treatment, 72 patients developed diabetes mellitus, including 47 cases after 90 Y-DOTATOC and 25 cases after combined treatment. The diabetes mellitus risk was higher before than after DOTATOC (estimate, 0.0032; P < 0.001), and overall survival was similar in patients with and without diabetes mellitus (hazard ratio, 1.13; 95% confidence interval, 0.91-1.39; n = 1,535; P = 0.27). Radiopeptide therapy does not appear to increase the risk of developing diabetes mellitus in NET patients, whereas diabetes mellitus does not appear to increase the mortality of NET patients undergoing receptor-targeted radiopeptide therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Emerging therapies for Clostridium difficile infections.

PubMed

McFarland, Lynne V

2011-09-01

Clostridium difficile infection (CDI) is the leading identifiable gastrointestinal disease in healthcare institutions, but the response rates to the two standard therapies for CDI are declining and so innovative therapies are being developed for CDI. The purpose of this paper is to review the data on the efficacy and safety of emerging therapies for CDI and assess their potential for effectiveness based on the clinical phase of development and marketing challenges. Emerging therapies for CDI are reviewed including new antibiotics, peptides, immune regulators, probiotics and toxin binders. PubMed, Medline and Google Scholar and online clinical trial registers are searched from 1976 to 2010 for articles unrestricted by language. Secondary searches by author, manufacturing companies and FDA websites are also performed. Of the emerging therapies for CDI, several may ultimately reduce the incidence of CDI and the economic burden of this disease on the healthcare system. Several emerging treatments (fidaxomicin, rifaximin and mAbs) show the most promise, although only one is currently being actively developed. Use of other clostridial strains, probiotic strains and immune enhancers have great potential as therapies, but require further development.

Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies.

PubMed

Hojjat-Farsangi, Mohammad

2014-08-08

Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK-TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK-TKIs have been developed for the treatment of cancer patients. Specific/selective RTK-TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK-TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.

[The use of music intervention in nursing practice for elderly dementia patients: a systematic review].

PubMed

Li, Yi-Hui; Chen, Shu-Ming; Chou, Man-Chun; Huang, Tsuey-Yuan

2014-04-01

Although music therapy is now applied widely as an intervention for elderly dementia patients, the effectiveness of this therapy is not yet well understood. This study conducts a systematic review of clinical studies that address the effectiveness of music therapy in elderly dementia patients. Databases including MEDLINE, Cochrane Library, ProQuest, EBMR, CINAHL, and CEPS were searched for relevant articles published between 2004 and 2013 using the key words "music" or "music therapy" with "dementia". An initial 272 original articles were identified. Applying inclusion criteria and excluding duplications left 18 articles that used randomized controlled trials to assess the effectiveness of music therapy in elderly participants for further analysis and synthesis. Music therapy was found effective at improving cognitive functions, mental symptoms, and eating problems. However, this therapy was not found effective at improving irritable behavior. Type of music and method of presentation were the most important factors affecting results. Most studies (61.1%) used songs familiar to ÷ favored by the participants; most studies delivered 30-minute interventions twice weekly; and most studies used a therapy duration of 6 hours. Finally, most studies (77.8%) had music therapy sessions performed by either music therapists or trained healthcare providers. This study supports that music therapy is an effective nursing intervention for elderly dementia patients. The authors hope that findings are a helpful reference for clinical nurses to develop practical music therapy procedures and protocols.

The Effects of Rm-CSF and Ril-6 Therapy on Immunosuppressed Antiorthostatically Suspended Mice

NASA Technical Reports Server (NTRS)

Armstong, Jason W.; Kirby-Dobbels, Kathy; Chapes, Steven K.

1995-01-01

Antiorthostatically suspended mice had suppressed macrophage development in both unloaded and loaded bones, indicating a systemic effect. Bone marrow cells from those mice secreted less macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) than did control mice. Because M-CSF and IL-6 are important to bone marrow macrophage maturation, we formulated the hypothesis that suppressed macrophage development occurred as a result of the depressed levels of either M-CSF or IL-6. To test the hypothesis, mice were administered recombinant M-CSF or IL-6 intraperitoneally. We showed that recombinant M-CSF therapy, but not recombinant IL-6 therapy, reversed the suppressive effects of orthostatic suspension on macrophage development. These data suggest that bone marrow cells that produce M-CSF are affected by antiorthostatic suspension and may contribute to the inhibited maturation of bone marrow macrophage progenitors.

Burns induced by cupping therapy in a burn center in northeast china.

PubMed

Jing-Chun, Zhao; Jia-Ao, Yu; Chun-Jing, Xian; Kai, Shi; Lai-Jin, Lu

2014-07-01

Cupping therapy as a curative skill has been developed and applied throughout history. Despite reports of adverse effects, this therapy is considered to be relatively safe with no systemic reviews documenting negative side effects. The aim of this study was to explore methods that avoid the adverse effects sometimes associated with this therapy. Clinical records of 14 outpatients and inpatients that visited the First Hospital of Jilin University (Changchun, China) for management of burn injuries caused by cupping therapy were retrospectively reviewed. Characteristics, history of injury, and treatment of each patient was collected and analyzed. Burn injury induced by cupping therapy was not uncommon. Most of the injuries were mild to moderate and cured by conservative methods without severe complications. The use of wet cupping was more prevalent among injured patients than dry cupping. Cupping therapy as an ancient alternative treatment is still popular with a large number of devoted practitioners. Although there is the potential for injury during the application of this therapy, this is mostly preventable. Standardized training for health care professionals and increased the awareness among the public about the proper methods to administer this therapy to avoid adverse effects is important.

Cost-Effectiveness of Proton Pump Inhibitor Co-Therapy in Patients Taking Aspirin for Secondary Prevention of Ischemic Stroke.

PubMed

Takabayashi, Nobuyoshi; Murata, Kyoko; Tanaka, Shiro; Kawakami, Koji

2015-10-01

Low-dose aspirin (ASA) is effective for secondary prevention of ischemic stroke but can increase the risks of hemorrhagic stroke, upper gastrointestinal bleeding (UGIB), and dyspepsia. Prophylactic administration of proton pump inhibitors (PPIs) reduces the risks of these digestive symptoms. We investigated the cost effectiveness of adding a PPI to ASA therapy for ischemic stroke patients in Japan. A Markov state-transition model was developed to compare the cost effectiveness of ASA monotherapy with ASA plus PPI co-therapy in patients with histories of upper gastrointestinal ulcers and ischemic stroke. The model takes into account ASA adherence rate and adverse effects due to ASA, including hemorrhagic stroke and UGIB. The analysis was performed from the perspective of healthcare payers in 2013. In the base case, total life-years by PPI co-therapy and monotherapy were 16.005 and 15.932, respectively. The difference in duration of no therapy (no ASA or PPI) between the therapies was 558.5 days, which would prevent 30.3 recurrences of ischemic stroke per 1000 person-years. The incremental cost-effectiveness ratio of PPI co-therapy relative to monotherapy was ¥1,191,665 (US$11,458) per life-year gained. In a one-way sensitivity analysis, PPI co-therapy was consistently cost effective at a willingness to pay of ¥5,000,000 (US$48,077) per life-year gained. In a probabilistic sensitivity analysis, the probability that PPI co-therapy was cost effective was 89.74% at the willingness to pay. Co-therapy with ASA plus PPI appears to be cost-effective compared with ASA monotherapy. The addition of PPI also appeared to prolong the duration of ASA therapy, thereby reducing the risk of ischemic stroke.

Therapeutic effects of combination using glucosamine plus tacrolimus (FK-506) on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Kim, C-H; Cheong, K A; Park, C D; Lee, A-Y

2012-05-01

Tacrolimus (FK-506) has been found to exhibit potent inhibitory effects on spontaneously developed dermatitis. We previously showed that glucosamine prevents the development of Atopic dermatitis (AD)-like skin lesions in NC/Nga mice. The aims of our study were to investigate the synergistic therapeutic efficacy of combination of glucosamine plus FK-506 in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 8 were used for treatment with glucosamine (500 mg/kg) alone, FK-506 (1.0 mg/kg) or in combination. The synergistic effects of combination therapy were evaluated by dermatitis scores, skin histology and immunological parameters such as IgE, Th2-mediated cytokines and chemokines, CD3(+) T cells and CLA(+) T cells. Combined therapy using glucosamine plus FK-506 improved the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores. The suppression of dermatitis by combined therapy was accompanied by a decrease in the plasma level of IgE and in the splenic level of IL-5, IL-13, TARC and eotaxin. Histological finding indicated that the dermal infiltration of inflammatory cells including mast cells and eosinophils was greatly reduced. Particularly, immunohistological evaluation reveals a reduction in CD3(+) T cells and CLA(+) cells in the combined therapy. Our findings suggest that combination therapy of glucosamine plus FK-506 was more synergistic efficacy than single-modality treatment with either alone to improve the development of established dermatitis in NC/Nga mice model. This combined immunosuppressive therapy may provide an effective therapeutic strategy for the treatment of AD. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Another Setting for Stewardship: High Rate of Unnecessary Antimicrobial Use in a VA Long-Term Care Facility

PubMed Central

Peron, Emily P.; Hirsch, Amy A.; Jury, Lucy A.; Jump, Robin L.P.; Donskey, Curtis J.

2015-01-01

BACKGROUND/OBJECTIVE Antimicrobials are frequently prescribed in long-term care facilities (LTCFs). In order to develop effective stewardship interventions, there is a need for data on current patterns of unnecessary antimicrobial prescribing among LTCF residents. The objective of this study was to examine the frequency of, reasons for, and adverse effects of unnecessary antimicrobial use in our Veterans Affairs (VA) LTCF. DESIGN Retrospective chart review. SETTING Cleveland VA Medical Center LTCF. PARTICIPANTS Randomly selected patients receiving antimicrobial therapy from October 1, 2008 to March 31, 2009. MEASUREMENTS Days of necessary and unnecessary antimicrobial therapy determined using Infectious Diseases Society of America guidelines, syndromes treated with unnecessary antimicrobials, and the frequency of development of Clostridium difficile infection (CDI), colonization or infection with antimicrobial resistant pathogens, and other adverse effects. RESULTS Of 1351 days of therapy prescribed in 100 regimens, 575 days (42.5%) were deemed unnecessary. Of the 575 unnecessary days of therapy, 334 (58%) were for antimicrobial regimens that were entirely unnecessary (n=42). Asymptomatic bacteriuria was the most common reason for entirely unnecessary regimens (n=21), resulting in 173 days of unnecessary therapy. Regimens that were partially unnecessary resulted in 241 (42%) days of unnecessary therapy, with longer than recommended treatment duration accounting for 226 (94%) unnecessary days of therapy. Within 30 days of completing the antimicrobial regimens, 5 patients developed CDI, 5 had colonization or infection with antimicrobial-resistant pathogens, and 10 experienced other adverse drug events. CONCLUSIONS In our VA LTCF, 43% of all days of antimicrobial therapy were unnecessary. Our findings suggest that antimicrobial stewardship interventions in LTCFs should focus on improving adherence to recommended treatment durations and eliminating inappropriate treatment of asymptomatic bacteriuria. PMID:23405923

Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction☆

PubMed Central

Koh, Kwang Kon; Han, Seung Hwan; Oh, Pyung Chun; Shin, Eak Kyun; Quon, Michael J.

2010-01-01

Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by ~30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin–angiotensin–aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin–angiotensin–aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. PMID:19800624

Electroconvulsive Therapy: A Primer for Mental Health Counselors.

ERIC Educational Resources Information Center

Leinbaugh, Tracy C.

2001-01-01

Electroconvulsive therapy is the treatment of choice for severe depressive episodes. Although little definitive research exists to explain its effectiveness, since its development in 1938 it has proven effective for the treatment of depression with psychotic features and suicidal ideation. Explains the procedure and discusses implications for the…

Applying fiber optical methods for toxicological testing in vitro

NASA Astrophysics Data System (ADS)

Maerz, Holger K.; Buchholz, Rainer; Emmrich, Frank; Fink, Frank; Geddes, Clive L.; Pfeifer, Lutz; Raabe, Ferdinand; Scheper, Thomas-Helmut; Ulrich, Elizabeth; Marx, Uwe

1999-04-01

The new medical developments, e.g. immune therapy, patient oriented chemotherapy or even gene therapy, create a questionable doubt to the further requirement of animal test. Instead the call for humanitarian reproductive in vitro models becomes increasingly louder. Pharmaceutical usage of in vitro has a long proven history. In cancer research and therapy, the effect of chemostatica in vitro in the so-called oncobiogram is being tested; but the assays do not always correlate with in vivo-like drug resistance and sensitivity. We developed a drug test system in vitro, feasible for therapeutic drug monitoring by the combination of tissue cultivation in hollow fiber bioreactors and fiber optic sensors for monitoring the pharmaceutical effect. Using two fiber optic sensors - an optical oxygen sensor and a metabolism detecting Laserfluoroscope, we were able to successfully monitor the biological status of tissue culture and the drug or toxic effects of in vitro pharmaceutical testing. Furthermore, we developed and patented a system for monitoring the effect of minor toxic compounds which can induce Sick Building Syndrome.

Targeting the Cholinergic System to Develop a Novel Therapy for Huntington's Disease.

PubMed

D'Souza, Gary X; Waldvogel, Henry J

2016-12-15

In this review, we outline the role of the cholinergic system in Huntington's disease, and briefly describe the dysfunction of cholinergic transmission, cholinergic neurons, cholinergic receptors and cholinergic survival factors observed in post-mortem human brains and animal models of Huntington's disease. We postulate how the dysfunctional cholinergic system can be targeted to develop novel therapies for Huntington's disease, and discuss the beneficial effects of cholinergic therapies in pre-clinical and clinical studies.

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

PubMed

Radman, Thomas; Lisanby, Sarah H

2017-04-01

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

Cost-effectiveness of supervised exercise therapy in heart failure patients.

PubMed

Kühr, Eduardo M; Ribeiro, Rodrigo A; Rohde, Luis Eduardo P; Polanczyk, Carisi A

2011-01-01

Exercise therapy in heart failure (HF) patients is considered safe and has demonstrated modest reduction in hospitalization rates and death in recent trials. Previous cost-effectiveness analysis described favorable results considering long-term supervised exercise intervention and significant effectiveness of exercise therapy; however, these evidences are now no longer supported. To evaluate the cost-effectiveness of supervised exercise therapy in HF patients under the perspective of the Brazilian Public Healthcare System. We developed a Markov model to evaluate the incremental cost-effectiveness ratio of supervised exercise therapy compared to standard treatment in patients with New York Heart Association HF class II and III. Effectiveness was evaluated in quality-adjusted life years in a 10-year time horizon. We searched PUBMED for published clinical trials to estimate effectiveness, mortality, hospitalization, and utilities data. Treatment costs were obtained from published cohort updated to 2008 values. Exercise therapy intervention costs were obtained from a rehabilitation center. Model robustness was assessed through Monte Carlo simulation and sensitivity analysis. Cost were expressed as international dollars, applying the purchasing-power-parity conversion rate. Exercise therapy showed small reduction in hospitalization and mortality at a low cost, an incremental cost-effectiveness ratio of Int$26,462/quality-adjusted life year. Results were more sensitive to exercise therapy costs, standard treatment total costs, exercise therapy effectiveness, and medications costs. Considering a willingness-to-pay of Int$27,500, 55% of the trials fell below this value in the Monte Carlo simulation. In a Brazilian scenario, exercise therapy shows reasonable cost-effectiveness ratio, despite current evidence of limited benefit of this intervention. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Preliminary study on the effectiveness of short group cognitive behavioral therapy (GCBT) on Indonesian older adults.

PubMed

Utoyo, Dharmayati Bambang; Lubis, Dharmayati Utoyo; Jaya, Edo Sebastian; Arjadi, Retha; Hanum, Lathifah; Astri, Kresna; Putri, Maha Decha Dwi

2013-01-01

This research aims to develop evidence based affordable psychological therapy for Indonesian older adults. An affordable psychological therapy is important as there is virtually no managed care or health insurance that covers psychological therapy in Indonesia. Multicomponent group cognitive behavior therapy (GCBGT) was chosen as a starting point due to its extensive evidence, short sessions, and success for a wide range of psychological problems. The group format was chosen to address both the economic and the cultural context of Indonesia. Then, the developed treatment is tested to common psychological problems in older adults' population (anxiety, chronic pain, depression, and insomnia). The treatment consists of 8 sessions with twice a week meetings for 2.5 hours. There are similarities and differences among the techniques used in the treatment for the different psychological problems. The final participants are 38 older adults that are divided into the treatment groups; 8 participants joined the anxiety treatment, 10 participants for the chronic pain treatment, 10 participants for depression treatment, and lastly, 10 participants joined the insomnia treatment. The research design is pre-test post-test with within group analysis. We used principal outcome measure that is specific for each treatment group, as well as additional outcome measures. Overall, the result shows statistical significance change with large effect size for the principal outcome measure. In addition, the result for the additional measures varies from slight improvement with small effect size to statistically significant improvement with large effect size. The result indicates that short multicomponent GCBT is effective in alleviating various common psychological problems in Indonesian older adults. Therefore, multicomponent GCBT may be a good starting point to develop an effective and affordable psychological therapy for Indonesian older adults. Lastly, this result adds to the accumulating body of evidence on the effectiveness of multicomponent GCBT outside western context.

Preliminary Study on the Effectiveness of Short Group Cognitive Behavioral Therapy (GCBT) on Indonesian Older Adults

PubMed Central

Lubis, Dharmayati Utoyo; Jaya, Edo Sebastian; Arjadi, Retha; Hanum, Lathifah; Astri, Kresna; Putri, Maha Decha Dwi

2013-01-01

This research aims to develop evidence based affordable psychological therapy for Indonesian older adults. An affordable psychological therapy is important as there is virtually no managed care or health insurance that covers psychological therapy in Indonesia. Multicomponent group cognitive behavior therapy (GCBGT) was chosen as a starting point due to its extensive evidence, short sessions, and success for a wide range of psychological problems. The group format was chosen to address both the economic and the cultural context of Indonesia. Then, the developed treatment is tested to common psychological problems in older adults' population (anxiety, chronic pain, depression, and insomnia). The treatment consists of 8 sessions with twice a week meetings for 2.5 hours. There are similarities and differences among the techniques used in the treatment for the different psychological problems. The final participants are 38 older adults that are divided into the treatment groups; 8 participants joined the anxiety treatment, 10 participants for the chronic pain treatment, 10 participants for depression treatment, and lastly, 10 participants joined the insomnia treatment. The research design is pre-test post-test with within group analysis. We used principal outcome measure that is specific for each treatment group, as well as additional outcome measures. Overall, the result shows statistical significance change with large effect size for the principal outcome measure. In addition, the result for the additional measures varies from slight improvement with small effect size to statistically significant improvement with large effect size. The result indicates that short multicomponent GCBT is effective in alleviating various common psychological problems in Indonesian older adults. Therefore, multicomponent GCBT may be a good starting point to develop an effective and affordable psychological therapy for Indonesian older adults. Lastly, this result adds to the accumulating body of evidence on the effectiveness of multicomponent GCBT outside western context. PMID:23437339

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

PubMed

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

ReNeuron Group plc.

PubMed

Sinden, John D

2006-01-01

ReNeuron is a UK-based pioneer in stem cell research and development. The Company has leading edge, proprietary somatic stem cell technologies from which it is developing groundbreaking cell therapy products. ReNeuron's focus is on cell therapy treatments designed to reverse the effects of major diseases such as stroke, diabetes and diseases of the eye.

Development of a New Psychosocial Treatment for Adult ADHD

ERIC Educational Resources Information Center

Solanto, Mary V.; Marks, David J.; Mitchell, Katherine J.; Wasserstein, Jeanette; Kofman, Michele D.

2008-01-01

Objective: The purpose of this study was to assess the effectiveness of a new manualized group Meta-Cognitive Therapy (MCT) for adults with ADHD that extends the principles and practices of cognitive-behavioral therapy to the development of executive self-management skills. Method: Thirty adults diagnosed with ADHD completed an 8- or 12-week…

Is fibroblast growth factor receptor 4 a suitable target of cancer therapy?

PubMed

Heinzle, Christine; Erdem, Zeynep; Paur, Jakob; Grasl-Kraupp, Bettina; Holzmann, Klaus; Grusch, Michael; Berger, Walter; Marian, Brigitte

2014-01-01

Fibroblast growth factors (FGF) and their tyrosine kinase receptors (FGFR) support cell proliferation, survival and migration during embryonic development, organogenesis and tissue maintenance and their deregulation is frequently observed in cancer development and progression. Consequently, increasing efforts are focusing on the development of strategies to target FGF/FGFR signaling for cancer therapy. Among the FGFRs the family member FGFR4 is least well understood and differs from FGFRs1-3 in several aspects. Importantly, FGFR4 deletion does not lead to an embryonic lethal phenotype suggesting the possibility that its inhibition in cancer therapy might not cause grave adverse effects. In addition, the FGFR4 kinase domain differs sufficiently from those of FGFRs1-3 to permit development of highly specific inhibitors. The oncogenic impact of FGFR4, however, is not undisputed, as the FGFR4-mediated hormonal effects of several FGF ligands may also constitute a tissue-protective tumor suppressor activity especially in the liver. Therefore it is the purpose of this review to summarize all relevant aspects of FGFR4 physiology and pathophysiology and discuss the options of targeting this receptor for cancer therapy.

Nanoparticles for Retinal Gene Therapy

PubMed Central

Conley, Shannon M.; Naash, Muna I.

2010-01-01

Ocular gene therapy is becoming a well-established field. Viral gene therapies for the treatment of Leber’s congentinal amaurosis (LCA) are in clinical trials, and many other gene therapy approaches are being rapidly developed for application to diverse ophthalmic pathologies. Of late, development of non-viral gene therapies has been an area of intense focus and one technology, polymer-compacted DNA nanoparticles, is especially promising. However, development of pharmaceutically and clinically viable therapeutics depends not only on having an effective and safe vector but also on a practical treatment strategy. Inherited retinal pathologies are caused by mutations in over 220 genes, some of which contain over 200 individual disease-causing mutations, which are individually very rare. This review will focus on both the progress and future of nanoparticles and also on what will be required to make them relevant ocular pharmaceutics. PMID:20452457

[Adoptive Cell Therapy with Immune Checkpoint Blockade].

PubMed

Aruga, Atsushi

2017-09-01

Cancer immunotherapy are taking a leading role of cancer therapy due to the development of the immune checkpoint blockade. To date, however, only about 20% of patients have clinical responses and the cancer-specific T cells in cancer site are required to obtain beneficial effects. There has been an innovative development in the field of adoptive cell therapy, especially receptor gene-modified T cells in recent years. The effector cells mostly express PD-1, therefore the cytotoxic reactivity of the effector cells are inhibited by PD-L1. The combination of the adoptive cell therapy and the immune checkpoint blockade is expected to enhance efficacy. On the other hand, the immune-related adverse events may also be enhanced, therefore, it is needed to develop the combination therapy carefully, improving the cancer antigen-specificity or dealing with the cytokine release syndrome.

Postictal ventricular tachycardia after electroconvulsive therapy treatment associated with a lithium-duloxetine combination.

PubMed

Heinz, Boeker; Lorenzo, Perniola; Markus, Risch; Holger, Himmighoffen; Beatrix, Roemer; Erich, Seifritz; Alain, Borgeat

2013-09-01

This report addresses the dilemma of continuing lithium prophylaxis and antidepressant therapy in view of cardiovascular adverse effects under electroconvulsive therapy (ECT) in patients with a long history of recurrent affective disorders. A severely depressed 48-year-old woman who had been treated with lithium for 18 years developed a ventricular tachycardia during ECT. Possible interaction with succinylcholine was taken into account, and rocuronium was used as an alternative muscle relaxant. Electroconvulsive therapy was continued without adverse effects after reduction of lithium and withdrawal from duloxetine. Systemic studies on cardiac adverse effects of serotonin and norepinephrine reuptake inhibitors and serotonin and norepinephrine reuptake inhibitor-lithium combinations during ECT are needed.

New and emerging therapies for acute and chronic graft versus host disease

PubMed Central

Hill, LaQuisa; Alousi, Amin; Kebriaei, Partow; Mehta, Rohtesh; Rezvani, Katayoun; Shpall, Elizabeth

2017-01-01

Graft versus host disease (GVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem-cell transplantation (HSCT). Despite the use of prophylactic GVHD regimens, a significant proportion of transplant recipients will develop acute or chronic GVHD following HSCT. Corticosteroids are standard first-line therapy, but are only effective in roughly half of all cases with ~50% of patients going on to develop steroid-refractory disease, which increases the risk of nonrelapse mortality. While progress has been made with improvements in survival outcomes over time, corticosteroids are associated with significant toxicities, and many currently available salvage therapies are associated with increased immunosuppression, infectious complications, and potential loss of the graft versus leukemia (GVL) effect. Thus, there is an unmet need for development of newer treatment strategies for both acute and chronic GVHD to improve long-term post-transplant outcomes and quality of life for HSCT recipients. Here, we provide a concise review of major emerging therapies currently being studied in the treatment of acute and chronic GVHD. PMID:29317998

Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy

PubMed Central

Key, Jaehong; Park, Kyeongsoon

2017-01-01

Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies. PMID:28282891

Evidence-based therapies for upper extremity dysfunction.

PubMed

Liepert, Joachim

2010-12-01

The diversity of interventions aimed at improving upper extremity dysfunction is increasing. This article reviews the effectiveness of different therapeutic approaches that have been published in 2009 and 2010. Evidence is based on randomized controlled trials, systematic reviews, and meta-analyses. Application of constraint-induced movement therapy in acute stroke patients was not more effective than a control intervention, and a more intense therapy may even be harmful. Botulinum toxin injections do not only reduce spasticity but, in children, also improve motor functions if combined with occupational therapy. Strength training improves arm function but not necessarily activities of daily living. Bilateral arm training is as effective as other interventions. Extrinsic feedback and sensory training may further improve motor functions. Mirror therapy was particularly effective for patients with initial hand plegia. For some interventions (e.g. constraint-induced movement therapy, botulinum toxin), efficacy is evident, for others (e.g. mental practice, virtual reality), well designed studies with sufficient numbers of patients are needed. The ultimate goal still is to develop evidence-based therapies for all different degrees of motor impairment.

Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy?

PubMed

Jinnah, H A; Comella, Cynthia L; Perlmutter, Joel; Lungu, Codrin; Hallett, Mark

2018-06-01

Numerous studies have established botulinum toxin (BoNT) to be safe and effective for the treatment of cervical dystonia (CD). Despite its well-documented efficacy, there has been growing awareness that a significant proportion of CD patients discontinue therapy. The reasons for discontinuation are only partly understood. This summary describes longitudinal studies that provided information regarding the proportions of patients discontinuing BoNT therapy, and the reasons for discontinuing therapy. The data come predominantly from un-blinded long-term follow-up studies, registry studies, and patient-based surveys. All types of longitudinal studies provide strong evidence that BoNT is both safe and effective in the treatment of CD for many years. Overall, approximately one third of CD patients discontinue BoNT. The most common reason for discontinuing therapy is lack of benefit, often described as primary or secondary non-response. The apparent lack of response is only rarely related to true immune-mediated resistance to BoNT. Other reasons for discontinuing include side effects, inconvenience, cost, or other reasons. Although BoNT is safe and effective in the treatment of the majority of patients with CD, approximately one third discontinue. The increasing awareness of a significant proportion of patients who discontinue should encourage further efforts to optimize administration of BoNT, to improve BoNT preparations to extend duration or reduce side effects, to develop add-on therapies that may mitigate swings in symptom severity, or develop entirely novel treatment approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

Play Therapy: Practice, Issues, and Trends

ERIC Educational Resources Information Center

Homeyer, Linda E.; Morrison, Mary O.

2008-01-01

Play therapy is an effective means of responding to the mental health needs of young children and is widely accepted as a valuable and developmentally appropriate intervention. The authors discuss the importance of play in development, the therapeutic benefits of play, the rich history of play therapy, and recent research and current issues and…

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

PubMed

Tsalik, Ephraim L; Li, Yanhong; Hudson, Lori L; Chu, Vivian H; Himmel, Tiffany; Limkakeng, Alex T; Katz, Jason N; Glickman, Seth W; McClain, Micah T; Welty-Wolf, Karen E; Fowler, Vance G; Ginsburg, Geoffrey S; Woods, Christopher W; Reed, Shelby D

2016-03-01

Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved. Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development.

Gene therapy on the move

PubMed Central

Kaufmann, Kerstin B; Büning, Hildegard; Galy, Anne; Schambach, Axel; Grez, Manuel

2013-01-01

The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. PMID:24106209

Enzymes approved for human therapy: indications, mechanisms and adverse effects.

PubMed

Baldo, Brian A

2015-02-01

Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies.

PubMed

Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Bubeck Wardenburg, Juliane; Fortenberry, James; Zajicek, Anne; Mairson, Emma; Typpo, Katri

2017-03-01

To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

The Effects of Mitiglinide and Repaglinide on Postprandial Hyperglycemia in Patients Undergoing Methylprednisolone Pulse Therapy.

PubMed

Tanaka, Kenichi; Okada, Yosuke; Mori, Hiroko; Torimoto, Keiichi; Arao, Tadashi; Tanaka, Yoshiya

2018-01-01

One adverse effect of methylprednisolone (MP) pulse therapy is an acute dose-dependent increase in the blood glucose level. Five patients with thyroid ophthalmopathy but normal glucose tolerance received MP pulse therapy (3 cycles, 3 days/week) and were assessed by continuous glucose monitoring. Steroid therapy increased the mean sensor glucose level, and all patients developed steroid-induced diabetes. The patients were treated alternately with mitiglinide (30 mg/day) and repaglinide (1.5 mg/day) during the second or third MP pulse therapy. The sensor glucose levels before lunch and dinner were more favorable during treatment with repaglinide than during treatment with mitiglinide. Repaglinide may be more clinically appropriate than mitiglinide.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

PubMed Central

Amengual, Julià L.; Rojo, Nuria; Veciana de las Heras, Misericordia; Marco-Pallarés, Josep; Grau-Sánchez, Jennifer; Schneider, Sabine; Vaquero, Lucía; Juncadella, Montserrat; Montero, Jordi; Mohammadi, Bahram; Rubio, Francisco; Rueda, Nohora; Duarte, Esther; Grau, Carles; Altenmüller, Eckart; Münte, Thomas F.; Rodríguez-Fornells, Antoni

2013-01-01

Background Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. Methods and Results In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. Conclusion Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations. PMID:23613966

Modelling Ebola virus dynamics: Implications for therapy.

PubMed

Martyushev, Alexey; Nakaoka, Shinji; Sato, Kei; Noda, Takeshi; Iwami, Shingo

2016-11-01

Ebola virus (EBOV) causes a severe, often fatal Ebola virus disease (EVD), for which no approved antivirals exist. Recently, some promising anti-EBOV drugs, which are experimentally potent in animal models, have been developed. However, because the quantitative dynamics of EBOV replication in humans is uncertain, it remains unclear how much antiviral suppression of viral replication affects EVD outcome in patients. Here, we developed a novel mathematical model to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and evaluated the effects of different antivirals. We found that nucleoside analogue- and siRNA-based therapies are effective if a therapy with a >50% inhibition rate is initiated within a few days post-symptom-onset. In contrast, antibody-based therapy requires not only a higher inhibition rate but also an earlier administration, especially for otherwise fatal cases. Our results demonstrate that an appropriate choice of EBOV-specific drugs is required for effective EVD treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel nonstatin strategies to lower low-density lipoprotein cholesterol.

PubMed

Davidson, Michael H

2009-01-01

There remains an unmet need to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients who are maximized on current therapy or intolerant to statins. Several novel agents have been developed to lower LDL-C, either as monotherapy or in combination with statins. These novel therapies include squalene synthase inhibitors, microsomal triglyceride transfer protein inhibitors, and antisense apolipoprotein B. Although each of these novel therapies effectively lowers LDL-C, challenges remain in the clinical development to assess long-term safety.

Patient-reported outcomes to support medical product labeling claims: FDA perspective.

PubMed

Patrick, Donald L; Burke, Laurie B; Powers, John H; Scott, Jane A; Rock, Edwin P; Dawisha, Sahar; O'Neill, Robert; Kennedy, Dianne L

2007-01-01

This article concerns development and use of patient-reported outcomes (PROs) in clinical trials to evaluate medical products. A PRO is any report coming directly from patients, without interpretation by physicians or others, about how they function or feel in relation to a health condition and its therapy. PRO instruments are used to measure these patient reports. PROs provide a unique perspective on medical therapy, because some effects of a health condition and its therapy are known only to patients. Properly developed and evaluated PRO instruments also have the potential to provide more sensitive and specific measurements of the effects of medical therapies, thereby increasing the efficiency of clinical trials that attempt to measure the meaningful treatment benefits of those therapies. Poorly developed and evaluated instruments may provide misleading conclusions or data that cannot be used to support product labeling claims. We review selected major challenges from Food and Drug Administration's perspective in using PRO instruments, measures, and end points to support treatment benefit claims in product labeling. These challenges highlight the need for sponsors to formulate desired labeling claim(s) prospectively, to acquire and document information needed to support these claim(s), and to identify existing instruments or develop new and more appropriate PRO instruments for evaluating treatment benefit in the defined population in which they will seek claims.

Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma.

PubMed

Reddy, Swathi B; Possick, Jennifer D; Kluger, Harriet M; Galan, Anjela; Han, Dale

2017-10-01

Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis. Of note, both patients developed sarcoidosis only after undergoing immune checkpoint inhibitor therapy. In 1 patient, sarcoidosis developed after initiation of anti-PD-1 therapy, 3 months after the last dose of anti-CTLA-4 monotherapy, suggesting a synergistic immune dysmodulating effect of both checkpoint inhibitors. Ultimately, both patients' symptoms and radiologic findings resolved with corticosteroid treatment, and both patients have tolerated retreatment with PD-1 inhibitors. Sarcoidosis is a rare complication of immune checkpoint inhibitors and can manifest with severe pulmonary manifestations. However, sarcoidosis in this setting is responsive to corticosteroids and does not necessarily recur with retreatment. It is yet unclear whether the development of sarcoidosis in these patients represents unmasking of preexisting autoimmune tendencies or is a marker of oncologic response.

Religiously Integrated Cognitive Behavioral Therapy: A New Method of Treatment for Major Depression in Patients With Chronic Medical Illness

PubMed Central

Pearce, Michelle J.; Koenig, Harold G.; Robins, Clive J.; Nelson, Bruce; Shaw, Sally F.; Cohen, Harvey J.; King, Michael B.

2015-01-01

Intervention studies have found that psychotherapeutic interventions that explicitly integrate clients’ spiritual and religious beliefs in therapy are as effective, if not more so, in reducing depression than those that do not for religious clients. However, few empirical studies have examined the effectiveness of religiously (vs. spiritually) integrated psychotherapy, and no manualized mental health intervention had been developed for the medically ill with religious beliefs. To address this gap, we developed and implemented a novel religiously integrated adaptation of cognitive–behavioral therapy (CBT) for the treatment of depression in individuals with chronic medical illness. This article describes the development and implementation of the intervention. First, we provide a brief overview of CBT. Next, we describe how religious beliefs and behaviors can be integrated into a CBT framework. Finally, we describe Religiously Integrated Cognitive Behavioral Therapy (RCBT), a manualized therapeutic approach designed to assist depressed individuals to develop depression-reducing thoughts and behaviors informed by their own religious beliefs, practices, and resources. This treatment approach has been developed for 5 major world religions (Christianity, Judaism, Islam, Buddhism, and Hinduism), increasing its potential to aid the depressed medically ill from a variety of religious backgrounds. PMID:25365155

Effects of a dyadic music therapy intervention on parent-child interaction, parent stress, and parent-child relationship in families with emotionally neglected children: a randomized controlled trial.

PubMed

Jacobsen, Stine L; McKinney, Cathy H; Holck, Ulla

2014-01-01

Work with families and families at risk within the field of music therapy have been developing for the last decade. To diminish risk for unhealthy child development, families with emotionally neglected children need help to improve their emotional communication and develop healthy parent-child interactions. While some researchers have investigated the effect of music therapy on either the parent or the child, no study has investigated the effect of music therapy on the observed interaction between the parent and child within the field of child protection. The purpose of this study was to investigate the effect of a dyadic music therapy intervention on observed parent-child interaction (mutual attunement, nonverbal communication, emotional parental response), self-reported parenting stress, and self-reported parent-child relationship in families at risk and families with emotionally neglected children, ages 5-12 years. This was a randomized controlled trial study conducted at a family care center in Denmark. Eighteen parent-child dyads were randomly assigned to receive 10 weekly music therapy sessions with a credentialed music therapist (n = 9) or treatment as usual (n = 9). Observational measures for parent-child interaction, self-reported measures for parenting stress and parent-child relationship were completed at baseline and 4 months post-baseline assessment. Results of the study showed that dyads who received music therapy intervention significantly improved their nonverbal communication and mutual attunement. Similarly, parents who participated in dyadic music therapy reported themselves to be significantly less stressed by the mood of the child and to significantly improve their parent-child relationship in terms of being better at talking to and understanding their children than parents who did not receive music therapy. Both groups significantly improved in terms of increased positive and decreased negative emotional parental response, parenting stress and stress in general. There were no significant between group differences in self-perceived autonomy, attachment, and parental competence. The dyadic music therapy intervention examined in this study improved emotional communication between parent and child and interaction after 6 to 10 sessions and can be considered as a viable treatment alternative or supplement for families at risk and families with emotionally neglected children. © the American Music Therapy Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hemorrhagic thoracic schwannoma presenting with intradural hematoma and acute paraplegia after spinal manipulation therapy.

PubMed

Hdeib, Alia; Goodwin, C Rory; Sciubba, Daniel; Bydon, Ali; Wolinsky, Jean-Paul; Witham, Timothy; Gokaslan, Ziya L

2016-01-01

Hemorrhagic conversion of spinal schwannomas represents a rare occurrence; also rare is the development of a spinal intradural hematoma after spinal manipulation therapy. We report a unique presentation of paraplegia in a patient who underwent spinal manipulation therapy and was found to have a hemorrhagic thoracic schwannoma at time of surgery in the setting of anti-platelet therapy use. In patients with spinal schwannomas, tumor hemorrhage is a rare occasion, which can be considered in the setting of additive effects of spinal manipulation therapy and antiplatelet therapy.

Long-term use of short- and long-acting nitrates in stable angina pectoris.

PubMed

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

Group Cognitive-Behavioral Therapy for Insomnia in a VA Mental Health Clinic

ERIC Educational Resources Information Center

Perlman, Lawrence M.; Arnedt, J. Todd; Earnheart, Kristie L.; Gorman, Ashley A.; Shirley, Katherine G.

2008-01-01

Effective cognitive-behavioral therapies for insomnia have been developed over the past 2 decades, but they have not been systematically evaluated in some clinical settings. While insomnia is common among veterans with mental health problems, the availability of effective treatments is limited. We report on the group application of a…

Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies

PubMed Central

Thaker, Nikhil G; Pollack, Ian F

2010-01-01

Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient’s tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG. PMID:19951140

Multifunctional Inorganic Nanoparticles: Recent Progress in Thermal Therapy and Imaging

PubMed Central

Cherukula, Kondareddy; Manickavasagam Lekshmi, Kamali; Uthaman, Saji; Cho, Kihyun; Cho, Chong-Su; Park, In-Kyu

2016-01-01

Nanotechnology has enabled the development of many alternative anti-cancer approaches, such as thermal therapies, which cause minimal damage to healthy cells. Current challenges in cancer treatment are the identification of the diseased area and its efficient treatment without generating many side effects. Image-guided therapies can be a useful tool to diagnose and treat the diseased tissue and they offer therapy and imaging using a single nanostructure. The present review mainly focuses on recent advances in the field of thermal therapy and imaging integrated with multifunctional inorganic nanoparticles. The main heating sources for heat-induced therapies are the surface plasmon resonance (SPR) in the near infrared region and alternating magnetic fields (AMFs). The different families of inorganic nanoparticles employed for SPR- and AMF-based thermal therapies and imaging are described. Furthermore, inorganic nanomaterials developed for multimodal therapies with different and multi-imaging modalities are presented in detail. Finally, relevant clinical perspectives and the future scope of inorganic nanoparticles in image-guided therapies are discussed. PMID:28335204

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

PubMed Central

Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

2013-01-01

Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

Biological effects and medical applications of infrared radiation

PubMed Central

Tsai, Shang-Ru; Hamblin, Michael R

2017-01-01

Infrared (IR) radiation is electromagnetic radiation with wavelengths between 760 nm and 100,000 nm. Low-level light therapy (LLLT) or photobiomodulation (PBM) therapy generally employs light at red and near-infrared wavelengths (600–100 nm) to modulate biological activity. Many factors, conditions, and parameters influence the therapeutic effects of IR, including fluence, irradiance, treatment timing and repetition, pulsing, and wavelength. Increasing evidence suggests that IR can carry out photostimulation and photobiomodulation effects particularly benefiting neural stimulation, wound healing, and cancer treatment. Nerve cells respond particularly well to IR, which has been proposed for a range of neurostimulation and neuromodulation applications, and recent progress in neural stimulation and regeneration are discussed in this review. The applications of IR therapy have moved on rapidly in recent years. For example, IR therapy has been developed that does not actually require an external power source, such as IR-emitting materials, and garments that can be powered by body heat alone. Another area of interest is the possible involvement of solar IR radiation in photoaging or photorejuvenation as opposites sides of the coin, and whether sunscreens should protect against solar IR? A better understanding of new developments and biological implications of IR could help us to improve therapeutic effectiveness or develop new methods of PBM using IR wavelengths. PMID:28441605

Biological effects and medical applications of infrared radiation.

PubMed

Tsai, Shang-Ru; Hamblin, Michael R

2017-05-01

Infrared (IR) radiation is electromagnetic radiation with wavelengths between 760nm and 100,000nm. Low-level light therapy (LLLT) or photobiomodulation (PBM) therapy generally employs light at red and near-infrared wavelengths (600-100nm) to modulate biological activity. Many factors, conditions, and parameters influence the therapeutic effects of IR, including fluence, irradiance, treatment timing and repetition, pulsing, and wavelength. Increasing evidence suggests that IR can carry out photostimulation and photobiomodulation effects particularly benefiting neural stimulation, wound healing, and cancer treatment. Nerve cells respond particularly well to IR, which has been proposed for a range of neurostimulation and neuromodulation applications, and recent progress in neural stimulation and regeneration are discussed in this review. The applications of IR therapy have moved on rapidly in recent years. For example, IR therapy has been developed that does not actually require an external power source, such as IR-emitting materials, and garments that can be powered by body heat alone. Another area of interest is the possible involvement of solar IR radiation in photoaging or photorejuvenation as opposites sides of the coin, and whether sunscreens should protect against solar IR? A better understanding of new developments and biological implications of IR could help us to improve therapeutic effectiveness or develop new methods of PBM using IR wavelengths. Copyright © 2016. Published by Elsevier B.V.

Is Parenteral Levothyroxine Therapy Safe in Intractable Hypothyroidism?

PubMed

Peynirci, Hande; Taskiran, Bengur; Erturk, Erdinc; Sisman, Pınar; Ersoy, Canan

2018-06-01

A 32-year old woman was admitted to the hospital due to intractable hypothyroidism refractory to high dose of oral l-thyroxine therapy. She underwent total thyroidectomy and radioactive iodine therapy due to papillary thyroid cancer. After excluding poor adherence to therapy and malabsorption, levothyroxine absorption test was performed. No response was detected. Transient neurologic symptoms developed during the test. She developed 3 attacks consisting of neurologic symptoms during high dose administration. The patient was considered a case of isolated l-thyroxine malabsorption. She became euthyroid after intramuscular twice weekly l-thyroxine therapy. There are a few case reports regarding isolated l-thyroxine. We report successful long term results of twice weekly administered intramuscular l-thyroxine therapy. We also draw attention to neurologic side effects of high dose l-thyroxine therapy. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

Uncommon strategies for a common problem: addressing racism in family therapy.

PubMed

Laszloffy, T A; Hardy, K V

2000-01-01

Race and racism have a profound effect on our daily lives and the practice of family therapy. Whether individual or institutional level, overt or covert, intentional or unintentional, there are a variety of ways in which racism can infiltrate the therapeutic process. Before therapists can take steps to address racism effectively within the context of family therapy, it is important to attend to the development of their racial awareness and racial sensitivity. These provide the critical foundation upon which specific skills and strategies associated with effectively identifying and responding to racism in therapy are based. This article defines racial awareness and sensitivity and provides suggestions for enhancing both. In the section that follows, three major ways in which racism can infiltrate the therapeutic process are described. Skills and strategies for addressing each of these in family therapy are presented.

[Tranylcypromine for chronic therapy-resistant agoraphobia with panic disorder and recurrent depressive disorder].

PubMed

Boerner, Reinhard J; Lühring, Frauke

2010-10-01

Tranylcypromine has been recommend as an option for therapy-resistant depressive and anxiety disorders. In this case report the effectiveness of this medication as a part of a combined therapy-program including pharmacological, behavioural and psychodynamic interventions could be demonstrated on an outpatient with a therapy-resistant depression and agoraphobia. The development of the illness, clinical symptoms and the 4 year ongoing therapy of a 69-year old patient are described in detail. After the failure of 13 antidepressant agents with considerable side effects, a one year sustained remission of depression as well as great improvement of agoraphobia could be achieved with tranylcypromine. In this situation, tranylcypromine showed itself, for the first time, to be a very effective and well tolerated antidepressant. © Georg Thieme Verlag KG Stuttgart · New York.

Experimental therapies for yellow fever

PubMed Central

Julander, Justin G.

2013-01-01

A number of viruses in the family Flaviviridae are the focus of efforts to develop effective antiviral therapies. Success has been achieved with inhibitors for the treatment of hepatitis C, and there is interest in clinical trials of drugs against dengue fever. Antiviral therapies have also been evaluated in patients with Japanese encephalitis and West Nile encephalitis. However, no treatment has been developed against the prototype flavivirus, yellow fever virus (YFV). Despite the availability of the live, attenuated 17D vaccine, thousands of cases of YF continue to occur each year in Africa and South America, with a significant mortality rate. In addition, a small number of vaccinees develop severe systemic infections with the 17D virus. This paper reviews current efforts to develop antiviral therapies, either directly targeting the virus or blocking detrimental host responses to infection. PMID:23237991

[Effect of interferon and ribavirin combination therapy in sixty-two patients with chronic hepatitis C originating from a single blood donor].

PubMed

Liu, San-du; Cheng, Ming-liang; Ren, Hong; Yang, Qing-kun; Shu, De-yun

2012-08-01

To investigate the efficacy of interferon alpha 2 b plus ribavirin combination therapy in sixty-two patients with chronic hepatitis c (CHC) infection originating from a single blood donor. The 62 patients who developed CHC following blood transfusion from a known single infected donor were treated with interferon and ribavirin combination therapy for 48 weeks and followed-up for 96 weeks. The therapy regimen consisted of subcutaneous administration of 3-500 MIU interferon alpha 2 b every other day and daily oral administration of 0.6-1.0 g of ribavirin. Patients were monitored during treatment and in follow-up for sustained virological response (SVR), early virology response (EVR), treatment end virology response (ETVR), biochemical response of withdrawals, and side effects. The SVR rate was 83.9% (52/62). The EVR rate was 95.2% (59/62). The ETVR rate was 87.1% (54/62). The biochemical response rate after withdrawal of treatment was 100.0%. Eight patients developed mildly abnormal thyroid function as a result of the interferon therapy, but all were able to complete the antiviral treatment regimen under the care of endocrinologists. Younger age, relatively short course of disease, low viral load, and better compliance, but not sex, were correlated to curative effect of the combination therapy. Interferon alpha 2 b plus ribavirin combination therapy had a significant curative effect on a group of 62 CHC patients originating from a single case, with 52 of the patients showing SVR out to 96 weeks after therapy. Antiviral treatment is recommended for hepatitis C virus-positive patients to eradicate the virus and prevent disease progression.

Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

PubMed

Han, Ji Won; Lee, Hyeonggon; Hong, Jong Woo; Kim, Kayoung; Kim, Taehyun; Byun, Hye Jin; Ko, Ji Won; Youn, Jong Chul; Ryu, Seung-Ho; Lee, Nam-Jin; Pae, Chi-Un; Kim, Ki Woong

2017-01-01

We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did.

Assessing the Treatment Effects in Apraxia of Speech: Introduction and Evaluation of the Modified Diadochokinesis Test

ERIC Educational Resources Information Center

Hurkmans, Joost; Jonkers, Roel; Boonstra, Anne M.; Stewart, Roy E.; Reinders-Messelink, Heleen A.

2012-01-01

Background: The number of reliable and valid instruments to measure the effects of therapy in apraxia of speech (AoS) is limited. Aims: To evaluate the newly developed Modified Diadochokinesis Test (MDT), which is a task to assess the effects of rate and rhythm therapies for AoS in a multiple baseline across behaviours design. Methods: The…

Acid suppression and surgical therapy for Barrett's oesophagus.

PubMed

de Jonge, Pieter J F; Spaander, Manon C; Bruno, Marco J; Kuipers, Ernst J

2015-02-01

Gastro-oesophageal reflux disease is a common medical problem in developed countries, and is a risk factor for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Both proton pump inhibitor therapy and antireflux surgery are effective at controlling endoscopic signs and symptoms of gastro-oesophageal reflux in patients with Barrett's oesophagus, but often fail to eliminate pathological oesophageal acid exposure. The current available studies strongly suggest that acid suppressive therapy, both pharmacological as well as surgical acid suppression, can reduce the risk the development and progression in patients with Barrett's oesophagus, but are not capable of complete prevention. No significant differences have been found between pharmacological and surgical therapy. For clinical practice, patients should be prescribed a proton pump inhibitor once daily as maintenance therapy, with the dose guided by symptoms. Antireflux surgery can be a good alternative to proton pump inhibitor therapy, but should be primarily offered to patients with symptomatic reflux, and not to asymptomatic patients with the rationale to protect against cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimizing the use of antithrombotic therapy for atrial fibrillation in older people: a pharmacist-led multidisciplinary intervention.

PubMed

Bajorek, Beata V; Krass, Ines; Ogle, Susan J; Duguid, Margaret J; Shenfield, Gillian M

2005-11-01

To develop, implement, and evaluate a pharmacist-led multidisciplinary intervention in a hospital setting that would optimize antithrombotic use in elderly atrial fibrillation patients. The hypothesis that there would be an increase in the proportion of patients receiving antithrombotic therapy at discharge was tested. Evidence-based algorithms were developed to define the criteria (stroke risk vs contraindications) by which an elderly patient's requirement for antithrombotic therapy was assessed. A major Sydney teaching hospital. Two hundred eighteen consecutively admitted elderly patients (mean age 85.2) were recruited over a 6-month period. A pharmacist-coordinated multidisciplinary review process was implemented to coordinate risk assessments and subsequently recommend appropriate antithrombotic therapy, as per the algorithms. The proportion of patients receiving antithrombotic therapy was assessed on admission (preintervention), at discharge (postintervention), and postdischarge (follow-up at 3 and 6 months). As a result of the intervention, 78 patients (35.8%) required changes to their existing antithrombotic therapy. Of these changes, 60 (76.9%) were "upgrades" to more-effective treatment options (e.g., from no therapy to any agent or from aspirin to warfarin). The remaining 18 (23.1%) changes were "downgrades" to less-effective, albeit safer, options. Despite a significant increase in anti thrombotic use overall (59.6% vs 81.2%, P<.001), fewer patients received warfarin postintervention, after having been assessed as inappropriate candidates (20.7% vs 17.4%, P=.39). A pharmacist-led multidisciplinary process was successfully developed and implemented within the hospital setting to increase overall antithrombotic use. Having addressed some of the known barriers and limitations to warfarin use, these algorithms may allow allied health workers, patients, and clinicians to work collaboratively to achieve optimal and, importantly, appropriate (i.e., safe and effective) antithrombotic use in at-risk elderly patients.

The effects of vestibular stimulation on a child with hypotonic cerebral palsy

PubMed Central

An, Sun-Joung Leigh

2015-01-01

[Purpose] The purpose of this case report is to present the effects of vestibular stimulation on a child with hypotonic cerebral palsy through the use of swings. [Case Description] The subject was a 19-month-old boy with a diagnosis of hypotonic cerebral palsy (CP) and oscillating nystagmus. The subject had received both physical therapy and occupational therapy two times per week since he was 5 months old but showed little to no improvement. [Methods] Pre and post-intervention tests were completed by the researcher using the Bayley Scales of Infant and Toddler Development II. The subject was provided with vestibular stimulation 3 times per week for 10 weeks in 1 hour sessions conducted by his mother as instructed by the researcher. During this research all other therapies were stopped to determine the effects of the vestibular stimulation and to exclude the effects of other therapies. [Results] The subject demonstrated improvement of 4 months in motor skills and of 3 months in mental skills as shown by the Bayley Scales of Infant and Toddler Development II. [Conclusion] Vestibular stimulation was effective in improving postural control, movement, emotional well-being, and social participation of a child with hypotonic cerebral palsy. PMID:25995606

Exploring alternative treatments for Helicobacter pylori infection

PubMed Central

Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma

2014-01-01

Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy. PMID:24587621

Neutron medical treatment of tumours — a survey of facilities

NASA Astrophysics Data System (ADS)

Wagner, F. M.; Loeper-Kabasakal, B.; Breitkreutz, H.

2012-03-01

Neutron therapy has two branches: Fast Neutron Therapy (FNT) and Boron Neutron Capture Therapy (BNCT). The mean neutron energies used for FNT range from 2 MeV to 25 MeV whereas the maximum energy for BNCT is about 10 keV. Neutron generators for FNT have been cyclotrons, accelerators and reactors, whereas BNCT is so far bound to reactors. Both therapies use the effects of high-LET radiation (secondary recoil protons and alpha particles, respectively) and can attack otherwise radioresistant tumours, however, with the hazard of adverse effects for irradiated healthy tissue. FNT has been administered to about 30,000 patients world-wide. From formerly 40 facilities, only eight are operational or stand-by today. The reasons for this development have been, on the one hand, related to technical and economical conditions; on the other hand, strong side effects and insufficient proof of clinical results in the early years as well as increasing competition with new clinical methods have reduced patient numbers. In fact, strict observations of indications, appropriate therapy-planning including low-LET radiation, and consequent treatment of side effects have lead to remarkable results in the meantime. BNCT initially was developed for the treatment of extremely aggressive forms of brain tumour, taking advantage of the action of the blood-brain-barrier which allows for a boronated compound to be selectively enriched in tumour cells. Meanwhile, also malignant melanoma (MM) and Head-and-Neck (H&T) tumours are treated because of their relative radioresistance. At present, epithermal beams with sufficient flux are available only at two facilities. Existing research reactors were indispensable in the development of BNCT, but are to be replaced by hospital-based epithermal neutron sources. Clinical results indicate significantly increased survival times, but the number of patients ever treated is still below 1,000. 3D-dose calculation systems have been developed at several facilities and guarantee a high safety for both therapies, FNT and BNCT.

Assessing Competencies in Couples and Family Therapy/Counseling: A Call to the Profession

ERIC Educational Resources Information Center

Perosa, Linda M.; Perosa, Sandra L.

2010-01-01

Psychometrically sound measures of family therapy competencies are necessary to assess the effectiveness of training on student performance. This article critiques the self-report and observer rating measures developed to date to assess the clinical skills of trainees in the individual and in the family therapy fields. Suggestions are made to…

Development of a center for light ion therapy and accurate tumor diagnostics at karolinska institutet and hospital

NASA Astrophysics Data System (ADS)

Brahme, Anders; Lind, Bengt K.

2002-04-01

Radiation therapy is today in a state of very rapid development with new intensity modulated treatment techniques continuously being developed. This has made intensity modulated electron and photon beams almost as powerful as conventional uniform beam proton therapy. To be able to cure also the most advanced hypoxic and radiation resistant tumors of complex local spread, intensity modulated light ion beams are really the ultimate tool and only slightly more expensive than proton therapy. The aim of the new center for ion therapy and tumor diagnostics in Stockholm is to develop radiobiologically optimized 3-dimensional pencil beam scanning techniques. Beside the "classical" approaches using low ionization density hydrogen ions (protons, but also deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be developed. In the first one lithium or beryllium ions, that induce the least detrimental biological effect to normal tissues for a given biological effect in a small volume of the tumor, will be key particles. In the second approach, referred patients will be given a high-dose high-precision "boost" treatment with carbon or oxygen ions during one week preceding the final treatment with conventional radiations in the referring hospital. The rationale behind these approaches is to reduce the high ionization density dose to the normal tissue stroma inside the tumor and to ensure a microscopically uniform dose delivery. The principal idea of the center is to closely integrate ion therapy into the clinical routine and research of a large radiotherapy department. The light ion therapy center will therefore be combined with advanced tumor diagnostics including MR and PET-CT imaging to facilitate efficient high-precision high-dose boost treatment of remitted patients. The possibility to do 3D tumor diagnostics and 3D dose delivery verification with the same PET camera will be the ultimate step in high quality adaptive radiation therapy where alterations in the delivered dose can be corrected by subsequent treatments

Image-guided therapies for myocardial repair: concepts and practical implementation

PubMed Central

Bengel, Frank M.; George, Richard T.; Schuleri, Karl H.; Lardo, Albert C.; Wollert, Kai C.

2013-01-01

Cell- and molecule-based therapeutic strategies to support wound healing and regeneration after myocardial infarction (MI) are under development. These emerging therapies aim at sustained preservation of ventricular function by enhancing tissue repair after myocardial ischaemia and reperfusion. Such therapies will benefit from guidance with regard to timing, regional targeting, suitable candidate selection, and effectiveness monitoring. Such guidance is effectively obtained by non-invasive tomographic imaging. Infarct size, tissue characteristics, muscle mass, and chamber geometry can be determined by magnetic resonance imaging and computed tomography. Radionuclide imaging can be used for the tracking of therapeutic agents and for the interrogation of molecular mechanisms such as inflammation, angiogenesis, and extracellular matrix activation. This review article portrays the hypothesis that an integrated approach with an early implementation of structural and molecular tomographic imaging in the development of novel therapies will provide a framework for achieving the goal of improved tissue repair after MI. PMID:23720377

Lineage plasticity-mediated therapy resistance in prostate cancer.

PubMed

Blee, Alexandra M; Huang, Haojie

2018-06-12

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

[Achievements and enlightenment of modern acupuncture therapy for stroke based on the neuroanatomy].

PubMed

Chen, Li-Fang; Fang, Jian-Qiao; Chen, Lu-Ni; Wang, Chao

2014-04-01

Up to now, in the treatment of stroke patients by acupuncture therapy, three main representative achievements involving scalp acupuncture intervention, "Xing Nao Kai Qiao" (restoring consciousness and inducing resuscitation) acupuncture technique and nape acupuncture therapy have been got. Regarding their neurobiological mechanisms, the scalp acupuncture therapy is based on the functional localization of the cerebral cortex, "Xing Nao Kai Qiao" acupuncture therapy is closely related to nerve stem stimulation, and the nape acupuncture therapy is based on the nerve innervation of the regional neck-nape area in obtaining therapeutic effects. In fact, effects of these three acupuncture interventions are all closely associated with the modern neuroanatomy. In the treatment of post-stroke spastic paralysis, cognitive disorder and depression with acupuncture therapy, modern neuroanatomical knowledge should be one of the key theoretical basis and new therapeutic techniques should be explored and developed continuously.

HIV Therapy Simulator: a graphical user interface for comparing the effectiveness of novel therapy regimens.

PubMed

Lim, Huat Chye; Curlin, Marcel E; Mittler, John E

2011-11-01

Computer simulation models can be useful in exploring the efficacy of HIV therapy regimens in preventing the evolution of drug-resistant viruses. Current modeling programs, however, were designed by researchers with expertise in computational biology, limiting their accessibility to those who might lack such a background. We have developed a user-friendly graphical program, HIV Therapy Simulator (HIVSIM), that is accessible to non-technical users. The program allows clinicians and researchers to explore the effectiveness of various therapeutic strategies, such as structured treatment interruptions, booster therapies and induction-maintenance therapies. We anticipate that HIVSIM will be useful for evaluating novel drug-based treatment concepts in clinical research, and as an educational tool. HIV Therapy Simulator is freely available for Mac OS and Windows at http://sites.google.com/site/hivsimulator/. jmittler@uw.edu. Supplementary data are available at Bioinformatics online.

Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients.

PubMed

Kelly, J; Hurley, D; Raghu, G

2000-04-01

CMV disease remains a major complication of lung transplantation and attempts to prevent it have met with marginal success. In a previous study we documented that universal prophylaxis did not prevent CMV disease but merely delayed it, and was very costly. We compared the efficacy and cost of pre-emptive therapy with ganciclovir, guided by CMV antigenemia, to that of historic controls that received universal prophylaxis with ganciclovir. CMV antigenemia assay was done routinely and pre-emptive therapy was initiated if greater than 25 CMV positive cells per 100,000 polymorphonuclear cells were found. Nineteen patients were enrolled; 6 of of whom received 12 courses of pre-emptive therapy. The incidence of CMV disease was 26% compared to 38% for the historical controls (p = 0.51). None of the patients that received pre-emptive therapy developed CMV disease following that therapy. Antigenemia failed to predict disease in 5 patients that developed it, and thus it is unknown if pre-emptive therapy could have prevented it. There was no mortality in either the study patients or historic controls directly related to CMV. The net savings with pre-emptive therapy was $2569 per patient. We conclude that pre-emptive therapy with ganciclovir is as safe and effective as universal prophylaxis in preventing CMV disease in lung transplant recipients, and is less expensive. The appropriate surveillance technique and timing remain to be determine to optimize the efficacy of pre-emptive therapy.

The Role of Sex Hormone Replacement Therapy on Self-Perceived Competence in Adolescents with Delayed Puberty.

ERIC Educational Resources Information Center

Schwab, Jacqueline; Kulin, Howard E.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan J.; Liben, Lyye S.; D'Arcangelo, M. Rose; Demers, Lawrence M.

2001-01-01

Examined role of sex steroids in development of self-perceived competence among adolescents receiving hormone therapy for delayed puberty. Found that hormone treatments had a significant positive effect for both males and females in perceived job competence. Significant positive effects were also obtained for perceptions of romantic appeal and…

Decreasing adverse outcomes of unmodified electroconvulsive therapy: suggestions and possibilities.

PubMed

Gallegos, Jesus; Vaidya, Punit; D'Agati, Douglas; Jayaram, Geetha; Nguyen, Thai; Tripathi, Adarsh; Trivedi, Jitendra K; Reti, Irving M

2012-06-01

Electroconvulsive therapy (ECT) is far and away the most effective treatment for depression and quite effective for a range of other psychiatric conditions that are unresponsive to medication. Electroconvulsive therapy in the developed world has been administered with anesthesia, muscle relaxants, and ventilation since the mid-1950s following 20 years of unmodified treatment. However, in much of the developing world, ECT continues to be administered unmodified because of lack of resources. We review the efficacy of unmodified compared with modified treatment. We also review the potential drawbacks of unmodified treatment including fear and anxiety, worse postictal confusion, fracture risk, and the negative effects of unmodified treatment on how ECT is perceived in the general community. Finally, we consider potential solutions in developing countries to minimize adverse outcomes of unmodified treatment by pretreating patients either with low-dose benzodiazepines or sedating, but not anesthetizing, dosages of anesthetic agents. Randomized controlled trials are necessary before either of these options could be considered an acceptable alternative to completely unmodified treatment when modified treatment is unavailable.

Helicobacter pylori and non-steroidal anti-inflammatory drugs: does infection affect the outcome of NSAID therapy?

PubMed Central

McCarthy, D. M.

1998-01-01

1. H. pylori gastritis appears to increase the likelihood of developing dyspeptic symptoms on NSAID therapy. 2. There is preliminary evidence that the histologic severity of H. pylori gastritis may be adversely affected by NSAID therapy, with a consequent increase in the risk of developing a peptic ulcer, possibly with complications. Whether this results from an effect on the inflammatory process or results from a quantitative increase in H. pylori colonization is unknown. In these respects, ASA may differ from other NSAIDs. 3. Ulcers are more likely to develop during the course of NSAID therapy in those infected with H. pylori; eradication of the infection reduces ulcer recurrence in the face of continued NSAID therapy, and it seems likely that this must reduce but not abolish the risk of GI bleeding in those using NSAIDs. Eradication also reduces the damage (and possibly risks) of low-dose aspirin therapy. 4. While H. pylori and NSAID use are independent risk factors for GI bleeding, whether or not they are interactive remains unresolved. 5. The effect of H. pylori infection on the risk of perforation during NSAID therapy, or conversely, the contribution of NSAID therapy to the risk of perforation in H. pylori-infected subjects, is also unclear at the present time. 6. Only large outcome studies of accurately diagnosed patients (with regard to H. pylori gastritis), and with much more specific detail as to the type of NSAID, dose and duration of therapy, employing only well-defined end-points, such as significant hemorrhage, perforation or death, and avoiding all surrogate markers short of these end points can hope to unravel this tangled web. PMID:10378355

Cross-linguistic transfer effects after phonologically based cognate therapy in a case of multilingual specific language impairment (SLI).

PubMed

Kambanaros, Maria; Michaelides, Michalis; Grohmann, Kleanthes K

2017-05-01

Clinicians globally recognize as exceptionally challenging the development of effective intervention practices for bi- or multilingual children with specific language impairment (SLI). Therapy in both or all of an impaired child's languages is rarely possible. An alternative is to develop treatment protocols that facilitate the transfer of therapy effects from a treated language to an untreated language. To explore whether cognates, words that share meaning and phonological features across languages, could be used to boost lexical retrieval in the context of multilingual SLI. This is dependent on exploiting the phonological information in the one, trained language as a mechanism for (phonological) language transfer to the other, untrained languages. The participant is an 8.5-year-old girl diagnosed with SLI who showed a severe naming deficit in her three spoken languages (Bulgarian, English and Greek). She received training on cognates (n = 20) using a picture-based naming task in English only, three times a week, over a 4-week period for 20 min each time. Phonological-based naming therapy was carried out using form-based strategies. There was a significant improvement during therapy and immediately after intervention on cognate performance in English which was maintained 1 month after intervention. Cognate production in Bulgarian and Greek also improved during all stages of the intervention. Improvement in the non-treated languages was slightly more than half of the improvement recorded in English. The findings reflected some degree of cross-linguistic transfer effects. Cross-linguistic transfer effects were evident during therapy and after therapy had finished and the effects were maintained 1 month post-treatment. Both the native language (Bulgarian) and the dominant language (Greek) benefitted equally from the treatment of cognates in English. Generalization to non-treatment words was evident, predominantly for English. The results suggest that cognates can indeed be used successfully as a WFD intervention strategy for multilingual children with SLI with lasting effects. © 2016 Royal College of Speech and Language Therapists.

A Review of the Research in Emotionally Focused Therapy for Couples.

PubMed

Wiebe, Stephanie A; Johnson, Susan M

2016-09-01

Emotionally Focused Therapy for Couples (EFT) is a brief evidence-based couple therapy based in attachment theory. Since the development of EFT, efficacy and effectiveness research has accumulated to address a range of couple concerns. EFT meets or exceeds the guidelines for classification as an evidence-based couple therapy outlined for couple and family research. Furthermore, EFT researchers have examined the process of change and predictors of outcome in EFT. Future research in EFT will continue to examine the process of change in EFT and test the efficacy and effectiveness of EFT in new applications and for couples of diverse backgrounds and concerns. © 2016 Family Process Institute.

Surgical and radiological effects upon the development of speech after total laryngectomy

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

Richardson, J.L.

1981-01-01

The data presented examine the relationship between postlaryngectomy communication method, and the extent of total laryngectomy and the use of radiation therapy. The expectations of speech therapy providers were also examined. The author interviewed 60 laryngectomy patients who were six months to 3 1/2 years postsurgery. Surgeries were grouped into four categories and correlated with communication method. The relationship was statistically significant with the most apparent deterrent effect exhibited only for the most extreme surgical excisions. There was no relationship with the use of radiation therapy. In many cases speech therapy providers' expectations were not supported by the data.

Targeted therapies for the treatment of leukemia.

PubMed

Stull, Dawn Marie

2003-05-01

To review novel targeted therapies for the treatment of leukemia. Professional journals, books, and government publications. Nonspecific cytotoxic chemotherapeutic agents provide marginal therapeutic benefit and significant toxicity when used in the treatment of leukemia. There is a tremendous need for new therapies with increased efficacy and decreased adverse effects. Advances in molecular science, genetics, and immunology, along with improved laboratory technology, have led to the discovery of unique targets integral to the growth and proliferation of malignant cells which are providing the foundation for the development of a new generation of antitumor agents. Nurses must be prepared to educate patients, administer novel therapies, and manage side effects.

Safe and targeted anticancer therapy for ovarian cancer using a novel class of curcumin analogs

PubMed Central

2013-01-01

A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey for a patient. Worldwide, approximately half of the individuals undergoing therapy for advanced cancer will succumb to the disease, or consequences of treatment. Well-known and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil, and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating side effects Therefore, development of new targeted anticancer therapies that can selectively kill cancer cells while sparing the surrounding healthy tissues is essential to develop more effective therapies. We have developed a new class of synthetic curcumin analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic (anticancer) activity, whereas the N-hydroxypyrroline (-NOH) moiety found on some variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity. The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer cell lines, and the safety has been evaluated in a number of non-cancerous cell lines. Both variations of the DAP compounds showed similar levels of cell death in ovarian cancer cells, however the compounds with the -NOH modification were less toxic to non-cancerous cells. The selective cytotoxicity of the DAP–NOH compounds suggests that they will be useful as safe and effective anticancer agents. This article reviews some of the key findings of our work with the DAP compounds, and compares this to some of the targeted therapies currently used in ovarian cancer therapy. PMID:23663277

Neutropenia during High Dose Intravenous Oxacillin Therapy

PubMed Central

Ahern, Mary Jean; Hicks, Jeanne E.; Andriole, Vincent T.

1976-01-01

Five patients who developed neutropenia following intravenous administration of high dose oxacillin for serious Staphylococcus aureus infection are described. Neutropenia was reversible with cessation of intravenous oxacillin therapy. Two patients were continued on oral oxacillin without untoward effects. PMID:997595

Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

PubMed Central

Aviran, Sharon; Shah, Priya S.; Schaffer, David V.; Arkin, Adam P.

2010-01-01

Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents. PMID:20711350

Implementation of a baby doll therapy protocol for people with dementia: Innovative practice.

PubMed

Braden, Barbara A; Gaspar, Phyllis M

2015-09-01

Dementia is exhibited by both emotional and physical states such as agitation. Chemical restraints, often used for agitated behaviors, are not always effective and produce untoward effects. Baby doll therapy is a nonpharmacologic therapy that can affect agitated behavior in dementia patients, yet a protocol for the therapy did not exist. An implementation protocol for doll therapy for those with dementia was developed and implemented with 16 residents in a dementia care center. Outcomes were measurements of the impact of the dolls on six areas of the resident's behavior and their reactions to the doll. Participants had an increase in level of happiness, activity/liveliness, interaction with staff and others, and ease of giving care. There was also a reduction in the level of anxiety. The increase in happiness was a statistically significant outcome. Baby doll therapy is an effective nonpharmacological approach for improving the well-being of patients with moderate to severe dementia. © The Author(s) 2014.

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies

PubMed Central

Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Wardenburg, Juliane Bubeck; Fortenberry, James; Zajicek, Anne; Typpo, Katri

2016-01-01

Objective To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome (MODS) presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Data Sources Literature review, research data, and expert opinion. Study Selection Not applicable. Data Extraction Moderated by an expert from the field, issues relevant to the association of MODS with a variety of conditions were presented, discussed and debated with a focus on identifying knowledge gaps and research priorities. Data Synthesis Summary of presentations and discussion supported and supplemented by relevant literature. Conclusions Among critically ill children, MODS is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this manuscript, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of MODS. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anti-cytokine therapies, anti-toxin treatments, anti-oxidant approaches and multiple forms of exogenous steroids. For the field to advance, these and other therapies must be assessed in rigorous manner and implemented accordingly. PMID:28248836

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

PubMed Central

Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma.

PubMed

Cabello, I; Servitje, O; Corbella, X; Bardés, I; Pintó, X

2017-04-01

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia. To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene. From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA. Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination. Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia. © 2017 British Association of Dermatologists.

Fixed-dose combination therapy for the prevention of cardiovascular disease

PubMed Central

de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903

[Can music therapy for patients with neurological disorders?].

PubMed

Myskja, Audun

2004-12-16

Recent developments in brain research and in the field of music therapy have led to the development of music-based methods specifically aimed at relieving symptoms of Parkinson's disease and other neurologic disorders. Rhythmic auditory stimulation uses external rhythmic auditory cues from song, music or metronome to aid patients improving their walking functioning and has been shown to be effective both within sessions and as a result of training over time. Melodic intonation therapy and related vocal techniques can improve expressive dysphasia and aid rehabilitation of neurologic disorders, particularly Parkinson's disease, stroke and developmental disorders.

Is Fibroblast Growth Factor Receptor 4 a Suitable Target of Cancer Therapy?

PubMed Central

Heinzle, Christine; Erdem, Zeynep; Paur, Jakob; Grasl-Kraupp, Bettina; Holzmann, Klaus; Grusch, Michael; Berger, Walter; Marian, Brigitte

2017-01-01

Fibroblast growth factors (FGF) and their tyrosine kinase receptors (FGFR) support cell proliferation, survival and migration during embryonic development, organogenesis and tissue maintenance and their deregulation is frequently observed in cancer development and progression. Consequently, increasing efforts are focusing on the development of strategies to target FGF/FGFR signaling for cancer therapy. Among the FGFRs the family member FGFR4 is least well understood and differs from FGFRs1-3 in several aspects. Importantly, FGFR4 deletion does not lead to an embryonic lethal phenotype suggesting the possibility that its inhibition in cancer therapy might not cause grave adverse effects. In addition, the FGFR4 kinase domain differs sufficiently from those of FGFRs1-3 to permit development of highly specific inhibitors. The oncogenic impact of FGFR4, however, is not undisputed, as the FGFR4-mediated hormonal effects of several FGF ligands may also constitute a tissue-protective tumor suppressor activity especially in the liver. Therefore it is the purpose of this review to summarize all relevant aspects of FGFR4 physiology and pathophysiology and discuss the options of targeting this receptor for cancer therapy. PMID:23944363

Inhaled gene therapy in lung cancer: proof-of-concept for nano-oncology and nanobiotechnology in the management of lung cancer.

PubMed

Zarogoulidis, Paul; Darwiche, Kaid; Hohenforst-Schmidt, Wolfgang; Huang, Haidong; Li, Qiang; Freitag, Lutz; Zarogoulidis, Konstantinos

2013-08-01

Lung cancer still remains one of the leading causes of death among cancer patients. Although novel targeted therapies have been established in everyday treatment practice, and conventional platinum-based doublets have demonstrated effective results regarding overall and progression-free survival, we have still failed to achieve long-term survival. Therefore, several strategies of applying locoregional therapy are under investigation. Aerosol chemotherapy is already under investigation and, taking this a step further, aerosol gene therapies with multiple delivery systems are being developed. Several efforts have demonstrated its efficiency and effectiveness, but there are still multiple factors that have to be considered and combined to achieve an overall more effective multifunctional treatment. In the current review, we present data regarding aerosol delivery systems, transporters, carriers, vectors, genes, toxicity, efficiency, specificity, lung microenvironment and delivery gene therapy systems. Finally, we present current studies and future perspectives.

Current therapy and drug pipeline for the treatment of patients with acromegaly.

PubMed

Kumar, Sampath Satish; Ayuk, John; Murray, Robert D

2009-04-01

Acromegaly is a multisystem disease resulting from chronic exposure to supraphysiological levels of growth hormone (GH), and is associated with significant morbidity and excess mortality. The etiology is almost exclusively an underlying pituitary adenoma. Current therapeutic interventions include surgery, radiotherapy, and medical therapy. Despite surgery, around 50% of patients fail to achieve the biochemical targets shown to correlate with normalization of mortality rates. Radiotherapy is efficacious in controlling tumor growth and GH secretion; still, achievement of biochemical targets may take up to a decade and a number of safety issues have been raised with this treatment modality. Medical therapy, therefore, has an important role as adjuvant therapy in patients who fail to achieve control with surgery, or while awaiting the effects of radiotherapy to be realized. Furthermore, medical therapy is increasingly being used as primary therapy. Current medical therapies include dopaminergic agonists, somatostatin analogs, and GH receptor (GHR) antagonists. Dopaminergic agonists achieve biochemical targets in up to 30% of patients, and somatostatin analogs in around 60%. The currently available GHR antagonist pegvisomant effectively controls insulin-like growth factor-I levels in over 90% of patients; however, it has no effect on the tumor itself and has considerable financial implications. Research into optimizing the somatostatin and dopaminergic systems has led to promising advances in agonist development. Moieties with selectivity for various combinations of somatostatin receptor subtype receptors have been examined, along with molecules that additionally show high affinity for the dopaminergic D2 receptor. Of the molecules studied in vitro, only pasireotide (SOM230) and BIM-23A760 are currently undergoing further development. Other innovations to improve convenience of currently available drugs are also being investigated. Significant advances in under standing of the somatostatin and dopaminergic system have aided drug development. This may lead to new clinically available therapies enabling control of acromegaly in a larger proportion of patients, and at an earlier stage in their disease management.

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

PubMed

Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

2017-12-15

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

PubMed Central

Chu, Yung-Lin; Raghu, Rajasekaran; Lu, Kuan-Hung; Liu, Chun-Ting; Lin, Shu-Hsi; Lai, Yi-Syuan; Cheng, Wei-Cheng; Lin, Shih-Hang; Sheen, Lee-Yan

2013-01-01

Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic (Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients. PMID:24716172

Autophagy therapeutic potential of garlic in human cancer therapy.

PubMed

Chu, Yung-Lin; Raghu, Rajasekaran; Lu, Kuan-Hung; Liu, Chun-Ting; Lin, Shu-Hsi; Lai, Yi-Syuan; Cheng, Wei-Cheng; Lin, Shih-Hang; Sheen, Lee-Yan

2013-07-01

Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic (Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

Using Music To Develop Peer Interaction: An Examination of the Response of Two Subjects with a Learning Disability.

ERIC Educational Resources Information Center

Hooper, Jeff

2002-01-01

A study examined the response of two adults who attended a music activity therapy program in which music activities encouraged peer interaction. Music activity therapy was compared with a control condition (i.e., ball and target games). Both conditions increased the level of positive interaction, however, music therapy was least effective.…

Searching for a treatment for Alport syndrome using mouse models

PubMed Central

Katayama, Kan; Nomura, Shinsuke; Tryggvason, Karl; Ito, Masaaki

2014-01-01

Alport syndrome (AS) is a hereditary nephritis caused by mutations in COL4A3, COL4A4 or COL4A5 encoding the type IV collagen α3, α4, and α5 chains, which are major components of the glomerular basement membrane. About 20 years have passed since COL4A3, COL4A4, and COL4A5 were identified and the first Alport mouse model was developed using a knockout approach. The phenotype of Alport mice is similar to that of Alport patients, including characteristic thickening and splitting of the glomerular basement membrane. Alport mice have been widely used to study the pathogenesis of AS and to develop effective therapies. In this review, the newer therapies for AS, such as pharmacological interventions, genetic approaches and stem cell therapies, are discussed. Although some stem cell therapies have been demonstrated to slow the renal disease progression in Alport mice, these therapies demand continual refinement as research advances. In terms of the pharmacological drugs, angiotensin-converting enzyme inhibitors have been shown to be effective in Alport mice. Novel therapies that can provide a better outcome or lead to a cure are still awaited. PMID:25374816

Searching for a treatment for Alport syndrome using mouse models.

PubMed

Katayama, Kan; Nomura, Shinsuke; Tryggvason, Karl; Ito, Masaaki

2014-11-06

Alport syndrome (AS) is a hereditary nephritis caused by mutations in COL4A3, COL4A4 or COL4A5 encoding the type IV collagen α3, α4, and α5 chains, which are major components of the glomerular basement membrane. About 20 years have passed since COL4A3, COL4A4, and COL4A5 were identified and the first Alport mouse model was developed using a knockout approach. The phenotype of Alport mice is similar to that of Alport patients, including characteristic thickening and splitting of the glomerular basement membrane. Alport mice have been widely used to study the pathogenesis of AS and to develop effective therapies. In this review, the newer therapies for AS, such as pharmacological interventions, genetic approaches and stem cell therapies, are discussed. Although some stem cell therapies have been demonstrated to slow the renal disease progression in Alport mice, these therapies demand continual refinement as research advances. In terms of the pharmacological drugs, angiotensin-converting enzyme inhibitors have been shown to be effective in Alport mice. Novel therapies that can provide a better outcome or lead to a cure are still awaited.

Phase II drugs currently being investigated for the treatment of hypogonadism.

PubMed

Udedibia, Emeka; Kaminetsky, Jed

2014-12-01

Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.

Short-term effect of short, intensive speech therapy on articulation and resonance in Ugandan patients with cleft (lip and) palate.

PubMed

Luyten, A; Bettens, K; D'haeseleer, E; Hodges, A; Galiwango, G; Vermeersch, H; Van Lierde, K

2016-01-01

The purpose of the current study was to assess the short-term effectiveness of short and intensive speech therapy provided to patients with cleft (lip and) palate (C(L)P) in terms of articulation and resonance. Five Ugandan patients (age: 7.3-19.6 years) with non-syndromic C(L)P received six hours of individualized speech therapy in three to four days. Speech therapy focused on correct phonetic placement and contrasts between oral and nasal airflow and resonance. Speech evaluations performed before and immediately after speech therapy, including perceptual and instrumental assessment techniques, were compared. Post-therapy, improvement of speech was noted for most of the patients, although to varying degrees. Clinically relevant progress of objective nasalance values and/or articulation was obtained in four patients. Overall, two patients showed normal speech intelligibility, while three patients required additional speech therapy. These preliminary short-term results demonstrate that short and intensive speech therapy can be effective for patients with C(L)P in countries with limited access to speech-language therapy. However, further research is needed on the long-term effectiveness and the advantages of applying this treatment protocol in countries with good access to speech therapy. The reader will be able to (1) list the challenges in resource poor-countries to achieve access to speech-language therapy services, (2) describe when the application of speech therapy is appropriate in patients with C(L)P, (3) describe the speech therapy that can be applied to reduce compensatory articulation and resonance disorders in patients with C(L)P, and (4) list the (possible) advantages of short, intensive speech therapy for both resource-poor and developed countries. Copyright © 2016 Elsevier Inc. All rights reserved.

Glucose-Responsive Sequential Generation of Hydrogen Peroxide and Nitric Oxide for Synergistic Cancer Starving-Like/Gas Therapy.

PubMed

Fan, Wenpei; Lu, Nan; Huang, Peng; Liu, Yi; Yang, Zhen; Wang, Sheng; Yu, Guocan; Liu, Yijing; Hu, Junkai; He, Qianjun; Qu, Junle; Wang, Tianfu; Chen, Xiaoyuan

2017-01-24

Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)-assisted conversion of glucose into gluconic acid and toxic H 2 O 2 , a novel treatment paradigm of starving-like therapy is developed for significant tumor-killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H 2 O 2 can oxidize l-Arginine (l-Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co-delivery of GOx and l-Arg, a novel glucose-responsive nanomedicine (l-Arg-HMON-GOx) has been for the first time constructed for synergistic cancer starving-like/gas therapy without the need of external excitation, which yields a remarkable H 2 O 2 -NO cooperative anticancer effect with minimal adverse effect. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Humoral immune response in infectious mononucleosis. Late emergence of anti-EA(R) and the effects of corticosteroid therapy.

PubMed

Fleisher, G R; Collins, M; Fager, S

1985-11-01

The antibody response to Epstein-Barr virus (EBV) antigens in patients with infectious mononucleosis (IM) was studied to assess antibody appearance to the restricted (R) component of the early antigen (EA) complex and to determine the effect of corticosteroids on all aspects of the humoral immune response. Sixty college students with heterophil-positive clinical IM, confirmed by EBV-specific serology, were followed for a period of 4-26 weeks, Half received prednisone for six days, and the remainder received no corticosteroid therapy. Regardless of therapy, 48% of the patients developed anti-EA(R) antibodies. The response to other antigens was similar in both groups with the exception that antibodies to the EB-associated nuclear antigen (EBNA) developed later during convalescence and at lower titers in the corticosteroid-treated group. We conclude that 1) anti-EA(R) antibodies develop with considerable frequency following IM and are not a marker, as previously proposed, of unusually severe disease, and 2) corticosteroid therapy may retard the formation of anti-EBNA antibodies but it does not otherwise influence the humoral immune response to EBV.

A Delphi survey of the views of adult male patients with personality disorders on psychoeducation and social problem-solving therapy.

PubMed

McMurran, Mary; Wilmington, Rebekah

2007-01-01

Psychoeducation and social problem-solving therapy are treatment components that work well in tandem for offenders with personality disorders, hence it is worthwhile to maintain and improve their effectiveness. The aim was to seek patients' views of these therapies to contribute to their development. A Delphi survey was conducted with all 12 male inpatients of a personality disorder hospital treatment unit. Round 1 produced 30 statements for psychoeducation and 59 for social problem-solving therapy to be rated in Round 2. There was consensus at a level of 70% for all items. Both psychoeducation and social problem-solving therapies were viewed as useful by these patients. The men also suggested improvements in psychoeducation, including minimizing the delay between assessment and feedback, provision of reference material, preparation for the work and support afterwards. Areas identified for improvement in social problem-solving therapy included more frequent review of progress, greater consistency of delivery, eliciting problems more effectively, providing reference material, supporting patients in group work, and the development of an advanced therapy. A Delphi approach to evaluation of therapies with the people receiving them is not only feasible but seems to offer a practical way of making useful clinical adjustments to the work. Further research with larger samples might usefully focus on whether such an approach enhances treatment compliance. 2007 John Wiley & Sons, Ltd

Robotic Mirror Therapy System for Functional Recovery of Hemiplegic Arms.

PubMed

Beom, Jaewon; Koh, Sukgyu; Nam, Hyung Seok; Kim, Wonshik; Kim, Yoonjae; Seo, Han Gil; Oh, Byung-Mo; Chung, Sun Gun; Kim, Sungwan

2016-08-15

Mirror therapy has been performed as effective occupational therapy in a clinical setting for functional recovery of a hemiplegic arm after stroke. It is conducted by eliciting an illusion through use of a mirror as if the hemiplegic arm is moving in real-time while moving the healthy arm. It can facilitate brain neuroplasticity through activation of the sensorimotor cortex. However, conventional mirror therapy has a critical limitation in that the hemiplegic arm is not actually moving. Thus, we developed a real-time 2-axis mirror robot system as a simple add-on module for conventional mirror therapy using a closed feedback mechanism, which enables real-time movement of the hemiplegic arm. We used 3 Attitude and Heading Reference System sensors, 2 brushless DC motors for elbow and wrist joints, and exoskeletal frames. In a feasibility study on 6 healthy subjects, robotic mirror therapy was safe and feasible. We further selected tasks useful for activities of daily living training through feedback from rehabilitation doctors. A chronic stroke patient showed improvement in the Fugl-Meyer assessment scale and elbow flexor spasticity after a 2-week application of the mirror robot system. Robotic mirror therapy may enhance proprioceptive input to the sensory cortex, which is considered to be important in neuroplasticity and functional recovery of hemiplegic arms. The mirror robot system presented herein can be easily developed and utilized effectively to advance occupational therapy.

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

PubMed

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

2009-05-21

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

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

PubMed Central

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

2009-01-01

Background Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology. Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. Methods/Design We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. Discussion This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. Trial Registration identifier NCT00847769. PMID:19460169

Weight loss endoscopy: Development, applications, and current status

PubMed Central

Kumar, Nitin

2016-01-01

Obesity and its comorbidities - including diabetes and obstructive sleep apnea - have taken a large and increasing toll on the United States and the rest of the world. The availability of commercial, clinical, and operative therapies for weight management have not been effective at a societal level. Endoscopic bariatric therapy is gaining acceptance as more effective than diet and lifestyle measures, and less invasive than bariatric surgery. Various endoscopic therapies are analogues of the restrictive or bypass components of bariatric surgery, utilizing gastric remodeling or intestinal anastomosis to achieve proven weight loss and metabolic benefits. Others, such as aspiration therapy, employ novel mechanisms of action. Intragastric balloons have recently been approved by the United States Food and Drug Administration, and a number of other technologies have completed large multicenter trials (such as AspireAssist aspiration therapy and Primary Obesity Surgery Endolumenal). Endoscopic sleeve gastroplasty and transoral outlet reduction for endoscopic revision of gastric bypass have proven safe and effective in a number of studies. As devices are approved for use, data will continue to accumulate for safety, effectiveness, and cost effectiveness. Bariatric endoscopists should be prepared to appropriately target and apply various endoscopic bariatric therapies in the context of a comprehensive long-term weight management program. PMID:27610017

Should patents for antiretrovirals be waived in the developing world? Annual varsity medical debate - London, 21 January 2011

PubMed Central

2011-01-01

The 2011 Varsity Medical Debate, between Oxford and Cambridge Universities, brought students and faculty together to discuss the waiving of patents for antiretroviral therapies in the developing world. With an estimated 29.5 million infected by Human Immunodeficiency Virus (HIV) in low- and middle-income countries and only 5.3 million of those being treated, the effective and equitable distribution of anti-retroviral therapy (ART) is an issue of great importance. The debate centred around three areas of contention. Firstly, there was disagreement about whether patents were the real barrier to the access of anti-retroviral therapy in the developing world. Secondly, there were differing views on the effectiveness of a patent pool. Thirdly, concerns were raised over the impact of waiving patents on research to produce new and better anti retro-viral drugs. PMID:21740573

Formalizing an integrative, multidisciplinary cancer therapy discovery workflow

PubMed Central

McGuire, Mary F.; Enderling, Heiko; Wallace, Dorothy I.; Batra, Jaspreet; Jordan, Marie; Kumar, Sushil; Panetta, John C.; Pasquier, Eddy

2014-01-01

Although many clinicians and researchers work to understand cancer, there has been limited success to effectively combine forces and collaborate over time, distance, data and budget constraints. Here we present a workflow template for multidisciplinary cancer therapy that was developed during the 2nd Annual Workshop on Cancer Systems Biology sponsored by Tufts University, Boston, MA in July 2012. The template was applied to the development of a metronomic therapy backbone for neuroblastoma. Three primary groups were identified: clinicians, biologists, and scientists (mathematicians, computer scientists, physicists and engineers). The workflow described their integrative interactions; parallel or sequential processes; data sources and computational tools at different stages as well as the iterative nature of therapeutic development from clinical observations to in vitro, in vivo, and clinical trials. We found that theoreticians in dialog with experimentalists could develop calibrated and parameterized predictive models that inform and formalize sets of testable hypotheses, thus speeding up discovery and validation while reducing laboratory resources and costs. The developed template outlines an interdisciplinary collaboration workflow designed to systematically investigate the mechanistic underpinnings of a new therapy and validate that therapy to advance development and clinical acceptance. PMID:23955390

Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation

PubMed Central

Prasanna, Pataje G. S.; Narayanan, Deepa; Hallett, Kory; Bernhard, Eric J.; Ahmed, Mansoor M.; Evans, Gregory; Vikram, Bhadrasain; Weingarten, Michael; Coleman, C. Norman

2015-01-01

Although radiation therapy is an important cancer treatment modality, patients may experience adverse effects. The use of a radiation-effect modulator may help improve the outcome and health-related quality of life (HRQOL) of patients undergoing radiation therapy either by enhancing tumor cell killing or by protecting normal tissues. Historically, the successful translation of radiation-effect modulators to the clinic has been hindered due to the lack of focused collaboration between academia, pharmaceutical companies and the clinic, along with limited availability of support for such ventures. The U.S. Government has been developing medical countermeasures against accidental and intentional radiation exposures to mitigate the risk and/or severity of acute radiation syndrome (ARS) and the delayed effects of acute radiation exposures (DEARE), and there is now a drug development pipeline established. Some of these medical countermeasures could potentially be repurposed for improving the outcome of radiation therapy and HRQOL of cancer patients. With the objective of developing radiation-effect modulators to improve radiotherapy, the Small Business Innovation Research (SBIR) Development Center at the National Cancer Institute (NCI), supported by the Radiation Research Program (RRP), provided funding to companies from 2011 to 2014 through the SBIR contracts mechanism. Although radiation-effect modulators collectively refer to radioprotectors, radiomitigators and radiosensitizers, the focus of this article is on radioprotection and mitigation of radiation injury. This specific SBIR contract opportunity strengthened existing partnerships and facilitated new collaborations between academia and industry. In this commentary, we assess the impact of this funding opportunity, outline the review process, highlight the organ/site-specific disease needs in the clinic for the development of radiation-effect modulators, provide a general understanding of a framework for gathering preclinical and clinical evidence to obtain regulatory approval and provide a basis for broader venture capital needs and support from pharmaceutical companies to fully capitalize on the advances made thus far in this field. PMID:26284423

Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation.

PubMed

Prasanna, Pataje G S; Narayanan, Deepa; Hallett, Kory; Bernhard, Eric J; Ahmed, Mansoor M; Evans, Gregory; Vikram, Bhadrasain; Weingarten, Michael; Coleman, C Norman

2015-09-01

Although radiation therapy is an important cancer treatment modality, patients may experience adverse effects. The use of a radiation-effect modulator may help improve the outcome and health-related quality of life (HRQOL) of patients undergoing radiation therapy either by enhancing tumor cell killing or by protecting normal tissues. Historically, the successful translation of radiation-effect modulators to the clinic has been hindered due to the lack of focused collaboration between academia, pharmaceutical companies and the clinic, along with limited availability of support for such ventures. The U.S. Government has been developing medical countermeasures against accidental and intentional radiation exposures to mitigate the risk and/or severity of acute radiation syndrome (ARS) and the delayed effects of acute radiation exposures (DEARE), and there is now a drug development pipeline established. Some of these medical countermeasures could potentially be repurposed for improving the outcome of radiation therapy and HRQOL of cancer patients. With the objective of developing radiation-effect modulators to improve radiotherapy, the Small Business Innovation Research (SBIR) Development Center at the National Cancer Institute (NCI), supported by the Radiation Research Program (RRP), provided funding to companies from 2011 to 2014 through the SBIR contracts mechanism. Although radiation-effect modulators collectively refer to radioprotectors, radiomitigators and radiosensitizers, the focus of this article is on radioprotection and mitigation of radiation injury. This specific SBIR contract opportunity strengthened existing partnerships and facilitated new collaborations between academia and industry. In this commentary, we assess the impact of this funding opportunity, outline the review process, highlight the organ/site-specific disease needs in the clinic for the development of radiation-effect modulators, provide a general understanding of a framework for gathering preclinical and clinical evidence to obtain regulatory approval and provide a basis for broader venture capital needs and support from pharmaceutical companies to fully capitalize on the advances made thus far in this field.

Contemporary Play Therapy: Theory, Research, and Practice

ERIC Educational Resources Information Center

Schaefer, Charles E., Ed.; Gerard Kaduson, Heidi, Ed.

2006-01-01

This highly practical book presents current developments in play therapy, including innovative applications for particular problems and populations. Contributors first discuss the latest ideas and techniques emerging from object-relations, experiential, dynamic, and narrative perspectives. Next, research evaluating the effectiveness of play…

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.

Systematic reviews of randomised clinical trials examining the effects of psychotherapeutic interventions versus "no intervention" for acute major depressive disorder and a randomised trial examining the effects of "third wave" cognitive therapy versus mentalization-based treatment for acute major depressive disorder.

PubMed

Jakobsen, Janus Christian

2014-10-01

Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy and psychodynamic therapy may be effective treatment options for major depressive disorder, but the effects have only had limited assessment in systematic reviews. The two modern forms of psychotherapy, "third wave" cognitive therapy and mentalization-based treatment, have both gained some ground as treatments of psychiatric disorders. No randomised trial has compared the effects of these two interventions for major depressive disorder. We performed two systematic reviews with meta-analyses and trial sequential analyses using The Cochrane Collaboration methodology examining the effects of cognitive therapy and psycho-dynamic therapy for major depressive disorder. We developed a thorough treatment protocol for a randomised trial with low risks of bias (systematic error) and low risks of random errors ("play of chance") examining the effects of third wave' cognitive therapy versus mentalization-based treatment for major depressive disorder. We conducted a randomised trial according to good clinical practice examining the effects of "third wave" cognitive therapy versus mentalisation-based treatment for major depressive disorder. The first systematic review included five randomised trials examining the effects of psychodynamic therapy versus "no intervention' for major depressive disorder. Altogether the five trials randomised 365 participants who in each trial received similar antidepressants as co-interventions. All trials had high risk of bias. Four trials assessed "interpersonal psychotherapy" and one trial "short psychodynamic supportive psychotherapy". Both of these interventions are different forms of psychodynamic therapy. Meta-analysis showed that psychodynamic therapy significantly reduced depressive symptoms on the Hamilton Depression Rating Scale (HDRS) compared with "no intervention" (mean difference -3.01 (95% confidence interval -3.98 to -2.03; p = 0.00001), no significant heterogeneity between trials). Trial sequential analysis confirmed this result. The second systematic review included 12 randomised trials examining the effects of cognitive therapy versus "no intervention" for major depressive disorder. Altogether a total of 669 participants were randomised. All trials had high risk of bias. Meta-analysis showed that cognitive therapy significantly reduced depressive symptoms on the HDRS compared with "no intervention" (four trials; mean difference -3.05 (95% confidence interval, -5.23 to -0.87; p = 0.006)). Trial sequential analysis could not confirm this result. The trial protocol showed that it seemed feasible to conduct a randomised trial with low risks of bias and low risks of random errors examining the effects of "third wave" cognitive therapy versus mentalization-based therapy in a setting in the Danish healthcare system. It turned out to be much more difficult to recruit participants in the randomised trial than expected. We only included about half of the planned participants. The results from the randomised trial showed that participants randomised to "third wave" therapy compared with participants randomised to mentalization-based treatment had borderline significantly lower HDRS scores at 18 weeks in an unadjusted analysis (mean difference -4.14 score; 95% CI -8.30 to 0.03; p = 0.051). In the adjusted analysis, the difference was significant (p = 0.039). Five (22.7%) of the participants randomised to "third wave" cognitive therapy had remission at 18 weeks versus none of the participants randomised to mentalization-based treatment (p = 0.049). Sequential analysis showed that these findings could be due to random errors. No significant differences between the two groups was found regarding Beck's Depression Inventory (BDI II), Symptom Checklist 90 Revised (SCL 90-R), and The World Health Organization-Five Well-being Index 1999 (WHO 5). We concluded that cognitive therapy and psychodynamic therapy might be effective interventions for depression measured on HDRS and BDI, but the review results might be erroneous due to risks of bias and random errors. Furthermore, the effects seem relatively small. The trial protocol showed that it was possible to develop a protocol for a randomised trial examining the effects of "third wave" cognitive therapy versus mentalization-based treatment with low risks of bias and low risks of random errors. Our trial results showed that "third wave" cognitive therapy might be a more effective intervention for depressive symptoms measured on the HDRS compared with mentalization-based treatment. The two interventions did not seem to differ significantly regarding BDI II, SCL 90-R, and WHO 5. More randomised trials with low risks of bias and low risks of random errors are needed to assess the effects of cognitive therapy, psychodynamic therapy, "third wave" cognitive therapy, and mentalization-based treatment.

Hypoxia as a target for tissue specific gene therapy.

PubMed

Rhim, Taiyoun; Lee, Dong Yun; Lee, Minhyung

2013-12-10

Hypoxia is a hallmark of various ischemic diseases such as ischemic heart disease, ischemic limb, ischemic stroke, and solid tumors. Gene therapies for these diseases have been developed with various therapeutic genes including growth factors, anti-apoptotic genes, and toxins. However, non-specific expression of these therapeutic genes may induce dangerous side effects in the normal tissues. To avoid the side effects, gene expression should be tightly regulated in an oxygen concentration dependent manner. The hypoxia inducible promoters and enhancers have been evaluated as a transcriptional regulation tool for hypoxia inducible gene therapy. The hypoxia inducible UTRs were also used in gene therapy for spinal cord injury as a translational regulation strategy. In addition to transcriptional and translational regulations, post-translational regulation strategies have been developed using the HIF-1α ODD domain. Hypoxia inducible transcriptional, translational, and post-translational regulations are useful for tissue specific gene therapy of ischemic diseases. In this review, hypoxia inducible gene expression systems are discussed and their applications are introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

Modeling ADHD-type arousal with unilateral frontal cortex damage in rats and beneficial effects of play therapy.

PubMed

Panksepp, Jaak; Burgdorf, Jeff; Turner, Cortney; Gordon, Nakia

2003-06-01

It has been recently shown that human adolescents with Attention Deficit/Hyperactivity Disorder (ADHD) have frontal lobe deficits, especially on the right sides of their brains (). ADHD is commonly treated with psychostimulants which may have adverse consequences. Hence, less invasive therapies need to be developed. In the present work, we tested the ability of right frontal lesions to induce hyperactivity in rats. We also evaluated the effects of chronic play therapy during early adolescence to reduce both hyperactivity and the elevated playfulness later in development. Play therapy was able to reduce both hyperactivity and excessive playfulness. In additional work, we found that access to rough-and-tumble play in normal animals could enhance subsequent behavioral indices of behavioral inhibition (i.e., freezing in response to a startle stimulus) that appeared to be independent of increased fearfulness and fatigue. Overall, these results suggest that (1) neonatal frontal lobe lesions can be used as an animal model of the overactivity in ADHD and (2) rough-and-tumble play therapy may be a new useful treatment for ADHD.

Cancer therapies in HIV cure research.

PubMed

Rasmussen, Thomas A; Anderson, Jenny L; Wightman, Fiona; Lewin, Sharon R

2017-01-01

This article provides an overview of anticancer therapies in various stages of clinical development as potential interventions to target HIV persistence. Epigenetic drugs developed for cancer have been investigated in vitro, ex vivo and in clinical trials as interventions aimed at reversing HIV latency and depleting the amount of virus that persists on antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV expression in patients on antiretroviral therapy but did not reduce the frequency of infected cells. Other interventions that may accelerate the decay of latently infected cells, in the presence or absence of latency-reversing therapy, are now being explored. These include apoptosis-promoting agents, nonhistone deacetylase inhibitor compounds to reverse HIV latency and immunotherapy interventions to enhance antiviral immunity such as immune checkpoint inhibitors and Toll-like receptor agonists. A curative strategy in HIV will likely need to both reduce the amount of virus that persists on antiretroviral therapy and improve anti-HIV immune surveillance. Although we continue to explore advances in the field of oncology including cancer immunotherapy, there are major differences in the risk-benefit assessment between HIV-infected individuals and patients with malignancies. Drug development specifically targeting HIV persistence will be the key to developing effective interventions with an appropriate safety profile.

The windowed sound therapy: a new empirical approach for an effectiv personalized treatment of tinnitus.

PubMed

Lugli, Marco; Romani, Romano; Ponzi, Stefano; Bacciu, Salvatore; Parmigiani, Stefano

2009-01-01

We auditorily stimulated patients affected by subjective tinnitus with broadband noise containing a notch around their tinnitus frequency. We assessed the long-term effects on tinnitus perception in patients listening to notched noise stimuli (referred to as windowed sound therapy [WST]) by measuring the variation of subjects' tinnitus loudness over a period of 2-12 months. We tested the effectiveness of WST using non-notched broadband noise and noise of water as control sound therapies. We found a significant long-term reduction of tinnitus loudness in subjects treated with notched noise but not in those treated with control stimulations. These results point to the importance of the personalized sound treatment of tinnitus sufferers for the development of an effective tinnitus sound therapy.

Assessing the Efficacy of Mobile Health Apps Using the Basic Principles of Cognitive Behavioral Therapy: Systematic Review.

PubMed

Rathbone, Amy Leigh; Clarry, Laura; Prescott, Julie

2017-11-28

Cognitive behavioral therapy (CBT) in its basic principle has developed itself as a stand-alone, substantial method of therapy. With effective application in therapy for a range of mental health issues, the spread of CBT methods to Web-based therapy sources is evident. The development of mobile phone apps using CBT principles is increasing within the research area. Despite the move to Web-based methods of therapy, it is argued that these methods lack the same efficacy of face-to-face therapy sessions. The aim of this review was to assess extent research findings with regard to the effectiveness of CBT-related mobile health (mHealth) apps. By assessing only studies employing a randomized controlled trial design, the review aimed to determine app efficacy within the highly regarded method of investigation. A comprehensive literature search was conducted across several databases. Search results were filtered, and results were subject to strict inclusion and exclusion criteria because of the nature of the review. Where possible, analysis of effect size was calculated and results reported. A total of 8 studies investigating the effectiveness of mHealth CBT-related apps across a range of mental health issues were reviewed. Three studies used the app against a control group, and 5 studies used the app intervention against another form of treatment or intervention. A range of effect sizes were seen across all included studies (d=-0.13 to 1.83; 0.03-1.44), with the largest effects often being seen when comparing the data from pre- to posttest for the app engaged group. The studies reviewed support the use of mHealth apps containing CBT principles for a range of mental health issues. However, the effectiveness over longer time periods should be assessed. Researchers and professionals should seek to collaborate effectively when creating new apps to enhance their effectiveness as a treatment for the general public. ©Amy Leigh Rathbone, Laura Clarry, Julie Prescott. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 28.11.2017.

Effects of low-dose light-emitting-diode therapy in combination with water bath for atopic dermatitis in NC/Nga mice.

PubMed

Kim, Chang-Hyun; Cheong, Kyung Ah; Lim, Won Suk; Park, Hyung-Moo; Lee, Ai-Young

2016-01-01

Light-emitting diode (LED) phototherapy and water bath therapy have beneficial effect on atopic dermatitis (AD)-like skin disease. However, not all current treatments work well and alternative therapies are need. The contribution of combination therapy with low-dose 850 nm LED and water bath was investigated on dermatophagoides farina (Df)-induced dermatitis in NC/Nga mice. Low-dose LED (10, 15, and 20 J/cm(2) ) irradiation, water bath (36 ± 1°C) were administered separately and together to the Df-induced NC/Nga mice in acrylic jar once a day for 2 weeks. Combined therapy with low-dose LED therapy and water bath therapy significantly ameliorated the development of AD-like skin lesions. These effects were correlated with the suppression of total IgE, NO, histamine, and Th2-mediated immune responses. Furthermore, combination therapy significantly reduced the infiltration of inflammatory cells and the induction of thymic stromal lymphopoietin (TSLP) in the skin lesions. The beneficial therapeutic effects of this combination therapy might regulate by the inhibition of various immunological responses including Th2-mediated immune responses, inflammatory mediators such as IgE, histamine, and NO, as well as inflammatory cells. The combination therapy of LED and water bath might be used as an efficacious, safe, and steroid-free alternative therapeutic strategy for the treatment of AD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis.

PubMed

Bjordal, Jan Magnus; Bensadoun, Rene-Jean; Tunèr, Jan; Frigo, Lucio; Gjerde, Kjersti; Lopes-Martins, Rodrigo Ab

2011-08-01

The purpose of this study is to review the effects of low-level laser therapy (LLLT) in the prevention and treatment of cancer therapy-induced oral mucositis (OM). A systematic review and meta-analysis of randomised placebo-controlled trials of LLLT performed during chemotherapy or radiation therapy in head and neck cancer patients. We found 11 randomised placebo-controlled trials with a total of 415 patients; methodological quality was acceptable at 4.10 (SD ± 0.74) on the 5-point Jadad scale. The relative risk (RR) for developing OM was significantly (p = 0.02) reduced after LLLT compared with placebo LLLT (RR = 2.03 (95% CI, 1.11 to 3.69)). This preventive effect of LLLT improved to RR = 2.72 (95% CI, 1.98 to 3.74) when only trials with adequate doses above 1 J were included. For treatment of OM ulcers, the number of days with OM grade 2 or worse was significantly reduced after LLLT to 4.38 (95% CI, 3.35 to 5.40) days less than placebo LLLT. Oral mucositis severity was also reduced after LLLT with a standardised mean difference of 1.33 (95% CI, 0.68 to 1.98) over placebo LLLT. All studies registered possible side-effects, but they were not significantly different from placebo LLLT. There is consistent evidence from small high-quality studies that red and infrared LLLT can partly prevent development of cancer therapy-induced OM. LLLT also significantly reduced pain, severity and duration of symptoms in patients with cancer therapy-induced OM.

Use of intravenous immunoglobulin in the Department of Neurology at Ninewells Hospital, 2008–2009: Indications for utilization and cost-effectiveness

PubMed Central

O’ Riordan, Jonathan; Swingler, Robert J.; Malek, Naveed M.

2010-01-01

This study was designed to identify the indications for prescription of intravenous immunoglobulin (IVIg) in neurology and the cost effectiveness of this therapy. Objectives: IVIg is a relatively costly therapy and the annual budget spent on providing this therapy for various indications at Ninewells Hospital was close to £1.5 million. In today’s economic times, a cost–benefit analysis of all therapies is prudent. This is of relevance to countries in the developing world as well where perhaps not everybody could afford such cost-intensive therapy. Materials and Methods: We audited 2 time periods over 12 months each in 2004–2005 and 2008–2009 to look at the patterns of utilization of IVIg over these periods. We searched the literature for alternative and cost-effective therapies for the most common indications for use of IVIg. Results: Fiscal costs on prescription of IVIg have rocketed up by almost 300% in this Neurology Department comparing data from 2004–2005 vs 2008–2009 and this is disproportionate to the increase in the annual admission rate (bed usage), partly because of the soaring costs of the drug available in the market and also because of the increased prescription of IVIg for numerous indications where clinical trials data are yet not so robust. Conclusion: We have looked at the cost of alternative therapies and offer some proposals that if implemented could potentially save £330,000 annually from the health budget at this NHS Trust. Perhaps similar models could evolve for better cost-effective utilization of IVIg in countries in the developing world where health budgeting is more acutely relevant. PMID:21264135

Novel form of miR-29b suppresses bleomycin-induced pulmonary fibrosis

PubMed Central

Yamada, Yuko; Takanashi, Masakatsu; Sudo, Katsuko; Ueda, Shinobu; Ohno, Shin-ichiro; Kuroda, Masahiko

2017-01-01

MicroRNA 29b (miR-29b) replacement therapy is effective for suppressing fibrosis in a mouse model. However, to develop clinical applications for miRNA mimics, the side effects of nucleic acid drugs have to be addressed. In this study, we focused on miRNA mimics in order to develop therapies for idiopathic pulmonary fibrosis. We developed a single-stranded RNA, termed “miR-29b Psh-match,” that has a unique structure to avoid problems associated with the therapeutic uses of miRNAs. A comparison of miR-29b Psh-match and double-stranded one, termed “miR-29b mimic” indicated that the single-stranded form was significantly effective towards fibrosis according to both in vivo and in vitro experiments. This novel form of miR-29b may become the foundation for developing an effective therapeutic drug for pulmonary fibrosis. PMID:28234907

BMI-1 targeting interferes with patient-derived tumor-initiating cell survival and tumor growth in prostate cancer

PubMed Central

Yusuff, Shamila; Davis, Stephani; Flaherty, Kathleen; Huselid, Eric; Patrizii, Michele; Jones, Daniel; Cao, Liangxian; Sydorenko, Nadiya; Moon, Young-Choon; Zhong, Hua; Medina, Daniel J.; Kerrigan, John; Stein, Mark N.; Kim, Isaac Y.; Davis, Thomas W.; DiPaola, Robert S.; Bertino, Joseph R.; Sabaawy, Hatem E.

2016-01-01

Purpose Current prostate cancer (PCa) management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy-resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TICs-tailored therapies appears to be a promising approach. Experimental design We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient derived prostate cancer cells and xenograft models to characterize the effects of pharmacological inhibitors of BMI-1. Results We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacological inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor (AR)-directed therapies, without toxic effects on normal tissues. Conclusions Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective PCa treatment. PMID:27307599

Hormonal development therapy (HDT) in hypogonadism in long-term view.

PubMed

Heinz, Marlene

2010-04-01

Since the 1960s, oestrogen deficiency in hypogonadism in girls has been successfully treated by a sort of analogous application of the menopausal hormone replacement therapy (HRT) scheme, here however, to induce and support sexual development in puberty and adolescence. The essential distinction between goals, ways and means of the two distinct hormonal treatments caused by menopause and by hypogonadism in puberty also suggests that the latter treatment is more characteristic of defining hormonal development therapy (HDT). Moreover, specific HDT in hypogonadism is essential for longitudinal growth of girls, functions of female reproductive system, bone and lipid metabolism and the immune, central nervous and cardiovascular systems. By contrast, the aim of menopausal replacement therapy in elderly women is treating negative effects of physiological loss of oestrogens as hot flush, lacks of female well-being and osteoporosis, while in hypogonadal girls there is of course nothing that might be replaced eventually. Especially in cases of absolute oestrogen deficiency, as in Turner syndrome and in other cases of premature ovarian failure, HDT has to be started at the age of expected puberty. An international consensus suggests possibly lifelong HDT for the lasting support of female development and functions. However, neither reliable studies about possible risks and side effects of continuous hormonal therapy in adult women with hypogonadismus nor a more precise consensus have emerged yet. Emphasising the term HDT particularly aims at putting more effort in getting over these paucities simultaneously. Indications, hormonal therapy, dosage, application and timing in puberty are described in this article. Aspects of long-term hormonal treatment are critically discussed. Copyright 2010 Elsevier Ltd. All rights reserved.

Complementary and alternative medicine use for treatment and prevention of late-life mood and cognitive disorders

PubMed Central

Lavretsky, Helen

2009-01-01

Late-life mood disorders and cognitive aging are the most common reasons for using complementary and alternative therapies. The amount of rigorous scientific data to support the efficacy of complementary therapies in the treatment of depression or cognitive impairment is extremely limited. The areas with the most evidence for beneficial effects are exercise, herbal therapy (Hypericum perforatum), the use of fish oil, and, to a lesser extent, acupuncture and relaxation therapies. There is a need for further research involving randomized, controlled trials to investigate the efficacy of complementary and alternative therapies in the treatment of depression and cognitive impairment in late-life. This research may lead to the development of effective treatment and preventive approaches for these serious conditions. PMID:19956796

Cost-Effectiveness of Nivolumab-Ipilimumab Combination Therapy Compared to Monotherapy for First-Line Treatment of Metastatic Melanoma in the United States

PubMed Central

Oh, Anna; Tran, Dang M; McDowell, Leann C; Keyvani, Dor; Barcelon, Jay Andrew; Merino, Oscar; Wilson, Leslie

2018-01-01

BACKGROUND The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations to third-party payer systems, physicians, and patients. OBJECTIVE Develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as first-line therapy in metastatic melanoma while accounting for differential effectiveness in PD-L1 positive and negative patients. METHODS A three-state Markov model (‘PD-L1 positive stable disease’, ‘PD-L1 negative stable disease’, and ‘Progression and/or Death’) was developed using a US societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 US dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. RESULTS Nivolumab-ipilimumab combination therapy is not the cost effective choice ($454,092 per progression-free quality-adjusted-life-year [PFQALY]) compared to nivolumab monotherapy in our base case analysis at a willingness-to-pay threshold of $100,000/PFQALY. Both combination therapy and nivolumab monotherapy were cost-effective choices compared to ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment but combination therapy had an improved ICER of $295,903/PFQALY. Combination therapy became dominated by nivolumab when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to <$21,555 per dose for combination therapy to have an ICER <$100,000/PFQALY, and to <$19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy. CONCLUSIONS Nivolumab-ipilimumab combination therapy is not cost-effective compared to nivolumab monotherapy, which is the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions and future cost-effectiveness studies are completed. PMID:28530525

Challenges and future in vaccines, drug development, and immunomodulatory therapy.

PubMed

Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

2014-08-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

Heidelberg Neuro-Music Therapy for chronic-tonal tinnitus - treatment outline and psychometric evaluation.

PubMed

Argstatter, Heike; Grapp, Miriam; Plinkert, Peter K; Bolay, Hans Volker

2012-01-01

Musical training positively influences the cortical plasticity of the brain and has proven to be effective in treating chronic tinnitus. A neuro-music therapy concept, the "Heidelberg Neuro-Music Therapy" treatment was developed and evaluated. A prospective, cross-sectional design was used. N = 135 patients (mean age 47 years) with chronic, tonal tinnitus attended a standardized protocol for Neuro-Music Therapy (either "standard therapy" ST or "compact therapy" CT). The results were compared to a cognitive behavioral placebo music therapy procedure (PT). Tinnitus distress was assessed using the German version of the Tinnitus-Questionnaire (TQ) at admission, at discharge and six months after therapy. Changes were assessed statistically and by means of clinical significance. TQ scores significantly improved - independent of group allocation. But more than 80% of the music therapy patients (both ST and CT) revealed a reliable improvement ("responder") compared to 44% in the PT group. Therapy impact seems to be lasting since TQ scores remained stable until follow-up at six months. The "Heidelberg Neuro-Music Therapy" is a method with fast onset and long lasting effect for patients with "tonal" tinnitus. A number of potential working factors accounting for the treatment success are highlighted.

Process and product development in the manufacturing of molecular therapeutics.

PubMed

Atkinson, E M; Christensen, J R

1999-08-01

In the development of molecular therapies, a great deal of attention has focused on tissue targets, gene delivery vectors, and expression cassettes. In order to become an approved therapy, however, a molecular therapeutic has to pass down the same product registration pathway as any other biological product. Moving from research into industrial production requires careful attention to regulatory, manufacturing and quality concerns. Early work on developing and characterizing robust and scaleable manufacturing processes will ultimately be rewarded by ease of implementation as the product is successful in clinical trials. Regulatory agencies require solid process and product characterization studies to demonstrate control and understanding of the molecular therapeutic. As the gene therapy industry matures, standards will continue to rise, creating an industry that is capable of producing safe, high-quality and effective therapies for many of the world's most difficult disease targets.

Advances in Age-related Macular Degeneration Understanding and Therapy

PubMed Central

Miller, Joan W; Bagheri, Saghar; Vavvas, Demetrios G

2017-01-01

While the development of anti-vascular endothelial growth factor (anti-VEGF) as a therapy for neovascular age-related macular degeneration (AMD) was a great success, the pathologic processes underlying dry AMD that eventually leads to photoreceptor dysfunction, death, and vision loss remain elusive to date, with a lack of effective therapies and increasing prevalence of the disease. There is an overwhelming need to improve the classification system of AMD, to increase our understanding of cell death mechanisms involved in both neovascular and non-neovascular AMD, and to develop better biomarkers and clinical endpoints to eventually be able to identify better therapeutic targets—especially early in the disease process. There is no doubt that it is a matter of time before progress will be made and better therapies will be developed for non-neovascular AMD. PMID:29142592

Problem solving therapy - use and effectiveness in general practice.

PubMed

Pierce, David

2012-09-01

Problem solving therapy (PST) is one of the focused psychological strategies supported by Medicare for use by appropriately trained general practitioners. This article reviews the evidence base for PST and its use in the general practice setting. Problem solving therapy involves patients learning or reactivating problem solving skills. These skills can then be applied to specific life problems associated with psychological and somatic symptoms. Problem solving therapy is suitable for use in general practice for patients experiencing common mental health conditions and has been shown to be as effective in the treatment of depression as antidepressants. Problem solving therapy involves a series of sequential stages. The clinician assists the patient to develop new empowering skills, and then supports them to work through the stages of therapy to determine and implement the solution selected by the patient. Many experienced GPs will identify their own existing problem solving skills. Learning about PST may involve refining and focusing these skills.

Lessons learned: a pilot study on occupational therapy effectiveness for children with sensory modulation disorder.

PubMed

Miller, Lucy Jane; Schoen, Sarah A; James, Katherine; Schaaf, Roseann C

2007-01-01

The purpose of this pilot study was to prepare for a randomized controlled study of the effectiveness of occupational therapy using a sensory integration approach (OT-SI) with children who have sensory processing disorders (SPD). A one-group pretest, posttest design with 30 children was completed with a subset of children with SPD, those with sensory modulation disorder. Lessons learned relate to (a) identifying a homogeneous sample with quantifiable inclusion criteria, (b) developing an intervention manual for study replication and a fidelity to treatment measure, (c) determining which outcomes are sensitive to change and relate to parents' priorities, and (d) clarifying rigorous methodologies (e.g., blinded examiners, randomization, power). A comprehensive program of research is needed, including multiple pilot studies to develop enough knowledge that high-quality effectiveness research in occupational therapy can be completed. Previous effectiveness studies in OT-SI have been single projects not based on a unified long-term program of research.

Immune-Stimulating Combinatorial Therapy for Prostate Cancer

DTIC Science & Technology

2016-10-01

infiltration. 2. Complementary to the studies in 1, we will sort myeloid, lymphoid and cancer cells from freshly dissociated tumors in cases where enough...MION) hyperthermia and external beam radiation therapy; and, 2) developed methodologies that will be used to elucidate the role of key immune cell ...radiation therapy, immunotherapy, prostate cancer, magnetic nanoparticle(s), abscopal effect, immune cells , tumor-infiltrating immune cells , T- cells , CD4

Proton Therapy for Thoracoabdominal Tumors

NASA Astrophysics Data System (ADS)

Sakurai, Hideyuki; Okumura, Toshiyuki; Sugahara, Shinji; Nakayama, Hidetsugu; Tokuuye, Koichi

In advanced-stage disease of certain thoracoabdominal tumors, proton therapy (PT) with concurrent chemotherapy may be an option to reduce side effects. Several technological developments, including a respiratory gating system and implantation of fiducial markers for image guided radiation therapy (IGRT), are necessary for the treatment in thoracoabdominal tumors. In this chapter, the role of PT for tumors of the lung, the esophagus, and liver are discussed.

Algorithm of the automated choice of points of the acupuncture for EHF-therapy

NASA Astrophysics Data System (ADS)

Lyapina, E. P.; Chesnokov, I. A.; Anisimov, Ya. E.; Bushuev, N. A.; Murashov, E. P.; Eliseev, Yu. Yu.; Syuzanna, H.

2007-05-01

Offered algorithm of the automated choice of points of the acupuncture for EHF-therapy. The recipe formed by algorithm of an automated choice of points for acupunctural actions has a recommendational character. Clinical investigations showed that application of the developed algorithm in EHF-therapy allows to normalize energetic state of the meridians and to effectively solve many problems of an organism functioning.

Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

PubMed Central

Chou, Roger; Fanciullo, Gilbert J.; Fine, Perry G.; Adler, Jeremy A.; Ballantyne, Jane C.; Davies, Pamela; Donovan, Marilee I.; Fishbain, David A.; Foley, Kathy M.; Fudin, Jeffrey; Gilson, Aaron M.; Kelter, Alexander; Mauskop, Alexander; O'Connor, Patrick G.; Passik, Steven D.; Pasternak, Gavril W.; Portenoy, Russell K.; Rich, Ben A.; Roberts, Richard G.; Todd, Knox H.; Miaskowski, Christine

2014-01-01

Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel following a systematic review of the evidence. PMID:19187889

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials.

PubMed

Wang, Junqi; Qin, Lan

2016-06-27

This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease.

[Dialectical Behavior Therapy (DBT)--developments and empirical evidence].

PubMed

Burmeister, Kerstin; Höschel, Klaus; von Auer, Anne Kristin; Reiske, Sophie; Schweiger, Ulrich; Sipos, Valerija; Philipsen, Alexandra; Priebe, Kathlen; Bohus, Martin

2014-07-01

Dialectical Behavior Therapy has been initially designed and evaluated as an outpatient-treatment program for chronic suicidal female patients. Within the last years, several adaptations of DBT for specific comorbidities, other settings or other disorders related to emotion dysregulation have been developed. This report reviews conceptual aspects and the scientific evidence of initially designed Dialectical Behavior Therapy and the adaptations. Systematic literature search and systematic review. Recently, two meta-analyses which are based on randomized controlled trials conclude robust and stabile effects of DBT Evidence from further RCTs and other studies show promise for the properties of many DBT adaptations. The current review of the literature suggests a good effectiveness of DBT, especially on complex disorders with deficits in the field of emotion regulation. © Georg Thieme Verlag KG Stuttgart · New York.

Psychological Therapies for Auditory Hallucinations (Voices): Current Status and Key Directions for Future Research

PubMed Central

Thomas, Neil; Hayward, Mark; Peters, Emmanuelle; van der Gaag, Mark; Bentall, Richard P.; Jenner, Jack; Strauss, Clara; Sommer, Iris E.; Johns, Louise C.; Varese, Filippo; García-Montes, José Manuel; Waters, Flavie; Dodgson, Guy; McCarthy-Jones, Simon

2014-01-01

This report from the International Consortium on Hallucinations Research considers the current status and future directions in research on psychological therapies targeting auditory hallucinations (hearing voices). Therapy approaches have evolved from behavioral and coping-focused interventions, through formulation-driven interventions using methods from cognitive therapy, to a number of contemporary developments. Recent developments include the application of acceptance- and mindfulness-based approaches, and consolidation of methods for working with connections between voices and views of self, others, relationships and personal history. In this article, we discuss the development of therapies for voices and review the empirical findings. This review shows that psychological therapies are broadly effective for people with positive symptoms, but that more research is required to understand the specific application of therapies to voices. Six key research directions are identified: (1) moving beyond the focus on overall efficacy to understand specific therapeutic processes targeting voices, (2) better targeting psychological processes associated with voices such as trauma, cognitive mechanisms, and personal recovery, (3) more focused measurement of the intended outcomes of therapy, (4) understanding individual differences among voice hearers, (5) extending beyond a focus on voices and schizophrenia into other populations and sensory modalities, and (6) shaping interventions for service implementation. PMID:24936081

The clinical case for proton beam therapy

PubMed Central

2012-01-01

Abstract Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence Proton beam therapy is a technically advanced and promising form of radiation therapy. PMID:23083010

Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis.

PubMed

Kamran, Haroon; Kupferstein, Eric; Sharma, Navneet; Karam, Jocelyne G; Myers, Alyson K; Youssef, Irini; Sowers, James R; Gustafson, Deborah R; Salifu, Moro O; McFarlane, Samy I

2018-01-01

Statins have long been prescribed for the primary and secondary prevention of cardiovascular disease (CVD) and kidney disease. Their benefits and efficacy are widely accepted in current clinical practice, but like any other therapeutic agents, they have adverse effects. One of the emerging concerns with statin therapy is the development of new-onset diabetes mellitus (NODM), a dreaded risk factor for CVD and kidney disease and widely viewed as CVD equivalent. Accumulating evidence indicates that NODM is a consequence of statin use. We conducted a meta-analysis of studies reporting on associations between NODM and statin use. Based on strict exclusion criteria, a total of 11 studies were selected. Their data were analyzed using Comprehensive Meta-Analysis® statistical software and reported as odds ratios (OR) with 95% confidence intervals (CI). The cumulative fixed effect for use of statin therapy and incident NODM was an OR of 1.61 (95% CI 1.55-1.68, p < 0.001). Our results suggest that statin therapy is associated with NODM, such that there is a small but significant risk of NODM among patients receiving statin for CVD prevention therapy. However, this high-risk population also has other diabetes risk factors (such as obesity and hypertension) contributing to the development of NODM. It is imperative that patients on statin therapy be monitored carefully for NODM. However, it can be argued that the risk of statin therapy is offset by the multitude of cardiovascular and kidney-protective effects provided by such an important and highly effective therapeutic agent. © 2018 S. Karger AG, Basel.

Status of and candidates for cell therapy in liver cirrhosis: overcoming the "point of no return" in advanced liver cirrhosis.

PubMed

Terai, Shuji; Tsuchiya, Atsunori

2017-02-01

The treatment of liver cirrhosis is currently being standardized and developed specifically to reduce activation of hepatic stellate cells (HSCs), inhibit fibrosis, increase degradation of matrix components, and reduce activated myofibroblasts. Cell therapy can be applied in the treatment of liver cirrhosis; however, the characteristic features of this therapy differ from those of other treatments because of the involvement of a living body origin and production of multiple cytokines, chemokines, matrix metalloproteinases (MMPs), and growth factors. Thus, cell therapies can potentially have multiple effects on the damaged liver, including alleviating liver cirrhosis and stimulating liver regeneration with affecting the host cells. Cell therapies initially involved autologous bone marrow cell infusion, and have recently developed to include the use of specific cells such as mesenchymal stem cells and macrophages. The associated molecular mechanisms, routes of administration, possibility of allogeneic cell therapy, and host conditions appropriate for cell therapies are now being extensively analyzed. In this review, we summarize the status and future prospects of cell therapy for liver cirrhosis.

A Mathematical Modeling Approach to Understanding the Effect of Anti‐Interleukin Therapy on Eosinophils

PubMed Central

Karelina, T; Voronova, V; Demin, O; Colice, G

2016-01-01

Emerging T‐helper type 2 (Th2) cytokine‐based asthma therapies, such as tralokinumab, lebrikizumab (anti‐interleukin (IL)‐13), and mepolizumab (anti‐IL‐5), have shown differences in their blood eosinophil (EOS) response. To better understand these effects, we developed a mathematical model of EOS dynamics. For the anti‐IL‐13 therapies, lebrikizumab and tralokinumab, the model predicted an increase of 30% and 10% in total and activated EOS in the blood, respectively, and a decrease in the total and activated EOS in the airways. The model predicted a rapid decrease in total and activated EOS levels in blood and airways for the anti‐IL‐5 therapy mepolizumab. All model‐based predictions were consistent with published clinical observations. The modeling approach provided insights into EOS response after treatment with Th2‐targeted therapies, and supports the hypothesis that an increase in blood EOS after anti‐IL‐13 therapy is part of the pharmacological action of these therapies. PMID:27885827

Effects of Cognitive-Behavioral Group Therapy for Depressive Mothers of Children with Behavior Problems

ERIC Educational Resources Information Center

Hye Ha, Eun

2006-01-01

The purpose of this study was to develop a cognitive behavioral group therapy (CBT) for depressed mothers of children between 5-12 years old, with behavior problems and to examine the effectiveness of the program. The CBT group met 8 times in total (2-hour weekly sessions for 8 weeks), followed by a booster session 3 months after the program was…

Increasing women’s sexual desire: The comparative effectiveness of estrogens and androgens

PubMed Central

Cappelletti, Maurand; Wallen, Kim

2016-01-01

Both estradiol and testosterone have been implicated as the steroid critical for modulating women’s sexual desire. By contrast, in all other female mammals only estradiol has been shown to be critical for female sexual motivation and behavior. Pharmaceutical companies have invested heavily in the development of androgen therapies for female sexual desire disorders, but today there are still no FDA approved androgen therapies for women. Nonetheless, testosterone is currently, and frequently, prescribed off-label for the treatment of low sexual desire in women, and the idea of testosterone as a cure-all for female sexual dysfunction remains popular. This paper places the ongoing debate concerning the hormonal modulation of women’s sexual desire within a historical context, and reviews controlled trials of estrogen and/or androgen therapies for low sexual desire in postmenopausal women. These studies demonstrate that estrogen-only therapies that produce periovulatory levels of circulating estradiol increase sexual desire in postmenopausal women. Testosterone at supraphysiological, but not at physiological, levels enhances the effectiveness of low-dose estrogen therapies at increasing women’s sexual desire; however, the mechanism by which supraphysiological testosterone increases women’s sexual desire in combination with an estrogen remains unknown. Because effective therapies require supraphysiological amounts of testosterone, it remains unclear whether endogenous testosterone contributes to the modulation of women’s sexual desire. The likelihood that an androgen-only clinical treatment will meaningfully increase women’s sexual desire is minimal, and the focus of pharmaceutical companies on the development of androgen therapies for the treatment of female sexual desire disorders is likely misplaced. PMID:26589379

Combined Therapy Conquers Resistant Tumors: Bortezomib and TRAIL | Center for Cancer Research

Cancer.gov

The principal strategy in the battle against cancer is simple: kill as many tumor cells as possible while sparing healthy cells. Unfortunately, traditional treatments, such as chemotherapy and radiation, have substantial side effects, and many cancers develop resistance to therapy.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

PubMed

Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy.

PubMed

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-09-02

BACKGROUND This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. MATERIAL AND METHODS The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. RESULTS Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. CONCLUSIONS We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy.

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy

PubMed Central

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-01-01

Background This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. Material/Methods The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. Results Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. Conclusions We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy. PMID:28864818

Music therapy as specific and complementary training for adults after cochlear implantation: A pilot study.

PubMed

Hutter, E; Argstatter, H; Grapp, M; Plinkert, P K

2015-09-01

Although cochlear implant (CI) users achieve good speech comprehension, they experience difficulty perceiving music and prosody in speech. As the provision of music training in rehabilitation is limited, a novel concept of music therapy for rehabilitation of adult CI users was developed and evaluated in this pilot study. Twelve unilaterally implanted, postlingually deafened CI users attended ten sessions of individualized and standardized training. The training started about 6 weeks after the initial activation of the speech processor. Before and after therapy, psychological and musical tests were applied in order to evaluate the effects of music therapy. CI users completed the musical tests in two conditions: bilateral (CI + contralateral, unimplanted ear) and unilateral (CI only). After therapy, improvements were observed in the subjective sound quality (Hearing Implant Sound Quality Index) and the global score on the self-concept questionnaire (Multidimensional Self-Concept Scales) as well as in the musical subtests for melody recognition and for timbre identification in the unilateral condition. Discussion Preliminary results suggest improvements in subjective hearing and music perception, with an additional increase in global self-concept and enhanced daily listening capacities. The novel concept of individualized music therapy seems to provide an effective treatment option in the rehabilitation of adult CI users. Further investigations are necessary to evaluate effects in the area of prosody perception and to separate therapy effects from general learning effects in CI rehabilitation.

Targeted alpha therapy using Radium-223: From physics to biological effects.

PubMed

Marques, I A; Neves, A R; Abrantes, A M; Pires, A S; Tavares-da-Silva, E; Figueiredo, A; Botelho, M F

2018-05-25

With the advance of the use of ionizing radiation in therapy, targeted alpha therapy (TAT) has assumed an important role around the world. This kind of therapy can potentially reduce side effects caused by radiation in normal tissues and increased destructive radiobiological effects in tumor cells. However, in many countries, the use of this therapy is still in a pioneering phase. Radium-223 ( 223 Ra), an alpha-emitting radionuclide, has been the first of its kind to be approved for the treatment of bone metastasis in metastatic castration-resistant prostate cancer. Nevertheless, the interaction mechanism and the direct effects of this radiopharmaceutical in tumor cells are not fully understood neither characterized at a molecular level. In fact, the ways how TAT is linked to radiobiological effects in cancer is not yet revised. Therefore, this review introduces some physical properties of TAT that leads to biological effects and links this information to the hallmarks of cancer. The authors also collected the studies developed with 223 Ra to correlate with the three categories reviewed - properties of TAT, 5 R's of radiobiology and hallmarks of cancer- and with the promising future to this radiopharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thinking About the Future Cognitive Remediation Therapy—What Works and Could We Do Better?

PubMed Central

Wykes, Til; Spaulding, Will D.

2011-01-01

This article reviews progress in the development of effective cognitive remediation therapy (CRT) and its translational process. There is now enough evidence that cognitive difficulties experienced by people with schizophrenia can change and that the agenda for the next generation of studies is to increase these effects systematically through cognitive remediation. We examine the necessary steps and challenges of moving CRT to treatment dissemination. Theories which have been designed to explain the effects of cognitive remediation, are important but we conclude that they are not essential for dissemination which could progress in an empirical fashion. One apparent barrier is that cognitive remediation therapies look different on the surface. However, they still tend to use many of the same training procedures. The only important marker for outcome identified in the current studies seems to be the training emphasis. Some therapies concentrate on massed practice of cognitive functions, whereas others also use direct training of strategies. These may produce differing effects as noted in the most recent meta-analyses. We recommend attention to several critical issues in the next generation of empirical studies. These include developing more complex models of the therapy effects that take into account participant characteristics, specific and broad cognitive outcomes, the study design, as well as the specific and nonspecific effects of treatment, which have rarely been investigated in this empirical programme. PMID:21860051

Telomerase and the search for the end of cancer.

PubMed

Mocellin, Simone; Pooley, Karen A; Nitti, Donato

2013-02-01

Many of the fundamental molecular mechanisms underlying tumor biology remain elusive and, thus, developing specific anticancer therapies remains a challenge. The recently discovered relationships identified among telomeres, telomerase, aging, and cancer have opened a new avenue in tumor biology research that may revolutionize anticancer therapy. This review summarizes the critical aspects of telomerase biology that underpin the development of novel telomerase-targeting therapies for malignant diseases, and special regard is given to the aspects of telomerase that make it such an appealing target, such as the widespread expression of telomerase in cancers. Despite significant progress, issues remain to be addressed before telomerase-based therapies are truly effective and we include critical discussion of the results obtained thus far. Copyright © 2012 Elsevier Ltd. All rights reserved.

Novel Strategies on Personalized Medicine for Breast Cancer Treatment: An Update.

PubMed

Chan, Carmen W H; Law, Bernard M H; So, Winnie K W; Chow, Ka Ming; Waye, Mary M Y

2017-11-15

Breast cancer is the most common cancer type among women worldwide. With breast cancer patients and survivors being reported to experience a repertoire of symptoms that are detrimental to their quality of life, the development of breast cancer treatment strategies that are effective with minimal side effects is therefore required. Personalized medicine, the treatment process that is tailored to the individual needs of each patient, is recently gaining increasing attention for its prospect in the development of effective cancer treatment regimens. Indeed, recent studies have identified a number of genes and molecules that may be used as biomarkers for predicting drug response and severity of common cancer-associated symptoms. These would provide useful clues not only for the determination of the optimal drug choice/dosage to be used in personalized treatment, but also for the identification of gene or molecular targets for the development of novel symptom management strategies, which ultimately would lead to the development of more personalized therapies for effective cancer treatment. In this article, recent studies that would provide potential new options for personalized therapies for breast cancer patients and survivors are reviewed. We suggest novel strategies, including the optimization of drug choice/dosage and the identification of genetic changes that are associated with cancer symptom occurrence and severity, which may help in enhancing the effectiveness and acceptability of the currently available cancer therapies.

Dementia and the Power of Music Therapy.

PubMed

Matthews, Steve

2015-10-01

Dementia is now a leading cause of both mortality and morbidity, particularly in western nations, and current projections for rates of dementia suggest this will worsen. More than ever, cost effective and creative non-pharmacological therapies are needed to ensure we have an adequate system of care and supervision. Music therapy is one such measure, yet to date statements of what music therapy is supposed to bring about in ethical terms have been limited to fairly vague and under-developed claims about an improvement in well-being. This article identifies the relevant sense of wellbeing at stake in the question of dementia therapies of this type. In broad terms the idea is that this kind of therapy has a restorative effect on social agency. To the extent that music arouses a person through its rhythms and memory-inducing effects, particularly in communal settings, it may give rise to the recovery of one's narrative agency, and in turn allow for both carer and patient to participate in a more meaningful and mutually engaging social connection. © 2015 John Wiley & Sons Ltd.

New Developments in Cognitive-Behavioral Therapy for Social Anxiety Disorder.

PubMed

Stangier, Ulrich

2016-03-01

Social anxiety disorder (SAD) is a highly prevalent and chronic disorder that causes considerable psychosocial impairment. This article reviews recent changes in the definition of SAD in DSM-5 and summarizes the current evidence for effective cognitive-behavioral treatments in adults, children, and adolescents. Current data suggests that cognitive-behavioral therapy (CBT) is efficacious in the treatment of this condition. Among different CBT approaches, individual cognitive therapy may be associated with the largest effect sizes. In this review, interventions targeting dysfunctional cognitive processes that contribute to the effective treatment of SAD are discussed. Some recent findings from neuroimaging research and studies on the augmentation of CBT using neuroenhancers indicate that changes in emotion regulation as well as fear extinction are important psychological mediators of positive outcome. Furthermore, internet-delivered CBT is a promising field of technological innovation that may improve access to effective treatments. Despite the availability of effective treatments, treatment-resistant SAD remains a common problem in clinical practice that requires more research efforts. Finally, potential areas for further development of CBT as well as its dissemination in health care are summarized.

The effects of massage therapy on physical growth and gastrointestinal function in premature infants: A pilot study.

PubMed

Choi, HyeJeong; Kim, Shin-Jeong; Oh, Jina; Lee, Myung-Nam; Kim, SungHee; Kang, Kyung-Ah

2016-09-01

To promote the growth and development of premature infants, effective and tender care is required in neonatal intensive care units (NICUs). The purpose of this study was to test the potential effects of massage therapy on increasing physical growth and promoting gastrointestinal function in premature infants. Twenty subjects were divided into two groups in the NICU of one general hospital located in South Korea. The experimental group (n = 10) were given massage therapy and the control group (n = 10) received routine care. Massage therapy was performed twice daily for 14 days, for 15 minutes per session. In the physical growth, height and chest circumference were significantly increased in the experimental group. In assessing gastrointestinal function, frequency of pre-feed gastric residual was significantly decreased and numbers of bowel movements were significantly increased in the experimental group. This study showed massage therapy has the potential effects on increasing physical growth and gastrointestinal function in premature infants. The massage in the NICU might be utilized as a part of developmental care, but more research needs to be done. NICU nurses need to be trained in massage therapy techniques to provide more effective clinical care for premature infants. © The Author(s) 2015.

Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy.

PubMed

Gao, Yuanzheng; Guo, Xiuming; Santostefano, Katherine; Wang, Yanlin; Reid, Tammy; Zeng, Desmond; Terada, Naohiro; Ashizawa, Tetsuo; Xia, Guangbin

2016-08-01

Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.

Recent patents on light based therapies: photodynamic therapy, photothermal therapy and photoimmunotherapy.

PubMed

Sanchez-Barcelo, Emilio J; Mediavilla, Maria D

2014-01-01

This article reviews the more recent patents in three kinds of therapeutic strategies using the application of visible light to irradiate photosensible substances (PSs) of different natures. The light-activation of these PSs is directly responsible for the desired therapeutic effects. This group of light therapies includes photodynamic therapy (PDT), photothermal therapy (PTT) and photoimmunotherapy (PIT). Therapeutic mechanisms triggered by the activation of the PSs depend basically (though not exclusively) on the release of reactive oxygen species (ROS) and the activation of immune responses (PDT and PIT) or the local generation of heat (PTT). The main difference between PIT and PDT is that in PIT, monoclonal antibodies (MABs) are associated to PSs to improve the selective binding of the PSs to the target tissues. All these therapeutic strategies offer the possibility of destroying tumor tissue without damaging the surrounding healthy tissue, which is not achievable with chemotherapy or radiotherapy. PDT is also used as an alternative or adjuvant antimicrobial therapy together with the traditional antibiotic therapy since these organisms are unlikely to develop resistance to the ROS induced by PDT. Furthermore, PDT also induces an immune response against bacterial pathogens. The current challenge in PDT, PIT and PTT is to obtain the highest level of selectivity to act on targeted sick tissues with the minimum effects on the surrounding healthy tissue. The development of new PSs with high affinity for specific tissues, new PSs- MABs conjugates to bind to specific kinds of tumors, and new light-sensible nanoparticles with low toxicity, will increase the clinical utility of these therapies.

The Effects of Herbs and Fruits on Leukaemia

PubMed Central

Saedi, Tayebeh Azam; Md Noor, Sabariah; Ismail, Patimah; Othman, Fauziah

2014-01-01

In developing countries, herbal therapy is the first and basis form of treatment for most types of diseases. About 75–80% of the world's population prefers herbal therapy as a major treatment due to its better adequacy and satisfactoriness, which enhance human body's symmetry with minimal side effects. Fruits and plants have been presented from the past as promising tools in becoming a natural anticancer agents. Many of these plant extracts are currently used in cancer therapy and prevention. This review paper will particularly explore and emphasize on herbs and fruits used in the treatment of the leukaemia. PMID:25250054

Complexities of gut microbiome dysbiosis in the context of HIV infection and antiretroviral therapy

PubMed Central

Li, Sam X.; Armstrong, Abigail J. S.; Neff, C. Preston; Shaffer, Michael; Lozupone, Catherine A.; Palmer, Brent E.

2016-01-01

HIV infection is associated with an altered gut microbiome that is not consistently restored with effective antiretroviral therapy (ART). Interpretation of the specific microbiome changes observed during HIV infection is complicated by factors like population, sample type, and ART – each of which may have dramatic effects on gut bacteria. Understanding how these factors shape the microbiome during HIV infection (which we refer to as the HIV-associated microbiome) is critical for defining its role in HIV disease, and for developing therapies that restore gut health during infection. PMID:26940481

Effects of rational-emotive therapy on psychophysiological and reported measures of test anxiety arousal.

PubMed

Barabasz, A F; Barabasz, M

1981-07-01

Developed audio taped lectures, taped therapy session models, and homework assignments designed to reduce irrational beliefs associated with test anxiety within Ellis' rational-emotive therapy (RET) approach. The initial sample consisted of 148 university students. Comparisons with an attention placebo counseling program, which was established to be equally credible by a post-experiment inquiry and a no-treatment group found the RET Ss to show significantly lower skin conductance responses to a test anxiety visualization and lower reported anxiety on a questionnaire. However, skin conductance responses to an alternative test anxiety visualization did not show treatment effects.

Diabetes and cardiovascular disease: the potential benefit of incretin-based therapies.

PubMed

Addison, Daniel; Aguilar, David

2011-04-01

The health burden of type 2 diabetes mellitus continues to increase worldwide. A substantial portion of this burden is due to the development of cardiovascular disease in patients with diabetes. Recent failures of clinical trials of intensive glucose control to reduce macrovascular events, coupled with reports of potential harm of certain diabetic therapy, have led to increased scrutiny as new diabetic therapies are developed. Incretin peptides are a group of gastrointestinal proteins that regulate glucose metabolism through multiple mechanisms, and incretin-based therapies have been developed to treat type 2 diabetes. These agents include glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-IV (DPP-IV) inhibitors. In addition to effects on glucose homeostasis, growing evidence suggest that these peptides may also affect the cardiovascular system. In this review, we discuss recent findings concerning the potential, yet untested, benefits of incretin-based pharmacotherapy in the treatment of cardiovascular disease.

Atopic dermatitis phenotypes and the need for personalized medicine

PubMed Central

Cabanillas, Beatriz; Brehler, Ann-Christin; Novak, Natalija

2017-01-01

Purpose of review To describe recent developments in therapies which target the molecular mechanisms in atopic dermatitis. Recent findings Current advances in the understanding of the molecular basis of atopic dermatitis are leading to the stratification of different atopic dermatitis phenotypes. New therapies offer the option to target-specific molecules involved in the pathophysiology of atopic dermatitis. Current new therapies under investigation aim to modulate specific inflammatory pathways associated with distinctive atopic dermatitis phenotypes, which would potentially translate into the development of personalized, targeted-specific treatments of atopic dermatitis. Summary Despite the unmet need for well tolerated, effective, and personalized treatment of atopic dermatitis, the current standard treatments of atopic dermatitis do not focus on the individual pathogenesis of the disease. The development of targeted, phenotype-specific therapies has the potential to open a new promising era of individualized treatment of atopic dermatitis. PMID:28582322

Spinal Manipulative Therapy for Adolescent Idiopathic Scoliosis: A Systematic Review.

PubMed

Théroux, Jean; Stomski, Norman; Losco, Christine Dominique; Khadra, Christelle; Labelle, Hubert; Le May, Sylvie

The purpose of this study was to perform a systematic review of clinical trials of spinal manipulative therapy for adolescent idiopathic scoliosis. Search strategies were developed for PubMed, CINHAL, and CENTRAL databases. Studies were included through June 2016 if they were prospective trials that evaluated spinal manipulative therapy (eg, chiropractic, osteopathic, physical therapy) for adolescent idiopathic scoliosis. Data were extracted and assessed by 2 independent reviewers. Cochrane risk of bias tools were used to assess the quality of the included studies. Data were reported qualitatively because heterogeneity prevented statistical pooling. Four studies satisfied the inclusion criteria and were critically appraised. The findings of the included studies indicated that spinal manipulative therapy might be effective for preventing curve progression or reducing Cobb angle. However, the lack of controls and small sample sizes precluded robust estimation of the interventions' effect sizes. There is currently insufficient evidence to establish whether spinal manipulative therapy may be beneficial for adolescent idiopathic scoliosis. The results of the included studies suggest that spinal manipulative therapy may be a promising treatment, but these studies were all at substantial risk of bias. Further high-quality studies are warranted to conclusively determine if spinal manipulative therapy may be effective in the management of adolescent idiopathic scoliosis. Copyright © 2017. Published by Elsevier Inc.

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes.

PubMed

Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

2017-01-01

Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide- co -glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP-mediated PSDT on MH7A synoviocytes. The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP-mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP-mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP-mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N -acetylcysteine. Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP-mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase-transition nanoparticle-mediated PSDT in the future.

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

PubMed Central

Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

2017-01-01

Background Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide-co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP–mediated PSDT on MH7A synoviocytes. Methods The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP–mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. Results The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP–mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP–mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N-acetylcysteine. Conclusion Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP–mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase-transition nanoparticle-mediated PSDT in the future. PMID:28123298

Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder

ERIC Educational Resources Information Center

Greenberg, Jennifer L.; Markowitz, Sarah; Petronko, Michael R.; Taylor, Caitlin E.; Wilhelm, Sabine; Wilson, G. Terence

2010-01-01

The onset of appearance-related concerns associated with body dysmorphic disorder (BDD) typically occurs in adolescence, and these concerns are often severe enough to interfere with normal development and psychosocial functioning. Cognitive behavioral therapy (CBT) is an effective treatment for adults with BDD. However, no treatment studies…

[Diseases linked to Helicobacter pylori infection].

PubMed

Gisbert, Javier P

2014-09-01

Below is a summary of the main conclusions that came from reports presented at this year's Digestive Disease Week (2014) relating to Helicobacter pylori infection. Despite the undeniable decline of the infection's frequency, in the near future, developed countries--or at least some sub-populations--will continue to have a significant prevalence of the infection. Clarithromycin, metronidazole and quinolone resistance rates are considerably high in most countries and these rates are on the rise. The eradication of H. pylori improves symptoms of functional dyspepsia, although only in a minority of patients; adding antidepressants to eradication therapy could improve long-term response. In patients who were admitted with gastrointestinal bleeding from peptic ulcers, it is necessary to thoroughly study the presence of H. pylori infection and administer eradication therapy as early as possible. Eradication of H. pylori in patients undergoing endoscopic resection of early-stage gastric cancer reduces incidence of metachronous tumors. We have some diagnostic innovations, such as carrying out various techniques--a rapid urease test, culture or PCR--based on gastric samples obtained by scraping the mucosa. The effectiveness of conventional triple therapy is clearly insufficient and continues to decline. The superiority of sequential therapy over conventional triple therapies has not been definitively established. Concomitant therapy is simpler and more effective than sequential therapy. Optimized concomitant therapy (with high doses of proton-pump inhibitors [PPI] and over 14 days) is highly effective, more so than standard concomitant therapy. For patients who are allergic to penicillin, 2 treatment options were essentially described: PPI-clarithromycin-metronidazole (clarithromycin-sensitive strains) and quadruple therapy with bismuth (when the bacterial sensitivity is unknown). If conventional triple therapy fails, second-line therapy with levofloxacin is effective and is also easier and better tolerated than quadruple therapy with bismuth. Triple therapy with levofloxacin is also a promising alternative if sequential or concomitant therapy fails. New-generation quinolones, such as moxifloxacin, could be useful as part of rescue eradication therapy. Even after 3 eradication therapies have failed, a fourth empirical rescue therapy (with rifabutin) could be effective. The eradication of H. pylori can finally be obtained in the vast majority of patients by using a rescue strategy of up to 4 consecutive empirical therapies, without conducting bacterial cultures. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

PubMed Central

Kawanami, Daiji; Matoba, Keiichiro; Sango, Kazunori; Utsunomiya, Kazunori

2016-01-01

An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications. PMID:27483245

Ocular side-effects associated with imatinib mesylate (Gleevec).

PubMed

Fraunfelder, Frederick W; Solomon, Jonathan; Druker, Brian J; Esmaeli, Bita; Kuyl, Jennifer

2003-08-01

This retrospective case series describes ocular side-effects associated with imatinib mesylate (Gleevec) and the clinical characteristics of these adverse reactions. A chart review of 104 patients on imatinib mesylate therapy from Oregon Health & Science University's Cancer Center were studied with regard to ocular side-effects. In addition, spontaneous reports from the Food and Drug Administration, the World Health Organization, and the National Registry of Drug-Induced Ocular Side-Effects databases were reviewed, including a Medline literature search. Seventy-three (70%) of the patients at OHSU developed periorbital edema and 19 patients (18%) developed epiphora after receiving imatinib mesylate. Average dose was 407.5+/-60 mg. Periorbital edema occurred an average of 68+/-48 days after initiation of therapy. WHO classification of side-effects is as follows: certain: periorbital edema; probable: epiphora; possible: extraocular muscle palsy, ptosis, blepharoconjunctivitis; unlikely: glaucoma, papilledema, retinal hemorrhage, photosensitivity, abnormal vision, and increased intraocular pressure. Periorbital edema and epiphora are the two most common ocular side-effects related to imatinib mesylate therapy. Clinical characteristics of imatinib mesylate induced periorbital edema are described. Management of ocular side-effects is conservative except in very rare cases of visually significant periorbital edema.

Gene therapy for arthritis

PubMed Central

Traister, Russell S.

2008-01-01

Arthritis is among the leading causes of disability in the developed world. There remains no cure for this disease and the current treatments are only modestly effective at slowing the disease's progression and providing symptomatic relief. The clinical effectiveness of current treatment regimens has been limited by short half-lives of the drugs and the requirement for repeated systemic administration. Utilizing gene transfer approaches for the treatment of arthritis may overcome some of the obstacles associated with current treatment strategies. The present review examines recent developments in gene therapy for arthritis. Delivery strategies, gene transfer vectors, candidate genes, and safety are also discussed. PMID:18176779

A 10-year follow-up study of completers versus dropouts following treatment with an integrated cognitive-behavioral group therapy for eating disorders.

PubMed

Okamoto, Yuri; Miyake, Yoshie; Nagasawa, Ichie; Shishida, Kazuhiro

2017-01-01

Cognitive-behavioral therapy (CBT) has been recommended for the treatment of eating disorders, and group therapy is known to have certain advantages over individual therapy. The aim of the current study was to compare the 10-year prognosis of patients who completed integrated group CBT with those who dropped out and to examine the effect of completion of group CBT on the prognosis. The participants were 65 adult patients with eating disorders. All patients were women and Japanese. The average age (19-37) of the patients was 25.1 ± 3.8 years, and the average body mass index (BMI) was 17.7 ± 2.0. We conducted integrated group CBT with the patients and compared eating disorder symptoms, mood states, coping styles, and self-esteem before and after therapy. Furthermore, we compared clinical features and the 10-year prognosis of patients who completed the treatment and those who dropped out. After 10 sessions of group therapy, Eating Attitudes Test scores, Profile of Mood States depression scores, and Coping Inventory for Stressful Situations emotion-oriented scores decreased, while Rosenberg's Self-Esteem Scale scores increased. Regarding the results of the 10-year follow up, the completer group had more patients with a good prognosis. In contrast, the dropout group had more patients with a poor prognosis. Those who completed the integrated group CBT had a good prognosis. Group therapy gives the patients an opportunity to form peer relationships, and helps them to develop communication and socialization skills. Furthermore, in the group therapy sessions, the patients develop self-awareness by listening to other members of the group and they also develop interpersonal relationships. This effect may be temporary, but experience of group therapy may provide hope for the patient and increase the chance of the patient continuing treatment. Retrospectively registered in University Hospital Medical Information Network in Japan: No. 000028868 (May 19th, 2017).

Superparamagnetic Fe3O4-PEG2K-FA@Ce6 Nanoprobes for in Vivo Dual-mode Imaging and Targeted Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Yin, Ting; Huang, Peng; Gao, Guo; Shapter, Joseph G.; Shen, Yulan; Sun, Rongjin; Yue, Caixia; Zhang, Chunlei; Liu, Yanlei; Zhou, Sui; Cui, Daxiang

2016-11-01

The development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG2K-FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG2K) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG2K-FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG2K-FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.

Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management.

PubMed

Saxena, Roopali; Rida, Padmashree C G; Kucuk, Omer; Aneja, Ritu

2016-06-01

Cancer, referred to as the 'disease of civilization', continues to haunt humanity due to its dreadful manifestations and limited success of therapeutic interventions such as chemotherapy in curing the disease. Although effective, chemotherapy has repeatedly demonstrated inadequacy in disease management due to its debilitating side effects arising from its deleterious nonspecific effects on normal healthy cells. In addition, development of chemoresistance due to mono-targeting often results in cessation of chemotherapy. This urgently demands development and implementation of multitargeted alternative therapies with mild or no side effects. One extremely promising strategy that yet remains untapped in the clinic is augmenting chemotherapy with dietary phytochemicals or extracts. Ginger, depository of numerous bioactive molecules, not only targets cancer cells but can also mitigate chemotherapy-associated side effects. Consequently, combination therapy involving ginger extract and chemotherapeutic agents may offer the advantage of being efficacious with reduced toxicity. Here we discuss the remarkable and often overlooked potential of ginger extract to manage cancer, the possibility of developing ginger-based combinational therapies, and the major roadblocks along with strategies to overcome them in clinical translation of such inventions. We are optimistic that clinical implementation of such combination regimens would be a much sought after modality in cancer management. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Management of Side Effects of Novel Therapies for Multiple Myeloma: Consensus Statements Developed by the International Myeloma Foundation’s Nurse Leadership Board

PubMed Central

Bertolotti, Page; Bilotti, Elizabeth; Colson, Kathleen; Curran, Kathleen; Doss, Deborah; Faiman, Beth; Gavino, Maria; Jenkins, Bonnie; Lilleby, Kathy; Love, Ginger; Mangan, Patricia A.; McCullagh, Emily; Miceli, Teresa; Miller, Kena; Rogers, Kathryn; Rome, Sandra; Sandifer, Stacey; Smith, Lisa C.; Tariman, Joseph D.; Westphal, Jeanne

2014-01-01

Nurses play an essential role in managing the care of patients with multiple myeloma, who require education and support to receive and adhere to optimal therapy. The International Myeloma Foundation created a Nurse Leadership Board comprised of oncology nurses from leading cancer centers and community practices. An assessment survey identified the need for specific recommendations for managing key side effects of novel antimyeloma agents. Myelosuppression, thromboembolic events, peripheral neuropathy, steroid toxicities, and gastrointestinal side effects were selected for the first consensus statements. The board developed recommendations for healthcare providers in any medical setting, including grading of side-effect toxicity and strategies for managing the side effects in general, with specific recommendations pertaining to the novel agents. PMID:18490252

Sensitivity of Breast Tumors to Oncolytic Viruses

DTIC Science & Technology

2005-08-01

reproductions will be in black and white. 14. ABSTRACT The goal of this project is to develop novel therapies for breast cancer based on the oncolytic...effect than breast cancer cells. However, in syngeneic breast cancer system in vivo, rM51R-M virus is only partially effective at killing breast tumors...aggressive tumors that are resistant to more conventional therapies. 15. SUBJECT TERMS Vesicular stomatitis virus, interleukin 12, breast cancer

The role of incretin-based therapies in prediabetes: a review.

PubMed

Ahmadieh, Hala; Azar, Sami T

2014-12-01

Prediabetes, a high-risk state for future development of diabetes, is prevalent globally. Abnormalities in the incretin axis are important in the progression of B-cell failure in type 2 diabetes. Incretin based therapy was found to improve B cell mass and glycaemic control in addition to having multiple beneficial effects on the systolic and diastolic blood pressure, weight loss in addition to their other beneficial effects on the liver and cardiovascular system. In prediabetes, several well-designed preventive trials have shown that lifestyle and pharmacologic interventions such as metformin, thiazolidinediones (TZD), acarbose and, nateglinide and orlistat, are effective in reducing diabetes development. In recent small studies, incretin based therapy (DPP IV inhibitors and GLP-1 agonists) have also been extended to patients with prediabetes since it was shown to better preserve B-cell function and mass in animal studies and in clinical trials and it was also shown to help maintain good long term metabolic control. Because of the limited studies and clinical experience, their side effects and costs currently guidelines do not recommend incretin-based therapies as an option for treatment in patients with prediabetes. With future clinical trials and studies they may be recommended for patients with impaired fasting glucose or impaired glucose tolerance. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis

PubMed Central

Oz, Helieh S.

2014-01-01

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Results Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams Conclusions This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis. PMID:25210646

Recent developments in research and treatment for social phobia (social anxiety disorder).

PubMed

Cottraux, Jean

2005-01-01

This review covers three themes of research that brought fresh data useful for clinical practice in a handicapping anxiety disorder: social phobia. Recent findings deriving from basic biological research, new forms of psychological therapies, and recent psychopharmacology controlled trials are reviewed. The basic neuroimaging research suggests that greater activation of the amygdala to novel versus familiar faces may be an underlying trait marker for social phobia. Social phobia may represent a phenotype that expresses a genetically driven trait of social withdrawal, which may be related to infantile inhibited temperament (Kagan's syndrome). The development of virtual reality therapy as therapeutic tool for social phobia appeared promising in one controlled, but not randomized, study. A controlled study suggests that social phobias in children can be effectively treated with cognitive behavioural therapy. This represents an extension of the work done with adults. Venlafaxine appears an effective short-term treatment for social anxiety disorder in two controlled studies. A new compound, pregabalin, appeared clearly effective in a positive controlled study. This trial marks the advent of a new pharmacological lineage for social phobia. Both venlafaxine and pregabalin, however, have been studied in short-term studies. Longer follow-up and relapse prevention studies are warranted. Neuroimaging research points to a temperamental basis for social phobia. Virtual reality therapy is an emerging tool to carry out exposure treatment. Group cognitive behavioural therapy can be extended successfully to children. Venlafaxine and pregabalin have a proven short-term effectiveness in social phobia.

The linkage between Churg-Strauss syndrome and leukotriene receptor antagonists: fact or fiction?

PubMed Central

McDanel, Deanna L; Muller, Barbara A

2005-01-01

Epidemiologic evidence has shown that the worldwide prevalence of asthma is increasing. The leukotriene receptor antagonists (LTRAs) represent a new class of therapy for asthma. They have been developed in the last decade and play a pivotal steroid-sparing role in treating the inflammatory component of asthma. Consequently, reports of Churg-Strauss syndrome (CSS), a rare form of systemic vasculitis, have been recognized as a potential side effect in individuals with moderate to severe asthma on LTRA therapy. The serious nature of this disorder is worthy of prompt recognition by clinicians and aggressive therapy to avoid the subsequent longstanding effects of vasculitis. To validate the postulated linkage between the LTRAs and CSS, this review comprehensively evaluates reported cases in the literature and supports a pathophysiological relationship between the LTRAs and the development of CSS. PMID:18360552

Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

PubMed Central

Glasgow, Micah D. K.; Chougule, Mahavir B.

2016-01-01

Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

PubMed

Hirano, Emi; Fuji, Hiroshi; Onoe, Tsuyoshi; Kumar, Vinay; Shirato, Hiroki; Kawabuchi, Koichi

2014-03-01

The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Memory reconsolidation and psychotherapeutic process.

PubMed

Liberzon, Israel; Javanbakht, Arash

2015-01-01

Lane et al. propose a heuristic model in which distinct, and seemingly irreconcilable, therapies can coexist. Authors postulate that memory reconsolidation is a key common neurobiological process mediating the therapeutic effects. This conceptualization raises a set of important questions regarding neuroscience and translational aspects of fear memory reconsolidation. We discuss the implications of the target article's memory reconsolidation model in the development of more effective interventions, and in the identification of less effective, or potentially harmful approaches, as well as concepts of contextualization, optimal arousal, and combined therapy.

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

PubMed Central

Rikabi, Sarah; French, Anna; Pinedo-Villanueva, Rafael; Morrey, Mark E; Wartolowska, Karolina; Judge, Andrew; MacLaren, Robert E; Mathur, Anthony; Williams, David J; Wall, Ivan; Birchall, Martin; Reeve, Brock; Atala, Anthony; Barker, Richard W; Cui, Zhanfeng; Furniss, Dominic; Bure, Kim; Snyder, Evan Y; Karp, Jeffrey M; Price, Andrew; Carr, Andrew; Brindley, David A

2014-01-01

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community. PMID:25383173

Structured Play Therapy Groups for Preschoolers: facilitating the emergence of social competence.

PubMed

Stone, Susan; Stark, Martha

2013-01-01

Over the years, we have developed a working model of Structured Play Therapy Groups for Preschoolers, an innovative treatment approach designed to address the needs of young children ages 3 to 5 struggling to adjust to the social demands of their preschool classrooms. These short-term therapy groups facilitate development of the young child's social competence and capacity to participate effectively in a classroom environment. Although the literature on therapy groups for children suggests that preschoolers are not yet evolved enough developmentally to engage actively in a group process, our experience indicates otherwise. The model of treatment presented here will therefore challenge that contention with the claim that not only can preschoolers participate in a structured therapy group of peers but they can, by virtue of that very participation, benefit in ways that will prepare them (as they transition from preschool to kindergarten) for the ever-increasing demands of their ever-expanding social milieus.

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

PubMed

Davies, Benjamin M; Rikabi, Sarah; French, Anna; Pinedo-Villanueva, Rafael; Morrey, Mark E; Wartolowska, Karolina; Judge, Andrew; MacLaren, Robert E; Mathur, Anthony; Williams, David J; Wall, Ivan; Birchall, Martin; Reeve, Brock; Atala, Anthony; Barker, Richard W; Cui, Zhanfeng; Furniss, Dominic; Bure, Kim; Snyder, Evan Y; Karp, Jeffrey M; Price, Andrew; Carr, Andrew; Brindley, David A

2014-01-01

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

Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies

PubMed Central

Brandi, Giovanni; Farioli, Andrea; Astolfi, Annalisa; Biasco, Guido; Tavolari, Simona

2015-01-01

Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease. PMID:26142706

Ozone Gas Effect on Mineral Content of Dentin exposed to Streptococcus mutans Biofilm: An Energy-dispersive X-ray Evaluation.

PubMed

Chaves, Rafaella M; Estrela, Carlos; Cardoso, Paula C; de Je Barata, Terezinha; de Souza, João B; de Torres, Érica M; Estrela, Cyntia Ra; Magalhães, Ana Pr; Lopes, Lawrence G

2017-04-01

This study aims to assess the effect of ozone gas on dentin exposed to Streptococcus mutans biofilm by evaluation of mineral content [log calcium-to-phosphorus (Ca/P)] using energy-dispersive X-ray (EDX) spectroscopy. Five human third molars were sectioned into four slices of dentin and distributed in four groups: I - control (no treatment); II - ozone therapy; III - biofilm development; IV - ozone therapy followed by biofilm development. Mineral content (log Ca/P) was evaluated by EDX. Data were analyzed by analysis of variance and Tukey's test (p < 0.05). Results showed that the mineral content of control group (I) was similar to ozone group (II), and was statistically higher than biofilm (III) and ozone + biofilm (IV). The lowest log Ca/P was determined in biofilm group (III). It can be concluded that ozone gas did not grant preventive effects of demineralization by S. mutans biofilm on dentin surface. Ozone gas therapy may be an alternative noninvasive treatment aiming to reduce the levels of caries-associated microorganisms. This therapy may, thereby, be an alternative and/or complementary treatment strategy in preventive dentistry.

Photo-pharmaceutical therapy: features and prospects

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Potapenko, Alexander Y.; Minenkov, Alexander A.

2001-07-01

This article is an attempt to analyze the concept, distinguishing features and possible application of photo- pharmaceutical therapy (PPT). Besides photopheresis, PUVA, and photodynamic therapy, PPT also embraces a broad spectrum of various combinations of light and drugs. PPT techniques can be classified according to the role of light in drug therapy into several groups: 1) Light activation of drugs before, during or after their administration, 2) light activation of cells of biotissue to potentiate the pharmaceutical effect of drugs, 3) light assisted drug delivery, 4) optical sensing of drug action at cellular and subcellular levels, and 5) selective photochemistry of drugs during their manufacturing. PPT seeks to describe the mechanisms of light-drug interaction, to time and sequence light-drug action, and to verify their synergetic effect. This article yields the results of developing new PPT modifications created in collaboration with some Russian scientific institutes and medical centers. The developed modifications are as follows: 1) drug pre-administration photoactivation, 2) antibody-photoconformation photoimmunotherapy, 3) photophonophoresis with a blend of photosensitizers and antibiotics, 4) photoelectrophoresis, 5) drug effect enhancement due to laser-induced blood circulation activation, 6) photoimmunization with alpha- fetoprotein, 7) photo-pharmaceutical dosimetry, and 8) a rapid drug toxicity photoassay.

Combination therapy for malaria in Africa: hype or hope?

PubMed Central

Bloland, P. B.; Ettling, M.; Meek, S.

2000-01-01

The development of resistance to drugs poses one of the greatest threats to malaria control. In Africa, the efficacy of readily affordable antimalarial drugs is declining rapidly, while highly efficacious drugs tend to be too expensive. Cost-effective strategies are needed to extend the useful life spans of antimalarial drugs. Observations in South-East Asia on combination therapy with artemisinin derivatives and mefloquine indicate that the development of resistance to both components is slowed down. This suggests the possibility of a solution to the problem of drug resistance in Africa, where, however, there are major obstacles in the way of deploying combination therapy effectively. The rates of transmission are relatively high, a large proportion of asymptomatic infection occurs in semi-immune persons, the use of drugs is frequently inappropriate and ill-informed, there is a general lack of laboratory diagnoses, and public health systems in sub-Saharan Africa are generally weak. Furthermore, the cost of combination therapy is comparatively high. We review combination therapy as used in South-East Asia and outline the problems that have to be overcome in order to adopt it successfully in sub-Saharan Africa. PMID:11196485

Stem cell origins and animal models of hepatocellular carcinoma.

PubMed

Aravalli, Rajagopal N; Steer, Clifford J; Sahin, M Behnan; Cressman, Erik N K

2010-05-01

Hepatocellular carcinoma (HCC) is a common malignant tumor that almost always occurs within a preexisting background of chronic liver disease and cirrhosis. Currently, medical therapy is not effective in treating most HCC, and the only hope of cure is either resection or liver transplantation. A small minority of patients is eligible for these therapies, which entail major morbidity at the very least. In spite of immense scientific advances during the past 3 decades, patient survival has improved very little. In order to reduce morbidity and mortality from HCC, improvements in early diagnosis and development of novel local and systemic therapies for advanced disease are essential, in addition to efforts geared towards primary prevention. Studies with experimental animal models that closely mimic human disease are very valuable in understanding physiological, cellular and molecular mechanisms underlying the disease. Furthermore, appropriate animal models have the potential to increase our understanding of the effects of image-guided minimally invasive therapies and thereby help to improve such therapies. In this review, we examine the evidence for stem cell origins of such tumors, critically evaluate existing models and reflect on how to develop new models for minimally invasive, image-guided treatment of HCC.

Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

PubMed Central

Jelveh, Salomeh; Chithrani, Devika B.

2011-01-01

The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research. PMID:24212654

Anti-cytokine therapy for prevention of atherosclerosis.

PubMed

Kirichenko, Tatiana V; Sobenin, Igor A; Nikolic, Dragana; Rizzo, Manfredi; Orekhov, Alexander N

2016-10-15

Currently a chronic inflammation is considered to be the one of the most important reasons of the atherosclerosis progression. A huge amount of researches over the past few decades are devoted to study the various mechanisms of inflammation in the development of atherosclerotic lesions. To review current capabilities of anti-inflammatory therapy for the prevention and treatment of atherosclerosis and its clinical manifestations. Appropriate articles on inflammatory cytokines in atherosclerosis and anti-inflammatory prevention of atherosclerosis were searched in PubMed Database from their respective inceptions until October 2015. "The role of inflammatory cytokines in the development of atherosclerotic lesions" describes available data on the possible inflammatory mechanisms of the atherogenesis with a special attention to the role of cytokines. "Modern experience of anti-inflammatory therapy for the treatment of atherosclerosis" describes modern anti-inflammatory preparations with anti-atherosclerotic effect including natural preparations. In "the development of anti-inflammatory herbal preparation for atherosclerosis prevention" an algorithm is demonstrated that includes screening of anti-cytokine activity of different natural products, the development of the most effective combination and estimation of its effect in cell culture model, in animal model of the acute aseptic inflammation and in a pilot clinical trial. A natural preparation "Inflaminat" based on black elder berries (Sambucus nigra L.), violet tricolor herb (Viola tricolor L.) and calendula flowers (Calendula officinalis L.) possessing anti-cytokine activity was developed using the designed algorithm. The results of the following 2-year double blind placebo-controlled clinical study show that "Inflaminat" reduces carotid IMT progression, i.e. has anti-atherosclerotic effect. Anti-cytokine therapy may be a promising direction in moderation of atherogenesis, especially when it begins on the early stages of subclinical atherosclerosis. The use of herbal preparations with anti-cytokine mechanism of action is the most perspective for timely prevention of atherosclerosis, as they have no significant side effects and can be prescribed for long-term administration. Copyright © 2015 Elsevier GmbH. All rights reserved.

Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor: A Review of Pharmacodynamics and Clinical Development.

PubMed

Clark, Amy S; Karasic, Thomas B; DeMichele, Angela; Vaughn, David J; O'Hara, Mark; Perini, Rodolfo; Zhang, Paul; Lal, Priti; Feldman, Michael; Gallagher, Maryann; O'Dwyer, Peter J

2016-02-01

Palbociclib (PD0332991) is a newly developed drug that received breakthrough designation and recent US Food and Drug Administration approval in combination with endocrine therapy in the treatment of hormone receptor positive, ERBB2-negative (formerly HER2 or HER2/neu) breast cancer in the first-line metastatic setting. Herein we describe the preclinical and translational data and early- and late-phase clinical trials in which palbociclib has been investigated in a broad array of tumor types. We discuss the pharmacodynamics, pharmacokinetics, toxic effects, and clinical response rates. On March 1, 2015, we conducted a review of the literature describing the development of palbociclib. We used the PubMed search terms "PD0332991," "palbociclib," and "CDK4/6 inhibitor" to find all published articles of interest, without limitation as to publication date. Palbociclib is a potent and specific oral cyclin-dependent kinase (CDK) 4/6 inhibitor that has strong preclinical data to support its activity in retinoblastoma protein-expressing tumors. Phase 1 trials have demonstrated safety, and phase 2 trials have shown single-agent activity in mantle-cell lymphoma, breast cancer, liposarcoma, and teratoma with reversible neutropenia as the main toxic effect. Addition of palbociclib to endocrine therapy improves progression-free survival in endocrine therapy-naïve and endocrine therapy-resistant metastatic settings. Palbociclib is well tolerated and has therapeutic potential for multiple cancers, including breast cancer, where its efficacy has been demonstrated alone and in combination with endocrine therapy. Additional combinations of palbociclib with endocrine therapy, chemotherapy, and targeted therapy have potential in various tumors, and phase 3 trials are under way.

Art therapy for people with psychosis: a narrative review of the literature.

PubMed

Attard, Angelica; Larkin, Michael

2016-11-01

Art therapy enables individuals to use art to creatively express themselves and communicate differently with themselves, others, and their reality. The National Institute for Health and Clinical Excellence guidelines for psychosis and schizophrenia suggest that arts therapies, which include art therapy, are considered to improve negative symptoms of psychosis. We examined the effectiveness of art therapy for people with psychosis and explored whether art therapy is a meaningful and acceptable intervention in this Review. Seven electronic databases were searched for empirical papers that concerned the use of art therapy for adults with psychosis that were published from 2007 onwards. The search identified 18 papers. High-quality quantitative articles provided inconclusive evidence for the effectiveness of art therapy in adults with psychosis. However, high-quality qualitative articles indicated that therapists and clients considered art therapy to be a beneficial, meaningful, and acceptable intervention, although this conclusion was based on a small number of studies. In this Review, we discuss the theoretical, clinical, and methodological issues in light of the development of more robust research, which is needed to corroborate individuals' experiences and guide evidence-based practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer.

PubMed

Singh, Prabhsimranjot; Toom, Sudhamshi; Huang, Yiwu

2017-05-12

Targeted therapy and immunotherapy have revolutionized treatment of various cancers in the past decade. Despite targeted therapy with trastuzumab in Her2-positive gastric cancer patients, survival has been dismal, mostly due to disease progression and toxicity related to the treatments. One area of active development is looking for ideal monoclonal antibodies (IMAB) specific to the proteins only on the tumor and hence avoiding unnecessary side effects. Claudin proteins with isoform 2 are one such protein, specific for several cancers, particularly gastric cancer and its metastases, leading to the development of anti-claudin 18.2 specific antibody, claudiximab. This review will highlight the latest development of claudiximab as first in class IMAB for the treatment of gastric cancer.

The fungal resistome: a risk and an opportunity for the development of novel antifungal therapies.

PubMed

Reales-Calderón, Jose A; Molero, Gloria; Gil, Concha; Martínez, José L

2016-08-01

The risks for toxicity of novel antifungal compounds, together with the emergence of resistance, makes the use of inhibitors of resistance, in combination with antifungal compounds, a suitable strategy for developing novel antifungal formulations. Among them, inhibitors of efflux pumps are suitable candidates. Increasing drug influx or interfering with the stress response may also improve the efficacy of antifungals. Therapies as induction of fungal apoptosis or immunostimulation are also good strategies for reducing the risks for resistance and to improve antifungals' efficacy. Understanding the effect of the acquisition of resistance on the fungal physiology and determining the collateral sensitivity networks are useful for the development of novel strategies based on combination of antifungals for improving the efficacy of the therapy.

Diabetes prevention program in a Mediterranean environment: individual or group therapy? An effectiveness evaluation.

PubMed

Endevelt, R; Peled, R; Azrad, A; Kowen, G; Valinsky, L; Heymann, A D

2015-04-01

Diabetes as a multifactorial disorder requires prevention measures based upon the modification of several risk factors simultaneously; otherwise, there is insufficient potential for prevention. Following the success of the American Diabetes Prevention Program (DPP), we implemented an intervention program in a large Israeli healthcare organization with an emphasize on Mediterranean Diet (MedDiet) and physical activity. The objective was to evaluate the effectiveness of two types of intervention, individual and group therapies, in reducing risk factors and in preventing or delaying the development of type 2 diabetes. Out of 180 primary care physicians, 85 who agreed to participate, were randomly assigned, between the years 2005 and 2006, into two groups: those who would refer pre-diabetes adult patients for individual therapy and those who would refer for group therapy. The two groups of patients consisted of 111 and 112 in each group. The intervention lasted for 6 months and discussed: the benefits of MedDiet, planning nutritional behavior and mindful eating, and the importance of physical activity. All patients were invited to participate in walking groups. Follow up lasted for 24 months and logistic, mixed models, and Cox regressions were employed. No statistically significant differences were detected between the two intervention groups in age; gender and clinical measurements at recruitment. Thirty nine percent of both groups developed diabetes (entered the DR by 2012), including 38.7% from the individual therapy and 39.3% from the group therapy (P=0.933). The mean time from 2005 until entry to the Diabetes Registry (DR) was 2.9 and 2.5 years for the individual and group therapy respectively (P=0.542). Both interventions were equally effective in achieving the desired outcomes and time until entry to the DR. For large health organizations with a high number of pre-diabetes patients and scarce resources, group therapy, where 12 people are reached out by one team member are preferable and more costly effective, than a one on one therapy. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow

USDA-ARS?s Scientific Manuscript database

Osteoporosis is characterized by destruction of bone architecture, resulting in decreased bone mass density (BMD) and increased fracture susceptibility. While current therapies focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabol...

Educational Benefits of Music in an Inclusive Classroom

ERIC Educational Resources Information Center

Sze, Susan; Yu, Sanna

2004-01-01

The purpose of this study is to highlight literature concerning the effects of music therapy on children with disabilities. The paper is organized in the following sections: (1) background of music and children with disabilities, (2) the aims of music therapy, (3) main contributions to cognitive, biopsychosocial development of children with…

Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.

PubMed

Jang, Bora; Kwon, Hyokyoung; Katila, Pramila; Lee, Seung Jin; Lee, Hyukjin

2016-03-01

Cancer causes >8.2 million deaths annually worldwide; thus, various cancer treatments have been investigated over the past decades. Among them, combination drug therapy has become extremely popular, and treatment with more than one drug is often necessary to achieve appropriate anticancer efficacy. With the development of nanoformulations and nanoparticulate-based drug delivery, researchers have explored the feasibility of dual delivery of biological therapeutics to overcome the current drawbacks of cancer therapy. Compared with the conventional single drug therapy, dual delivery of therapeutics has provided various synergistic effects in addition to offering multimodality to cancer treatment. In this review, we highlight and summarize three aspects of dual-delivery systems for cancer therapy. These include (1) overcoming drug resistance by the dual delivery of chemical drugs with biological therapeutics for synergistic therapy, (2) targeted and controlled drug release by the dual delivery of drugs with stimuli-responsive nanomaterials, and (3) multimodal theranostics by the dual delivery of drugs and molecular imaging probes. Furthermore, recent developments, perspectives, and new challenges regarding dual-delivery systems for cancer therapy are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a Synthetic Lethal Drug Combination That Targets the Energy Generation Triangle for Liver Cancer Therapy

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-16-1-0162 TITLE: Development of a Synthetic Lethal Drug Combination That Targets the Energy Generation Triangle for...in HCC cells to compensate energy loss. Compared to normal liver, HCC up-regulates expression of genes involved in FA biosynthesis and down-regulates... energy generation triangle” (glycolysis, oxidative phosphorylation, and FAO) as a translational, effective and safe therapy for HCC. 15. SUBJECT

Psychological therapies for auditory hallucinations (voices): current status and key directions for future research.

PubMed

Thomas, Neil; Hayward, Mark; Peters, Emmanuelle; van der Gaag, Mark; Bentall, Richard P; Jenner, Jack; Strauss, Clara; Sommer, Iris E; Johns, Louise C; Varese, Filippo; García-Montes, José Manuel; Waters, Flavie; Dodgson, Guy; McCarthy-Jones, Simon

2014-07-01

This report from the International Consortium on Hallucinations Research considers the current status and future directions in research on psychological therapies targeting auditory hallucinations (hearing voices). Therapy approaches have evolved from behavioral and coping-focused interventions, through formulation-driven interventions using methods from cognitive therapy, to a number of contemporary developments. Recent developments include the application of acceptance- and mindfulness-based approaches, and consolidation of methods for working with connections between voices and views of self, others, relationships and personal history. In this article, we discuss the development of therapies for voices and review the empirical findings. This review shows that psychological therapies are broadly effective for people with positive symptoms, but that more research is required to understand the specific application of therapies to voices. Six key research directions are identified: (1) moving beyond the focus on overall efficacy to understand specific therapeutic processes targeting voices, (2) better targeting psychological processes associated with voices such as trauma, cognitive mechanisms, and personal recovery, (3) more focused measurement of the intended outcomes of therapy, (4) understanding individual differences among voice hearers, (5) extending beyond a focus on voices and schizophrenia into other populations and sensory modalities, and (6) shaping interventions for service implementation. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Trajectory and outcomes of speech language therapy in the Prader-Willi syndrome (PWS): case report.

PubMed

Misquiatti, Andréa Regina Nunes; Cristovão, Melina Pavini; Brito, Maria Claudia

2011-03-01

The aim of this study was to describe the trajectory and the outcomes of speech-language therapy in Prader-Willi syndrome through a longitudinal study of the case of an 8 year-old boy, along four years of speech-language therapy follow-up. The therapy sessions were filmed and documental analysis of information from the child's records regarding anamnesis, evaluation and speech-language therapy reports and multidisciplinary evaluations were carried out. The child presented typical characteristics of Prader-Willi syndrome, such as obesity, hyperfagia, anxiety, behavioral problems and self aggression episodes. Speech-language pathology evaluation showed orofacial hypotony, sialorrhea, hypernasal voice, cognitive deficits, oral comprehension difficulties, communication using gestures and unintelligible isolated words. Initially, speech-language therapy had the aim to promote the language development emphasizing social interaction through recreational activities. With the evolution of the case, the main focus became the development of conversation and narrative abilities. It were observed improvements in attention, symbolic play, social contact and behavior. Moreover, there was an increase in vocabulary, and evolution in oral comprehension and the development of narrative abilities. Hence, speech-language pathology intervention in the case described was effective in different linguistic levels, regarding phonological, syntactic, lexical and pragmatic abilities.

Optimal nonpharmacological management of agitation in Alzheimer's disease: challenges and solutions.

PubMed

Millán-Calenti, José Carlos; Lorenzo-López, Laura; Alonso-Búa, Begoña; de Labra, Carmen; González-Abraldes, Isabel; Maseda, Ana

2016-01-01

Many patients with Alzheimer's disease will develop agitation at later stages of the disease, which constitutes one of the most challenging and distressing aspects of dementia. Recently, nonpharmacological therapies have become increasingly popular and have been proven to be effective in managing the behavioral symptoms (including agitation) that are common in the middle or later stages of dementia. These therapies seem to be a good alternative to pharmacological treatment to avoid unpleasant side effects. We present a systematic review of randomized controlled trials (RCTs) focused on the nonpharmacological management of agitation in Alzheimer's disease (AD) patients aged 65 years and above. Of the 754 studies found, eight met the inclusion criteria. This review suggests that music therapy is optimal for the management of agitation in institutionalized patients with moderately severe and severe AD, particularly when the intervention includes individualized and interactive music. Bright light therapy has little and possibly no clinically significant effects with respect to observational ratings of agitation but decreases caregiver ratings of physical and verbal agitation. Therapeutic touch is effective for reducing physical nonaggressive behaviors but is not superior to simulated therapeutic touch or usual care for reducing physically aggressive and verbally agitated behaviors. Melissa oil aromatherapy and behavioral management techniques are not superior to placebo or pharmacological therapies for managing agitation in AD. Further research in clinical trials is required to confirm the effectiveness and long-term effects of nonpharmacological interventions for managing agitation in AD. These types of studies may lead to the development of future intervention protocols to improve the well-being and daily functioning of these patients, thereby avoiding residential care placement.

Individual Cognitive Stimulation Therapy for dementia (iCST): study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Improving the quality of care for people with dementia and their carers has become a national priority in many countries. Cognitive Stimulation Therapy (CST) groups can be beneficial in improving cognition and quality of life for people with dementia. The aim of the current study is to develop and evaluate a home-based individual Cognitive Stimulation Therapy (iCST) programme for people with dementia which can be delivered by their family carer. Methods This multi-centre, pragmatic randomised controlled trial (RCT) will compare the effectiveness and cost-effectiveness of iCST for people with dementia with a treatment as usual control group. The intervention consists of iCST sessions delivered by a carer for 30 minutes, 3 times a week over 25 weeks. For people with dementia the primary outcome measures are cognition assessed by the ADAS-Cog, and quality of life assessed by QoL-AD. For carers, quality of life using the SF-12 is the primary outcome measure. Using a 5% significance level, comparison of 306 participants will yield 80% power to detect an effect size of 0.35 for cognition as measured by the ADAS-Cog, and quality of life as measured by the QoL-AD. Quality of life for the carer will be measured using the SF-12. The trial will include a cost-effectiveness analysis from a public sector perspective. Discussion The UK Department of Health has recently stressed that improving access to psychological therapies is a national priority, but many people with dementia are unable to access psychological interventions. The development of a home-based individual version of CST will provide an easy to use, widely available therapy package that will be evaluated for effectiveness and cost-effectiveness in a multi centre RCT. PMID:22998983

Optimal nonpharmacological management of agitation in Alzheimer’s disease: challenges and solutions

PubMed Central

Millán-Calenti, José Carlos; Lorenzo-López, Laura; Alonso-Búa, Begoña; de Labra, Carmen; González-Abraldes, Isabel; Maseda, Ana

2016-01-01

Many patients with Alzheimer’s disease will develop agitation at later stages of the disease, which constitutes one of the most challenging and distressing aspects of dementia. Recently, nonpharmacological therapies have become increasingly popular and have been proven to be effective in managing the behavioral symptoms (including agitation) that are common in the middle or later stages of dementia. These therapies seem to be a good alternative to pharmacological treatment to avoid unpleasant side effects. We present a systematic review of randomized controlled trials (RCTs) focused on the nonpharmacological management of agitation in Alzheimer’s disease (AD) patients aged 65 years and above. Of the 754 studies found, eight met the inclusion criteria. This review suggests that music therapy is optimal for the management of agitation in institutionalized patients with moderately severe and severe AD, particularly when the intervention includes individualized and interactive music. Bright light therapy has little and possibly no clinically significant effects with respect to observational ratings of agitation but decreases caregiver ratings of physical and verbal agitation. Therapeutic touch is effective for reducing physical nonaggressive behaviors but is not superior to simulated therapeutic touch or usual care for reducing physically aggressive and verbally agitated behaviors. Melissa oil aromatherapy and behavioral management techniques are not superior to placebo or pharmacological therapies for managing agitation in AD. Further research in clinical trials is required to confirm the effectiveness and long-term effects of nonpharmacological interventions for managing agitation in AD. These types of studies may lead to the development of future intervention protocols to improve the well-being and daily functioning of these patients, thereby avoiding residential care placement. PMID:26955265

Music therapy for people with schizophrenia and schizophrenia-like disorders.

PubMed

Mössler, Karin; Chen, Xijing; Heldal, Tor Olav; Gold, Christian

2011-12-07

Music therapy is a therapeutic method that uses musical interaction as a means of communication and expression. The aim of the therapy is to help people with serious mental disorders to develop relationships and to address issues they may not be able to using words alone. To review the effects of music therapy, or music therapy added to standard care, compared with 'placebo' therapy, standard care or no treatment for people with serious mental disorders such as schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (December 2010) and supplemented this by contacting relevant study authors, handsearching of music therapy journals and manual searches of reference lists. All randomised controlled trials (RCTs) that compared music therapy with standard care, placebo therapy, or no treatment. Studies were reliably selected, quality assessed and data extracted. We excluded data where more than 30% of participants in any group were lost to follow-up. We synthesised non-skewed continuous endpoint data from valid scales using a standardised mean difference (SMD). If statistical heterogeneity was found, we examined treatment 'dosage' and treatment approach as possible sources of heterogeneity. We included eight studies (total 483 participants). These examined effects of music therapy over the short- to medium-term (one to four months), with treatment 'dosage' varying from seven to 78 sessions. Music therapy added to standard care was superior to standard care for global state (medium-term, 1 RCT, n = 72, RR 0.10 95% CI 0.03 to 0.31, NNT 2 95% CI 1.2 to 2.2). Continuous data identified good effects on negative symptoms (4 RCTs, n = 240, SMD average endpoint Scale for the Assessment of Negative Symptoms (SANS) -0.74 95% CI -1.00 to -0.47); general mental state (1 RCT, n = 69, SMD average endpoint Positive and Negative Symptoms Scale (PANSS) -0.36 95% CI -0.85 to 0.12; 2 RCTs, n=100, SMD average endpoint Brief Psychiatric Rating Scale (BPRS) -0.73 95% CI -1.16 to -0.31); depression (2 RCTs, n = 90, SMD average endpoint Self-Rating Depression Scale (SDS) -0.63 95% CI -1.06 to -0.21; 1 RCT, n = 30, SMD average endpoint Hamilton Depression Scale (Ham-D) -0.52 95% CI -1.25 to -0.21 ); and anxiety (1 RCT, n = 60, SMD average endpoint SAS -0.61 95% CI -1.13 to -0.09). Positive effects were also found for social functioning (1 RCT, n = 70, SMD average endpoint Social Disability Schedule for Inpatients (SDSI) score -0.78 95% CI -1.27 to -0.28). Furthermore, some aspects of cognitive functioning and behaviour seem to develop positively through music therapy. Effects, however, were inconsistent across studies and depended on the number of music therapy sessions as well as the quality of the music therapy provided. Music therapy as an addition to standard care helps people with schizophrenia to improve their global state, mental state (including negative symptoms) and social functioning if a sufficient number of music therapy sessions are provided by qualified music therapists. Further research should especially address the long-term effects of music therapy, dose-response relationships, as well as the relevance of outcomes measures in relation to music therapy.

[A recent trial of chemo-radiation with S-1 against gastric cancer].

PubMed

Saikawa, Yoshiro; Kiyota, Tsuyoshi; Nakamura, Rieko; Wada, Norihito; Yoshida, Masashi; Kubota, Tetsuro; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki

2006-06-01

A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

PubMed Central

Qin, Lan

2016-01-01

Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools.

PubMed

Nafissi, Nafiseh; Foldvari, Marianna

2015-01-01

Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The fields of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

Fucoidan-coated CuS nanoparticles for chemo-and photothermal therapy against cancer

PubMed Central

Jang, Bian; Moorthy, Madhappan Santha; Manivasagan, Panchanathan; Xu, Li; Song, Kyeongeun; Lee, Kang Dae; Kwak, Minseok; Oh, Junghwan; Jin, Jun-O

2018-01-01

In advanced cancer therapy, the combinational therapeutic effect of photothermal therapy (PTT) using near-infrared (NIR) light-responsive nanoparticles (NPs) and anti-cancer drug delivery-mediated chemotherapy has been widely applied. In the present study, using a facile, low-cost, and solution-based method, we developed and synthesized fucoidan, a natural polymer isolated from seaweed that has demonstrated anti-cancer effect, and coated NPs with it as an ideal candidate in chemo-photothermal therapy against cancer cells. Fucoidan-coated copper sulfide nanoparticles (F-CuS) act not only as a nanocarrier to enhance the intracellular delivery of fucoidan but also as a photothermal agent to effectively ablate different cancer cells (e.g., HeLa, A549, and K562), both in vitro and in vivo, with the induction of apoptosis under 808 nm diode laser irradiation. These results point to the potential usage of F-CuS in treating human cancer. PMID:29560098

Nanomedicine as an emerging approach against intracellular pathogens

PubMed Central

Armstead, Andrea L; Li, Bingyun

2011-01-01

Diseases such as tuberculosis, hepatitis, and HIV/AIDS are caused by intracellular pathogens and are a major burden to the global medical community. Conventional treatments for these diseases typically consist of long-term therapy with a combination of drugs, which may lead to side effects and contribute to low patient compliance. The pathogens reside within intracellular compartments of the cell, which provide additional barriers to effective treatment. Therefore, there is a need for improved and more effective therapies for such intracellular diseases. This review will summarize, for the first time, the intracellular compartments in which pathogens can reside and discuss how nanomedicine has the potential to improve intracellular disease therapy by offering properties such as targeting, sustained drug release, and drug delivery to the pathogen’s intracellular location. The characteristics of nanomedicine may prove advantageous in developing improved or alternative therapies for intracellular diseases. PMID:22228996

The path to successful commercialization of cell and gene therapies: empowering patient advocates.

PubMed

Bauer, Gerhard; Abou-El-Enein, Mohamed; Kent, Alastair; Poole, Brian; Forte, Miguel

2017-02-01

Often, novel gene and cell therapies provide hope for many people living with incurable diseases. To facilitate and accelerate a successful regulatory approval and commercialization path for effective, safe and affordable cell and gene therapies, the involvement of patient advocacy groups (PAGs) should be considered early in the development process. This report provides a thorough overview of the various roles PAGs play in the clinical translation of cell and gene therapies and how they can bring about positive changes in the regulatory process, infrastructure improvements and market stability. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Music therapy and the effects on laboring women.

PubMed

Robinson, Amber

2002-01-01

Wiand's (1997) study supported the use of music therapy to decrease pain and anxiety. The results of this study could be used to support a research utilization project to educate nurses on the potential benefits of music therapy among laboring women. Nurses and physicians could collaborate together to educate clients on music therapy to decrease pain and anxiety. Feasibility issues would include education of the nurses to use music therapy and the cost of developing different types of music. Future research could be done to study a larger sample size. Other research is needed to determine what type of music works best with laboring women.

Additional Octreotide Therapy to Sirolimus Achieved a Decrease in Sirolimus-refractory Chylous Effusion Complicated with Lymphangioleiomyomatosis.

PubMed

Namba, Masashi; Masuda, Takeshi; Nakamura, Takashi; Horimasu, Yasushi; Miyamoto, Shintaro; Nakashima, Taku; Iwamoto, Hiroshi; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru

2017-12-15

Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We herein report a case of a 34-year-old woman with LAM who developed refractory chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce chylous effusion, we administered octreotide, which is often used to control postoperative chylous effusion, in addition to the sirolimus therapy. This combination therapy reduced the chylothorax and chylous ascites. For patients with LAM, octreotide therapy in addition to sirolimus may be effective for treating sirolimus-refractory chylous effusion.

Corticosteroid treatment in Sydenham's chorea.

PubMed

Fusco, C; Spagnoli, C

2018-03-01

Sydenham's chorea (SC) is an immune-mediated hyperkinetic movement disorder, developing after group A Beta-hemolytic streptococcal (GABHS) infection. Aside from conventional symptomatic treatment (carbamazepine, valproate, neuroleptics), the use of steroids has also been advocated, mainly in severe, drug-resistant cases or if clinically disabling side effects develop with first line therapies. Based on the description of 5 cases followed in the Child Neurology Unit of Santa Maria Nuova Hospital in Reggio Emilia and on the available medical literature on this topic, we propose considering the use of corticosteroids therapy in children with SC, with the administration of IV methyl-prednisolone followed by oral deflazacort in severe cases and of oral deflazacort alone in mild and moderate degrees of involvement. In our experience this therapy is effective both in the short and long-term period, in different clinical presentations (chorea paralytica, distal chorea, hemichorea, "classic" chorea, association with mood disorder or dyspraxia) and very well tolerated (no significant side effects were recorded). Copyright © 2017. Published by Elsevier Ltd.

Mindfulness-based cognitive therapy for depression: trends and developments.

PubMed

MacKenzie, Meagan B; Kocovski, Nancy L

2016-01-01

Mindfulness-based cognitive therapy (MBCT) was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in negative repetitive thoughts. This review provides an overview of current trends in MBCT research, including efficacy and questions regarding the specific effects of MBCT in light of recent comparisons with structurally equivalent control conditions, mechanisms of change, and moderators of treatment outcome. In addition, future directions are discussed, such as challenges with training an adequate number of therapists and disseminating this therapy.

A Case of Clinically Amyopathic Dermatomyositis with Interstitial Pneumonia that Was Successfully Treated with Plasma Exchange.

PubMed

Yagishita, Mizuki; Kondo, Yuya; Terasaki, Toshihiko; Terasaki, Mayu; Shimizu, Masaru; Honda, Fumika; Oyama, Ayako; Takahashi, Hiroyuki; Yokosawa, Masahiro; Asashima, Hiromitsu; Hagiwara, Shinya; Tsuboi, Hiroto; Matsumoto, Isao; Sumida, Takayuki

2018-02-28

Patients with clinically amyopathic dermatomyositis (CADM), a subset of dermatomyositis characterized by a lack of muscle involvement, frequently develop rapidly progressive and treatment-resistant interstitial lung disease. We report the case of a 49-year-old man who was diagnosed with CADM. He developed interstitial pneumonia, which did not respond to combination therapy with methylprednisolone pulse therapy, cyclophosphamide, and cyclosporine. We therefore attempted plasma exchange. After 7 courses of therapeutic plasma exchange, the interstitial pneumonia gradually improved. This case suggests that plasma exchange might be an effective therapeutic option for patients with progressive interstitial lung disease in steroid- and immunosuppressive therapy-refractive CADM.

Developing Induced Pluripotent Stem Cell-Based Therapy for the Masses.

PubMed

Rao, Mahendra S; Atala, Anthony

2016-02-01

The discovery of induced pluripotent stem cells and the ability to manufacture them using clinically compliant protocols has the potential to revolutionize the field of regenerative medicine. However, realizing this potential requires the development of processes that are reliable, reproducible, and cost-effective and that at the same time do not compromise the safety of the individuals receiving this therapy. In the present report, we discuss how cost reductions can be obtained using our experience with obtaining approval of biologic agents, autologous therapy, and the recent approval of cord blood banks. Significance: For therapy to be widely available, the cost of manufacturing stem cells must be reduced. The steps proposed in the present report, when implemented, have the potential to reduce these costs significantly. ©AlphaMed Press.

Current and emerging global themes in the bioethics of regenerative medicine: the tangled web of stem cell translation.

PubMed

Chan, Sarah

2017-10-01

Probably the most serious problem facing the field of regenerative medicine today is the challenge of effective translation and development of viable stem cell-based therapies. Particular concerns have been raised over the growing market in unproven cell therapies. In this article, I explore recent developments in the stem cell therapy landscape and argue that while the sale of unproven therapies undoubtedly poses ethical concerns, it must be understood as part of a larger problem at the interface between biomedicine, healthcare, publics, policy and the market. Addressing this will require a broader perspective incorporating the shifting relationships between different stakeholder groups, the global politics of research and innovation, and the evolving role of publics and patients with respect to science.

Current and emerging global themes in the bioethics of regenerative medicine: the tangled web of stem cell translation

PubMed Central

Chan, Sarah

2017-01-01

Probably the most serious problem facing the field of regenerative medicine today is the challenge of effective translation and development of viable stem cell-based therapies. Particular concerns have been raised over the growing market in unproven cell therapies. In this article, I explore recent developments in the stem cell therapy landscape and argue that while the sale of unproven therapies undoubtedly poses ethical concerns, it must be understood as part of a larger problem at the interface between biomedicine, healthcare, publics, policy and the market. Addressing this will require a broader perspective incorporating the shifting relationships between different stakeholder groups, the global politics of research and innovation, and the evolving role of publics and patients with respect to science. PMID:29119870

[Recent Advances in Immunotherapy for Non-Small Cell Lung Cancer].

PubMed

Muto, Satoshi; Suzuki, Hiroyuki

2018-02-01

Cancer immunotherapy for non-small cell lung cancer began around 1970 with nonspecific immunomodulators and cytokine therapies. This has since developed into cell therapy including lymphokine-activated killer cells(LAK)and tumor infiltrating lymphocytes(TIL), as well as cancer vaccine therapy. However, no clear indication of effectiveness has been reported. Despite the high expectation over the effectiveness of cancer vaccine therapy, the treatment strategy was deemed unsuccessful, and focus turned to the study of immune escape mechanism, which is now regarded as standard treatment for non-small cell lung cancer. With the advent of immune checkpoint inhibitors, cancer immunotherapy has finally become a standard treatment for non-small cell lung cancer. There are still several obstacles to overcome including the identification of a predictive biomarker for improved efficacy, as well as the establishment of multidrug or multimodality combination therapy. PD-L1 expression is currently used as a predictive biomarker for anti-PD-1 therapy, but does not meet the expectations of the aimed results. Although tumor mutation burden is considered another promising biomarker, there remain clinical problems, for example the need of next generation sequencer. It was reported that combination therapy of immune checkpoint inhibitor after chemoradiation therapy was also effective. However, it remains unclear of what is required to further improve the clinical effects. In this article, we will review the history of cancer immunotherapy for non-small cell lung cancer and discuss the future prospects.

Neuropsychological Effects of Neuromodulation Techniques for Treatment-Resistant Depression: A Review

PubMed Central

Moreines, Jared L.; McClintock, Shawn M.; Holtzheimer, Paul E.

2010-01-01

Electroconvulsive therapy (ECT) and ablative neurosurgical procedures are established interventions for treatment-resistant depression (TRD), but their use may be limited in part by neuropsychological adverse effects. Additional neuromodulation strategies are being developed that aim to match or exceed the efficacy of ECT/ablative surgery with a better neurocognitive side effect profile. In this review, we briefly discuss the neurocognitive effects of ECT and ablative neurosurgical procedures, then synthesize the available neurocognitive information for emerging neuromodulation therapies including repetitive transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, vagus nerve stimulation, and deep brain stimulation. The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions. PMID:21255751

Gold nanoparticle-cell labeling methodology for tracking stem cells within the brain

NASA Astrophysics Data System (ADS)

Betzer, Oshra; Meir, Rinat; Motiei, Menachem; Yadid, Gal; Popovtzer, Rachela

2017-02-01

Cell therapy provides a promising approach for diseases and injuries that conventional therapies cannot cure effectively. Mesenchymal stem cells (MSCs) can be used as effective targeted therapy, as they exhibit homing capabilities to sites of injury and inflammation, exert anti-inflammatory effects, and can differentiate in order to regenerate damaged tissue. Despite the potential efficacy of cell therapy, applying cell-based therapy in clinical practice is very challenging; there is a need to uncover the mystery regarding the fate of the transplanted cells. Therefore, in this study, we developed a method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), and combined with gold nanoparticles as labeling agents. We applied this technique for non-invasive imaging of MSCs transplanted in a rat model for depression, a highly prevalent and disabling neuropsychiatric disorder lacking effective treatment. Our results, which demonstrate that cell migration could be detected as early as 24 hours and up to one month post-transplantation, revealed that MSCs specifically navigated and homed to distinct depression related brain regions. This research further reveals that cell therapy is a beneficial approach for treating neuropsychiatric disorders; Behavioral manifestations of core symptoms of depressive behavior, were significantly attenuated following treatment. We expect This CT-based technique to lead to a significant enhancement in cellular therapy both for basic research and clinical applications of brain pathologies.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

PubMed Central

Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

2016-01-01

Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

Cortical reorganization in recent-onset tinnitus patients by the Heidelberg Model of Music Therapy

PubMed Central

Krick, Christoph M.; Grapp, Miriam; Daneshvar-Talebi, Jonas; Reith, Wolfgang; Plinkert, Peter K.; Bolay, Hans Volker

2015-01-01

Pathophysiology and treatment of tinnitus still are fields of intensive research. The neuroscientifically motivated Heidelberg Model of Music Therapy, previously developed by the German Center for Music Therapy Research, Heidelberg, Germany, was applied to explore its effects on individual distress and on brain structures. This therapy is a compact and fast application of nine consecutive 50-min sessions of individualized therapy implemented over 1 week. Clinical improvement and long-term effects over several years have previously been published. However, the underlying neural basis of the therapy's success has not yet been explored. In the current study, the therapy was applied to acute tinnitus patients (TG) and healthy active controls (AC). Non-treated patients were also included as passive controls (PTC). As predicted, the therapeutic intervention led to a significant decrease of tinnitus-related distress in TG compared to PTC. Before and after the study week, high-resolution MRT scans were obtained for each subject. Assessment by repeated measures design for several groups (Two-Way ANOVA) revealed structural gray matter (GM) increase in TG compared to PTC, comprising clusters in precuneus, medial superior frontal areas, and in the auditory cortex. This pattern was further applied as mask for general GM changes as induced by the therapy week. The therapy-like procedure in AC also elicited similar GM increases in precuneus and frontal regions. Comparison between structural effects in TG vs. AC was calculated within the mask for general GM changes to obtain specific effects in tinnitus patients, yielding GM increase in right Heschl's gyrus, right Rolandic operculum, and medial superior frontal regions. In line with recent findings on the crucial role of the auditory cortex in maintaining tinnitus-related distress, a causative relation between the therapy-related GM alterations in auditory areas and the long-lasting therapy effects can be assumed. PMID:25745385

Nanoscale theranostics for physical stimulus-responsive cancer therapies.

PubMed

Chen, Qian; Ke, Hengte; Dai, Zhifei; Liu, Zhuang

2015-12-01

Physical stimulus-responsive therapies often employing multifunctional theranostic agents responsive to external physical stimuli such as light, magnetic field, ultra-sound, radiofrequency, X-ray, etc., have been widely explored as novel cancer therapy strategies, showing encouraging results in many pre-clinical animal experiments. Unlike conventional cancer chemotherapy which often accompanies with severe toxic side effects, physical stimulus-responsive agents usually are non-toxic by themselves and would destruct cancer cells only under specific external stimuli, and thus could offer greatly reduced toxicity and enhanced treatment specificity. In addition, physical stimulus-responsive therapies can also be combined with other traditional therapeutics to achieve synergistic anti-tumor effects via a variety of mechanisms. In this review, we will summarize the latest progress in the development of physical stimulus-responsive therapies, and discuss the important roles of nanoscale theranostic agents involved in those non-conventional therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Modern approaches to the use of neurotropic physical therapy in arterial hypertension].

PubMed

Orekhova, E M; Konchugova, T V; Kul'chitskaya, D B; Korchazhkina, N B; Egorova, L A; Chuich, N G

2016-01-01

The development and introduction into clinical practice of non-pharmacological methods for the prevention and treatment of arterial hypertension is a primary objective of modern physical therapy, especially as regards the neurotropic influences. This article was designed to report the results of the investigation into the hypotensive effect of transcerebral magnetic therapy obtained during the treatment of 60 patients presenting with arterial hypertension. The study included the comparative examination of two randomly formed groups containing 30 patients each. The patients of the main group received transcerebral magnetic therapy (to the frontal region) while those in the group of comparison were given magnetotherapy at the collar region. The study has demonstrated that transcerebral magnetic therapy given to the patients of the main group was a more efficient treatment than magnetotherapy at the collar region since it produced a more pronounced hypotensive effect irrespective of the initial hemodynamic type.

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors.

PubMed

Martin, Donel M; Gálvez, Verònica; Loo, Colleen K

2015-06-19

Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview - Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview - Short Form scores following right unilateral electroconvulsive therapy. Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for patients with lower baseline cognitive status or older age. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors

PubMed Central

Gálvez, Verònica; Loo, Colleen K.

2015-01-01

Background: Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Methods: Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview – Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results: Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview – Short Form scores following right unilateral electroconvulsive therapy. Conclusions: Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for patients with lower baseline cognitive status or older age. PMID:26091817

Contributing to operations of community agencies through integrated fieldwork experiences.

PubMed

Klinger, Lisa; Bossers, Ann

2009-06-01

Occupational therapists are change agents who are well equipped to participate in community development. Community development projects can help agencies in many ways, including determining needs, educating stakeholders, developing novel programs, finding and creating resources, marketing the agency, and creating or implementing policy. In order for service agencies to profit, they need an understanding of the skills occupational therapists can offer. The best way to gain that knowledge may be through direct experience. This paper describes the benefits that flow to community agency partners and to occupational therapy students from an innovative, integrated fieldwork model that links students with service agencies. This approach has demonstrated many benefits to community partners, while allowing all students in an occupational therapy program to have community development experience. This is a cost-effective way to demonstrate the value of occupational therapy and to deliver multiple community development projects.

The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy.

PubMed

Ghiringhelli, François; Apetoh, Lionel

2014-01-01

Preclinical studies have revealed an unexpected ability of the immune system to contribute to the success of chemotherapy and radiotherapy. Anticancer therapies can trigger immune system activation by promoting the release of danger signals from dying tumor cells and/or the elimination of immunosuppressive cells. We have, however, recently discovered that some chemotherapies, such as 5-fluorouracil and gemcitabine, exert conflicting effects on anticancer immune responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived suppressive cells in tumor-bearing rodents, these chemotherapies promoted the release of IL-1β and the development of pro-angiogenic IL-17-producing CD4 T cells. The ambivalent effects of chemotherapy on immune responses should thus be carefully considered to design effective combination therapies based on chemotherapy and immune modulators. Herein, we discuss how the initial findings underscoring the key role of the immune system in mediating the antitumor efficacy of anticancer agents could begin to translate into effective therapies in humans.

Immunotherapy is different: Implications for vaccine clinical trial design.

PubMed

Simon, Richard

2017-09-02

Cancer Immunotherapetics differ fundamentally from most cancer therapies in that they involve manipulation of the immune system to induce an anti-tumor response. This fundamental difference results in differences in the pre-clinical and clinical development of immunotherapeutics. Even the regulatory culture of developing one drug at a time and demonstrating that it, when added to standard therapy, prolongs patient survival, is often not suitable for the development of effective immunotherapy regimens. In this commentary, we explore some of these differences and describe novel clinical trial designs which may be useful in immunotherapeutics regimen development.

Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly?

PubMed

Valentino, L A; Holme, P A

2015-11-01

Inhibitor development in haemophilia patients is challenging especially when undergoing surgical procedures. The development of an inhibitor precludes using factor VIII (FVIII) therapy thereby requiring a bypassing agent (BPA) for surgical bleeding prophylaxis if the FVIII inhibitor titre >5 BU. Concomitant use of anti-inhibitor coagulant complex (AICC) and tranexamic acid has been reported in the literature as a beneficial treatment for this population. Anti-inhibitor coagulant complex is known to cause an increase in thrombin generation and tranexamic acid inhibits fibrinolysis. Hence, the combined used of AICC and tranexamic acid has been limited due to safety concerns over possibilities of increased risk of thrombotic events and disseminated intravascular coagulation. However, the rationale for concomitant therapy is to obtain a potential synergistic effect and to increase clot stability. We conducted a literature review of past studies and individual case reports of concomitant use of AICC and tranexamic acid, which was extensively used during dental procedures. Evidence also exists for concomitant use of the combined therapy in orthopaedic procedures, control of gastrointestinal bleeding, epistaxis and cerebral haemorrhages. Some patients who received the combined therapy had failed monotherapy with a single BPA prior to combined therapy. There were no reports of thrombotic complications related to the concomitant therapy and haemostasis was achieved in all cases. Anti-inhibitor coagulant complex and tranexamic acid therapy was found to be safe, well-tolerated and effective therapy in haemophilia patients with inhibitors. Additional randomized controlled studies should be performed to confirm these findings. © 2015 John Wiley & Sons Ltd.

Integrative medicine in hematology/oncology: benefits, ethical considerations, and controversies.

PubMed

Rosenthal, David S; Dean-Clower, Elizabeth

2005-01-01

Integrative Medicine (IM), a newly emerging field, has evolved from Complementary and Alternative Medicine (CAM). CAM refers to diverse medical and health care systems, practices, and products that are not presently considered part of conventional medicine and generally have limited scientific evidence. In the US, CAM is a multi-billion dollar, unregulated industry with potential benefits and risks to consumers, including cancer patients, who are high utilizers of complementary therapies. Patients' CAM use often is unsupervised by physicians, yet patients need the advice and guidance of their hematologists/oncologists as part of total cancer care. Ethical and legal issues physicians need to address include inquiring about and educating patients regarding potential interactions (e.g., drug-herb, radiation-antioxidant) or product contaminants, while discussing other therapies that may alleviate symptoms and/or improve quality of life. Administratively, CAM offerings in medical settings require relevant policies and procedures, such as properly credentialing practitioners and providing financial assistance counseling for those who cannot afford fee-for-service. Unlike "Alternative Medicine," the goal of IM is to combine mainstream medical therapies and CAM therapies (e.g., acupuncture, meditation, music therapy) that have some high-quality scientific evidence of safety and effectiveness. The Society for Integrative Oncology (SIO), a new international organization of oncology professionals studying and integrating effective complementary therapies in cancer care, serves as a forum for presenting scientific data on these therapies while emphasizing the importance of developing infrastructure that promotes IM principles and practices. The ultimate goal is to develop multidisciplinary expertise and therapeutic synergy between conventional and complementary therapies.

Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance.

PubMed

Thadani, Udho

2014-08-01

Nitrate therapy has been an effective treatment for ischemic heart disease for over 100 years. The anti-ischemic and exercise-promoting benefits of sublingually administered nitrates are well established. Nitroglycerin is indicated for the relief of an established attack of angina and for prophylactic use, but its effects are short lived. In an effort to increase the duration of beneficial effects, long-acting orally administered and topical applications of nitrates have been developed; however, following their continued or frequent daily use, patients soon develop tolerance to these long-acting nitrate preparations. Once tolerance develops, patients begin losing the protective effects of the long-acting nitrate therapy. By providing a nitrate-free interval, or declining nitrate levels at night, one can overcome or reduce the development of tolerance, but cannot provide 24-h anti-anginal and anti-ischemic protection. In addition, patients may be vulnerable to occurrence of rebound angina and myocardial ischemia during periods of absent nitrate levels at night and early hours of the morning, and worsening of exercise capacity prior to the morning dose of the medication. This has been a concern with nitroglycerin patches but not with oral formulations of isosorbide-5 mononitrates, and has not been adequately studied with isosorbide dinitrate. This paper describes problems associated with nitrate tolerance, reviews mechanisms by which nitrate tolerance and loss of efficacy develop, and presents strategies to avoid nitrate tolerance and maintain efficacy when using long-acting nitrate formulations.

Creative music therapy to promote brain structure, function, and neurobehavioral outcomes in preterm infants: a randomized controlled pilot trial protocol.

PubMed

Haslbeck, Friederike Barbara; Bucher, Hans-Ulrich; Bassler, Dirk; Hagmann, Cornelia

2017-01-01

Preterm birth is associated with increased risk of neurological impairment and deficits in cognition, motor function, and behavioral problems. Limited studies indicate that multi-sensory experiences support brain development in preterm infants. Music appears to promote neurobiological processes and neuronal learning in the human brain. Creative music therapy (CMT) is an individualized, interactive therapeutic approach based on the theory and methods of Nordoff and Robbins. CMT may promote brain development in preterm infants via concurrent interaction and meaningful auditory stimulation. We hypothesize that preterm infants who receive creative music therapy during neonatal intensive care admission will have developmental benefits short- and long-term brain function. A prospective, randomized controlled single-center pilot trial involving 60 clinically stable preterm infants under 32 weeks of gestational age is conducted in preparation for a multi-center trial. Thirty infants each are randomized to either standard neonatal intensive care or standard care with CMT. Music therapy intervention is approximately 20 min in duration three times per week. A trained music therapist sings for the infants in lullaby style, individually entrained and adjusted to the infant's rhythm and affect. Primary objectives of this study are feasibility of protocol implementation and investigating the potential mechanism of efficacy for this new intervention. To examine the effect of this new intervention, non-invasive, quantitative magnetic resonance imaging (MRI) methods at corrected age and standardized neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development third edition at a corrected age of 24 months and Kaufman Assessment Battery for Children at 5 years will be performed. All assessments will be performed and analyzed by blinded experts. To our knowledge, this is the first randomized controlled clinical trial to systematically examine possible effects of creative music therapy on short- and long-term brain development in preterm infants. This project lies at the interface of music therapy, neuroscience, and medical imaging. New insights into the potential role and impact of music on brain function and development may be elucidated. If such a low-cost, low-risk intervention is demonstrated in a future multi-center trial to be effective in supporting brain development in preterm neonates, findings could have broad clinical implications for this vulnerable patient population. ClinicalTrials.gov, NCT02434224.

Assessment of an intervention aimed at early discontinuation of intravenous antimicrobial therapy in a Brazilian University hospital.

PubMed

Bonella, Gislaine Ferraresi; Fontes, Astrídia Marília de Souza; Jorge, Miguel Tanús; Silveira, Alexandre Barcelos Morais da

2016-01-01

Many interventions demonstrate success in adapting the duration of intravenous antibiotic therapy, but few studies have been conducted in developing countries. The aim of this study was to evaluate the effectiveness of an intervention in the induction of early discontinuation of intravenous antimicrobial therapy and/or its switch to oral therapy. The study employed a before-after intervention design that consisted of displaying a message in the computerized prescription on the third day and suspension of the prescription on the fifth day of intravenous antimicrobial therapy. A total of 465 patients were followed during the control period (CP) and 440 in the intervention period (IP). The intravenous therapy was switched to oral therapy for 11 (2.4%) patients during the CP and 25 (5.7%) in the IP (p=0.011), and was discontinued for 82 (17.6%) patients during the CP and 106 (24.1%) in the IP (p=0.017). During the IP there was a significant increase of patients who had their antimicrobial treatment discontinued before the seventh day of intravenous treatment, 37.40% (49/131) in the IP and 16.13% (15/93) in the CP (p=0.0005). The duration of intravenous antimicrobial therapy decreased by one day, but it was not significant (p=0.136). It is concluded that the proposed intervention is effective in promoting the early discontinuation of antimicrobial treatment and/or switch to oral therapy. As long as a computerized system for prescription already exists, it is easy and inexpensive to be implemented, especially in hospitals in developing countries. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

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

Kok, H. Petra, E-mail: H.P.Kok@amc.uva.nl; Crezee, Johannes; Franken, Nicolaas A.P.

2014-03-01

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy{sup −1}) and β (Gy{sup −2}) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normalmore » tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.« less

The effect of docetaxel on developing oedema in patients with breast cancer: a systematic review.

PubMed

Hugenholtz-Wamsteker, W; Robbeson, C; Nijs, J; Hoelen, W; Meeus, M

2016-03-01

Docetaxel is extensively used in chemotherapy for the treatment of breast cancer. Little attention has been given to oedema as a possible side effect of docetaxel-containing therapies. Until now, no review was conducted to evaluate docetaxel-containing therapies versus docetaxel-free therapies on the magnitude of the risk of developing oedema. In this systematic review, we investigated the risk of developing oedema in patients being treated for breast cancer with or without docetaxel. In this systematic literature review, we searched PubMed and Web of Knowledge for studies on breast cancer patients treated with chemotherapy containing docetaxel. We included clinical trials comparing docetaxel versus docetaxel-free chemotherapy. Oedema had to be reported and measured as a key outcome or an adverse effect. Methodological checklists were used to assess the risk of bias within the selected studies. Seven randomised clinical trials were included. Six trials were of moderate methodological quality. All trials showed an increased rate of oedema in the docetaxel-treatment arm. The trial of weakest methodological quality reported the highest incidence of oedema. The results moderately suggest that adjuvant chemotherapy containing docetaxel is related to a significantly increased risk of developing oedema, compared with docetaxel-free chemotherapy. © 2014 John Wiley & Sons Ltd.

HIV cure strategies: how good must they be to improve on current antiretroviral therapy?

PubMed

Sax, Paul E; Sypek, Alexis; Berkowitz, Bethany K; Morris, Bethany L; Losina, Elena; Paltiel, A David; Kelly, Kathleen A; Seage, George R; Walensky, Rochelle P; Weinstein, Milton C; Eron, Joseph; Freedberg, Kenneth A

2014-01-01

We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.

The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

PubMed

Rafiq, Qasim A; Ortega, Ilida; Jenkins, Stuart I; Wilson, Samantha L; Patel, Asha K; Barnes, Amanda L; Adams, Christopher F; Delcassian, Derfogail; Smith, David

2015-11-01

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

Near-infrared light-responsive nanomaterials in cancer therapeutics.

PubMed

Shanmugam, Vijayakumar; Selvakumar, S; Yeh, Chen-Sheng

2014-09-07

Noninvasive techniques, such as breath tests (urea breath test), blood pressure measurements using a sphygmomanometer and electrocardiography, were employed by a physician to perform classical diagnosis. The use of state-of-the-art noninvasive therapies at the organ level in modern medicine has gradually become possible. However, cancer treatment demands spatially and temporally controlled noninvasive therapy at the cell level because nonspecific toxicity often causes complicated side effects. To increase survival in cancer patients further, combination therapy and combination drugs are explored which demand high specificity to avoid combined-drug side effects. We believe that high specificity could be obtained by implementing near-infrared (NIR) light-assisted nanoparticles in photothermal therapy, chemotherapy, and photodynamic therapy. To refine this therapy and subsequently achieve high efficiency, novel nanomaterials have been designed and modified either to enhance the uptake and drug delivery to the cancer site, or control treatment to administer therapy efficiently. These modifications and developments have been demonstrated to achieve spatial and temporal control when conducting an in vivo xenograft, because the NIR light penetrated effectively the biological tissue. The nanoplatforms discussed in this review are grouped under the following subheadings: Au nanorods (NRs), Au nanoshells, other Au-related nanomaterials, graphene oxide, upconversion nanoparticles, and other related materials (including materials such as CuS, Fe3O4-related systems, and carbon nanotubes (CNTs)).

ALS Biomarkers for Therapy Development: State of the Field & Future Directions

PubMed Central

Benatar, Michael; Boylan, Kevin; Jeromin, Andreas; Rutkove, Seward B.; Berry, James; Atassi, Nazem; Bruijn, Lucie

2015-01-01

Biomarkers have become the focus of intense research in the field of amyotrophic lateral sclerosis (ALS), with the hope that they might aid therapy development efforts. Notwithstanding the discovery of many candidate biomarkers, none have yet emerged as validated tools for drug development. In this review we present a nuanced view of biomarkers based on the perspective of the FDA; highlight the distinction between discovery and validation; describe existing and emerging resources; review leading biological fluid-based, electrophysiological and neuroimaging candidates relevant to therapy development efforts; discuss lessons learned from biomarker initiatives in related neurodegenerative diseases; and outline specific steps that we, as a field, might take in order to hasten the development and validation of biomarkers that will prove useful in enhancing efforts to develop effective treatments for ALS patients. Most important among these perhaps is the proposal to establish a federated ALS Biomarker Consortium (ABC) in which all interested and willing stakeholders may participate with equal opportunity to contribute to the broader mission of biomarker development and validation. PMID:26574709

Delivery of optimized inpatient anticoagulation therapy: consensus statement from the anticoagulation forum.

PubMed

Nutescu, Edith A; Wittkowsky, Ann K; Burnett, Allison; Merli, Geno J; Ansell, Jack E; Garcia, David A

2013-05-01

To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in 8 key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education, (7) care transitions, and (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national organizations have introduced initiatives to reduce the likelihood of patient harm associated with the use of anticoagulants. Health care organizations are under increasing pressure to develop systems to ensure the safe and effective use of anticoagulants in the inpatient setting. This document provides consensus guidelines for anticoagulant therapy in the inpatient setting and serves as a companion document to prior guidelines relevant for outpatients.

Recent advances in ultrasound-triggered therapy.

PubMed

Yang, Chaopin; Li, Yue; Du, Meng; Chen, Zhiyi

2018-04-27

As a non-invasive and real-time diagnostic technique, ultrasound has provided a novel strategy for targeted treatment. With the rapid development of ultrasonic technique and ultrasound contrast agents (UCAs), spatiotemporally controllable application of ultrasound with or without UCAs makes it possible for site-specific delivery of therapeutic agents and targeted modulation with minimal side effects, which indicated a promising therapy in clinical use. This review will describe the main mechanism of targeted therapy induced by ultrasound briefly, then focus on the current application of ultrasound mediated targeted therapy in various fields including tumour, cardiovascular disease, central nervous system, skeletal muscle system diseases and stem cells therapy. In addition, ongoing challenges of ultrasound-mediated targeted therapy for further research and its clinical use are reviewed.

Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy.

PubMed

Chowdhury, P S; Chamoto, K; Honjo, T

2018-02-01

Programmed death 1 (PD-1) is an immune checkpoint molecule that negatively regulates T-cell immune function through the interaction with its ligand PD-L1. Blockage of this interaction unleashes the immune system to fight cancer. Immunotherapy using PD-1 blockade has led to a paradigm shift in the field of cancer drug discovery, owing to its durable effect against a wide variety of cancers with limited adverse effects. A brief history and development of PD-1 blockade, from the initial discovery of PD-1 to the recent clinical output of this therapy, have been summarized here. Despite its tremendous clinical success rate over other cancer treatments, PD-1 blockade has its own pitfall; a significant fraction of patients remains unresponsive to this therapy. The key to improve the PD-1 blockade therapy is the development of combination therapies. As this approach has garnered worldwide interest, here, we have summarized the recent trends in the development of PD-1 blockade-based combination therapies and the ongoing clinical trials. These include combinations with checkpoint inhibitors, radiation therapy, chemotherapy and several other existing cancer treatments. Importantly, FDA has approved PD-1 blockade agent to be used in combination with either CTLA-4 blockade or chemotherapy. Responsiveness to the PD-1 blockade therapy is affected by tumour and immune system-related factors. The role of the immune system, especially T cells, in determining the responsiveness has been poorly studied compared with those factors related to the tumour side. Energy metabolism has emerged as one of the important regulatory mechanisms for the function and differentiation of T cells. We have documented here the recent results regarding the augmentation of PD-1 blockade efficacy by augmenting mitochondrial energy metabolism of T cell. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

NASA Astrophysics Data System (ADS)

Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

2009-03-01

Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

Therapeutic Effect of Angiostatin Gene Transfer in a Murine Model of Endometriosis

PubMed Central

Dabrosin, Charlotta; Gyorffy, Steve; Margetts, Peter; Ross, Catherine; Gauldie, Jack

2002-01-01

Endometriosis, the growth of ectopic endometrial tissue, is a chronic recurrent disease affecting 10% of the female population causing dyspareunia, pelvic pain, dysmenorrhea, and infertility. Suppression of ovarian activity is the cornerstone of medical therapy with limited benefit and severe adverse effects. Angiogenesis plays a major role in the development of endometriosis suggesting that anti-angiogenic therapy would offer a new therapeutic approach. We report successful treatment of endometriosis in estrogen-supplemented ovariectomized mice by transient overexpression (6 to 10 days of duration) of the gene for a natural angiogenesis inhibitor angiostatin, delivered to the peritoneum by a replication-deficient adenovirus vector (AdAngiostatin). Established endometriosis was eradicated in 14 of 14 AdAngiostatin-treated animals, whereas 11 of 13 control animals showed full disease development. Administered to normal cycling mice for the same transient period, AdAngiostatin caused impaired ovarian function with suppressed corpus luteum development, decreased production of estradiol and progesterone, decreased ovarian and uterine weight, and increased body weight. AdAngiostatin treatment lowered the levels of sex steroids but did not induce total castration. Gene therapy with angiogenic inhibitors is a highly effective treatment for endometriosis, even in a host with preserved estrogen levels. However, local or targeted delivery of the gene must be considered to avoid prolonged systemic effects and impaired ovarian function. PMID:12213719

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis.

PubMed

Kitz, Jenna; Lowes, Lori E; Goodale, David; Allan, Alison L

2018-04-28

The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch ® and Parsortix™ platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside.

Opioids and Opioid Maintenance Therapies: Their Impact on Monocyte-Mediated HIV Neuropathogenesis

PubMed Central

Jaureguiberry-Bravo, Matias; Wilson, Rebecca; Carvallo, Loreto; Berman, Joan W.

2017-01-01

Background HIV-1 enters the CNS within two weeks after peripheral infection and results in chronic neuroinflammation that leads to HIV associated neurocognitive disorders (HAND) in more than 50% of infected people. HIV enters the CNS by transmigration of infected monocytes across the blood brain barrier. Intravenous drug abuse is a major risk factor for HIV-1 infection, and opioids have been shown to alter the progression and severity of HAND. Methadone and buprenorphine are opioid derivates that are used as opioid maintenance therapies. They are commonly used to treat opioid dependency in HIV infected substance abusers, but their effects on monocyte migration relevant to the development of cognitive impairment are not well characterized. Conclusion Here, we will discuss the effects of opioids and opioid maintenance therapies on the inflammatory functions of monocytes and macrophages that are related to the development of neuroinflammation in the context of HIV infection. PMID:27009099

Acceptance and Commitment Therapy and Contextual Behavioral Science: Examining the Progress of a Distinctive Model of Behavioral and Cognitive Therapy

PubMed Central

Hayes, Steven C.; Levin, Michael E.; Plumb-Vilardaga, Jennifer; Villatte, Jennifer L.; Pistorello, Jacqueline

2012-01-01

A number of recent authors have compared acceptance and commitment therapy (ACT) and traditional cognitive behavior therapy (CBT). The present article describes ACT as a distinct and unified model of behavior change, linked to a specific strategy of scientific development, which we term “contextual behavioral science.” We outline the empirical progress of ACT and describe its distinctive development strategy. A contextual behavioral science approach is an inductive attempt to build more adequate psychological systems based on philosophical clarity; the development of basic principles and theories; the development of applied theories linked to basic ones; techniques and components linked to these processes and principles; measurement of theoretically key processes; an emphasis on mediation and moderation in the analysis of applied impact; an interest in effectiveness, dissemination, and training; empirical testing of the research program across a broad range of areas and levels of analysis; and the creation of a more effective scientific and clinical community. We argue that this is a reasonable approach, focused on long-term progress, and that in broad terms it seems to be working. ACT is not hostile to traditional CBT, and is not directly buoyed by whatever weaknesses traditional CBT may have. ACT should be measured at least in part against its own goals as specified by its own developmental strategy. PMID:23611068

The History and Challenges Surrounding Ovarian Stimulation in the Treatment of Infertility

PubMed Central

Beall, Stephanie A.; Decherney, Alan

2014-01-01

OBJECTIVE To examine the history of superovulation for ovulation induction, its contributions to reproductive medicine and its impact on multiple births. DESIGN A search of the relevant literature using Pubmed and other online tools. RESULT(S) Infertility has been a condition known and studied for thousands of years. However, it was not until this past century that effective treatments were developed. With the advancement of our knowledge of the hypothalamic-pituitary axis, therapies utilizing gonadotropins were developed to stimulate ovulation. Not only were we now able to treat anovulatory infertility, but also induce superovulation for in vitro fertilization. With these successes came consequences, including increased multiple pregnancies. Several countries recognized the high costs associated with multiple births and implemented regulations on the infertility industry. The rate of triplet and higher-order multiples has declined over the past decade. This is largely attributed to a decreased number of embryos transferred. Nonetheless, the twin rate has remained consistently high. CONCLUSION(S) Superovulation has become a routine medical therapy used for ovulation induction and in vitro fertilization. With the development of this technology have come effective therapies for infertility and new ethical and medical challenges. Since the advent of gonadotropin therapy we have already developed technologies to improve monitoring and decrease hyperstimulation and high order multiple pregnancies. In the future, we anticipate new tools devised to optimize one embryo for one singleton live birth. PMID:22463773

Acceptance and commitment therapy and contextual behavioral science: examining the progress of a distinctive model of behavioral and cognitive therapy.

PubMed

Hayes, Steven C; Levin, Michael E; Plumb-Vilardaga, Jennifer; Villatte, Jennifer L; Pistorello, Jacqueline

2013-06-01

A number of recent authors have compared acceptance and commitment therapy (ACT) and traditional cognitive behavior therapy (CBT). The present article describes ACT as a distinct and unified model of behavior change, linked to a specific strategy of scientific development, which we term "contextual behavioral science." We outline the empirical progress of ACT and describe its distinctive development strategy. A contextual behavioral science approach is an inductive attempt to build more adequate psychological systems based on philosophical clarity; the development of basic principles and theories; the development of applied theories linked to basic ones; techniques and components linked to these processes and principles; measurement of theoretically key processes; an emphasis on mediation and moderation in the analysis of applied impact; an interest in effectiveness, dissemination, and training; empirical testing of the research program across a broad range of areas and levels of analysis; and the creation of a more effective scientific and clinical community. We argue that this is a reasonable approach, focused on long-term progress, and that in broad terms it seems to be working. ACT is not hostile to traditional CBT, and is not directly buoyed by whatever weaknesses traditional CBT may have. ACT should be measured at least in part against its own goals as specified by its own developmental strategy. Copyright © 2011. Published by Elsevier Ltd.

Gene Therapy in the Cornea: 2005-present

PubMed Central

Mohan, Rajiv R.; Tovey, Jonathan C.K.; Sharma, Ajay; Tandon, Ashish

2011-01-01

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat corneal abnormalities have begun to surface. Identification of next generation viral and nanoparticle vectors, characterization of delivered gene levels, localization, and duration in the cornea, and significant success in controlling corneal disorders, particularly fibrosis and angiogenesis, in experimental animal disease models, with no major side effects have propelled gene therapy a step closer towards establishing gene-based therapies for corneal blindness. Recently, researchers have assessed the delivery of therapeutic genes for corneal diseases and disorders due to trauma, infections, chemical, mechanical, and surgical injury, and/or abnormal wound healing. This review provides an update on the developments in gene therapy for corneal diseases and discusses the barriers that hinder its utilization for delivering genes in the cornea. PMID:21967960

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

PubMed

Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

2014-11-01

Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Robot therapy: a new approach for mental healthcare of the elderly - a mini-review.

PubMed

Shibata, Takanori; Wada, Kazuyoshi

2011-01-01

Mental healthcare of elderly people is a common problem in advanced countries. Recently, high technology has developed robots for use not only in factories but also for our living environment. In particular, human-interactive robots for psychological enrichment, which provide services by interacting with humans while stimulating their minds, are rapidly spreading. Such robots not only simply entertain but also render assistance, guide, provide therapy, educate, enable communication, and so on. Robot therapy, which uses robots as a substitution for animals in animal-assisted therapy and activity, is a new application of robots and is attracting the attention of many researchers and psychologists. The seal robot named Paro was developed especially for robot therapy and was used at hospitals and facilities for elderly people in several countries. Recent research has revealed that robot therapy has the same effects on people as animal therapy. In addition, it is being recognized as a new method of mental healthcare for elderly people. In this mini review, we introduce the merits and demerits of animal therapy. Then we explain the human-interactive robot for psychological enrichment, the required functions for therapeutic robots, and the seal robot. Finally, we provide examples of robot therapy for elderly people, including dementia patients. Copyright © 2010 S. Karger AG, Basel.

Novel Androgen Deprivation Therapy (ADT) in the Treatment of Advanced Prostate Cancer.

PubMed

Aragon-Ching, Jeanny B; Dahut, William L

2010-07-01

Androgen deprivation therapy has been the mainstay of treatment for advanced and metastatic prostate cancer. The use of novel agents targeting the androgen receptor and its signaling pathways offers a promising approach that is both safe and effective. We describe the rationale behind the use of these compounds in clinical development and the existing challenges as to how best to incorporate these new and emerging therapies in the changing treatment paradigm of metastatic prostate cancer.

Gene therapy and editing: Novel potential treatments for neuronal channelopathies.

PubMed

Wykes, R C; Lignani, G

2018-04-01

Pharmaceutical treatment can be inadequate, non-effective, or intolerable for many people suffering from a neuronal channelopathy. Development of novel treatment options, particularly those with the potential to be curative is warranted. Gene therapy approaches can permit cell-specific modification of neuronal and circuit excitability and have been investigated experimentally as a therapy for numerous neurological disorders, with clinical trials for several neurodegenerative diseases ongoing. Channelopathies can arise from a wide array of gene mutations; however they usually result in periods of aberrant network excitability. Therefore gene therapy strategies based on up or downregulation of genes that modulate neuronal excitability may be effective therapy for a wide range of neuronal channelopathies. As many channelopathies are paroxysmal in nature, optogenetic or chemogenetic approaches may be well suited to treat the symptoms of these diseases. Recent advances in gene-editing technologies such as the CRISPR-Cas9 system could in the future result in entirely novel treatment for a channelopathy by repairing disease-causing channel mutations at the germline level. As the brain may develop and wire abnormally as a consequence of an inherited or de novo channelopathy, the choice of optimal gene therapy or gene editing strategy will depend on the time of intervention (germline, neonatal or adult). This article is part of the Special Issue entitled 'Channelopathies.' Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Play Therapy for Severe Psychological Trauma. [Videotape

ERIC Educational Resources Information Center

Gil, Eliana

In this 36-minute educational video, a play and family therapist elucidates the nature of trauma, how to recognize it clinically, and how to manage its powerful effects upon children's development with the use of specific play materials and techniques. With a reenacted clinical interview, footage from an actual play therapy session, and a detailed…

A case of Todd's Palsy following unilateral electroconvulsive therapy

PubMed Central

Bell, Christine; Lepping, Peter; Clifford, John; Gardner-Thorpe, Catherine

2012-01-01

This case describes a woman undergoing unilateral electroconvulsive therapy (ECT) who developed a Todd's Palsy following the treatment, and which resolved when converted to bilateral ECT. We go on to hypothesize that this rare side effect may be an indication of the need to switch laterality during a course of ECT. PMID:22988330

Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer

PubMed Central

Uemura, Norihisa; Kondo, Tadashi

2014-01-01

Neoadjuvant therapy has been proven to be extremely valuable and is widely used for advanced esophageal cancer. However, a significant proportion of treated patients (60%-70%) does not respond well to neoadjuvant treatments and develop severe adverse effects. Therefore, predictive markers for individualization of multimodality treatments are urgently needed in esophageal cancer. Recently, molecular biomarkers that predict the response to neoadjuvant therapy have been explored in multimodal approaches in esophageal cancer and successful examples of biomarker identification have been reported. In this review, promising candidates for predictive molecular biomarkers developed by using multiple molecular approaches are reviewed. Moreover, treatment strategies based on the status of predicted biomarkers are discussed, while considering the international differences in the clinical background. However, in the absence of adequate treatment options related to the results of the biomarker test, the usefulness of these diagnostic tools is limited and new effective therapies for biomarker-identified nonresponders to cancer treatment should be concurrent with the progress of predictive technologies. Further improvement in the prognosis of esophageal cancer patients can be achieved through the introduction of novel therapeutic approaches in clinical practice. PMID:25133032

Current Pharmaceutical Treatments and Alternative Therapies of Parkinson's Disease

PubMed Central

Dong, Jie; Cui, Yanhua; Li, Song; Le, Weidong

2016-01-01

Over the decades, pharmaceutical treatments, particularly dopaminergic (DAergic) drugs have been considered as the main therapy against motor symptoms of Parkinson's disease (PD). It is proposed that DAergic drugs in combination with other medications, such as monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, anticholinergics and other newly developed non-DAergic drugs can make a better control of motor symptoms or alleviate levodopa-induced motor complications. Moreover, non-motor symptoms of PD, such as cognitive, neuropsychiatric, sleep, autonomic and sensory disturbances caused by intrinsic PD pathology or drug-induced side effects, are gaining increasing attention and urgently need to be taken care of due to their impact on quality of life. Currently, neuroprotective therapies have been investigated extensively in pre-clinical studies, and some of them have been subjected to clinical trials. Furthermore, non-pharmaceutical treatments, including deep brain stimulation (DBS), gene therapy, cell replacement therapy and some complementary managements, such as Tai chi, Yoga, traditional herbs and molecular targeted therapies have also been considered as effective alternative therapies to classical pharmaceutics. This review will provide us updated information regarding the current drugs and non-drugs therapies for PD. PMID:26585523

Economics of fluid therapy in critically ill patients.

PubMed

Lyu, Peter F; Murphy, David J

2014-08-01

Fluid therapy practices are an ongoing debate in critical care as evidence continues to emerge on the clinical effectiveness of different fluids and regimens. Although fluid therapy is a frequent and often costly treatment in the ICU, cost considerations have been largely absent from these studies. To facilitate a more structured approach to understanding fluid therapy costs and their role in clinical practice, we summarize currently available options and describe a framework for identifying and organizing relevant costs. Fluid therapy is a complex area of care that has been rarely studied from a cost-effectiveness perspective. We identify seven cost areas that capture fluid therapy-related costs during preutilization, point-of-utilization, and postutilization periods. These costs are driven by decisions on the type of fluid and administration strategy. Although estimates for some cost areas could be informed by medical literature, other cost areas remain unclear and require further investigation. Given the growing emphasis on the value of care, providers must recognize the important cost consequences of clinical decisions in fluid therapy. Future research into fluid therapy costs is needed and can be guided by this framework. Developing a complete cost picture is an initial and necessary step for improving values for patients, hospitals, and healthcare systems.

[A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

PubMed

Suzuki, Kei; Sekine, Takao

2014-05-01

A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

Non-alcoholic fatty liver disease (NAFLD) models in drug discovery.

PubMed

Cole, Banumathi K; Feaver, Ryan E; Wamhoff, Brian R; Dash, Ajit

2018-02-01

The progressive disease spectrum of non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is a rapidly emerging public health crisis with no approved therapy. The diversity of various therapies under development highlights the lack of consensus around the most effective target, underscoring the need for better translatable preclinical models to study the complex progressive disease and effective therapies. Areas covered: This article reviews published literature of various mouse models of NASH used in preclinical studies, as well as complex organotypic in vitro and ex vivo liver models being developed. It discusses translational challenges associated with both kinds of models, and describes some of the studies that validate their application in NAFLD. Expert opinion: Animal models offer advantages of understanding drug distribution and effects in a whole body context, but are limited by important species differences. Human organotypic in vitro and ex vivo models with physiological relevance and translatability need to be used in a tiered manner with simpler screens. Leveraging newer technologies, like metabolomics, proteomics, and transcriptomics, and the future development of validated disease biomarkers will allow us to fully utilize the value of these models to understand disease and evaluate novel drugs in isolation or combination.

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

PubMed

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

PubMed

Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

A review of the physical and metabolic effects of cross-sex hormonal therapy in the treatment of gender dysphoria.

PubMed

Seal, Leighton J

2016-01-01

This review focuses on the effect that cross-gender sex steroid therapy has on metabolic and hormonal parameters. There is an emphasis on those changes that result in significant clinical effects such as the positive effects of the development of secondary sexual characteristics and negative effects such as haemostatic effects and thromboembolism in transwomen or dyslipidaemia in transmen. There is also a description of the current hormonal regimens used at the largest UK gender identity clinic. The overall safety of these treatments in the context of long-term outcome data is reviewed. © The Author(s) 2015.

Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

PubMed Central

GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

2016-01-01

MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy.

PubMed

Lin, Han; Chen, Yu; Shi, Jianlin

2018-03-21

Tumour chemotherapy employs highly cytotoxic chemodrugs, which kill both cancer and normal cells by cellular apoptosis or necrosis non-selectively. Catalysing/triggering the specific chemical reactions only inside tumour tissues can generate abundant and special chemicals and products locally to initiate a series of unique biological and pathologic effects, which may enable tumour-specific theranostic effects to combat cancer without bringing about significant side effects on normal tissues. Nevertheless, chemical reaction-initiated selective tumour therapy strongly depends on the advances in chemistry, materials science, nanotechnology and biomedicine. This emerging cross-disciplinary research area is substantially different from conventional cancer-theranostic modalities in clinics. In response to the fast developments in cancer theranostics based on intratumoural catalytic chemical reactions, this tutorial review summarizes the very-recent research progress in the design and synthesis of representative nanoplatforms with intriguing nanostructures, compositions, physiochemical properties and biological behaviours for versatile catalytic chemical reaction-enabled cancer treatments, mainly by either endogenous tumour microenvironment (TME) triggering or exogenous physical irradiation. These unique intratumoural chemical reactions can be used in tumour-starving therapy, chemodynamic therapy, gas therapy, alleviation of tumour hypoxia, TME-responsive diagnostic imaging and stimuli-responsive drug release, and even externally triggered versatile therapeutics. In particular, the challenges and future developments of such a novel type of cancer-theranostic modality are discussed in detail to understand the future developments and prospects in this research area as far as possible. It is highly expected that this kind of unique tumour-specific therapeutics by triggering specific in situ catalytic chemical reactions inside tumours would provide a novel but efficient methodology for benefiting personalized biomedicine in combating cancer.

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

Lee, N

Purpose: Ocular proton therapy has the following advantages: i) sparing optic nerve, ii) the minimal dose is delivered to surrounding normal tissues. Since the proton therapy center was opened in 2007, 30 patients with ocular tumor have been treated at National Cancer Center using single scattering technique. To develop a solid eye phantom which can verify the output and the beam range with EBT3 film for independent patient QA in ocular proton therapy. Methods: The proton therapy is very effective to treat ocular tumor, because of the Bragg peak feature. In general, the beam shape of eye treatment is aboutmore » 3 cm in diameter and the beam range is under 5 cm. However, proton therapy has uncertainty of beam range problem due to various stopping power of normal tissue, bone, air and so on, so that we should verify the beam range before treatment. For this purpose, a new PMMA phantom with wedge has been developed to use the film dosimetry and the ionization chamber. It is able to place a film on the slope of the phantom, which the spread out Bragg Peak by the water equivalent thickness value of PMMA can be made on the film. We considered to relation with quenching effect of proton energy and range for simple second check. In addition, the ionization chamber (Pin-point chamber, PTW 31014) can be inserted into a hole in the phantom to measure the absolute dose. Results: The output difference and beam range difference were less than 2% and 1.0 mm, respectively, between the measurement and the plan. Conclusion: An eye phantom was developed and its performance was evaluated successfully and it was useful to verify the output. Also with EBT3 film with the quenching effect for measurement depth-dose profile, range to patient QA.« less

Combination of magnetic resonance imaging and diffuse optical spectroscopy to predict radiation response in the breast: an exploratory pilot study

NASA Astrophysics Data System (ADS)

Klifa, C.; Hattangadi, J.; Watkins, M.; Li, A.; Sakata, T.; Tromberg, B.; Hylton, N.; Park, C.

2007-02-01

Radiation therapy (RT) is a standard treatment after lumpectomy for breast cancer, involving a typical course of approximately 6-7 weeks of daily treatment. Many women find this cumbersome and costly, and therefore many are left with the option of mastectomy. Many groups are now investigating novel ways to deliver RT, by using different techniques and shortening the course of treatment. However, the efficacy and side effects of these strategies are not known. In this project, we wish to develop noninvasive imaging tools that would allow us to measure radiation dose effects in women with breast cancer. We hope this will lead to new ways to identify individuals who may not need radiation therapy, who may safely be treated with new accelerated techniques, or who should be treated with the standard radiation therapy approach. We propose to study the effect of radiation therapy using a combination of two imaging modalities: 1) magnetic resonance imaging (MRI) which will provide detailed information on breast structures and blood vessels and 2) near infra-red diffuse optical spectroscopy (DOS), which measures local biologic properties of breast tissue. Our hypothesis is that by using a combination of modalities we will be able to better characterize radiation effects in breast tissue, by measuring differences between the radiated and non-irradiated breast. The development of novel non-invasive tools providing information about how individuals respond to radiation therapy can lead to important improvement of radiation treatment, and ultimately help guide individualized treatment programs in the future.

Food allergy therapy: is a cure within reach?

PubMed

Nowak-Węgrzyn, Anna; Muraro, Antonella

2011-04-01

There is an unmet medical need for an effective food allergy therapy; thus, development of therapeutic interventions for food allergy is a top research priority. The food allergen-nonspecific therapies for food-induced anaphylaxis include monoclonal anti-IgE antibodies and Chinese herbs. The food allergen-specific therapies include oral, sublingual, and epicutaneous immunotherapy with native food allergens and mutated recombinant proteins. Diet containing heated milk and egg may represent an alternative approach to oral immunomodulation. Oral food immunotherapy remains an investigational treatment to be further studied before advancing into clinical practice. Copyright © 2011 Elsevier Inc. All rights reserved.

Regulation of advanced therapy medicinal products in Europe and the role of academia.

PubMed

Pearce, Kim F; Hildebrandt, Martin; Greinix, Hildegard; Scheding, Stefan; Koehl, Ulrike; Worel, Nina; Apperley, Jane; Edinger, Matthius; Hauser, Andrea; Mischak-Weissinger, Eva; Dickinson, Anne M; Lowdell, Mark W

2014-03-01

Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them. European academic and non-industrial facilities (n = 747) were contacted, and a representative sample of 50 replied to a detailed questionnaire. Experienced centres were further selected in every Member State (MS) for semi-structured interviews. Indicators of ATMP production and development success were statistically assessed, and opinions about directive implementation were documented. Facilities experienced in manufacturing cell therapy transplant products are the most successful in developing ATMPs. New centres lacking this background struggle to enter the field, and there remains a shortage of facilities in academia participating in translational research. This is compounded by heterogeneous implementation of the regulations across MS. GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field. Copyright © 2014 International Society for Cellular Therapy. All rights reserved.

Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages

NASA Astrophysics Data System (ADS)

Qin, Jinbao; Peng, Zhiyou; Li, Bo; Ye, Kaichuang; Zhang, Yuxin; Yuan, Fukang; Yang, Xinrui; Huang, Lijia; Hu, Junqing; Lu, Xinwu

2015-08-01

Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography (CT) imaging. These Au NRs were then applied to an apolipoprotein E knockout (Apo E) mouse model to evaluate their effects on in vivo CT imaging and their effectiveness as for the subsequent photothermal therapy of macrophages in femoral artery restenosis under 808 nm laser irradiation. In vitro photothermal ablation treatment using Au NRs exhibited a significant cell-killing efficacy of macrophages, even at relatively low concentrations of Au NRs and low NIR powers. In addition, the in vivo results demonstrated that the Au NRs are effective for in vivo imaging and photothermal therapy of inflammatory macrophages in femoral artery restenosis. This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation-associated diseases.Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography (CT) imaging. These Au NRs were then applied to an apolipoprotein E knockout (Apo E) mouse model to evaluate their effects on in vivo CT imaging and their effectiveness as for the subsequent photothermal therapy of macrophages in femoral artery restenosis under 808 nm laser irradiation. In vitro photothermal ablation treatment using Au NRs exhibited a significant cell-killing efficacy of macrophages, even at relatively low concentrations of Au NRs and low NIR powers. In addition, the in vivo results demonstrated that the Au NRs are effective for in vivo imaging and photothermal therapy of inflammatory macrophages in femoral artery restenosis. This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation-associated diseases. Electronic supplementary information (ESI) available: Figures. See DOI: 10.1039/c5nr02521d

Serving Rural Families of Developmentally Disabled in a Cost-Effective Manner.

ERIC Educational Resources Information Center

Hedge, Russell; Johnson, Willard

Providing cost-effective services in 15 counties of Southeast Kansas, the Infant and Early Childhood Intervention Program (IECIP) teaches parents to provide daily one-to-one therapy in gross and fine perceptual motor development, speech and language development, social adjustment, and behavior management for developmentally delayed children from…

Nivolumab-induced vitiligo in a metastatic melanoma patient: A case report.

PubMed

Edmondson, Lindsay A; Smith, Leticia V; Mallik, Alka

2017-12-01

The programmed-death-1 inhibitors selectively block programmed-death-1 interaction with its receptor, which restores active T-cell response directed at tumor cells, inducing an anti-tumor effect. This nonspecific activation of the immune system can also lead to a wide spectrum of side effects. Nivolumab has been used effectively to prolong survival in patients with metastatic melanoma and is recommended as a category 1 agent for systemic therapy in metastatic or unresectable melanoma per the National Comprehensive Cancer Network guidelines. We present a case of a 64-year-old woman who began nivolumab therapy for metastatic melanoma. After six doses of nivolumab therapy, the patient experienced generalized hypopigmentation on her face, chest, back, arms, and lower extremities. Although vitiligo has been reported in as many as 10.7% of patients undergoing nivolumab therapy in some clinical trials, we believe this is the first case to describe the progression of nivolumab-induced vitiligo in a metastatic melanoma patient. This case provides significant insight into the onset, symptoms, development, and treatment options for patients experiencing vitiligo as a result of nivolumab therapy.

Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy

PubMed Central

O'Neill, Daniel; Jones, Dominic; Wade, Mark; Grey, James; Nakjang, Sirintra; Guo, Wenrui; Cork, David; Davies, Barry R.; Wedge, Steve R.; Robson, Craig N.; Gaughan, Luke

2015-01-01

The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated ARW741L/C mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of ARW741L highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, ARW741L transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients. PMID:26267320

Pulmonary hypertension associated with thalassemia syndromes

PubMed Central

Fraidenburg, Dustin R.; Machado, Roberto F.

2016-01-01

Chronic hemolytic anemia has increasingly been identified as an important risk factor for the development of pulmonary hypertension. Within the thalassemia syndromes, there are multiple mechanisms, both distinct and overlapping, by which pulmonary hypertension develops and that differ among β-thalassemia major or intermedia patients. Pulmonary hypertension in β-thalassemia major correlates with the severity of hemolysis, yet in patients whose disease is well treated with chronic transfusion therapy, the development of pulmonary hypertension can be related to cardiac dysfunction and the subsequent toxic effects of iron overload rather than hemolysis. β-thalassemia intermedia, on the other hand, has a higher incidence of pulmonary hypertension owing to the low level of hemolysis that exists over years without the requirement for frequent transfusions, while splenectomy is shown to play an important role in both types. Standard therapies such as chronic transfusion have been shown to mitigate pulmonary hypertension, and appropriate chelation therapy can avoid the toxic effects of iron overload, yet is not indicated in many patients. Limited evidence exists for the use of pulmonary vasodilators or other therapies, such as l-carnitine, to treat pulmonary hypertension associated with thalassemia. Here we review the most recent findings regarding the pathogenic mechanisms, epidemiology, presentation, diagnosis, and treatment of pulmonary hypertension in thalassemia syndromes. PMID:27008311

Depletion kinetics of circulating prostate cancer cells studied by in vivo flow cytometer

NASA Astrophysics Data System (ADS)

Liu, Guangda; Guo, Jin; Li, Yan; Chen, Yun; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

2010-11-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

Studying depletion kinetics of circulating prostate cancer cells by in vivo flow cytometer

NASA Astrophysics Data System (ADS)

Liu, Guangda; Gu, Zhengqin; Guo, Jin; Li, Yan; Chen, Yun; Chen, Tong; Wang, Cheng; Wei, Xunbin

2011-03-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

Monitoring tumor metastasis by in vivo imaging and flow cytometer

NASA Astrophysics Data System (ADS)

Gu, Zhenqin; Guo, Jin; Liu, Guangda; Li, Yan; Chen, Yun; Chen, Tong; Wang, Chen; Wei, Xunbin

2009-08-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

Food allergy diagnosis and therapy: where are we now?

PubMed Central

Syed, Aleena; Kohli, Arunima; Nadeau, Kari C

2014-01-01

Food allergy is a growing worldwide epidemic that adversely effects up to 10% of the population. Causes and risk factors remain unclear and diagnostic methods are imprecise. There is currently no accepted treatment for food allergy. Therefore, there is an imminent need for greater understanding of food allergies, revised diagnostics and development of safe, effective therapies. Oral immunotherapy provides a particularly promising avenue, but is still highly experimental and not ready for clinical use. PMID:23998729

A cost-effectiveness model to personalize antiviral therapy in naive patients with genotype 1 chronic hepatitis C.

PubMed

Iannazzo, Sergio; Colombatto, Piero; Ricco, Gabriele; Oliveri, Filippo; Bonino, Ferruccio; Brunetto, Maurizia R

2015-03-01

Rapid virologic response is the best predictor of sustained virologic response with dual therapy in genotype-1 chronic hepatitis C, and its evaluation was proposed to tailor triple therapy in F0-F2 patients. Bio-mathematical modelling of viral dynamics during dual therapy has potentially higher accuracy than rapid virologic in the identification of patients who will eventually achieve sustained response. Study's objective was the cost-effectiveness analysis of a personalized therapy in naïve F0-F2 patients with chronic hepatitis C based on a bio-mathematical model (model-guided strategy) rather than on rapid virologic response (guideline-guided strategy). A deterministic bio-mathematical model of the infected cell dynamics was validated in a cohort of 135 patients treated with dual therapy. A decision-analytic economic model was then developed to compare model-guided and guideline-guided strategies in the Italian setting. The outcomes of the cost-effectiveness analysis with model-guided and guideline-guided strategy were 19.1-19.4 and 18.9-19.3 quality-adjusted-life-years. Total per-patient lifetime costs were €25,200-€26,000 with model-guided strategy and €28,800-€29,900 with guideline-guided strategy. When comparing model-guided with guideline-guided strategy the former resulted more effective and less costly. The adoption of the bio-mathematical predictive criterion has the potential to improve the cost-effectiveness of a personalized therapy for chronic hepatitis C, reserving triple therapy for those patients who really need it. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema.

PubMed

Haig, Jennifer; Barbeau, Martin; Ferreira, Alberto

2016-07-01

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing 'death' state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.

Quality cell therapy manufacturing by design.

PubMed

Lipsitz, Yonatan Y; Timmins, Nicholas E; Zandstra, Peter W

2016-04-01

Transplantation of live cells as therapeutic agents is poised to offer new treatment options for a wide range of acute and chronic diseases. However, the biological complexity of cells has hampered the translation of laboratory-scale experiments into industrial processes for reliable, cost-effective manufacturing of cell-based therapies. We argue here that a solution to this challenge is to design cell manufacturing processes according to quality-by-design (QbD) principles. QbD integrates scientific knowledge and risk analysis into manufacturing process development and is already being adopted by the biopharmaceutical industry. Many opportunities to incorporate QbD into cell therapy manufacturing exist, although further technology development is required for full implementation. Linking measurable molecular and cellular characteristics of a cell population to final product quality through QbD is a crucial step in realizing the potential for cell therapies to transform healthcare.

Progress towards personalized therapeutics: biologic- and risk-directed therapy for neuroblastoma.

PubMed

Gustafson, William Clay; Matthay, Katherine K

2011-10-01

Neuroblastoma, a tumor of the developing peripheral sympathetic nervous system, is the most common and deadly extracranial solid tumor of childhood. Risk-stratification and risk-adapted therapy play a large role in the modern treatment of neuroblastoma. Recently, through extensive international collaboration, new guidelines for risk stratification have emerged that will aid in international cooperative studies, as well as clarifying therapeutic options for patients. Current therapies for low- and intermediate-risk neuroblastoma have resulted in excellent prognoses for these risk strata, and current efforts are concentrated on chemotherapy reduction. By contrast, much more gradual progress has been made in improving survival for high-risk neuroblastoma patients, despite significant chemotherapy intensification. Current investigations focus on overcoming resistance by elucidating the molecular/genetic causes of neuroblastoma tumorigenesis and progression, with the aim of developing more effective biologically targeted therapies for this disease.

Evolution of Endovascular Therapy in Acute Stroke: Implications of Device Development

PubMed Central

Balasubramaian, Adithya; Mitchell, Peter; Dowling, Richard

2015-01-01

Intravenous thrombolysis is an effective treatment for acute ischaemic stroke. However, vascular recanalization rates remain poor especially in the setting of large artery occlusion. On the other hand, endovascular intra-arterial therapy addresses this issue with superior recanalization rates compared with intravenous thrombolysis. Although previous randomized controlled studies of intra-arterial therapy failed to demonstrate superiority, the failings may be attributed to a combination of inferior intra-arterial devices and suboptimal selection criteria. The recent results of several randomized controlled trials have demonstrated significantly improved outcomes, underpinning the advantage of newer intra-arterial devices and superior recanalization rates, leading to renewed interest in establishing intra-arterial therapy as the gold standard for acute ischaemic stroke. The aim of this review is to outline the history and development of different intra-arterial devices and future directions in research. PMID:26060800

A Look to Future Directions in Gene Therapy Research for Monogenic Diseases

PubMed Central

Porteus, Matthew H; Connelly, Jon P; Pruett, Shondra M

2006-01-01

The concept of gene therapy has long appealed to biomedical researchers and clinicians because it promised to treat certain diseases at their origins. In the last several years, there have been several trials in which patients have benefited from gene therapy protocols. This progress, however, has revealed important problems, including the problem of insertional oncogenesis. In this review, which focuses on monogenic diseases, we discuss the problem of insertional oncogenesis and identify areas for future research, such as developing more quantitative assays for risk and efficacy, and ways of minimizing the genotoxic effects of gene therapy protocols, which will be important if gene therapy is to fulfill its conceptual promise. PMID:17009872

Medicinal Leech Therapy for Glans Penis Congestion After Primary Bladder Exstrophy-Epispadias Repair in an Infant: A Case Report.

PubMed

Wagenheim, Gavin N; Au, Jason; Gargollo, Patricio C

2016-01-01

Many postoperative complications have been reported after repair of classic bladder exstrophy. We present a case of medicinal leech therapy for glans penis congestion following exstrophy repair in an infant. A 2-week-old male with classic bladder exstrophy underwent complete primary repair. On postoperative day 1, he developed rapidly worsening glans penis venous congestion. Medicinal leech therapy was instituted with antibiotics and blood transfusions to maintain a hematocrit >30%. After 24 hours, venous congestion improved and therapy was discontinued. The patient's remaining hospital course was uncomplicated. Medicinal leeches are an effective therapy to relieve glans penis venous congestion. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

PubMed

Sheikhbahaei, Sara; Mena, Esther; Pattanayak, Puskar; Taghipour, Mehdi; Solnes, Lilja B; Subramaniam, Rathan M

2017-01-01

A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Bacterial meningitis - principles of antimicrobial treatment.

PubMed

Jawień, Miroslaw; Garlicki, Aleksander M

2013-01-01

Bacterial meningitis is associated with significant morbidity and mortality despite the availability of effective antimicrobial therapy. The management approach to patients with suspected or proven bacterial meningitis includes emergent cerebrospinal fluid analysis and initiation of appropriate antimicrobial and adjunctive therapies. The choice of empirical antimicrobial therapy is based on the patient's age and underlying disease status; once the infecting pathogen is isolated, antimicrobial therapy can be modified for optimal treatment. Successful treatment of bacterial meningitis requires the knowledge on epidemiology including prevalence of antimicrobial resistant pathogens, pathogenesis of meningitis, pharmacokinetics and pharmacodynamics of antimicrobial agents. The emergence of antibiotic-resistant bacterial strains in recent years has necessitated the development of new strategies for empiric antimicrobial therapy for bacterial meningitis.

Respiratory flows during early childhood: Computational models to examine therapeutic aerosols in the developing airways

NASA Astrophysics Data System (ADS)

Tenenbaum-Katan, Janna; Hofemeier, Philipp; Sznitman, Josué; Janna Tenenbaum-Katan Team

2015-11-01

Inhalation therapy is the cornerstone of early-childhood respiratory treatments, as well as a rising potential for systemic drug delivery and pulmonary vaccination. As such, indispensable understanding of respiratory flow phenomena, coupled with particle transport at the deep regions of children's lungs is necessary to attain efficient targeting of aerosol therapy. However, fundamental research of pulmonary transport is overwhelmingly focused on adults. In our study, we have developed an anatomically-inspired computational model of representing pulmonary acinar regions at several age points during a child's development. Our numerical simulations examine respiratory flows and particle deposition maps within the acinar model, accounting for varying age dependant anatomical considerations and ventilation patterns. Resulting deposition maps of aerosols alter with age, such findings might suggest that medication protocols of inhalation therapy in young children should be considered to be accordingly amended with the child's development. Additionally to understanding basic scientific concepts of age effects on aerosol deposition, our research can potentially contribute practical guidelines to therapy protocols, and its' necessary modifications with age. We acknowledge the support of the ISF and the Israeli ministry of Science.

Gene therapy in pancreatic cancer

PubMed Central

Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

2014-01-01

Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC. PMID:25309069

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma

PubMed Central

Pritchard, Eleanor M.; Dyer, Michael A.; Guy, R. Kiplin

2017-01-01

While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors. PMID:26202204

Driving personalized medicine: capturing maximum net present value and optimal return on investment.

PubMed

Roth, Mollie; Keeling, Peter; Smart, Dave

2010-01-01

In order for personalized medicine to meet its potential future promise, a closer focus on the work being carried out today and the foundation it will provide for that future is imperative. While big picture perspectives of this still nascent shift in the drug-development process are important, it is more important that today's work on the first wave of targeted therapies is used to build specific benchmarking and financial models against which further such therapies may be more effectively developed. Today's drug-development teams need a robust tool to identify the exact drivers that will ensure the successful launch and rapid adoption of targeted therapies, and financial metrics to determine the appropriate resource levels to power those drivers. This special report will describe one such benchmarking and financial model that is specifically designed for the personalized medicine field and will explain how the use of this or similar models can help to capture the maximum net present value of targeted therapies and help to realize optimal return on investment.

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.

PubMed

Pritchard, Eleanor M; Dyer, Michael A; Guy, R Kiplin

2016-01-01

While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.

Ferret and pig models of cystic fibrosis: prospects and promise for gene therapy.

PubMed

Yan, Ziying; Stewart, Zoe A; Sinn, Patrick L; Olsen, John C; Hu, Jim; McCray, Paul B; Engelhardt, John F

2015-03-01

Large animal models of genetic diseases are rapidly becoming integral to biomedical research as technologies to manipulate the mammalian genome improve. The creation of cystic fibrosis (CF) ferrets and pigs is an example of such progress in animal modeling, with the disease phenotypes in the ferret and pig models more reflective of human CF disease than mouse models. The ferret and pig CF models also provide unique opportunities to develop and assess the effectiveness of gene and cell therapies to treat affected organs. In this review, we examine the organ disease phenotypes in these new CF models and the opportunities to test gene therapies at various stages of disease progression in affected organs. We then discuss the progress in developing recombinant replication-defective adenoviral, adeno-associated viral, and lentiviral vectors to target genes to the lung and pancreas in ferrets and pigs, the two most affected organs in CF. Through this review, we hope to convey the potential of these new animal models for developing CF gene and cell therapies.

Intra-articular therapies for osteoarthritis.

PubMed

Yu, Shirley P; Hunter, David J

2016-10-01

Conventional medical therapies for osteoarthritis are mainly palliative in nature, aiming to control pain and symptoms. Traditional intra-articular therapies are not recommended in guidelines as first line therapy, but are potential alternatives, when conventional therapies have failed. Current and future intra-articular drug therapies for osteoarthritis are highlighted, including corticosteroids, hyaluronate, and more controversial treatments marketed commercially, namely platelet rich plasma and mesenchymal cell therapy. Intraarticular disease modifying osteoarthritis drugs are the future of osteoarthritis treatments, aiming at structural modification and altering the disease progression. Interleukin-1β inhibitor, bone morphogenic protein-7, fibroblast growth factor 18, bradykinin B2 receptor antagonist, human serum albumin, and gene therapy are discussed in this review. The evolution of drug development in osteoarthritis is limited by the ability to demonstrate effect. High quality trials are required to justify the use of existing intra-articular therapies and to advocate for newer, promising therapies. Challenges in osteoarthritis therapy research are fundamentally related to the complexity of the pathological mechanisms of osteoarthritis. Novel drugs offer hope in a disease with limited medical therapy options. Whether these future intra-articular therapies will provide clinically meaningful benefits, remains unknown.

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology.

PubMed

Kontoghiorghe, Christina N; Kolnagou, Annita; Kontoghiorghes, George J

2015-11-23

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

PubMed

Masson, Patrick

2011-09-25

After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Fail-Safe Therapy by Gamma-Ray Irradiation Against Tumor Formation by Human-Induced Pluripotent Stem Cell-Derived Neural Progenitors.

PubMed

Katsukawa, Mitsuko; Nakajima, Yusuke; Fukumoto, Akiko; Doi, Daisuke; Takahashi, Jun

2016-06-01

Cell replacement therapy holds great promise for Parkinson's disease (PD), but residual undifferentiated cells and immature neural progenitors in the therapy may cause tumor formation. Although cell sorting could effectively exclude these proliferative cells, from the viewpoint of clinical application, there exists no adequate coping strategy in the case of their contamination. In this study, we analyzed a component of proliferative cells in the grafts of human-induced pluripotent stem cell-derived neural progenitors and investigated the effect of radiation therapy on tumor formation. In our differentiating protocol, analyses of neural progenitors (day 19) revealed that the proliferating cells expressed early neural markers (SOX1, PAX6) or a dopaminergic neuron progenitor marker (FOXA2). When grafted into the rat striatum, these immature neurons gradually became postmitotic in the brain, and the rosette structures disappeared at 14 weeks. However, at 4-8 weeks, the SOX1(+)PAX6(+) cells formed rosette structures in the grafts, suggesting their tumorigenic potential. Therefore, to develop a fail-safe therapy against tumor formation, we investigated the effect of radiation therapy. At 4 weeks posttransplantation, when KI67(+) cells comprised the highest ratio, radiation therapy with (137)Cs Gammacell Exactor for tumor-bearing immunodeficient rats showed a significant decrease in graft volume and percentage of SOX1(+)KI67(+) cells in the graft, thus demonstrating the preventive effect of gamma-ray irradiation against tumorigenicity. These results give us critical criteria for the safety of future cell replacement therapy for PD.

Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE.

PubMed

Alexander, Brian M; Ba, Sujuan; Berger, Mitchel S; Berry, Donald A; Cavenee, Webster K; Chang, Susan M; Cloughesy, Timothy F; Jiang, Tao; Khasraw, Mustafa; Li, Wenbin; Mittman, Robert; Poste, George H; Wen, Patrick Y; Yung, W K Alfred; Barker, Anna D

2018-02-15

Glioblastoma (GBM) is a deadly disease with few effective therapies. Although much has been learned about the molecular characteristics of the disease, this knowledge has not been translated into clinical improvements for patients. At the same time, many new therapies are being developed. Many of these therapies have potential biomarkers to identify responders. The result is an enormous amount of testable clinical questions that must be answered efficiently. The GBM Adaptive Global Innovative Learning Environment (GBM AGILE) is a novel, multi-arm, platform trial designed to address these challenges. It is the result of the collective work of over 130 oncologists, statisticians, pathologists, neurosurgeons, imagers, and translational and basic scientists from around the world. GBM AGILE is composed of two stages. The first stage is a Bayesian adaptively randomized screening stage to identify effective therapies based on impact on overall survival compared with a common control. This stage also finds the population in which the therapy shows the most promise based on clinical indication and biomarker status. Highly effective therapies transition in an inferentially seamless manner in the identified population to a second confirmatory stage. The second stage uses fixed randomization to confirm the findings from the first stage to support registration. Therapeutic arms with biomarkers may be added to the trial over time, while others complete testing. The design of GBM AGILE enables rapid clinical testing of new therapies and biomarkers to speed highly effective therapies to clinical practice. Clin Cancer Res; 24(4); 737-43. ©2017 AACR . ©2017 American Association for Cancer Research.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

PubMed

Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

2016-01-01

Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Cost-effectiveness of treatment regimens for the eradication of Helicobacter pylori in duodenal ulcer.

PubMed

Vakil, N; Fennerty, M B

1996-02-01

Eradication of Helicobacter pylori with antimicrobials was recommended by a recent NIH consensus panel for all infected patients with peptic ulcer disease. The precise regimen that should be used for eradication of the infection remains uncertain because of the variety of regimens described, variable results with the regimens, and difficulties in predicting drug compliance outside clinical trials. A decision analysis tree was developed with three regimens that are widely used regimens for the eradication of H. pylori: 1) 2-wk triple drug therapy (metronidazole, bismuth, tetracycline with H2 receptor antagonist), 2) 2-wk omeprazole and amoxicillin, and 3) 2-wk omeprazole and clarithromycin. Traditional H2 receptor antagonist therapy was used for comparison. A 2-yr time period was chosen for study to allow sufficient time for relapse and to evaluate its effect on the treatment strategy. Probabilities for eradication, compliance, and metronidazole resistance were determined from published data, and assumptions were tested by sensitivity analysis. Standard 2-wk triple drug therapy was the least expensive strategy ($720), and conventional H2 receptor antagonist therapy was the most expensive ($1791). Costs with 2-wk therapy with omeprazole and clarithromycin ($768) were lower than with omeprazole and amoxicillin ($1028). Treatment to eradicate H. pylori in infected patients with duodenal ulcer is a less expensive strategy than traditional therapy with H2 receptor antagonists. Triple drug therapy is the optimal regimen in areas where metronidazole resistance rates are < 36% and compliance is > 53%. Omeprazole and amoxicillin is not cost-effective unless eradication rates are greater than 74%. Dual drug therapy with omeprazole and clarithromycin is effective in regions where metronidazole resistance is high or where it is anticipated that there would be poor compliance with the more complicated triple drug therapy regimen.

Effectiveness of Part C Early Intervention Physical, Occupational, and Speech Therapy Services for Preterm or Low Birth Weight Infants in Wisconsin, United States

PubMed Central

McManus, Beth M.; Carle, Adam C.; Poehlmann, Julie

2013-01-01

Objective To determine the effectiveness of policy-driven therapy (ie, Part C early intervention [EI]) in the context of varying maternal supports among preterm infants in Wisconsin. Methods A longitudinal study of mother–infant dyads recruited from 3 newborn intensive care units in southeastern Wisconsin. Participation in EI-based therapy was collected at 36 months via parent-report. Cognitive function was measured at 16 months by use of the Bayley Scales of Infant Development (Mental Developmental Index), 2nd edition and at 24 and 36 months postterm via use of the Stanford-Binet Intelligence scale, 5th edition. Maternal support was measured at 4 months with the Maternal Support Scale. Propensity score matching was used to reduce selection bias. Latent growth models of matched pairs estimated the effect of EI therapy on cognitive function trajectories. Ordinary least squares regression estimated the differential effect of EI therapy on cognitive function at 16, 24, and 36 months postterm for mothers reporting more maternal supports. Results Of the 128 infants, 41 received EI therapy and, of those, 32 (78%) were successfully matched with controls. The results of the matched analysis (n = 64) reveal that 1) receipt of therapy is inversely associated with cognitive function baseline (P = .04) and positively associated with trajectories (P =.03), 2) the number of maternal supports is positively associated with cognitive function for families receiving Part C early intervention, at 16 months (P = .05), 24 months (P <.01), and 36 months (P = .05) postterm. Conclusions Participation in EI therapy may be associated with more optimal cognitive function trajectories. Among preterm children whose mothers have more supports, receiving therapy appears particularly beneficial. PMID:22230187

[The role of neurotrophic factors in regeneration of the nervous system].

PubMed

Machaliński, Bogusław; Lażewski-Banaszak, Piotr; Dąbkowska, Elżbieta; Paczkowska, Edyta; Gołąb-Janowska, Monika; Nowacki, Przemysław

2012-01-01

Neurotrophic factors regulate survival, development, and function of nervous tissue. They act via two different classes of receptors and activation of various signaling pathways in the target cells. Illumination of their physiological role in the maintenance of central nervous system homeostasis as well as regeneration of damaged tissue have ignited expectations to heal neurodegenerative diseases, including amyotrophic late-ral sclerosis and Parkinson disease. Advances in pharmaco-therapy, gene therapy, and stem cell biology have enabled development of novel therapies with application of regenerating cell transplantation. In the foreseeable future, it may lead to the establishment of safe and effective ways of treatment of these severe and currently incurable diseases.

Treatment of Hepatitis C Virus Infection in Children Less than 12 Years of Age in Developing Countries.

PubMed

Aziz, Sina

2014-12-01

The treatment of hepatitis c virus (HCV) infection in children is difficult as few options are available. The standard therapy is combination pegylated interferon (PEG-IFN) α-2a or 2b and ribavirin, and the duration of therapy depends on HCV genotype. New oral drug therapies available for adults have still not been approved for treatment in children. Here, we review the causes of HCV infection in children, the therapeutic options for children, and the side effects of these treatments. The problems faced by physicians managing HCV infection in children less than 12 years of age in a developing country are also discussed.

Gene Therapy for the Treatment of Diabetic Neuropathy

PubMed Central

Mata, Marina; Chattopadhyay, Munmun; Fink, David J

2009-01-01

Neuropathy is a common, untreatable complication of both type 1 and type 2 diabetes. In animal models peptide neurotrophic factors can be used to protect against the development of neuropathy, but the combination of short half-life and off-target effects of these potent pleiotropic peptides has limited translation to human therapy. Gene transfer is a promising strategy that might circumvent these limitations. In this essay we review the basic methods of gene transfer and the preclinical data in rodent models that support the utility of this approach in the treatment of diabetic neuropathy. The path to a clinical applications and potential pitfalls in developing gene therapy for the treatment of diabetic neuropathy are considered. PMID:18990298

Update on gene therapy of inherited immune deficiencies.

PubMed

Engel, Barbara C; Kohn, Donald B; Podsakoff, Greg M

2003-10-01

Gene therapy has been under development as a way to correct inborn errors for many years. Recently, patients with two forms of inherited severe combined immunodeficiency (SCID), adenosine deaminase and X-linked, treated by three different clinical investigative teams, have shown significant immune reconstitution leading to protective immunity. These advances irrefutably prove the concept that hematopoietic progenitor cell gene therapy can ameliorate these diseases. However, due to proviral insertional oncogenesis, two individuals in one of the X-SCID studies developed T-cell leukemia more than two years after the gene transfer. Depending upon the results of long-term follow-up, the successes together with the side effects highlight the relative merits of this therapeutic approach.

DJINNI: A Novel Technology Supported Exposure Therapy Paradigm for SAD Combining Virtual Reality and Augmented Reality.

PubMed

Ben-Moussa, Maher; Rubo, Marius; Debracque, Coralie; Lange, Wolf-Gero

2017-01-01

The present paper explores the benefits and the capabilities of various emerging state-of-the-art interactive 3D and Internet of Things technologies and investigates how these technologies can be exploited to develop a more effective technology supported exposure therapy solution for social anxiety disorder. "DJINNI" is a conceptual design of an in vivo augmented reality (AR) exposure therapy mobile support system that exploits several capturing technologies and integrates the patient's state and situation by vision-based, audio-based, and physiology-based analysis as well as by indoor/outdoor localization techniques. DJINNI also comprises an innovative virtual reality exposure therapy system that is adaptive and customizable to the demands of the in vivo experience and therapeutic progress. DJINNI follows a gamification approach where rewards and achievements are utilized to motivate the patient to progress in her/his treatment. The current paper reviews the state of the art of technologies needed for such a solution and recommends how these technologies could be integrated in the development of an individually tailored and yet feasible and effective AR/virtual reality-based exposure therapy. Finally, the paper outlines how DJINNI could be part of classical cognitive behavioral treatment and how to validate such a setup.

DJINNI: A Novel Technology Supported Exposure Therapy Paradigm for SAD Combining Virtual Reality and Augmented Reality

PubMed Central

Ben-Moussa, Maher; Rubo, Marius; Debracque, Coralie; Lange, Wolf-Gero

2017-01-01

The present paper explores the benefits and the capabilities of various emerging state-of-the-art interactive 3D and Internet of Things technologies and investigates how these technologies can be exploited to develop a more effective technology supported exposure therapy solution for social anxiety disorder. “DJINNI” is a conceptual design of an in vivo augmented reality (AR) exposure therapy mobile support system that exploits several capturing technologies and integrates the patient’s state and situation by vision-based, audio-based, and physiology-based analysis as well as by indoor/outdoor localization techniques. DJINNI also comprises an innovative virtual reality exposure therapy system that is adaptive and customizable to the demands of the in vivo experience and therapeutic progress. DJINNI follows a gamification approach where rewards and achievements are utilized to motivate the patient to progress in her/his treatment. The current paper reviews the state of the art of technologies needed for such a solution and recommends how these technologies could be integrated in the development of an individually tailored and yet feasible and effective AR/virtual reality-based exposure therapy. Finally, the paper outlines how DJINNI could be part of classical cognitive behavioral treatment and how to validate such a setup. PMID:28503155

Music therapy can lower the heart rates of severely sick children.

PubMed

Uggla, L; Bonde, L O; Svahn, B M; Remberger, M; Wrangsjö, B; Gustafsson, B

2016-10-01

Paediatric recipients of haematopoietic stem cell transplants (HSCT) are at increased risk of developing post-traumatic stress disorder (PTSD), and there is a need to identify interventions that can alleviate stress in this group. The aim of this study was to examine the previously unexplored effect of music therapy on children undergoing HSCT, by analysing physiological parameters and comparing them with a control group. We performed a randomised clinical pilot study of 24 patients up to the age of 16 undergoing HSCT at Karolinska University Hospital, Huddinge, Sweden. Music therapy, including expressive and receptive elements, was performed twice a week in the treatment group and compared to standard care in the control group. Physiological parameters were evaluated according to the hospital's protocols. The music therapy group had significantly reduced evening heart rates compared to the control group (p < 0.001), and the effect was sustainable for four to eight hours after the intervention. There were no significant differences in saturation or blood pressure observed between the groups. Music therapy significantly lowered the heart rate of children undergoing HSCT for at least four to eight hours, indicating reduced stress levels and potentially lowering the risk of developing PTSD. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

PubMed Central

Frick, Karyn M.

2009-01-01

The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

Newer influenza antivirals, biotherapeutics and combinations.

PubMed

Hayden, Frederick G

2013-01-01

This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high-risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host-directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host-directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed. © 2012 Blackwell Publishing Ltd.

A critical appraisal of the clinical utility of proton therapy in oncology

PubMed Central

Wang, Dongxu

2015-01-01

Proton therapy is an emerging technology for providing radiation therapy to cancer patients. The depth dose distribution of a proton beam makes it a preferable radiation modality as it reduces radiation to the healthy tissue outside the tumor, compared with conventional photon therapy. While theoretically beneficial, its clinical values are still being demonstrated from the increasing number of patients treated with proton therapy, from several dozen proton therapy centers around the world. High equipment and facility costs are often the major obstacle for its wider adoption. Because of the high cost and lack of definite clinical evidence of its superiority, proton therapy treatment faces criticism on its cost-effectiveness. Technological development is causing a gradual lowering of costs, and research and clinical studies are providing further evidence on its clinical utility. PMID:26604838

A novel model of persistent retinal neovascularization for the development of sustained anti-VEGF therapies.

PubMed

Li, Yong; Busoy, Joanna Marie; Zaman, Ben Alfyan Achirn; Tan, Queenie Shu Woon; Tan, Gavin Siew Wei; Barathi, Veluchamy Amutha; Cheung, Ning; Wei, Jay Ji-Ye; Hunziker, Walter; Hong, Wanjin; Wong, Tien Yin; Cheung, Chui Ming Gemmy

2018-05-28

Anti-vascular endothelial growth factor (VEGF) therapies lead to a major breakthrough in treatment of neovascular retinal diseases such as age-related macular degeneration or diabetic retinopathy. Current management of these conditions require regular and frequent intravitreal injections to prevent disease recurrence once the effect of the injected drug wears off. This has led to a pressing clinical need of developing sustained release formulations or therapies with longer duration. A major drawback in developing such therapies is that the currently available animal models show spontaneous regression of vascular leakage. They therefore not only fail to recapitulate retinal vascular disease in humans, but also prevent to discern if regression is due to prolonged therapeutic effect or simply reflects spontaneous healing. Here, we described the development of a novel rabbit model of persistent retinal neovascularization (PRNV). Retinal Müller glial are essential for maintaining the integrity of the blood-retinal barrier. Intravitreal injection of DL-alpha-aminoadipic acid (DL-AAA), a selective retinal glial (Müller) cell toxin, results in persistent vascular leakage for up to 48 weeks. We demonstrated that VEGF concentrations were significantly increased in vitreous suggesting VEGF plays a significant role in mediating the leakage observed. Intravitreal administration of anti-VEGF drugs (e.g. bevacizumab, ranibizumab and aflibercept) suppresses vascular leakage for 8-10 weeks, before recurrence of leakage to pre-treatment levels. All three anti-VEGF drugs are very effective in re-ducing angiographic leakage in PRNV model, and aflibercept demonstrated a longer duration of action compared with the others, reminiscent of what is observed with these drugs in human in the clinical setting. Therefore, this model provides a unique tool to evaluate novel anti-VEGF formulations and therapies with respect to their duration of action in comparison to the currently used drugs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Monoclonal antibodies as cancer therapeutics.

PubMed

Elloumi, Jihene; Jellali, Karim; Jemel, Ikram; Aifa, Sami

2012-04-01

Three main targets were subjected for the most approved monoclonal antibodies (mAbs) in cancer therapy: EGFR in solid cancer, the clusters of differentiation in blood cancer and VEGF in angiogenesis. Meanwhile side effects, the elevated costs and resistance problems are limiting the efficiency of mAbs as targeted therapy. The combinatory therapy with chemo or radiotherapy has improved the efficiency of mAbs. The present review aims to shed more light on the immunotherapy and the related patents that were developed for cancer treatment.

Novel Androgen Deprivation Therapy (ADT) in the Treatment of Advanced Prostate Cancer

PubMed Central

Aragon-Ching, Jeanny B.; Dahut, William L.

2011-01-01

Androgen deprivation therapy has been the mainstay of treatment for advanced and metastatic prostate cancer. The use of novel agents targeting the androgen receptor and its signaling pathways offers a promising approach that is both safe and effective. We describe the rationale behind the use of these compounds in clinical development and the existing challenges as to how best to incorporate these new and emerging therapies in the changing treatment paradigm of metastatic prostate cancer. PMID:21922023

What are People's Experiences of a Novel Cognitive Behavioural Therapy for Bipolar Disorders? A Qualitative Investigation with Participants on the TEAMS Trial.

PubMed

Joyce, Emmeline; Tai, Sara; Gebbia, Piersanti; Mansell, Warren

2017-05-01

Background Psychological interventions for bipolar disorders typically produce mixed outcomes and modest effects. The need for a more effective intervention prompted the development of a new cognitive behavioural therapy, based on an integrative cognitive model ('Think Effectively About Mood Swings' [TEAMS] therapy). Unlike previous interventions, TEAMS addresses current symptoms and comorbidities, and helps clients achieve long-term goals. A pilot randomized controlled trial (the TEAMS trial) of the therapy has recently concluded. This study explored participants' experiences of TEAMS, recommendations for improvement and experiences of useful changes post-therapy. Methods Fourteen TEAMS therapy participants took part in semi-structured interviews. Their accounts were analysed using interpretative thematic analysis. Two researchers coded the dataset independently. Member checks were conducted of the preliminary themes. Results Two overarching themes; 'useful elements of therapy' and 'changes from therapy' encompassed 12 emerging subthemes. Participants appreciated having opportunities to talk and described the therapy as person-centred and delivered by caring, approachable and skilled therapists. Some recommended more sessions than the 16 provided. Helpful therapeutic techniques were reported to be, normalization about moods, methods to increase understanding of moods, relapse-prevention, reappraisal techniques and metaphors. However, some did not find therapeutic techniques helpful. Post-therapy, many reported changes in managing mood swings more effectively and in their thinking (although some participants reported changes in neither). Many described increased acceptance of themselves and of having bipolar disorder, increased productivity and reduced anxiety in social situations. Conclusions The present study evaluates participants' therapy experiences in detail, including aspects of therapy viewed as helpful, and meaningful post-therapy outcomes. Copyright © 2016 John Wiley & Sons, Ltd. This is the first paper to qualitatively explore people's experiences of individual psychotherapy for bipolar disorders. It highlights elements of psychotherapy described as particularly helpful or unhelpful and the clinical changes viewed as most impactful. Participants reported benefitting in a number of ways from TEAMS therapy. They valued learning to reappraise and problem-solve situations and manage moods. Participants identified TEAMS techniques as helpful, such as exploring advantages and disadvantages of moods, and building healthy self-states. Copyright © 2016 John Wiley & Sons, Ltd.

The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients.

PubMed

Kurtovic-Kozaric, Amina; Hasic, Azra; Radich, Jerald P; Bijedic, Vildan; Nefic, Hilada; Eminovic, Izet; Kurtovic, Sabira; Colakovic, Ferida; Kozaric, Mirza; Vranic, Semir; Bovan, Nada S

2016-02-01

Cancer patients in developing and low-income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14-month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0-5 months, 6-12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6-12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6-12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib. © 2015 John Wiley & Sons Ltd.

Trypanosoma cruzi: effects of azadirachtin and ecdysone on the dynamic development in Rhodnius prolixus larvae.

PubMed

Cortez, M R; Provençano, A; Silva, C E; Mello, C B; Zimmermann, L T; Schaub, G A; Garcia, E S; Azambuja, P; Gonzalez, M S

2012-07-01

The effects of azadirachtin and ecdysone on the Trypanosoma cruzi population in the Rhodnius prolixus gut were investigated. T. cruzi were rarely found in the gut compartments of azadirachtin-treated larvae. High parasite numbers were observed in the stomach of the control and ecdysone groups until 10 days after treatment and in the small intestine and rectum until 25 days after treatment. High percentages of round forms developed in the stomachs of all groups, whereas azadirachtin blocked the development of protozoan intermediate forms. This effect was counteracted by ecdysone therapy. In the small intestine and rectum, epimastigotes predominated for all groups, but more of their intermediates developed in the control and ecdysone groups. Azadirachtin supported the development of round forms and their intermediates into trypomastigotes. In the rectum, trypomastigotes did not develop in the azadirachtin group and developed much later after ecdysone therapy. The parallel between the effects of azadirachtin and ecdysone on the host and parasite development is discussed on the basis of the present results because ecdysone appears to act directly or indirectly in determining the synchronic development of T. cruzi forms from round to epimastigotes, but not metacyclic trypomastigotes, in the invertebrate vector. Copyright © 2012 Elsevier Inc. All rights reserved.

Cushing disease as possible cause of persistent growth failure despite growth hormone therapy in a small for gestational age male.

PubMed

Heneghan, MaryKathleen; Alemzadeh, Ramin

2011-12-01

Growth hormone (GH) therapy in children with small for gestational age (SGA) has been shown to be of significant therapeutic benefit. We report the case of an 11-year-old Caucasian male who developed early adrenarche, hypertension and insulin resistance on GH therapy for SGA and profound short stature (ht -5 SD). This patient demonstrated a poor response to GH therapy and developed physical and biochemical findings of insulin resistance responsive to metformin therapy. He remained hypertensive, however, and continued to have elevated serum dehydroepiandrosterone sulfate levels. Urinary free cortisol excretion was subsequently found to be elevated. The diagnosis of Cushing's disease was confirmed with inferior petrosal sinus sampling and pituitary MRI. The patient underwent partial adenohypophysectomy with resulting normalization of plasma cortisol levels and associated symptoms. Our patient's diagnosis of Cushing's disease was complicated by his past history of poor growth since birth and history of SGA. The signs of Cushing's disease did not overtly appear until GH therapy was initiated to help treat severe short stature. It is possible that the metabolic effects of GH therapy unmasked the presence of underlying Cushing's disease.

[Effectivity of an occlusion-supporting PC-based visual training programme by horizontal drifting sinus gratings in children with amblyopia].

PubMed

Bau, V; Rose, K; Pollack, K; Spoerl, E; Pillunat, L E

2012-10-01

The studies of Kämpf et al. suggested an efficiency of a computer-based stimulation therapy by drifting sinus gratings in patients with anisometropic and/or strabismic amblyopia but provided no clear evidence. This is the first trial with amblyopic patients without previous treatment at the beginning of amblyopia therapy. A prospective, randomised, single-blinded, placebo-controlled study of n = 15 patients with anisometropic and/or strabismic amblyopia without previous treatment was performed. Age of the patients was between 4 and 10 years, mean 6.3 years (± 2.0), all after full correction of refraction errors and refractive adaptation. Stimulation therapy was performed 5 times a week over 4 weeks, respectively 2 × 20 min, a drifting sinus grating of constant spatial and temporal frequency was combined with computer games (n = 8). Control group had only computer games with a neutral background (n = 7). In both groups patching was only done in stimulation times. Stimulation and control group did not differ due to age, gender, and cause of amblyopie, baseline visual acuity, and time of wearing glasses. There was no significant difference in the development of visual acuity over the stimulation period between stimulation and control groups. Stimulation therapy with drifting sinus gratings did not improve the development of visual acuity in the first phase of amblyopia treatment combined with minimal occlusion therapy. Accordingly, the stimulation therapy is not adequate to replace sufficient occlusion therapy. Whether this therapy could support patching therapy and improve acuity development in later therapy phases cannot be assumed from this trial. Georg Thieme Verlag KG Stuttgart · New York.

TU-CD-303-02: Beyond Radiation Induced Double Strand Breaks - a New Horizon for Radiation Therapy Research

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

Chang, S.

Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation alsomore » initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of these advances in cancer biology research will give medical physicists a new perspective in daily clinical physics practice and in future radiation therapy technological development. Furthermore, academic medical physics should continue to be an integral part of the multidisciplinary cancer research community, harnessing our newly acquired understanding of radiation effects, and developing novel cost-effective treatment strategies to better combat cancer. Learning Objectives: Understand that localized radiation can lead to non-localized secondary effects such as radiation-induced immune response, bystander effect, and abscopal effect. Understand that the non-localized radiation effects may be harnessed to improve cancer treatment. Learn examples of physics participation in multidisciplinary research to advance cancer biology. Recognize the challenges and possibilities of physics applications in cancer research. Chang: NIH 5RC2CA148487-02 and 1U54CA151652-01 Graves: IDEA award (19IB-0106) from the California Breast Cancer Research Program (CBCRP), and by NIH P01 CA67166.« less

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

PubMed Central

Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

2016-01-01

As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

Breast cellulitis after conservative surgery and radiotherapy

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

Rescigno, J.; McCormick, B.; Brown, A.E.

1994-04-30

Cellulitis is a previously unreported complication of conservative surgery and radiation therapy for early stage breast cancer. Patients who presented with breast cellulitis after conservative therapy are described. Eleven patients that developed cellulitis of the breast over a 38-month period of observation are the subject of this report. Clinical characteristics of patients with cellulitis and their treatment and outcome are reported. Potential patient and treatment-related correlates for the development of cellulitis are analyzed. The risk of cellulitis persists years after initial breast cancer therapy. The clinical course of the patients was variable: some patients required aggressive, long-duration antibiotic therapy, whilemore » others had rapid resolution with antibiotics. Three patients suffered from multiple episodes of cellulitis. Patients with breast cancer treated with conservative surgery and radiotherapy are at risk for breast cellulitis. Systematic characterization of cases of cellulitis may provide insight into diagnosis, prevention, and more effective therapy for this uncommon complication. 15 refs., 1 fig., 2 tabs.« less

Brain size and neuropsychological functioning in long-term survivors of pediatric acute lymphoblastic leukemia.

PubMed

Mulcahy Levy, Jean M; Hunger, Stephen P

2013-10-01

With the increased survival of pediatric cancer patients the interest in the late effects of treatments is rapidly increasing. Long-term survival rates for children with acute lymphoblastic leukemia (ALL) now approach 90%. Treatment for ALL includes intensified central nervous system (CNS)-directed therapy, which is associated with risks for long-term neurocognitive effects. It is becoming clear that current therapies can have not only a detrimental effect on IQ, processing speed, and memory, but also on structural changes that lead to permanent alterations of the organization of the CNS. Understanding how the CNS is affected by the treatments is a critical step in evaluating current therapies and developing interventions to decrease the incidence and severity of long-term changes in brain anatomy and function.

Brain size and neuropsychological functioning in long-term survivors of pediatric acute lymphoblastic leukemia

PubMed Central

Mulcahy Levy, Jean M

2013-01-01

With the increased survival of pediatric cancer patients the interest in the late effects of treatments is rapidly increasing. Long-term survival rates for children with acute lymphoblastic leukemia (ALL) now approach 90%. Treatment for ALL includes intensified central nervous system (CNS)-directed therapy, which is associated with risks for long-term neurocognitive effects. It is becoming clear that current therapies can have not only a detrimental effect on IQ, processing speed, and memory, but also on structural changes that lead to permanent alterations of the organization of the CNS. Understanding how the CNS is affected by the treatments is a critical step in evaluating current therapies and developing interventions to decrease the incidence and severity of long-term changes in brain anatomy and function. PMID:26835308

A glycoporphyrin story: from chemistry to PDT treatment of cancer mouse models.

PubMed

Lupu, M; Maillard, Ph; Mispelter, J; Poyer, F; Thomas, C D

2018-06-01

Photodynamic therapy (PDT) represents a non-toxic and non-mutagenic antitumor therapy. The photosensitizer's (PS) chemo-physical properties are essential for the therapy, being responsible for the biological effects induced in the targeted tissues. In this study, we present the synthesis and development of some glycoconjugated porphyrins based on lectin-type receptor interaction. They were tested in vitro for finally choosing the most effective chemical structure for an optimum antitumor outcome. The most effective photosensitizer is substituted by three diethylene glycol α-d-mannosyl groups. In vivo studies allow firstly the determination of some characteristics of the biological processes triggered by the initial photochemical activation. Secondly, they make it possible to improve the therapeutic protocol in the function of the structural architecture of the targeted tumor tissue.

Gender Matters: Working with Adult Male Survivors of Trauma

ERIC Educational Resources Information Center

Mejia, Ximena E.

2005-01-01

There has been a great deal of attention given to the application of feminist therapy in treating women, but there is little written about feminist therapy and its applications in treating men. Gender role analysis has proven to be effective in developing hope, resilience, and transcendence-3 primary sources in times of emotional distress. This…

Is spiritual healing a valid and effective therapy?

PubMed Central

Hodges, R D; Scofield, A M

1995-01-01

This paper briefly reviews the evidence supporting the reality of healing as a scientifically-attested phenomenon, the techniques and mechanisms of healing and the potential value of this therapy if it were developed and integrated into the medical services. The need for further extensive research is indicated and strategies for such research are suggested. PMID:7745566

Cognitive-Behavioral Therapy for PTSD and Depression Symptoms Reduces Risk for Future Intimate Partner Violence among Interpersonal Trauma Survivors

ERIC Educational Resources Information Center

Iverson, Katherine M.; Gradus, Jaimie L.; Resick, Patricia A.; Suvak, Michael K.; Smith, Kamala F.; Monson, Candice M.

2011-01-01

Objective: Women who develop symptoms of posttraumatic stress disorder (PTSD) and depression subsequent to interpersonal trauma are at heightened risk for future intimate partner violence (IPV) victimization. Cognitive-behavioral therapy (CBT) is effective in reducing PTSD and depression symptoms, yet limited research has investigated the…

Two-Day, Intensive Cognitive-Behavioral Therapy for Panic Disorder: A Case Study

ERIC Educational Resources Information Center

Deacon, Brett

2007-01-01

Cognitive-behavioral therapy (CBT) is a highly effective treatment for panic disorder. However, few patients have access to this treatment, particularly those living in rural areas. In a pilot study, the author previously described the efficacy of a 2-day, intensive, exposure-based CBT intervention that was developed for the purpose of delivering…

Extending Cognitive-Behavioral Therapy for Late-Life Anxiety to Home Care: Program Development and Case Examples

ERIC Educational Resources Information Center

Diefenbach, Gretchen J.; Tolin, David F.; Gilliam, Christina M.; Meunier, Suzanne A.

2008-01-01

Data suggesting that cognitive-behavioral therapy (CBT) is efficacious for late-life anxiety are accumulating; however, effectiveness has not been well established. Incorporating CBT for anxiety into home care is needed to facilitate access to evidenced-based treatment for a growing population of community-dwelling, functionally impaired elderly…

Interpersonal Theory and Music Techniques: A Case Study for a Family With a Depressed Adolescent

ERIC Educational Resources Information Center

Hendricks, C. Bret; Bradley, Loretta J.

2005-01-01

Interpersonal psychotherapy (IPT-A) is a brief, time-limited therapy developed for use with adolescents diagnosed with major depression. IPT-A has been shown to be effective with adolescents in family counseling milieus. Music therapy techniques also have been successfully used to treat adolescent depression. This article provides mental health…

Moderators and Non-Specific Predictors of Treatment Outcome for Anxiety Disorders : A Comparison of Cognitive Behavioral Therapy to Acceptance and Commitment Therapy

ERIC Educational Resources Information Center

Wolitzky-Taylor, Kate B.; Arch, Joanna J.; Rosenfield, David; Craske, Michelle G.

2012-01-01

Objective: Understanding for whom, and under what conditions, treatments exert their greatest effects is essential for developing personalized medicine. Research investigating moderators of outcome among evidence-based treatments for anxiety disorders is lacking. The current study examined several theory-driven and atheoretical putative moderators…

Nanotechnology-Based Strategies for siRNA Brain Delivery for Disease Therapy.

PubMed

Zheng, Meng; Tao, Wei; Zou, Yan; Farokhzad, Omid C; Shi, Bingyang

2018-05-01

Small interfering RNA (siRNA)-based gene silencing technology has demonstrated significant potential for treating brain-associated diseases. However, effective and safe systemic delivery of siRNA into the brain remains challenging because of biological barriers such as enzymatic degradation, short circulation lifetime, the blood-brain barrier (BBB), insufficient tissue penetration, cell endocytosis, and cytosolic transport. Nanotechnology offers intriguing potential for addressing these challenges in siRNA brain delivery in conjunction with chemical and biological modification strategies. In this review, we outline the challenges of systemic delivery of siRNA-based therapy for brain diseases, highlight recent advances in the development and engineering of siRNA nanomedicines for various brain diseases, and discuss our perspectives on this exciting research field for siRNA-based therapy towards more effective brain disease therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

PubMed Central

Yoshida, Toshiyuki; Washio, Kaoru; Iwata, Takanori; Okano, Teruo; Ishikawa, Isao

2012-01-01

It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy. PMID:22315604

ALCOHOLIC HEPATITIS: TRANSLATIONAL APPROACHES TO DEVELOP TARGETED THERAPIES

PubMed Central

Mandrekar, Pranoti; Bataller, Ramon; Tsukamoto, Hidekazu; Gao, Bin

2016-01-01

Alcoholic liver disease (ALD) is a leading cause of liver related mortality worldwide. In contrast to recent advances in therapeutic strategies for patients with viral hepatitis, there is a significant lack of novel therapeutic options for patients with ALD. In particular, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of ALD. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with AH is very high (20–50% at 3 months). Available therapies are not effective in many patients and targeted approaches are imminently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. This review article summarizes the unmet needs for translational studies on the pathogenesis of AH, pre-clinical translational tools, and emerging drug targets to benefit the AH patient. PMID:26940353

A review of “music and movement” therapies for children with autism: embodied interventions for multisystem development

PubMed Central

Srinivasan, Sudha M.; Bhat, Anjana N.

2013-01-01

The rising incidence of Autism Spectrum Disorders (ASDs) has led to a surge in the number of children needing autism interventions. This paper is a call to clinicians to diversify autism interventions and to promote the use of embodied music-based approaches to facilitate multisystem development. Approximately 12% of all autism interventions and 45% of all alternative treatment strategies in schools involve music-based activities. Musical training impacts various forms of development including communication, social-emotional, and motor development in children with ASDs and other developmental disorders as well as typically developing children. In this review, we will highlight the multisystem impairments of ASDs, explain why music and movement therapies are a powerful clinical tool, as well as describe mechanisms and offer evidence in support of music therapies for children with ASDs. We will support our claims by reviewing results from brain imaging studies reporting on music therapy effects in children with autism. We will also discuss the critical elements and the different types of music therapy approaches commonly used in pediatric neurological populations including autism. We provide strong arguments for the use of music and movement interventions as a multisystem treatment tool for children with ASDs. Finally, we also make recommendations for assessment and treatment of children with ASDs, and provide directions for future research. PMID:23576962

Relating improvisational music therapy with severely and multiply disabled children to communication development.

PubMed

Rainey Perry, Mary M

2003-01-01

The effect of different levels of preintentional and intentional communication development on musical interaction with children with severe and multiple disabilities has not been explored in the music therapy literature. Aside from stage of communication development, what are the particular influences of disability on musical interaction with children who have preintentional and early intentional communication? A qualitative research project explored these issues. Ten school-aged children with severe and multiple disabilities participated in the project. The most common medical diagnosis was cerebral palsy. Analysis of video recordings and other data confirmed that the children's level of communication development was reflected in individual music therapy. Specifically, children at different levels of communication development varied in their abilities to initiate, anticipate, and sustain participation in turn taking, and to maintain attention to and engagement in the interaction. Both turn taking and playing and singing together were found to be important forms of communication during music therapy. Communication problems related to disability included: difficulties in using objects as a focus of joint attention, difficulties in interpreting the interactive environment, being sufficiently motivated to communicate, severely limited means of interaction, attaining and maintaining an appropriate level of arousal, and lack of interest in interaction and the outside environment. Further study of how music therapy can be related to general issues in communication for individuals with severe and multiple disabilities is recommended.

Integrin antagonists as potential therapeutic options for the treatment of Crohn’s disease

PubMed Central

McLean, Leon P.; Cross, Raymond K.

2016-01-01

Introduction Anti-integrin therapy for the treatment of patients with Crohn’s disease is rapidly evolving. Two agents, natalizumab and vedolizumab, are approved by the United States Food and Drug Administration for the treatment of Crohn’s disease, with vedolizumab the primary anti-integrin used due to a more favorable safety profile. Several other anti-integrins are in various stages of development. Areas Covered This review discusses the current state of anti-integrin therapy as well as suggestions for positioning of these agents in clinical practice. Emerging anti-integrin therapies, their underlying mechanisms of action, and available safety and clinical data are also reviewed. Expert Opinion Anti-integrins are effective for the treatment of Crohn’s disease, even in patients refractory to other therapies. Their use should be considered in patients with Crohn’s disease who do not respond to, develop non-response to, or have contraindications to anti-TNF therapy. Anti-integrin therapies can be offered as a first biologic therapy, in particular for older patients, patients with concurrent multiple sclerosis (natalizumab only), and in patients with contraindications to anti-TNF therapy. In patients with more severe symptoms, providers should consider co-induction with corticosteroids if possible to hasten remission. PMID:26822204

Epidemiology, natural history, and management of urinary tract infections in pregnancy.

PubMed

Andriole, V T; Patterson, T F

1991-03-01

The urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic UTIs in women with bacteriuria. Although the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated, it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic UTI and that symptomatic infections are associated with significant maternal and fetal risks. Because the majority of symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a complete urologic evaluation after delivery.

Emerging topical onychomycosis therapies - quo vadis?

PubMed

Elkeeb, Rania; Hui, Xiaoying; Murthy, Narasimha; Maibach, Howard I

2014-12-01

Onychomycosis, a common chronic fungal infection affecting fingernails and toenails, globally may affect 10 - 30% of the population. This chronic disease is difficult to eradicate. The goal of developing a highly effective and safe topical treatment has not yet been reached as it depends on the type of onychomycosis and the variety of invaders. Topical drug delivery to the nail is highly desirable in treating nail disorders. However, efficacy of topical therapies is low due to their limited permeability across the nail plate. Advances have especially been made by the development of new therapeutic options including new drug entities, new formulations and reformulations. This overview updates emerging topical treatments for onychomycosis, research progress and future perspectives. Development of novel effective noninvasive topical therapy for treating onychomycosis and other nail diseases such as psoriasis is long overdue. Previously there was a lack of basic knowledge about nail and its barrier properties, but with the recent increased interest in this field both from industry and academia, we hope extensive research will continue in this field to bring about successful and safe treatments for such chronic diseases.

Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

PubMed Central

Sherman, Alexandra; Biswas, Moanaro; Herzog, Roland W.

2017-01-01

Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors”) remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg), in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A. PMID:29225598

Nanotheranostics ˗ Application and Further Development of Nanomedicine Strategies for Advanced Theranostics

PubMed Central

Muthu, Madaswamy S.; Leong, David Tai; Mei, Lin; Feng, Si-Shen

2014-01-01

Nanotheranostics is to apply and further develop nanomedicine strategies for advanced theranostics. This review summarizes the various nanocarriers developed so far in the literature for nanotheranostics, which include polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles, carbon nanotubes, and nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents for better theranostic effects with fewer side effects. The theranostic nanomedicine can achieve systemic circulation, evade host defenses and deliver the drug and diagnostic agents at the targeted site to diagnose and treat the disease at cellular and molecular level. The therapeutic and diagnostic agents are formulated in nanomedicine as a single theranostic platform, which can then be further conjugated to biological ligand for targeting. Nanotheranostics can also promote stimuli-responsive release, synergetic and combinatory therapy, siRNA co-delivery, multimodality therapies, oral delivery, delivery across the blood-brain barrier as well as escape from intracellular autophagy. The fruition of nanotheranostics will be able to provide personalized therapy with bright prognosis, which makes even the fatal diseases curable or at least treatable at the earliest stage. PMID:24723986

Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy

PubMed Central

Cervantes-Madrid, Diana; Romero, Yair; Dueñas-González, Alfonso

2015-01-01

Abnormal metabolism is another cancer hallmark. The two most characterized altered metabolic pathways are high rates of glycolysis and glutaminolysis, which are natural targets for cancer therapy. Currently, a number of newer compounds to block glycolysis and glutaminolysis are being developed; nevertheless, lonidamine and 6-diazo-5-oxo-L-norleucine (DON) are two old drugs well characterized as inhibitors of glycolysis and glutaminolysis, respectively, whose clinical development was abandoned years ago when the importance of cancer metabolism was not fully appreciated and clinical trial methodology was less developed. In this review, a PubMed search using the words lonidamine and 6-diazo-5-oxo-L-norleucine (DON) was undertaken to analyse existing information on the preclinical and clinical studies of these drugs for cancer treatment. Data show that they exhibit antitumor effects; besides there is also the suggestion that they are synergistic. We conclude that lonidamine and DON are safe and potentially effective drugs that need to be reevaluated in combination as metabolic therapy of cancer. PMID:26425550

Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients

PubMed Central

Hawley, Sarah T.; Haymart, Megan R.

2016-01-01

Background. The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. Materials and Methods. A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men. Results. Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect. Conclusion. Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment. Implications for Practice: The standard treatment for thyroid cancer includes total thyroidectomy with or without radioactive iodine ablation, often followed by thyrotropin suppression therapy. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy, and discordant results have been reported on its adverse effects on bone. The present review provides physicians with existing data on the skeletal effects of thyrotropin suppression therapy, highlighting the need for further research to identify the groups at risk of adverse skeletal effects. This knowledge will aid in developing tailored thyroid cancer treatment. PMID:26659220

Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients.

PubMed

Papaleontiou, Maria; Hawley, Sarah T; Haymart, Megan R

2016-02-01

The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men. Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect. Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment. The standard treatment for thyroid cancer includes total thyroidectomy with or without radioactive iodine ablation, often followed by thyrotropin suppression therapy. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy, and discordant results have been reported on its adverse effects on bone. The present review provides physicians with existing data on the skeletal effects of thyrotropin suppression therapy, highlighting the need for further research to identify the groups at risk of adverse skeletal effects. This knowledge will aid in developing tailored thyroid cancer treatment. ©AlphaMed Press.

Engineering Delivery Vehicles for Genome Editing.

PubMed

Nelson, Christopher E; Gersbach, Charles A

2016-06-07

The field of genome engineering has created new possibilities for gene therapy, including improved animal models of disease, engineered cell therapies, and in vivo gene repair. The most significant challenge for the clinical translation of genome engineering is the development of safe and effective delivery vehicles. A large body of work has applied genome engineering to genetic modification in vitro, and clinical trials have begun using cells modified by genome editing. Now, promising preclinical work is beginning to apply these tools in vivo. This article summarizes the development of genome engineering platforms, including meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas9, and their flexibility for precise genetic modifications. The prospects for the development of safe and effective viral and nonviral delivery vehicles for genome editing are reviewed, and promising advances in particular therapeutic applications are discussed.

[Lipodystrophy and metabolic disturbances as complications of antiretroviral therapy].

PubMed

Bociaga-Jasik, Monika; Kieć-Wilk, Beata; Kalinowska-Nowak, Anna; Mach, Tomasz; Garlicki, Aleksander

2010-01-01

Effective treatment of HIV infection with antiretroviral drugs significantly improve prognosis. Reduction of mortality and life prolongations in patients receiving such therapy have been also connected with the risk of side effects development. Among these complications metabolic disturbances such as lipodystrophy, dyslipidaemia, and insulin resistance which are present according some authors in up to 50% of patients receiving HAART play an important role. In spite of different investigations molecular basis of lipodystrophy development during HAART have not be fully understood, and the latest research revealed a lot of new aspects connected w adipocyte tissue pathophysiology, which were not taken up to know into consideration. In the presented publication the most important information about pathogenesis of lipodystrophy development in HIV infected patients treated with ARV drugs have been presented.

American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer

PubMed Central

Burstein, Harold J.; Prestrud, Ann Alexis; Seidenfeld, Jerome; Anderson, Holly; Buchholz, Thomas A.; Davidson, Nancy E.; Gelmon, Karen E.; Giordano, Sharon H.; Hudis, Clifford A.; Malin, Jennifer; Mamounas, Eleftherios P.; Rowden, Diana; Solky, Alexander J.; Sowers, MaryFran R.; Stearns, Vered; Winer, Eric P.; Somerfield, Mark R.; Griggs, Jennifer J.

2010-01-01

Purpose To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor–positive breast cancer. Methods A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. Results An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. Conclusion The Update Committee recommends that postmenopausal women with hormone receptor–positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy. PMID:20625130

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

PubMed Central

Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich

2010-01-01

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. PMID:20148638

Potential for Stem Cell-Based Periodontal Therapy

PubMed Central

Bassir, Seyed Hossein; Wisitrasameewong, Wichaya; Raanan, Justin; Ghaffarigarakani, Sasan; Chung, Jamie; Freire, Marcelo; Andrada, Luciano C.; Intini, Giuseppe

2015-01-01

Periodontal diseases are highly prevalent and are linked to several systemic diseases. The goal of periodontal treatment is to halt the progression of the disease and regenerate the damaged tissue. However, achieving complete and functional periodontal regeneration is challenging because the periodontium is a complex apparatus composed of different tissues, including bone, cementum, and periodontal ligament. Stem cell-based regenerative therapy may represent an effective therapeutic tool for periodontal regeneration due to their plasticity and ability to differentiate into different cell lineages. This review presents and critically analyzes the available information on stem cell-based therapy for the regeneration of periodontal tissues and suggests new avenues for the development of more effective therapeutic protocols. PMID:26058394

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

PubMed

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

2017-06-01

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

Rapid isolation of gluten-digesting bacteria from human stool and saliva by using gliadin-containing plates

PubMed Central

Sarantopoulos, Christos; Ongchangco, Deryn; Sry, Jeremy; Cesario, Thomas

2014-01-01

The number of individuals with gluten intolerance has increased dramatically over the last years. To date, the only therapy for gluten intolerance is the complete avoidance of dietary gluten. To sustain a strictly gluten-free diet, however, is very challenging. Therefore, there is need for a non-dietary therapy. Any such treatment must appreciate that the immunogenic part of gluten are gliadin peptides which are poorly degraded by the enzymes of the gastrointestinal tract. Probiotic therapy and oral enzyme therapy containing gluten-degrading bacteria (GDB) and their gliadin-digesting enzymes are possible new approaches for the treatment of gluten intolerance, however effectively isolating GDB for these treatments is problematic. The goal of this study was to develop an easy technique to isolate GDB rapidly and efficiently with the hope it might lead to newer ways of developing either probiotics or traditional medicines to treat gluten intolerance. Several researchers have already isolated successfully GDB by using gluten minimal or limited agar plates. Although these plates can be used to isolate bacteria which can tolerate gluten, further assays are needed to investigate if the same bacteria can also digest gluten. The agar plates we developed can detect bacteria which cannot only tolerate gluten but are able to digest it as well. Therefore, we were able to combine two steps into one step. Using such technologies, we were able to isolate five GDB from saliva and stool, and identified three bacterial reference strains with gluten-degrading activity. The technique we developed to isolate bacteria with gluten-degrading activity is fast, effective, and easy to use. The GDB isolated by our technology could have potential as part of a probiotic or enzymatic therapy for people with gluten intolerance. PMID:25519429

Effects of manual therapy on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly: a randomised controlled pilot study.

PubMed

Cabrera-Martos, I; Valenza, M C; Valenza-Demet, G; Benítez-Feliponi, A; Robles-Vizcaíno, C; Ruiz-Extremera, A

2016-11-01

Despite growing evidence regarding nonsynostotic plagiocephaly and their repercussions on motor development, there is little evidence to support the use of manual therapy as an adjuvant option. The aim of this study was to evaluate the effects of a therapeutic approach based on manual therapy as an adjuvant option on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly. This is a randomised controlled pilot study. The study was conducted at a university hospital. Forty-six infants with severe nonsynostotic plagiocephaly (types 4-5 of the Argenta scale) referred to the Early Care and Monitoring Unit were randomly allocated to a control group receiving standard treatment (repositioning and an orthotic helmet) or to an experimental group treated with manual therapy added to standard treatment. Infants were discharged when the correction of the asymmetry was optimal taken into account the previous clinical characteristics. The outcome measures were treatment duration and motor development assessed with the Alberta Infant Motor Scale (AIMS) at baseline and at discharge. Asymmetry after the treatment was minimal (type 0 or 1 according to the Argenta scale) in both groups. A comparative analysis showed that treatment duration was significantly shorter (p < 0.001) in the experimental group (109.84 ± 14.45 days) compared to the control group (148.65 ± 11.53 days). The motor behaviour was normal (scores above the 16th percentile of the AIMS) in all the infants after the treatment. Manual therapy added to standard treatment reduces the treatment duration in infants with severe nonsynostotic plagiocephaly.

Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery across Biological Barriers

PubMed Central

Kievit, Forrest M.; Zhang, Miqin

2012-01-01

Cancer nanotheranostics aims to combine imaging and therapy of cancer through use of nanotechnology. The ability to engineer nanomaterials to interact with cancer cells at the molecular level can significantly improve the effectiveness and specificity of therapy to cancers that are currently difficult to treat. In particular, metastatic cancers, drug-resistant cancers, and cancer stem cells impose the greatest therapeutic challenge that requires targeted therapy to treat effectively. Targeted therapy can be achieved with appropriate designed drug delivery vehicles such as nanoparticles, adult stem cells, or T cells in immunotherapy. In this article, we first review the different types of materials commonly used to synthesize nanotheranostic particles and their use in imaging. We then discuss biological barriers that these nanoparticles encounter and must bypass to reach the target cancer cells, including the blood, liver, kidneys, spleen, and particularly the blood-brain barrier. We then review how nanotheranostics can be used to improve targeted delivery and treatment of cancer cells using nanoparticles, adult stem cells, and T cells in immunotherapy. Finally, we discuss development of nanoparticles to overcome current limitations in cancer therapy. PMID:21842473

Current advancement in radiation therapy for uterine cervical cancer.

PubMed

Nakano, Takashi; Ohno, Tatsuya; Ishikawa, Hitoshi; Suzuki, Yoshiyuki; Takahashi, Takeo

2010-01-01

Radiation therapy is one of the effective curative treatments for uterine cervical cancer. However poor clinical results for the advanced stages require further improvement of the treatment. Intensive studies on basic and clinical research have been made to improve local control, primarily important for long term survival in radiation therapy. Regarding current advancement in radiation therapy for uterine cervical cancer, the following three major subjects are pointed out; technological development to improve dose distribution by image guided radiation therapy technology, the concomitant anticancer chemotherapy with combination of radiation therapy, and radiation biological assessment of the radiation resistance of tumors. The biological factors overviewed in this article include hypoxia relating factors of HIF-1alpha, SOD, cell cycle parameters of pMI, proliferation factors of Ki67, EGFR, cerbB2, COX-2, cycle regulation proteins p53, p21, apoptosis regulation proteins Bcl2 and Bax and so on. Especially, the variety of these radiation biological factors is important for the selection of an effective treatment method for each patient to maximize the treatment benefit.

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.

Ozone therapy effectiveness in patients with ulcerous lesions due to diabetes mellitus.

PubMed

Rosul, Myroslav V; Patskan, Bohdan M

2016-01-01

Development of purulo-necrotic foot lesions is one of the most dangerous surgical complications of diabetes mellitus, it causes high lethality, early disability, considerable economical expenses on treatment and rehabilitation. Mentioned above determine substantial actuality of diabetic foot problem and condition the necessity of further search of new ways and effective methods of lower extremities lesions complex treatment. of our research was to study the effectiveness of ozone use in complex therapy among patients with diabetic foot. Under our observation were 47 patients with I and II stages of diabetic foot that correspond to superficial and deep ulcers without involving of subcutaneous tissue, ligaments, tendons and muscles into the process, without bone lesion, phlegmons and abscess forming according to Meggit-Wagner (1978) classification. Depending on treatment every group of patients was divided into subgroups. B group composed patients that received traditional therapy.A group composed patients that along with traditional therapy course received course of systemic and regional ozone therapy for 12-14 days, one session per day. Cytological examination of discharge from wounds was carried, lipid peroxidation state and antioxidant protection state was assessed. Ozone use has more evident clinical effect, significantly affects the phase course of wound process, promotes the improvement of lipid peroxidation and antioxidant protection indexes, reduces the length of hospital stay and term of treatment of patients with diabetic foot. СONCLUSIONS: Studies conducted showed that including of ozone therapy into complex surgical treatment has positive effect on wound process.

Cell and molecular mechanisms of pathogenesis and treatment of cancer.

PubMed Central

Rew, D. A.

1998-01-01

Surgery remains the mainstay of treatment for most classes of human solid tumours, with the principal exception of lymphomas, but it is insufficient in many cases to guarantee cure. With few exceptions, recurrent and metastatic solid tumours continue to defy attempts to develop effective adjuvant therapies. Recent insights into tumour biology reveal an increasingly complex picture of cell and molecular processes which confer heterogeneity and resistance to treatment upon tumours. These insights may also yield new targets for more effective adjuvant therapies. PMID:9616488

Equitable service provision for inclusive education and effective early intervention.

PubMed

Wicks, K M

1998-01-01

This paper illustrates one model of providing an integrated paediatric speech and language therapy service which attempts to meet the demands of both inclusive education and effective early intervention. A move has been made from location-oriented therapy provision to offering children and their families equal opportunities to have appropriate intervention according to need. The model incorporates the philosophy of inclusive education and supports the development of current specialist educational establishments into resource bases of expertise for children with special needs in mainstream schools.

B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti-TNF-α Agents on B Lymphocytes: A Review of the Literature.

PubMed

Pala, Ozlem; Diaz, Alain; Blomberg, Bonnie B; Frasca, Daniela

2018-06-01

The aim of this article was to review published research related to B lymphocytes in rheumatoid arthritis, their role in the pathogenesis of the disease, the effects of tumor necrosis factor (TNF)-α inhibitors on B lymphocytes, the risk for infection, and responses to vaccines. A PubMed search was conducted to review recent advances related to B lymphocytes and the effects of anti-TNF-α on B lymphocytes in rheumatoid arthritis. B lymphocytes play an important role in the pathogenesis of rheumatoid arthritis. In this review, we summarize the major mechanisms by which B lymphocytes play a pathologic role in the development and propagation of the disease, as B lymphocytes are recruited to the synovial fluid, where they contribute to local inflammation through the secretion of pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) and present antigens to T cells. We discuss the effects of TNF-α, either direct or indirect, on B lymphocytes expressing receptors for this cytokine. We also show that total B-cell numbers have been reported to be reduced in the blood of patients with rheumatoid arthritis versus healthy controls, but are significantly increased up to normal levels in patients undergoing anti-TNF-α therapy. As for B-cell subsets, controversial results have been reported, with studies showing decreased frequencies of total memory B cells (and memory subsets) and others showing no differences in patients versus healthy controls. Studies investigating the effects of anti-TNF-α therapy have also given controversial results, with therapy found to increase (or not) the frequency of memory B lymphocytes, in patients with rheumatoid arthritis versus healthy controls. Those highly variable results could have been due to differences in patient characteristics and limited numbers of subjects. Finally, we summarize the effects of blocking TNF-α with anti-TNF-α agents on possible infections that patients with rheumatoid arthritis may contract, as well as on responses to vaccination. B lymphocytes play a significant role in the pathogenesis of rheumatoid arthritis, and B cell-depletion therapy has a major effect on the course of the disease. The advances in treatment of rheumatoid arthritis include the development of targeted therapies. Anti-TNF-α therapies are widely used despite potentially serious adverse events. The data on the effects of anti-TNF-α therapies on B lymphocytes are limited and conflicting. There is a need for larger studies to better understand the effects of newly discovered therapies on the different cells of the immune system. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Translational experimental therapeutics: The translation of laboratory-based discovery into disease-related therapy.

PubMed

Kieburtz, Karl; Olanow, C Warren

2007-04-01

In the past decade, there has been an increasing emphasis on laboratory-based translational research. This has led to significant scientific advances in our understanding of disease mechanisms and in the development of novel approaches to therapy such as gene therapy, RNA interference, and stem cells. However, the translation of these remarkable scientific achievements into new and effective disease-modifying therapies has lagged behind these scientific accomplishments. We use the term "translational experimental therapeutics" to describe the pathway between the discovery of a basic disease mechanism or novel therapeutic approach and its translation into an effective treatment for patients with a specific disease. In this article, we review the components of this pathway, and discuss issues that might impede this process. Only by optimizing this pathway can we realize the full therapeutic potential of current scientific discoveries and translate the astounding advances that have been accomplished in the laboratory into effective treatments for our patients. Copyright (c) 2007 Mount Sinai School of Medicine.

Ingredients and change processes in occupational therapy for children: a grounded theory study.

PubMed

Armitage, Samantha; Swallow, Veronica; Kolehmainen, Niina

2017-05-01

There is limited evidence about the effectiveness of occupational therapy interventions for participation outcomes in children with coordination difficulties. Developing theory about the interventions, i.e. their ingredients and change processes, is the first step to advance the evidence base. To develop theory about the key ingredients of occupational therapy interventions for children with coordination difficulties and the processes through which change in participation might happen. Grounded theory methodology, as described by Kathy Charmaz, was used to develop the theory. Children and parents participated in semi-structured interviews to share their experiences of occupational therapy and processes of change. Data collection and analysis were completed concurrently using constant comparison methods. Five key ingredients of interventions were described: performing activities and tasks; achieving; carer support; helping and supporting the child; and labelling. Ingredients related to participation by changing children's mastery experience, increasing capability beliefs and sense of control. Parents' knowledge, skills, positive emotions, sense of empowerment and capability beliefs also related to children's participation. The results identify intervention ingredients and change pathways within occupational therapy to increase participation. It is unclear how explicitly and often therapists consider and make use of these ingredients and pathway.

Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient's compliance.

PubMed

Adewoyin, Ademola Samson; Oghuvwu, Omokiniovo Sunday; Awodu, Omolade Augustina

2017-03-01

The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects. A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review. The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-compliance included poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects. Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.

Carbon dioxide water-bath treatment augments peripheral blood flow through the development of angiogenesis.

PubMed

Xu, Yan-Jun; Elimban, Vijayan; Dhalla, Naranjan S

2017-08-01

In this study, we investigated the effects of CO 2 water-bath therapy on blood flow and angiogenesis in the ischemic hind limb, as well as some plasma angiogenic factors in peripheral ischemic model. The hind limb ischemia was induced by occluding the femoral artery for 2 weeks in rats and treated with or without CO 2 water-bath therapy at 37 °C for 4 weeks (20 min treatment every day for 5 days per week). The peak blood flow and minimal and mean blood flow in the ischemic skeletal muscle were markedly increased by the CO 2 water-bath therapy. This increase in blood flow was associated with development of angiogenesis in the muscle, as well as reduction in the ischemia-induced increase in plasma malondialdehyde levels. Although plasma vascular endothelial growth factor and nitric oxide levels were increased in animals with peripheral ischemia, the changes in these biomarkers were not affected by CO 2 water-bath therapy. These results suggest that augmentation of blood flow in the ischemic hind limb by CO 2 water-bath therapy may be due to the development of angiogenesis and reduction in oxidative stress.

[Antibiotics in the critically ill].

PubMed

Kolak, Radmila R

2010-01-01

Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

Gene therapy of the brain: the trans-vascular approach.

PubMed

Schlachetzki, Felix; Zhang, Yun; Boado, Ruben J; Pardridge, William M

2004-04-27

Many chronic neurologic diseases do not respond to small molecule therapeutics, and have no effective long-term therapy. Gene therapy offers the promise of an effective cure for both genetic and acquired brain disease. However, the limiting problem in brain gene therapy is delivery to brain followed by regulation of the expression of the transgene. Present day gene vectors do not cross the blood-brain barrier (BBB). Consequently, brain gene therapy requires craniotomy and the local injection of a viral gene vector. However, there are few brain disorders that can be effectively treated with local injection. Most applications of gene therapy require global expression in the brain of the exogenous gene, and this can only be achieved with a noninvasive delivery through the BBB--the trans-vascular route to brain. An additional consideration is the potential toxicity of all viral and nonviral approaches, which may either integrate into the host genome and cause insertional mutagenesis or cause inflammation in the brain. Nonviral, noninvasive gene therapy of the brain is now possible with the development of a new approach to targeting therapeutic genes to the brain following an IV administration. This approach utilizes genetically engineered molecular Trojan horses, which ferry the gene across the BBB and into neurons. Global and reversible expression of therapeutic genes in the human brain without surgery and without viral vectors is now possible.

Measuring the contribution of art therapy in multidisciplinary treatment of personality disorders: The construction of the Self‐expression and Emotion Regulation in Art Therapy Scale (SERATS)

PubMed Central

van Hooren, Susan; van der Veld, William M.; Hutschemaekers, Giel

2017-01-01

Abstract Despite the use of art therapy in clinical practice, its appreciation and reported beneficial results, no instruments are available to measure specific effects of art therapy among patients with personality disorders cluster B/C in multidisciplinary treatment. In the present study, we described the development and psychometric evaluation of the Self‐expression and Emotion Regulation in Art Therapy Scale (SERATS). Structural validity (exploratory and confirmatory factor analysis), reliability, construct validity and sensitivity to change were examined using two independent databases (n = 335; n = 34) of patients diagnosed with personality disorders cluster B/C. This resulted in a nine‐item effect scale with a single factor with a high internal reliability and high test–retest reliability; it demonstrated discriminant validity and sensitivity to change. In conclusion, the SERATS is brief and content‐valid and offers objective and reliable information on self‐expression and emotion regulation in art therapy among patients with personality disorders cluster B/C. Although more research on construct validity is needed, the SERATS is a promising tool to be applied as an effect scale and as a monitoring tool during art therapy treatment. © 2017 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd PMID:28730717

Unresolved antiretroviral treatment management issues in HIV-infected children.

PubMed

Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

2012-02-01

Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

[Saccharomyces boulardii in the treatment and prevention of antibiotic-associated diarrhea].

PubMed

Micklefield, G

2014-04-17

Antibiotic-associated diarrhea (AAD) is the most frequent side effect of antibiotic therapy. Clinical signs and symptoms comprise mild and self-limiting courses of diarrhea as well as life threatening courses like pseudomembranous colitis or toxic megacolon. Therapy is symptomatic, antidiarrheal drugs like Saccharomyces boulardii are the therapy of choice. Available studies on S. boulardii in the prevention of AAD are presented as a review. In 14 out of 17 studies including 4,627 patients the administration of S. boulardii achieved a protective effect between 43.7% and 87.3%. A meta-analysis (5 studies, 1,076 patients) showed a significant reduction of the risk to develop an AAD from 17.2% to 6.7%,in a furthermeta-analysis (4 studies on eradication of H. pylori, 1,215 patients) the significant reductionwasfrom 12.2% to 5.6%. There is very good evidence for the yeast S. boulardii to be effective in the prevention of AAD especially in hospitalized adults. The simultaneous administration of S. boulardii to antibiotics resulted in a significant reduction to develop AAD by more than half.

Ranitidine-Associated Sleep Disturbance: Case Report and Review of H2 Antihistamine-Related Central Nervous System Adverse Effects.

PubMed

Werbel, Tyler; Cohen, Philip R

2018-04-03

Ranitidine is an H2 antihistamine used as an off-label therapy for recalcitrant verruca vulgaris. We describe a man who developed a sleep disturbance after initiating therapy with ranitidine and review similar adverse effects associated with other drugs in this class. The patient was a 40-year-old man with an eight-year history of a wart on his right plantar foot that was recalcitrant to several topical therapies. Adjunctive treatment with ranitidine 150 mg twice daily was initiated. He developed sleep disturbance with bizarre dreams and gastrointestinal symptoms. All symptoms resolved after discontinuation of the medication and recurred when he restarted the drug. PubMed was searched for the following terms: disturbance, dream, ranitidine, verruca, wart, and Zantac. The papers containing these terms and their references were reviewed. Sleep disturbance caused by ranitidine is an uncommon adverse event in patients receiving the drug. However, similar reactions have been observed with other H2 antihistamines such as cimetidine and famotidine. Clinicians should be aware that sleep disturbance secondary to ranitidine is a potential side effect of this medication.

Massage therapy improves the development of HIV-exposed infants living in a low socio-economic, peri-urban community of South Africa.

PubMed

Perez, E M; Carrara, H; Bourne, L; Berg, A; Swanevelder, S; Hendricks, M K

2015-02-01

The aim of this study was to assess the effect of massage therapy on the growth and development of infants of HIV-infected mothers in a low socio-economic community in Cape Town. It was a prospective, randomised, controlled intervention trial that included massage therapy and control groups of HIV-infected mothers and their normal birth weight infants who were enrolled in the prevention of mother-to-child transmission (PMTCT) programme. Participants were recruited at the 6-week clinic visit and followed up every 2 weeks until their infants were 9 months of age. Mother-infant pairs in the massage therapy and control groups included 73 and 88 at 6 weeks and 55 and 58 at 9 months, respectively. Mothers in the intervention group were trained to massage their infants for 15 min daily. The socioeconomic status, immunity, relationship with the partner and mental pain of mothers; the infants' dietary intake, anthropometry and development (Griffiths Mental Development Scales); and haematological and iron status of mothers and infants were assessed at baseline and follow-up. Nine infants (5.3%) were HIV-infected on the HIV DNA PCR test at 6 weeks. Despite significantly higher levels of maternal mental pain, infants in the massage therapy compared to control group scored higher in all five of the Griffiths Scales of Mental Development and significantly higher in the mean quotient (p=0.002) and mean percentile (p=0.004) for the hearing and speech scale at 9 months. Based on the mean difference in scores, the massage therapy group showed greater improvement for all five scales compared to the control group. The mean difference in scores was significantly greater for the hearing and speech quotient (21.9 vs. 11.2) (p<0.03) and the general quotient percentile (19.3 vs. 7.7) (p=0.03) in the massage therapy compared to the control group. These scales remained significant when adjusting for the relationship with the partner and maternal mental pain. Both groups had lower scores in the performance scale at 9 months although this was significantly worse in the control compared to the massage therapy group when adjusting for maternal CD4 count, anaemia, relationship with the partner and mental pain. There were no significant differences in the anthropometric measurements between the two groups. In conclusion, based on the Griffiths Scales, massage therapy improved the overall development and had a significant effect on the hearing and speech and general quotient of HIV-exposed infants in this study. Copyright © 2015 Elsevier Inc. All rights reserved.

Natural compounds and combination therapy in colorectal cancer treatment.

PubMed

Rejhová, A; Opattová, A; Čumová, A; Slíva, D; Vodička, P

2018-01-20

Colorectal cancer (CRC) therapy using conventional chemotherapeutics represents a considerable burden for the patient's organism because of high toxicity while the response is relatively low. Our review summarizes the findings about natural compounds as chemoprotective agents for decreasing risk of CRC. It also identifies natural compounds which possess anti-tumor effects of various characteristics, mainly in vitro on colorectal cell lines or in vivo studies on experimental models, but also in a few clinical trials. Many of natural compounds suppress proliferation by inducing cell cycle arrest or induce apoptosis of CRC cells resulting in the inhibition of tumor growth. A novel employment of natural substances is a so-called combination therapy - administration of two or more substances - conventional chemotherapeutics and a natural compound or more natural compounds at a time. Some natural compounds may sensitize to conventional cytotoxic therapy, reinforce the drug effective concentration, intensify the combined effect of both administered therapeutics or exert cytotoxic effects specifically on tumor cells. Moreover, combined therapy by targeting multiple signaling pathways, uses various mechanisms to reduce the development of resistance to antitumor drugs. The desired effect could be to diminish burden on the patient's organism by replacing part of the dose of a conventional chemotherapeutic with a natural substance with a defined effect. Many natural compounds are well tolerated by the patients and do not cause toxic effects even at high doses. Interaction of conventional chemotherapeutics with natural compounds introduces a new aspect in the research and therapy of cancer. It could be a promising approach to potentially achieve improvements, while minimizing of adverse effects associated with conventional chemotherapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of surfactant/budesonide therapy on oxidative modifications in the lung in experimental meconium-induced lung injury.

PubMed

Mikolka, P; Kopincova, J; Tomcikova Mikusiakova, L; Kosutova, P; Antosova, M; Calkovska, A; Mokra, D

2016-02-01

Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free radicals compared to controls (P < 0.05). Surfactant therapy, but particularly combined surfactant + budesonide therapy reduced markers of oxidative stress versus untreated animals (P < 0.05). In conclusion, budesonide added into surfactant enhanced effect of therapy on oxidative damage of the lung.

[TRT and psychotherapy in the treatment of tinnitus].

PubMed

Schaaf, H; Gieler, U

2010-10-01

Basic requirements and results of tinnitus retraining therapy (TRT) as well as other habituation therapies with psychotherapeutic approaches in the treatment of tinnitus are examined closely in this literature review. In German-speaking countries experts generally aim for involvement of psychotherapists beyond the classic TRT developed by Jastreboff and Hazell. On the basis of a validated diagnostic test such as the Tinnitus Questionnaire according to Hiller and Goebel (1998), such a therapy regime is more effective than the "classic" procedure. Under different treatment approaches, cognitive behavioural therapy elements have been proven to be effective-even as a component of the TRT-as well as integrated variants in psychodynamic therapies. We have to give consideration to the fact that in all studies about the selection and inclusion criteria selective test conditions were established which suggest that in each case diverse patient groups were studied. In the overall picture it becomes apparent that depending on the severity of the tinnitus and accompanying hearing problems a dysfunction-oriented and staged approach makes sense.

Current Trends in Robot-Assisted Upper-Limb Stroke Rehabilitation: Promoting Patient Engagement in Therapy.

PubMed

Blank, Amy A; French, James A; Pehlivan, Ali Utku; O'Malley, Marcia K

2014-09-01

Stroke is one of the leading causes of long-term disability today; therefore, many research efforts are focused on designing maximally effective and efficient treatment methods. In particular, robotic stroke rehabilitation has received significant attention for upper-limb therapy due to its ability to provide high-intensity repetitive movement therapy with less effort than would be required for traditional methods. Recent research has focused on increasing patient engagement in therapy, which has been shown to be important for inducing neural plasticity to facilitate recovery. Robotic therapy devices enable unique methods for promoting patient engagement by providing assistance only as needed and by detecting patient movement intent to drive to the device. Use of these methods has demonstrated improvements in functional outcomes, but careful comparisons between methods remain to be done. Future work should include controlled clinical trials and comparisons of effectiveness of different methods for patients with different abilities and needs in order to inform future development of patient-specific therapeutic protocols.

Nutraceuticals in Prostate Disease: The Urologist’s Role

PubMed Central

Curtis Nickel, J; Shoskes, Daniel; Roehrborn, Claus G; Moyad, Mark

2008-01-01

Interest in and use of complementary and alternative therapies, especially nutraceuticals, is high in prostate disease. These therapies have shown potential in benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer. Some have produced results equal to or better than pharmaceuticals currently prescribed for BPH. In category III prostatitis, some nutraceuticals may offer relief to patients who get little from standard therapy. Because it is becoming apparent that inflammation may play a role in the progression of BPH and development of prostate cancer, nutraceuticals, which commonly have anti-inflammatory properties, may play a role. These therapies have also shown potential in prostate cancer treatment and prevention, especially those that also reduce cardiovascular events or risk. Nevertheless, uses of some nutraceuticals in prostate disease have had less desirable consequences, showing lack of efficacy, adulteration, and/or severe side effects or drug interactions. By ensuring that these therapies undergo careful study for effectiveness, quality, and safety, urologists can look forward to adding them to their evidence-based armamentarium for prostate disease. PMID:18836556

Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.

PubMed

Hassan, Sally; Simaria, Ana S; Varadaraju, Hemanthram; Gupta, Siddharth; Warren, Kim; Farid, Suzanne S

2015-01-01

To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales. A bioprocess economics and optimization tool was built to assess competing cell expansion and downstream processing (DSP) technologies. Tangential flow filtration was generally more cost-effective for the lower cells/lot achieved in planar technologies and fluidized bed centrifugation became the only feasible option for handling large bioreactor outputs. DSP bottlenecks were observed at large commercial lot sizes requiring multiple large bioreactors. The DSP contribution to the cost of goods/dose ranged between 20-55%, and 50-80% for planar and bioreactor flowsheets, respectively. This analysis can facilitate early decision-making during process development.

The novel language-systematic aphasia screening SAPS: screening-based therapy in combination with computerised home training.

PubMed

Krzok, Franziska; Rieger, Verena; Niemann, Katharina; Nobis-Bosch, Ruth; Radermacher, Irmgard; Huber, Walter; Willmes, Klaus; Abel, Stefanie

2018-03-01

SAPS-'Sprachsystematisches Aphasiescreening'-is a novel language-systematic aphasia screening developed for the German language, which already had been positively evaluated. It offers a fast assessment of modality-specific psycholinguistic components at different levels of complexity and the derivation of impairment-based treatment foci from the individual performance profile. However, SAPS has not yet been evaluated in combination with the new SAPS-based treatment. To replicate the practicality of SAPS and to investigate the effectiveness of a SAPS-based face-to-face therapy combined with computerised home training in a feasibility study. To examine the soundness of the treatment design, to determine treatment-induced changes in patient performance as measured by SAPS, to assess parallel changes in communicative abilities, and to differentiate therapy effects achieved by face-to-face therapy versus add-on effects achieved by later home training. Sixteen participants with post-stroke aphasia (PWAs) were included into the study. They were administered the SAPS and communicative testing before and after the treatment regimen. Each PWA received one therapy session followed by home training per day, with the individual treatment foci being determined according to initial SAPS profile, and duration of treatment and possible change of focus dependent on performance assessed by continuous therapy monitoring. The combination of therapy and home training based on the SAPS was effective for all participants. We showed significant improvements for impairment-based SAPS performance and, with high inter-individual variability, in everyday communication. These two main targets of speech and language therapy were correlated and SAPS improvements after therapy were significantly higher than after home training. SAPS offers the assessment of an individual performance profile in order to derive sufficiently diversified, well-founded and specific treatment foci and to follow up changes in performance. The appending treatment regimen has shown to be effective for our participants. Thus, the study revealed feasibility of our approach. © 2017 Royal College of Speech and Language Therapists.

Comparing Active and Passive Distraction-Based Music Therapy Interventions on Preoperative Anxiety in Pediatric Patients and Their Caregivers.

PubMed

Millett, Christopher R; Gooding, Lori F

2018-01-13

Young children who experience high levels of preoperative anxiety often exhibit distress behaviors, experience more surgical complications, and are at a higher risk for developing a variety of negative postoperative consequences. A significant factor in pediatric preoperative anxiety is the level of anxiety present in their caregivers. Active and passive music therapy interventions addressing anxiety prior to invasive procedures have been met with success. The purpose of this study was to investigate the comparative effectiveness of two distraction-based music therapy interventions on reducing preoperative anxiety in young pediatric surgical patients and their caregivers. A total of 40 pediatric patient and caregiver dyads undergoing ambulatory surgery were included in this study. Pediatric preoperative anxiety was measured pre- and post-intervention using the modified Yale Pediatric Anxiety Scale, while caregiver anxiety was measured through self-report using the short-form Strait-Trait Anxiety Inventory-Y6. Participants were randomized to either an active or passive intervention group for a preoperative music therapy session. Results indicated a significant reduction in preoperative anxiety for both patients and their caregivers regardless of intervention type. Neither active nor passive music therapy interventions were significantly more effective than the other. For future studies, the researchers recommend an increased sample size, controlling for various factors such as sedative premedication use, and testing interventions with patients in various stages of development. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

PubMed

da Rocha, E L; Porto, L M; Rambo, C R

2014-01-01

Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

Target therapy: new drugs or new combinations of drugs in malignant pleural mesothelioma.

PubMed

Zucali, Paolo A

2018-01-01

Malignant pleural mesothelioma (MPM) is a disease with a poor prognosis due to its aggressive nature. The management of patients with MPM is controversial. Considering that the contribution of surgery and radiation therapy in the management of this disease is not yet established, systemic treatments are predominantly considered during the course of MPM. Unfortunately, the currently therapeutic armamentarium is scarce and its outcomes still appear modest. New treatment strategies are needed. In preclinical setting, cell cycle regulation, apoptosis, growth factor pathways, and angiogenesis pathways involved in the development of MPM have been identified. However, in clinical setting, several drugs targeting these pathways resulted without a significant activity. A deeper knowledge of the biology and pathogenesis of this disease is required to develop more effective tools for diagnosis, therapy and prevention. This paper reviews therapeutic advances in MPM, with a particular focus on new drugs and new association of drugs of target therapy.

Genital condyloma virus infection following pelvic radiation therapy: report of seven cases

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

Lowell, D.M.; Livolsi, V.A.; Ludwig, M.E.

1983-01-01

Six women who underwent radiation therapy for gynecologic malignancies demonstrated cytologic evidence of condyloma virus infection 2 or more years following radiation. Histologic confirmation was obtained in two of the cases. A seventh patient developed in situ and invasive squamous cell carcinoma in a vulvar condyloma acuminatum following radiation therapy for Hodgkin's disease. This venereal infection is found most frequently in sexually active younger women (average age, 27 years). It is felt that depressed cell-mediated immunity consequent to the radiation therapy allowed the development of this infection in the older patients described in this report. The evolution of invasive squamousmore » cell carcinoma in the condyloma acuminatum may indicate a possible oncogenic or cocarcinogenic effect of the virus. The immunologic responses to infection caused by the human papillomavirus group are discussed, as well as its potential for malignant transformation.« less

Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial.

PubMed

Ferreira, Luciano Ambrosio; Grossmann, Eduardo; Januzzi, Eduardo; Gonçalves, Rafael Tardin Rosa Ferraz; Mares, Fernando Antonio Guedes; de Paula, Marcos Vinicius Queiroz; Carvalho, Antonio Carlos Pires

2015-01-01

Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study) and the use of the occlusal splint plate alone (control). We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p < 0.05). However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p < 0.05) already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term.

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies

PubMed Central

Wingstrand, Vibe Lindeblad; Jensen, David H.; Bork, Kristian; Sebbesen, Lars; Balle, Jesper; Fischer-Nielsen, Anne; von Buchwald, Christian

2016-01-01

Objectives Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring. Data Sources PubMed, Embase, the Cochrane Library and Google Scholar were searched. Methods Controlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude. Results Seven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η’) and elastic modulus (G’), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds. Conclusion The results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies. PMID:27631373

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies.

PubMed

Wingstrand, Vibe Lindeblad; Grønhøj Larsen, Christian; Jensen, David H; Bork, Kristian; Sebbesen, Lars; Balle, Jesper; Fischer-Nielsen, Anne; von Buchwald, Christian

2016-01-01

Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring. PubMed, Embase, the Cochrane Library and Google Scholar were searched. Controlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude. Seven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η') and elastic modulus (G'), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds. The results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies.

Group treatment for depression in mothers of young children compared to standard individual therapy.

PubMed

Frisch, Ulrike; Hofecker-Fallahpour, Maria; Stieglitz, Rolf-Dieter; Riecher-Rössler, Anita

2013-01-01

Studies on specific psychotherapy for depressed mothers of small children are rare. The aim of the present study was to investigate the effectiveness of a newly developed cognitive-behavioral group intervention for depressed mothers compared to standard individual therapy. In a naturalistic design, 31 mothers suffering from depressive disorders with children aged ≤4 years who had consecutively been admitted to our specialized clinic for mentally ill mothers were assigned to the group treatment, and the following 21 were admitted to the control group receiving standard individual therapy. The group treatment consisted of 12 group sessions and 1 couple session and was administered to five consecutive groups. Participants completed interviews and questionnaires - the Beck Depression Inventory and the Symptom Checklist- 90-R - before and 3 months after therapy. The treatment group and the control group showed a significant improvement in their depression, with no significant differences between the two treatment strategies. The women in group therapy, however, required fewer antidepressants, and group treatment was observed to be more effective in reducing anger and hostility. This form of group treatment for depressed women in early motherhood may have some important advantages over individual therapy; effects were small, however, and should be replicated in a further study. Copyright © 2012 S. Karger AG, Basel.

Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial

PubMed Central

Ferreira, Luciano Ambrosio; Grossmann, Eduardo; Januzzi, Eduardo; Gonçalves, Rafael Tardin Rosa Ferraz; Mares, Fernando Antonio Guedes; de Paula, Marcos Vinicius Queiroz; Carvalho, Antonio Carlos Pires

2015-01-01

Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study) and the use of the occlusal splint plate alone (control). We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p < 0.05). However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p < 0.05) already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term. PMID:26351510

Opioid tolerance and dependence -- do they matter?

PubMed

Jage, Jürgen

2005-04-01

The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long-term therapy with short-acting opioids predisposes to tolerance and addiction. Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others. This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug-aberrant behavior, drug history, psychopathology, and somatization.

The use of ECT and MST in treating depression.

PubMed

Allan, Charlotte L; Ebmeier, Klaus P

2011-10-01

Electroconvulsive therapy (ECT) has been used clinically since 1938. Its most common use is in the treatment of depression: first line treatment where rapid recovery is a priority, but more frequently as an effective treatment for patients who do not respond to pharmacological and psychological approaches. Whilst it is widely hailed as an effective treatment, concerns about its effect on cognition remain. The development of magnetic seizure therapy (MST) over the past decade has attempted to devise a therapy with comparable efficacy to ECT, but without the associated cognitive side effects. The rationale for this is that MST uses magnetic fields to induce seizures in the cortex, without electrical stimulation of brain structures involved with memory. MST has been used successfully in the treatment of depression, yet there is a dearth of literature in comparison with ECT. We present a systematic review of the literature on ECT (from 2009-2011) and MST (from 2001-2011).

Communicating in context: a priority for gene therapy researchers.

PubMed

Robillard, Julie M

2015-03-01

History shows that public opinion of emerging biotechnologies has the potential to impact the research process through mechanisms such as funding and advocacy. It is critical, therefore, to consider public attitudes towards modern biotechnology such as gene therapy and more specifically towards the ethics of gene therapy, alongside advances in basic and clinical research. Research conducted through social media recently assessed how online users view the ethics of gene therapy and showed that while acceptability is high, significant ethical concerns remain. To address these concerns, the development of effective and evidence-based communication strategies that engage a wide range of stakeholders should be a priority for researchers.

Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy

PubMed Central

Brooks-Kayal, Amy R.; Bath, Kevin G.; Berg, Anne T.; Galanopoulou, Aristea S.; Holmes, Gregory L.; Jensen, Frances E.; Kanner, Andres M.; O’Brien, Terence J.; Whittemore, Vicky H.; Winawer, Melodie R.; Patel, Manisha; Scharfman, Helen E.

2014-01-01

Summary Many symptoms of neurologic or psychiatric illness—such as cognitive impairment, depression, anxiety, attention deficits, and migraine—occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure. PMID:23909853

Intelligent ePR system for evidence-based research in radiotherapy: proton therapy for prostate cancer.

PubMed

Le, Anh H; Liu, Brent; Schulte, Reinhard; Huang, H K

2011-11-01

Proton therapy (PT) utilizes high energy particle proton beam to kill cancer cells at the target region for target cancer therapy. Due to the physical properties of the proton beam, PT delivers dose with higher precision and no exit dose compared to conventional radiotherapy. In PT, patient data are distributed among multiple systems, a hindrance to research on efficacy and effectiveness. A data mining method and a treatment plan navigator utilizing the infrastructure and data repository of a PT electronic patient record (ePR) was developed to minimize radiation toxicity and improve outcomes in prostate cancer treatment. MATERIALS/METHOD(S): The workflow of a proton therapy treatment in a radiation oncology department was reviewed, and a clinical data model and data flow were designed. A prototype PT ePR system with DICOM compliance was developed to manage prostate cancer patient images, treatment plans, and related clinical data. The ePR system consists of four main components: (1) Data Gateway; (2) ePR Server; (3) Decision Support Tools; and (4) Visualization and Display Tools. Decision support and visualization tools are currently developed based on DICOM images, DICOM-RT and DICOM-RT-ION objects data from prostate cancer patients treated with hypofractionation protocol proton therapy were used for evaluating ePR system effectiveness. Each patient data set includes a set of computed tomography (CT) DICOM images and four DICOM-RT and RT-ION objects. In addition, clinical outcomes data collected from PT cases were included to establish a knowledge base for outcomes analysis. A data mining search engine and an intelligent treatment plan navigator (ITPN) were developed and integrated with the ePR system. Evaluation was based on a data set of 39 PT patients and a hypothetical patient. The ePR system was able to facilitate the proton therapy workflow. The PT ePR system was feasible for prostate cancer patient treated with hypofractionation protocol in proton therapy. This ePR system improves efficiency in data collection and integration to facilitate outcomes analysis.

Family therapy for adolescent anorexia nervosa.

PubMed

Blessitt, Esther; Voulgari, Stamatoula; Eisler, Ivan

2015-11-01

Research into the efficacy and practice of family therapy for the treatment of adolescent anorexia nervosa has been ongoing for the past 4 decades. Research results continue to highlight the effective role of family therapy for the treatment of anorexia in adolescents. This review aims to present findings and opinions from relevant articles published over the past 12 months, related to the treatment of adolescent anorexia, utilizing family therapy and multi-family therapy. A number of recent articles continue to explore family therapy for adolescent anorexia, with particular emphasis being placed on attempting to pinpoint those elements of the approaches that may hold significance in relation to recovery from this dangerous illness and the development of new interventions that draw on the evidence to date for a family approach to the treatment of anorexia. Ongoing research is needed to identify the active ingredients of family therapy for anorexia.

The application of prodrug-based nano-drug delivery strategy in cancer combination therapy.

PubMed

Ge, Yanxiu; Ma, Yakun; Li, Lingbing

2016-10-01

Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. Copyright © 2016 Elsevier B.V. All rights reserved.

Proton Pump Inhibitors in Gastroesophageal Reflux Disease: Friend or Foe.

PubMed

Gyawali, C Prakash

2017-09-01

Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.

Skin damage associated with intravenous therapy: common problems and strategies for prevention.

PubMed

Thayer, Debra

2012-01-01

Infusion therapy is among the most common health care interventions, with approximately 90% of hospitalized patients receiving vascular access and an estimated 1.3 million home infusion therapies delivered annually. Whereas most individuals complete their therapy uneventfully, others experience alterations in skin integrity, some significant enough to disrupt therapy. There are limited published data on the incidence of skin damage associated with infusion therapy, and the etiology of damage has not been previously described in detail. Wound, ostomy, and continence (WOC) nurses have developed a significant understanding of skin-related problems and effective prevention strategies from over 40 years of experience with ostomy patients--another population in which adhesive wear is a constant and localized, superficial skin damage is common. This article will offer a WOC nursing perspective of skin damage and seek to provide a context for understanding and preventing skin damage in the infusion therapy patient.

Recent advances in radiation cancer therapy

NASA Astrophysics Data System (ADS)

Ma, C.-M. Charlie

2007-03-01

This paper presents the recent advances in radiation therapy techniques for the treatment of cancer. Significant improvement has been made in imaging techniques such as CT, MRI, MRS, PET, ultrasound, etc. that have brought marked advances in tumor target and critical structure delineation for treatment planning and patient setup and target localization for accurate dose delivery in radiation therapy of cancer. Recent developments of novel treatment modalities including intensity-modulated x-ray therapy (IMXT), energy- and intensity modulated electron therapy (MERT) and intensity modulated proton therapy (IMPT) together with the use of advanced image guidance have enabled precise dose delivery for dose escalation and hypofractionation studies that may result in better local control and quality of life. Particle acceleration using laser-induced plasmas has great potential for new cost-effective radiation sources that may have a great impact on the management of cancer using radiation therapy.

Supportive therapy for schizophrenia: possible mechanisms and implications for adjunctive psychosocial treatments.

PubMed

Penn, David L; Mueser, Kim T; Tarrier, Nick; Gloege, Andrew; Cather, Corrine; Serrano, Daniel; Otto, Michael W

2004-01-01

This article posits that the positive findings for supportive therapy (ST) in recent trials may indicate an important but undervalued aspect of psychosocial interventions for schizophrenia. In developing this thesis, we consider the possible mechanisms underlying the beneficial effects of ST observed in recent trials of cognitive behavioral therapy for schizophrenia. We place this evidence in the context of a review of psychological models of mental health, the therapeutic alliance, and research on social cognition and social support in schizophrenia. We conclude this article by describing a new theoretically driven intervention for schizophrenia, functional cognitive-behavioral therapy (FCBT), which improves functional outcomes by integrating evidence-based advances in cognitive behavioral therapy with the strengths of ST approaches.

Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy.

PubMed

Sánchez-Taltavull, Daniel; Vieiro, Arturo; Alarcón, Tomás

2016-10-01

HIV-1 infected patients are effectively treated with highly active anti-retroviral therapy (HAART). Whilst HAART is successful in keeping the disease at bay with average levels of viral load well below the detection threshold of standard clinical assays, it fails to completely eradicate the infection, which persists due to the emergence of a latent reservoir with a half-life time of years and is immune to HAART. This implies that life-long administration of HAART is, at the moment, necessary for HIV-1-infected patients, which is prone to drug resistance and cumulative side effects as well as imposing a considerable financial burden on developing countries, those more afflicted by HIV, and public health systems. The development of therapies which specifically aim at the removal of this latent reservoir has become a focus of much research. A proposal for such therapy consists of elevating the rate of activation of the latently infected cells: by transferring cells from the latently infected reservoir to the active infected compartment, more cells are exposed to the anti-retroviral drugs thus increasing their effectiveness. In this paper, we present a stochastic model of the dynamics of the HIV-1 infection and study the effect of the rate of latently infected cell activation on the average extinction time of the infection. By analysing the model by means of an asymptotic approximation using the semi-classical quasi steady state approximation (QSS), we ascertain that this therapy reduces the average life-time of the infection by many orders of magnitudes. We test the accuracy of our asymptotic results by means of direct simulation of the stochastic process using a hybrid multi-scale Monte Carlo scheme.

[Phytoestrogens in the treatment of menopause].

PubMed

Remport, Júlia; Blázovics, Anna

2017-08-01

In previous centuries many women did not even live until their menopause years due to poor economic conditions, deficiencies of medicine, epidemics and wars. Nowadays in the developed countries, people live until they are 75-80 years old, and with the expansion of average age, the number of people affected by menopause and the years spent in that state increase. Nowadays women spend one third of their lives in the menopausal stage. The only effective way to treat unpleasant symptoms for centuries was with the use of herbs, and the knowledge about them spread through oral tradition. In the 20th century, this therapeutic form was pushed into the background by the development of synthetic drug production and the introduction of hormone replacement therapy. Thanks to the influence of media in the 20th century, women began to have the social need for preserving their beauty and youth for as long as they could. Hormone replacement therapy enjoyed great popularity because women were temporarily relieved of their life quality-impairing menopausal symptoms, but years later it turned out that hormone replacement therapy could pose serious risks. A distinct advantage of herbal therapy is the more advantageous side-effect-profile opposite the used synthetics in hormone replacement therapy. Women are therefore happy to turn to valuable and well-tried natural therapies, which have been used for thousands of years. There is growing interest in herbal remedies. Studying the effects of phytoestrogens has now become an active area for research. However, the results of studies in animals and humans are controversial, some sources suggest that phytoestrogens are effective and safe, other authors claim that they are ineffective in menopause or they have particularly dangerous properties, and cannot be recommended to everyone. It is important to address this issue for the sake of health, mental health and safety of women, and so it is necessary to assess the benefits and the risks before applying them. Orv Hetil. 2017; 158(32): 1243-1251.

Value of MR contrast media in image-guided body interventions.

PubMed

Saeed, Maythem; Wilson, Mark

2012-01-28

In the past few years, there have been multiple advances in magnetic resonance (MR) instrumentation, in vivo devices, real-time imaging sequences and interventional procedures with new therapies. More recently, interventionists have started to use minimally invasive image-guided procedures and local therapies, which reduce the pain from conventional surgery and increase drug effectiveness, respectively. Local therapy also reduces the systemic dose and eliminates the toxic side effects of some drugs to other organs. The success of MR-guided procedures depends on visualization of the targets in 3D and precise deployment of ablation catheters, local therapies and devices. MR contrast media provide a wealth of tissue contrast and allows 3D and 4D image acquisitions. After the development of fast imaging sequences, the clinical applications of MR contrast media have been substantially expanded to include pre- during- and post-interventions. Prior to intervention, MR contrast media have the potential to localize and delineate pathologic tissues of vital organs, such as the brain, heart, breast, kidney, prostate, liver and uterus. They also offer other options such as labeling therapeutic agents or cells. During intervention, these agents have the capability to map blood vessels and enhance the contrast between the endovascular guidewire/catheters/devices, blood and tissues as well as direct therapies to the target. Furthermore, labeling therapeutic agents or cells aids in visualizing their delivery sites and tracking their tissue distribution. After intervention, MR contrast media have been used for assessing the efficacy of ablation and therapies. It should be noted that most image-guided procedures are under preclinical research and development. It can be concluded that MR contrast media have great value in preclinical and some clinical interventional procedures. Future applications of MR contrast media in image-guided procedures depend on their safety, tolerability, tissue specificity and effectiveness in demonstrating success of the interventions and therapies.

The effect of laughter therapy on radiation dermatitis in patients with breast cancer: a single-blind prospective pilot study

PubMed Central

Kong, Moonkyoo; Shin, Sung Hee; Lee, Eunmi; Yun, Eun Kyoung

2014-01-01

Background There have not yet been any published studies on the effects of laughter therapy on radiation-induced dermatitis in breast cancer patients treated with radiotherapy (RT). We assessed the effectiveness of laughter therapy in preventing radiation dermatitis in patients with breast cancer. Methods Thirty-seven patients were prospectively enrolled in this study. Eighteen patients were assigned to the experimental group and the other 19 patients were assigned to the control group. The patients who were assigned to the experimental group received laughter therapy during RT. Laughter therapy was started at the onset of RT and was provided twice a week until completion of RT. The patients who were assigned to the control group only received RT without laughter therapy. The grade of radiation dermatitis was scored by a radiation oncologist who was blinded to subject assignment. The patients’ evaluation of pain within the RT field was also assessed. Results In the experimental group, radiation dermatitis of grade 3, 2, and 1 developed in five (33.3%), five (33.3%), and five patients (33.3%), respectively. In comparison, in the control group, radiation dermatitis of grade 3, 2, 1, and 0 developed in seven (36.8%), nine (47.4%), two (10.5%), and one patient (5.3%), respectively. The experimental group exhibited a lower incidence of grade 2 or worse radiation dermatitis than the control group (33.3% versus 47.4%). The mean maximal pain scores in the experimental and control group were 2.53 and 3.95, respectively. The experimental group complained of less severe pain than the control group during RT. However, these differences were not statistically significant. Conclusion The results of this study show that laughter therapy can have a beneficial role in preventing radiation dermatitis in patients with breast cancer. To confirm the results of our study, well-designed randomized studies with large sample sizes are required. PMID:25395864

Pharmacoeconomic analysis of consolidation therapy with pemetrexed after first-line chemotherapy for non-small cell lung cancer.

PubMed

Tsuchiya, Takanori; Fukuda, Takashi; Furuiye, Masashi; Kawabuchi, Koichi

2011-12-01

Prolongation of progression-free survival and overall survival have been reported with consolidation therapy after first-line chemotherapy in non-small cell lung cancer, but only a few pharmacoeconomic analyses have been performed. We performed a pharmacoeconomic analysis to assess the cost-effectiveness of consolidation therapy with pemetrexed compared with non-consolidation therapy. We developed a Markov model to evaluate the incremental cost-effectiveness ratio (ICER) of consolidation therapy with pemetrexed compared with non-consolidation therapy based on previous reports. We analyzed all histology groups together, and individually analyzed non-squamous cell carcinoma, in which pemetrexed has been shown to be more effective, and squamous cell carcinoma, in which pemetrexed has been shown to be less effective. We conducted a Monte-Carlo simulation to assess the uncertainty for our analysis model and the willingness to pay using thresholds. The ICER for consolidation therapy with pemetrexed was about US$ 109,024/life years gained (LYG) (JPY 12.5 million/LYG) and US$ 203,022/quality-adjusted life years (QALY) (JPY 23.3 million/QALY) for all histology. For non-squamous cell carcinoma, respective values were US$ 80,563/LYG (JPY 9.3 million/LYG) and US$ 150,115/QALY (JPY 17.3 million/QALY). Both % of probability at a threshold of JPY 5.0 million (US$ 43,478) for all histology and non-squamous cell carcinoma were less than 0.1%. This result indicates that it is difficult to use consolidation therapy as the standard of care in Japan while being covered by general medical insurance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of Morita Therapy-Based Consultation for a School-Refusing Adolescent with Psychogenic Fever

ERIC Educational Resources Information Center

Maeda, Naoki

2017-01-01

Morita therapy, developed by Shoma Morita (1874-1938) in Japan, is a type of psychotherapy that has been applied to deal with neurotic symptoms. This therapeutic approach is based on the conviction that neurotic symptoms are universal issues that eventually subside if the symptoms are accepted and everyday activities are carried out. By examining…

TSL Family Therapy Followed by Improved Marital Quality and Reduced Oxidative Stress

ERIC Educational Resources Information Center

Kim, Jae Yop; Kim, Dong Goo; Nam, Seok In

2012-01-01

Objectives: The current study evaluated the effectiveness of a form of family therapy developed in Korea. The "Thank you--Sorry--Love" (TSL) model was applied to a group of elderly retired men to improve the quality of their marriage and to reduce their stress. Methods: Thirty married retired Korean men were assigned to three groups.…

Efficacy of the Lexicon Pirate Strategy Therapy for Improving Lexical Learning in School-Age Children: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Motsch, Hans-Joachim; Marks, Dana-Kristin

2015-01-01

Lexicon Pirate was originally developed as a strategy intervention programme to treat lexical disorders of pre-school children. To evaluate the therapy's effectiveness for school-age students, a randomized controlled trial (RCT, N = 157) was conducted. Based on a pre--post-test design, the programme's impacts were compared with a control group…

Developing Therapies for Heart Failure with Preserved Ejection Fraction: Current State and Future Directions

PubMed Central

Butler, Javed; Fonarow, Gregg C.; Zile, Michael R.; Lam, Carolyn S.; Roessig, Lothar; Schelbert, Erik B.; Shah, Sanjiv J.; Ahmed, Ali; Bonow, Robert O.; Cleland, John GF; Cody, Robert J.; Chioncel, Ovidiu; Collins, Sean P.; Dunnmon, Preston; Filippatos, Gerasimos; Lefkowitz, Martin P.; Marti, Catherine N.; McMurray, John J.; Misselwitz, Frank; Nodari, Savina; O’Connor, Christopher; Pfeffer, Marc A.; Pieske, Burkert; Pitt, Bertram; Rosano, Guiseppe; Sabbah, Hani N.; Senni, Michele; Solomon, Scott D.; Stockbridge, Norman; Teerlink, John R.; Georgiopoulou, Vasiliki V.; Gheorghiade, Mihai

2014-01-01

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the FDA and included representatives from academia, industry and regulatory agencies. This document summarizes the proceedings from this meeting. PMID:24720916

[Advances in nanoparticle-targeting tumor associated macrophages for cancer imaging and therapy].

PubMed

Fengliang, Guo; Guping, Tang; Qinglian, H U

2017-03-25

Tumor tissues are composed of tumor cells and complicate microenvironment. Tumor associated macrophages (TAMs) as an important component in tumor microenvironment, play fundamental roles in tumor progression, metastasis and microenvironment regulation. Recently, studies have found that nanotechnology, as an emerging platform, provides unique potential for cancer imaging and therapy. With the nanotechnology, TAMs imaging presents direct evidence for cancer development, progression, and the effectiveness of cancer treatments; it also can regulate the immunosuppression of tumor microenvironment and improve therapeutic efficiency through TAMs targeted killing or phenotypic transformation. In this article, we illustrate the function of TAMs and review the latest development in nano-carriers and their applications in tumor associated macrophage targeting cancer imaging and therapy.

Immunotherapy in managing metastatic melanoma: which treatment when?

PubMed

Amaral, Teresa; Meraz-Torres, Francisco; Garbe, Claus

2017-12-01

Ten to fifteen percent of melanoma patients develop distant or unresectable metastasis requiring systemic treatment. Around 45% of the patients diagnosed with metastatic cutaneous melanoma harbor a BRAFV600 mutation and derive benefit from combined targeted therapy with MAPK pathway inhibitors. These offer a rapid response that translates into improvement of symptoms and increased quality of life. However, resistance often develops with subsequent progressive disease. Immunotherapy with checkpoint inhibitors may be offered to BRAF-mutated and wild-type patients and is associated with longer and durable responses that can continue over years. Areas covered: In this review, the authors discuss the late evidence for targeted and immunotherapy in melanoma patients, as well as therapy sequencing. Immunotherapy in special populations is also addressed. Expert opinion: Effective treatments are currently available. However, there are still unanswered questions of the best therapy sequence, the clear superiority of combined immunotherapy versus monotherapy in all patients, and therapy duration. Since different promising treatments will become available, clinical trials comparing the diverse options in terms of safety, efficacy and cost- effectiveness are required to make the right decisions. Consequently, patients should be encouraged to participate in clinical trials, whenever possible.

Beyond interferon: rationale and prospects for newer treatment paradigms for chronic hepatitis C

PubMed Central

Cortez, Karoll J.

2015-01-01

Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-α based combination therapy to an all-oral, directly acting antiviral therapy. PMID:25553238

New systemic strategies for overcoming resistance to targeted therapies in non-small cell lung cancer.

PubMed

Genova, Carlo; Rijavec, Erika; Biello, Federica; Rossi, Giovanni; Barletta, Giulia; Dal Bello, Maria Giovanna; Vanni, Irene; Coco, Simona; Alama, Angela; Grossi, Francesco

2017-01-01

Although the achievements in the treatment of advanced non-small cell lung cancer (NSCLC) have been translated in improved disease control, response rate and survival, especially in the case of patients with targetable oncogenic drivers, acquired resistance is common after initial benefit; furthermore, primary resistance can occasionally be observed. Due to its clinical implications, the management of treatment-resistant NSCLC is a top topic of the current research, and many efforts are being put in the study of the mechanisms at the base of resistance and in the development of effective therapeutic countermeasures. Areas covered: This review aims at identifying the most relevant novel chemical therapies designed to overcome resistance in NSCLC, including recently approved agents, as well as compounds in clinical development. Expert opinion: An improved knowledge of the mechanisms causing resistance to treatments in NSCLC translates into effective innovative chemical therapies able to overcome such occurrence, and the paradigms of this progress are represented by novel inhibitors of the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK); however, the study of novel systemic therapies in this setting is challenging, and further efforts in this setting are highly needed.

New developments in breast cancer therapy: role of iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Thoidingjam, Shivani; Bhan Tiku, Ashu

2017-06-01

Breast cancer is one of the leading causes of deaths in females worldwide. The high metastatic rate and drug resistance makes it one of the difficult cancers to treat. Early diagnosis and treatment are keys to better survival of breast cancer patients. Conventional treatment approaches like chemotherapy, radiotherapy and surgery suffer from major drawbacks. Novel approaches to improve cancer therapy with minimal damage to normal tissues and better quality of life for cancer patients need to be developed. Among various approaches used for treatment and diagnosis of breast cancer, use of nanoparticles (NPs) is coming up as a new and promising treatment regime. It can help overcome various limitations of conventional therapies like non-targeted effects, resistance to treatment, late diagnosis, etc. Among various nanoparticles studied for their biomedical applications, especially for breast cancer therapy, iron oxide nanoparticles (IONPs) are perhaps the most exciting due to their biocompatibility, biodegradability, size and properties like superparamagnetism. Besides, IONPs are also the only metal oxide nanoparticles approved for clinical use in magnetic resonance imaging (MRI) which is an added advantage for early detection. Therefore in this mini review, we are discussing the developments made in the use of IONPs for breast cancer therapy over the short span of the last five years i.e. 2010-2015. Since late diagnosis and therapy resistance are important drawbacks in breast cancer therapy, the potential of IONPs to overcome these limitations are also evaluated.