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Sample records for therapy therapeutic efficacy

  1. Self-Efficacy for Therapeutic Mode Use among Occupational Therapy Students in Norway

    Science.gov (United States)

    Opseth, Thea Moos; Carstensen, Tove; Yazdani, Farzaneh; Ellingham, Brian; Thørrisen, Mikkel Magnus; Bonsaksen, Tore

    2017-01-01

    Background: The intentional relationship model (IRM) proposes six distinct ways of relating to clients. A new instrument for measuring self-efficacy for using the therapeutic modes in occupational therapy practice was recently found to have good psychometric properties. To date, however, no research has investigated factors associated with…

  2. Medical Therapies for Stricturing Crohn's Disease: Efficacy and Cross-Sectional Imaging Predictors of Therapeutic Failure.

    Science.gov (United States)

    Campos, Cécile; Perrey, Antoine; Lambert, Céline; Pereira, Bruno; Goutte, Marion; Dubois, Anne; Goutorbe, Felix; Dapoigny, Michel; Bommelaer, Gilles; Hordonneau, Constance; Buisson, Anthony

    2017-06-01

    Medical therapy efficacy remains controversial in stricturing Crohn's disease. Cross-sectional imaging, especially magnetic resonance imaging, has been suggested as very helpful to guide therapeutic decision making. To assess efficacy and predictors of therapeutic failure in patients receiving medical treatments for stricturing Crohn's disease. In this retrospective study, therapeutic failure was defined as symptomatic stricture leading to surgical or endoscopic therapeutics, hospitalization, treatment discontinuation or additional therapy and short-term clinical response as clinical improvement assessed by two physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance imaging and 22 CT scan) before starting medical therapy were analyzed independently by two radiologists. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CI). Among 84 patients, therapeutic failure rate within 60 months was 66.6%. In multivariate analysis, Crohn's disease diagnosis after 40 years old (HR 3.9, 95% CI [1.37-11.2], p = 0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80], p = 0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p = 0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p = 0.006) were associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI [0.40-0.71], p = 0.015) prevented it. Considering 108 therapeutic sequences, the short-term clinical response rate was 65.7%. In multivariate analysis, male gender (OR 0.15, 95% CI [0.03-0.64], p = 0.011), fistula with abscess (OR 0.09, 95% CI [0.01-0.77], p = 0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p = 0.047) were associated with short-term clinical failure. Anti-TNF combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging should be systematically performed to help medical management in stricturing Crohn's disease.

  3. The Course of Self-Efficacy for Therapeutic Use of Self in Norwegian Occupational Therapy Students: A 10-Month Follow-Up Study

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    Kathrin Schwank

    2018-01-01

    Full Text Available Background. Occupational therapy students need to develop self-efficacy for managing the therapeutic relationship in practice. This study examined the 10-month trajectories of Norwegian students’ self-efficacy for use of self. Methods. Eighty-nine students completed self-efficacy questionnaires related to the use of self after a workshop and at 3- and 10-month follow-up. Changes on the three outcome measures (self-efficacy for therapeutic mode use, for recognizing clients’ interpersonal characteristics, and for managing interpersonal events were analyzed with repeated measures ANOVA. Results. Across the follow-up period, the students improved their self-efficacy for therapeutic mode use (partial η2 = 0.44, p<0.001, for recognizing clients’ interpersonal characteristics (partial η2 = 0.81, p<0.001, and for managing interpersonal events (partial η2=0.32, p<0.001. Conclusion. The increased self-efficacy for use of self that was found at 3-month follow-up was maintained at 10-month follow-up. The results indicate that students may experience a boost in self-efficacy for therapeutic use of self after a brief workshop and that these changes can be sustained over time.

  4. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  5. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  6. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

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    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  7. Efficacy of therapeutic ultrasound and exercise therapy in the ...

    African Journals Online (AJOL)

    Results: Findings of the study revealed no significant difference in VAS, ROM and WOMAC scores in the study and control groups. Conclusions: This study confirms that therapeutic ultrasound is of no additional benefit to exercise therapy in the management of chronic osteoarthritis. Key words: Ultrasound; Exercise; ...

  8. Therapeutic genes for anti-HIV/AIDS gene therapy.

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    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  9. Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

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    Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

    2014-01-01

    Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

  10. The therapeutic relationship in e-therapy for mental health: a systematic review.

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    Sucala, Madalina; Schnur, Julie B; Constantino, Michael J; Miller, Sarah J; Brackman, Emily H; Montgomery, Guy H

    2012-08-02

    E-therapy is defined as a licensed mental health care professional providing mental health services via e-mail, video conferencing, virtual reality technology, chat technology, or any combination of these. The use of e-therapy has been rapidly expanding in the last two decades, with growing evidence suggesting that the provision of mental health services over the Internet is both clinically efficacious and cost effective. Yet there are still unanswered concerns about e-therapy, including whether it is possible to develop a successful therapeutic relationship over the Internet in the absence of nonverbal cues. Our objective in this study was to systematically review the therapeutic relationship in e-therapy. We searched PubMed, PsycINFO, and CINAHL through August 2011. Information on study methods and results was abstracted independently by the authors using a standardized form. From the 840 reviewed studies, only 11 (1.3%) investigated the therapeutic relationship. The majority of the reviewed studies were focused on the therapeutic alliance-a central element of the therapeutic relationship. Although the results do not allow firm conclusions, they indicate that e-therapy seems to be at least equivalent to face-to-face therapy in terms of therapeutic alliance, and that there is a relationship between the therapeutic alliance and e-therapy outcome. Overall, the current literature on the role of therapeutic relationship in e-therapy is scant, and much more research is needed to understand the therapeutic relationship in online environments.

  11. Efficacy of various schemes of therapy of patients with radiation limb edema

    International Nuclear Information System (INIS)

    Kuz'mina, E.G.; Degtyareva, A.A.; Zubova, N.D.; Guseva, L.I.; Klimanov, M.E.

    1987-01-01

    The efficacy of various therapeutic schemes: medicinal (basic therapy - BT), acupuncture (AP) and laser therapy (LT) against a background of basic therapy - was assessed and compared in 36 patients with radiation limb edema. It was established that a degree of a decrease in edemas, the improvement of indices of rheovasography grew in the following order: BT → AP → LT. The recovery of the lymph flow and immunological indices were the same in all therapeutic schemes

  12. Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

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    Jeehoon Kang

    2016-11-01

    Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

  13. Molecular Imaging of Gene Expression and Efficacy following Adenoviral-Mediated Brain Tumor Gene Therapy

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    Alnawaz Rehemtulla

    2002-01-01

    Full Text Available Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD along with an optical reporter gene (luciferase. Following intratumoral injection of the vector into orthotopic 9L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging

  14. The mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization

    International Nuclear Information System (INIS)

    Li Weiduo; Yang Jianyong; Zhuang Wenquan; Chen Wei; Li Heping

    2002-01-01

    Objective: To explore the mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization. Methods: Twenty-five patients of Graves' disease treated with interventional embolization were followed up for 24-57 months. T 3 and T 4 were monitored at pre-operation, six months, 12 months, 2, 3 and 4 years after operation, respectively. Other references included pulse, thyroid size, and vessel's murmur. Results: Twenty-two patients completely relieved from the hyperthyroidism during the follow-up. Only one patient suffered from recurrence. Other two patients were still on maintaining dosage of antithyroid drug therapy. No hypothyroidism or hypoparathyroidism was found during this term. Conclusion: Mid-to-long term follow-up showed satisfactory efficacy of interventional therapy, offering another alternative for treatment of refractory Graves' disease

  15. Therapeutic efficacy of chemotherapy with ACNU and radiation therapy for malignant glioma in the cerebral hemisphere

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    Miyagami, Mitsusuke; Katayama, Yoichi; Nakamura, Saburo [Nihon Univ., Tokyo (Japan). School of Medicine

    2000-10-01

    Seventy-two patients with malignant gliomas (57 with glioblastoma and 15 with anaplastic astrocytoma) in the cerebral hemisphere were studied retrospectively to evaluate the therapeutic efficacy of chemotherapy with nimustine and radiation after surgery. Survival was analyzed with the Kaplan-Meier method in 21 patients treated with radiotherapy after surgery and 51 patients treated with nimustine and radiotherapy after surgery. Histological classification age, and the extent of resection of the tumors were significantly correlated with survival. The median survival time was 8 months in patients treated with radiotherapy and 15 months in patients treated with nimustine and radiotherapy. The 2- and 5-year survival rates were 12% and 0% in patients treated with radiotherapy and 33% and 22% in patients treated with nimustine and radiotherapy. Thus, a significant difference in survival was recognized, and chemotherapy with nimustine was found to be useful as an adjuvant therapy for glioblastoma after surgery. However, survival time did not differ between intravenous and intra-arterial infusion of nimustine. (author)

  16. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of 131I in Hyperthyroidism

    International Nuclear Information System (INIS)

    Kartamihardja, A. Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended

  17. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of (131)I in Hyperthyroidism.

    Science.gov (United States)

    Kartamihardja, A Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended.

  18. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of 131I in Hyperthyroidism

    Science.gov (United States)

    Kartamihardja, A. Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended. PMID:27134556

  19. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

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    Oh, Doo-Byoung

    2015-08-01

    Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

  20. Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

    Science.gov (United States)

    Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

    2008-06-01

    Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

  1. Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

    International Nuclear Information System (INIS)

    Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

    2008-01-01

    Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

  2. Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins

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    Alison Smith

    2016-01-01

    Full Text Available Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents.

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

    International Nuclear Information System (INIS)

    Postiglione, Ilaria; Chiaviello, Angela; Palumbo, Giuseppe

    2011-01-01

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

  4. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy

    Science.gov (United States)

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

  5. Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

    Science.gov (United States)

    Anusuya, Shanmugam; Natarajan, Jeyakumar

    2012-12-01

    Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. [Efficacy of a cognitive-behavioral group therapy in patients with fear of blushing].

    Science.gov (United States)

    Lobjoie, C; Pélissolo, A

    2012-09-01

    Cognitive behavioral therapy (CBT) has shown to be effective in the treatment of social anxiety disorders (SAD). However, fear of social blushing is almost never measured as a therapeutic outcome variable, even though some data suggest that this dimension constitutes a specific syndrome in social anxiety spectrum, justifying specific therapeutic strategies. For these reasons, we developed a group therapy program including a combination of task concentration training (TCT) and other CBT strategies targeting fear of blushing. We aimed to investigate the efficacy of this program in an open trial conducted in 55 patients suffering from SAD (Diagnostic and statistical manual of mental disorders IV criteria) with fear of blushing. Throughout a program including eleven weekly sessions, systematic measurements of fear of blushing and other anxiety and personality dimensions were performed at inclusion, at the end of the therapy and 3 months later, in order to explore the therapeutic effects of the program on fear of blushing, social anxiety, and other dimensions (Liebowitz social anxiety scale, blushing propensity questionnaire, Rathus assertiveness scale, Rosenberg self-esteem scale, Hospital anxiety and depression scale, Sheehan disability scale). The statistical analyses compared the scores of all measurements at inclusion, at the end of the therapy, and 6 months later. We also calculated the effect size obtained after treatment, and performed a logistic regression to determine the factors associated with a remission of fear of blushing after therapy. The main outcome criterion - the Salpêtrière fear of blushing questionnaire (SFBQ) score - was significantly reduced after treatment (Passertiveness, self-esteem, anxiety, depression and disability showed significant improvement after treatment and reductions remained stable at 3-month follow-up. To be a female and to have a low SFBQ score at inclusion appeared as two independent predictors of good improvement. Despite

  7. Safety and Efficacy of Warfarin Therapy in Kawasaki Disease.

    Science.gov (United States)

    Baker, Annette L; Vanderpluym, Christina; Gauvreau, Kimberly A; Fulton, David R; de Ferranti, Sarah D; Friedman, Kevin G; Murray, Jenna M; Brown, Loren D; Almond, Christopher S; Evans-Langhorst, Margaret; Newburger, Jane W

    2017-10-01

    To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

    Directory of Open Access Journals (Sweden)

    Sayeda Yasmin-Karim

    2018-04-01

    Full Text Available Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs, with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

  9. Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy.

    Science.gov (United States)

    Chirmule, Narendra; Jawa, Vibha; Meibohm, Bernd

    2012-06-01

    The development of therapeutic proteins requires the understanding of the relationship between the dose, exposure, efficacy, and toxicity of these molecules. Several intrinsic and extrinsic factors contribute to the challenges for measuring therapeutic proteins in a precise and accurate manner. In addition, induction of an immune response to therapeutic protein results in additional complexities in the analysis of the pharmacokinetic profile, toxicity, safety, and efficacy of this class of molecules. Assessment of immunogenicity of therapeutic proteins is a required aspect of regulatory filings for a licensing application and for the safe and efficacious use of these compounds. A systematic strategy and well-defined criteria for measuring anti-drug antibodies (ADA) have been established, to a large extent, through coordinated efforts. These recommendations are based on risk assessment and include the determination of ADA content (concentration/titer), affinity, immunoglobulin isotype/subtype, and neutralization capacity. This manuscript reviews the requirements necessary for understanding the nature of an ADA response in order to discern the impact of immunogenicity on pharmacokinetics/pharmacodynamics and efficacy.

  10. Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated ...

    African Journals Online (AJOL)

    Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga. Aaron Mabuza, John Govere, David Durrheim, Nicros Mangomezulu, Barry Bredenkamp, Karen Barnes, Brian Sharp ...

  11. Combined analgesics in (headache pain therapy: shotgun approach or precise multi-target therapeutics?

    Directory of Open Access Journals (Sweden)

    Fiebich Bernd L

    2011-03-01

    Full Text Available Abstract Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix" are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA, paracetamol (acetaminophen and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden

  12. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    2011-01-01

    Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

  13. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

    2011-03-31

    Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

  14. Factors Associated with Therapeutic Efficacy of Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Syndrome.

    Directory of Open Access Journals (Sweden)

    Sheng-Mou Hsiao

    Full Text Available To analyze the predictors of therapeutic efficacy after intravesical botulinum toxin A injection for overactive bladder syndrome (OAB refractory to antimuscarinic therapy.All consecutively OAB patients, who visited the urologic outpatient clinics of a medical center and refractory to antimuscarinic treatment, were prospectively enrolled. All enrolled patients received intravesical injection of 100 U onabotulinumtoxinA (Botox. The Global Response Assessment (GRA score ≥ 2 at 3 months after Botox injection was defined as a successful treatment, otherwise failed.Overall, 89 patients received intravesical injection. Eighty patients, including 42 men and 38 women, had received follow-up at 3 months. The overall success rate was 63.8%. The global response assessment, urgency severity score, urgency, urgency urinary incontinence and frequency episodes, and functional bladder capacity improved after treatment. However, post-void residual volume (PVR increased, and voiding efficiency (VE decreased after treatment. Female gender (odds ratio = 3.75 was the only independent factor associated with the success. Female gender (coefficient = 0.74, low baseline overactive bladder symptoms score (coefficient = -0.12 and the presence of OAB-wet (coefficient = 0.79 were independent factors associated with therapeutic efficacy (i.e., GRA score. VE (odds ratio = 0.062 was the only predictor for a large PVR at 3 months. The optimum cutoff value of VE was <87% with the area under the ROC curve being 0.64 (sensitivity = 63.8%, specificity = 57.1%.The therapeutic effects of Botox can persist till 6 months after treatment. Female gender, low overactive bladder symptoms score and OAB-wet are associated better therapeutic efficacy, and low baseline VE is associated with large PVR. These findings can serve as an initial guide or assist in consultation regarding the treatment of OAB patients with Botox injection.ClinicalTrials.gov NCT01657409.

  15. Therapeutic Efficacy of Bipolar Radiofrequency Thermotherapy for Patients with Chronic Prostatitis: A Retrospective Analysis of 26 Cases

    OpenAIRE

    Lim, Ju Young; Shim, Seung Bum; Yoo, Dong Hoon; Park, Young Woong; Kim, Jong Yeon; Noh, Joon Hwa

    2012-01-01

    Purpose Chronic prostatitis (CP) does not yet have a universally successful therapy. Alternative treatments including thermotherapy have been adopted in the multimodal management of pain and voiding dysfunction. We retrospectively analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for patients who were unsatisfied with conventional medication for CP. Materials and Methods A retrospective study between October 2009 and September 2010 of 26 patients who were under 50 year...

  16. Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

    International Nuclear Information System (INIS)

    Obermiller, Patrice S; Tait, David L; Holt, Jeffrey T

    2000-01-01

    Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care

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

    Science.gov (United States)

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

    2011-02-01

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

  18. Efficacy and safety of acupuncture therapy for nerve deafness: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Jiang, Yuebo; Shi, Xian; Tang, Yan

    2015-01-01

    Acupuncture is one of the important parts of therapeutic methods in traditional Chinese medicine, and has been widely used for the treatment of nerve deafness in recent years. The current study was to evaluate the efficacy and safety of acupuncture therapy for nerve deafness compared with conventional medicine therapy. PubMed, the Chinese National Knowledge Infrastructure Database, the Chinese Science and Technology Periodical Database, the Chinese Biomedical Database, the Wanfang Database were searched for articles published to identify randomized controlled trials evaluating efficacy and side effects between acupuncture and conventional medicine therapies up to 2013/06. A total of 12 studies, including 527 patients assessed the efficacy and safety of acupuncture therapy for nerve deafness. Overall, the efficacy of acupuncture was significantly better than that of the conventional western medication (RR: 1.54, 95% CI: 1.36-1.74) or traditional Chinese medicines (RR: 1.51, 95% CI: 1.24-1.84), and the efficacy of acupuncture in combination with conventional western medication or traditional Chinese medicine was better than that of the conventional western medication alone (RR: 1.51, 95% CI: 1.29-1.77) or traditional Chinese medicine alone (RR: 1.59, 95% CI: 1.30-1.95). Based on the comparison of number of deafness patients who were completely cured, the efficacy of acupuncture in combination with traditional Chinese medicines was better than that of traditional Chinese medicine alone (RR: 4.62, 95% CI: 1.38-15.47). Acupuncture therapy can significantly improve the hearing of patients with nerve deafness, and the efficacy of acupuncture in combination with medication is superior to medication alone.

  19. A comparison of efficacy of photoradiation therapy and other conventional treatment modalities on experimental MS-2 sarcoma

    International Nuclear Information System (INIS)

    Pazzoni, Gabriella; Savi, Giuseppina; Melloni, Elsa; Marchesini, Renato; Fava, Giannino; Locati, Lucia; Zunino, Franco

    1984-01-01

    The therapeutic efficacy of photoradiation therapy (PRT) following hematoporthyrin derivative (HpD) administration was compared in the experimental MS-2 tumour model to that of conventional treatment methods for local control of neoplastic diseases (i.e. surgery and radiotherapy). The therapeutic effects of PRT and surgical removal of primary tumour were comparable in these experiments. However, optimal effects were critically dependent on the stage of tumour development. In addition, the therapeutic advantage of PRT over radiotherapy suggests an interesting role of a new approach in tumours resistant to this conventional treatment. (author)

  20. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  1. Therapeutic efficacy and toxicity of a single and double application of boron neutron capture therapy (BNCT) in a hamster cheek pouch oral precancer model

    International Nuclear Information System (INIS)

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

    2012-01-01

    Tumor development from tissue with potentially malignant disorders (PMD) gives rise to second primary tumors. We previously demonstrated the partial inhibitory effect on tumor development of Boron Neutron Capture Therapy (BNCT) mediated by the boron compounds BPA (boronophenylalanine) and decahydrodecaborate (GB-10) in a hamster pouch oral precancer model. Seeking to optimize BNCT, the aim of the present study was to contribute to the knowledge of BNCT radiobiology for oral precancer and assess new BNCT protocols in terms of inhibition of tumor development and radiotoxicity. Groups of cancerized hamsters were locally exposed to single or double applications (2 weeks apart) of BPA-BNCT or (GB-10 + BPA)-BNCT at a total dose of 8Gy to tissue with PMD; to a single application of BPA-BNCT at 6Gy and to a double application (4 weeks apart) of BPA-BNCT or (BPA + GB-10)-BNCT at a total dose of 10Gy. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumor development from tissue with PMD and mucositis were followed for 8 months. The marked therapeutic efficacy of single applications of BNCT at 6 and 8Gy were associated to severe radiotoxicity. Dose fractionation into 2 applications reduced mucositis but also reduced therapeutic efficacy, depending on dose and interval between applications. A double application (4 weeks apart) of (GB-10 + BPA)-BNCT at a total dose of 10Gy rendered the best therapeutic advantage, i.e. 63% - 100% inhibition of tumor development with only slight mucositis in 67% of cases. The data reported herein show that issues such as dose levels and dose fractionation, interval between applications, and choice of boron compounds are pivotal to therapeutic advantage and must be tailored for a particular pathology and anatomic site. The present study determined treatment conditions that would contribute to optimize BNCT for precancer and that would warrant cautious assessment in a clinical scenario (author)

  2. The mediational role of panic self-efficacy in cognitive behavioral therapy for panic disorder: A systematic review and meta-analysis

    DEFF Research Database (Denmark)

    Fentz, Hanne Nørr; Arendt, Mikkel; OToole, Mia Skytte

    2014-01-01

    Cognitive models of panic disorder (PD) with and without agoraphobia have stressed the role of catastrophic beliefs of bodily symptoms as a central mediating variable of the efficacy of cognitive behavioral therapy (CBT). Perceived ability to cope with or control panic attacks, panic self......-efficacy, has also been proposed to play a key role in therapeutic change; however, this cognitive factor has received much less attention in research. The aim of the present review is to evaluate panic self-efficacy as a mediator of outcome in CBT for PD using descriptive and meta-analytic procedures. We...... an association between change in panic self-efficacy and change in outcome during therapy (criterion 2); three tested, and one established formal statistical mediation of panic self-efficacy (criterion 3); while four tested and three found change in panic self-efficacy occurring before the reduction of panic...

  3. Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma

    International Nuclear Information System (INIS)

    Bouchet, Audrey; Bräuer-Krisch, Elke; Prezado, Yolanda; El Atifi, Michèle; Rogalev, Léonid; Le Clec'h, Céline; Laissue, Jean Albert; Pelletier, Laurent; Le Duc, Géraldine

    2016-01-01

    Purpose: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Methods and Materials: Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. Results: MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. Conclusions: These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses.

  4. Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Bouchet, Audrey, E-mail: audrey.m.bouchet@gmail.com [Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble (France); Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble (France); Bräuer-Krisch, Elke; Prezado, Yolanda [Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble (France); El Atifi, Michèle [Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble (France); Grenoble University Hospital, Grenoble (France); Rogalev, Léonid; Le Clec' h, Céline [Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble (France); Laissue, Jean Albert [University of Bern, Bern (Switzerland); Pelletier, Laurent, E-mail: laurent.pelletier@ujf-grenoble.fr [Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble (France); Grenoble University Hospital, Grenoble (France); Le Duc, Géraldine [Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble (France)

    2016-08-01

    Purpose: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Methods and Materials: Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. Results: MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. Conclusions: These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses.

  5. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  6. Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    International Nuclear Information System (INIS)

    Nigg, D.W.

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  7. Short-term therapeutic effects of combined therapy with metformin hydrochloride for aplastic anemia

    Directory of Open Access Journals (Sweden)

    Xue-chun LU

    2012-03-01

    Full Text Available Objective To screen and select new drugs for aplastic anemia (AA and evaluate their clinical efficacy by clinical bioinformatics methods. Methods First, we established genome expression profiles of AA patients, and conducted similarity analyses with the pharmacogenomics database to screen and select drugs with possible efficacy. Intractable AA patients who received immunosuppressors and/or androgen for more than six months showing no clinical efficacy were enrolled in the study to evaluate therapeutic effects of the therapeutic regime. Clinical efficacy and adverse effects were evaluated after six months. Results The clinical bioinformatics results showed therapeutic effects of metformin hydrochloride on AA. Forty-three intractable AA patients (15 with severe AA were treated with metformin hydrochloride combined with cyclosporin A (CsA and stanozolol. Twenty-seven transfusion-dependent patients (100% became transfusion independent after a 6-month therapy. The hemoglobin level completely returned to normal in 37 out of 40 anemia patients (92.5%. In the 40 patients with platelet count lower than 20×109/L, the platelet count of 28 patients (90.3% increased to higher than 50×109/L. The white cell count increased to higher than 3.5×109/L in 30 out of 35 patients (88.6% with white cell count lower than 2.5×109/L. Among 40 anemic patients, 1 was found to have abnormal renal function, but it recovered to the normal range after ending CsA treatment. Eighteen patients were found to have elevated transaminase levels which were lowered to normal range after using liver protectants and reducing the dosage of stanozolol. There were no instances of hypoglycemia in all patients throughout the treatment. Conclusion Combination of metformin hydrochloride, CsA and stanozolol is effective in refractory aplastic anemia with acceptable toxicity.

  8. Therapeutic efficacy of Chymotrypsin in acute bovine mastitis

    Directory of Open Access Journals (Sweden)

    Marco Leal G

    2016-05-01

    Full Text Available Objective. To evaluate the therapeutic efficacy of a proteolytic drug “chymotrypsin” combined with beta-lactam antibiotics in cows with acute mastitis. Material and Methods. Fourteen cows with acute mastitis. Three cows were treated with a beta-latam antibiotic (BLA and the other eleven cows were treated with chymotrypsin plus beta-lactam antibiotic (C+BLA. The response was evaluated according to the semiological findings, somatic cell count (SCC and a microbiological culture. Results. There was a therapeutic efficacy comparing the pre and post treatment period (SCC reduction, p<0.01 and a reduction of clinical signs in 84.7% of treated quarters in the first day of treatment (C+BLA compared with (BLA. Conclusions. Chymotrypsin improves the treatment of acute mastitis when is combined with BLA, controlling the infected mammary glands, compared with the group treated only with amoxicilina and clavulanic acid.

  9. Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs

    Directory of Open Access Journals (Sweden)

    Ildiko Barabasi

    2016-11-01

    Full Text Available Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs 1Ildikó BARABÁSI, 1Cristina ȘTEFǍNUȚ, 1Laurenţ OGNEAN 1University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400037, Manastur street, no.3-5, Cluj-Napoca, Romania *Corresponding author: lognean@yahoo.com   Keywords: dogs, erythrocyte concentrate, hematocrit, immune-mediated hemolytic anemia, transfusion therapy Introduction: The minimum dose of whole blood products as well as erythrocyte concentrate has been under a lot of debate, new equations for calculating the optimal dose being made up from a large variety of hematologists (Kisielewicz et al 2014; Helm and Knottenbelt, 2010; Gibson, 2007. Aim: The therapeutical efficacy of erythrocyte concentrates in dogs with different types of anemia by measuring the hematocrit level 6 hours after the transfusion and a complete blood count 5 days post-transfusion therapy. Materials and methods: Blood tests were performed with ADIVA hematological analyzer; the 6 hour post-transfusion hematocrit was determined by a micro hematocrit. On admission every patient received a routine blood test that included 40 hematological parameters and 21 biochemical parameters. In addition, a detailed examination of the blood smears was also performed by the ADIVA hematological analyzer with 26 parameters that mostly referred to red blood cell and white blood cell morphology. Blood typing was done using the RapidVet quick test kit. Patients received only type specific blood and to limit transfusion reaction occurrences, in addition, a crossmatch test was performed before every transfusion. Statistical analysis was accomplished with GraphPadInStat 3.0 and the graphical depiction of the obtained results was made using the Origin 8.5. graphics program. Results: Statistical analysis reveal that the total red blood cell count underwent very significant changes (p=0.0052 as well as the hemoglobin (p=0.0085. The hematocrit

  10. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  11. Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy.

    Science.gov (United States)

    Sugarman, Jordan; Tsai, Sue; Santamaria, Pere; Khadra, Anmar

    2013-05-01

    Nanoparticles (NPs) coated with β-cell-specific peptide major histocompatibility complex (pMHC) class I molecules can effectively restore normoglycemia in spontaneously diabetic nonobese diabetic mice. They do so by expanding pools of cognate memory autoreactive regulatory CD8+ T cells that arise from naive low-avidity T-cell precursors to therapeutic levels. Here we develop our previously constructed mathematical model to explore the effects of compound design parameters (NP dose and pMHC valency) on therapeutic efficacy with the underlying hypothesis that the functional correlates of the therapeutic response (expansion of autoregulatory T cells and deletion of autoantigen-loaded antigen-presenting cells by these T cells) are biphasic. We show, using bifurcation analysis, that the model exhibits a 'resonance'-like behavior for a given range of NP dose in which bistability between the healthy state (possessing zero level of effector T-cell population) and autoimmune state (possessing elevated level of the same population) disappears. A heterogeneous population of model mice subjected to several treatment protocols under these new conditions is conducted to quantify both the average percentage of autoregulatory T cells in responsive and nonresponsive model mice, and the average valency-dependent minimal optimal dose needed for effective therapy. Our results reveal that a moderate increase (≥1.6-fold) in the NP-dependent expansion rate of autoregulatory T-cell population leads to a significant increase in the efficacy and the area corresponding to the effective treatment regimen, provided that NP dose ≥8 μg. We expect the model developed here to generalize to other autoimmune diseases and serve as a computational tool to understand and optimize pMHC-NP-based therapies.

  12. Efficacy of cognitive-behavioral therapy for obsessive-compulsive disorder.

    Science.gov (United States)

    McKay, Dean; Sookman, Debbie; Neziroglu, Fugen; Wilhelm, Sabine; Stein, Dan J; Kyrios, Michael; Matthews, Keith; Veale, David

    2015-05-30

    Cognitive-behavioral therapy (CBT), which encompasses exposure with response prevention (ERP) and cognitive therapy (CT), has demonstrated efficacy in the treatment of obsessive-compulsive disorder (OCD). However, the samples studied (reflecting the heterogeneity of OCD), the interventions examined (reflecting the heterogeneity of CBT), and the definitions of treatment response vary considerably across studies. This review examined the meta-analyses conducted on ERP and cognitive therapy (CT) for OCD. Also examined was the available research on long-term outcome associated with ERP and CT. The available research indicates that ERP is the first line evidence based psychotherapeutic treatment for OCD and that concurrent administration of cognitive therapy that targets specific symptom-related difficulties characteristic of OCD may improve tolerance of distress, symptom-related dysfunctional beliefs, adherence to treatment, and reduce drop out. Recommendations are provided for treatment delivery for OCD in general practice and other service delivery settings. The literature suggests that ERP and CT may be delivered in a wide range of clinical settings. Although the data are not extensive, the available research suggests that treatment gains following ERP are durable. Suggestions for future research to refine therapeutic outcome are also considered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. The Slaying of a Beautiful Hypothesis: The Efficacy of Counseling and the Therapeutic Process

    Science.gov (United States)

    Hauser, Mike; Hays, Danica G.

    2010-01-01

    Although the efficacy of counseling has been empirically linked to the therapeutic process, the emphasis in much of the literature remains on technique use. This article discusses 3 components of therapeutic efficacy (i.e., common factors, working alliance, and counselor attributes) and provides implications for counselors and counselor training.…

  14. Therapeutic effects of protein kinase N3 small interfering RNA and doxorubicin combination therapy on liver and lung metastases

    Science.gov (United States)

    Hattori, Yoshiyuki; Kikuchi, Takuto; Nakamura, Mari; Ozaki, Kei-Ichi; Onishi, Hiraku

    2017-01-01

    It has been reported that suppression of protein kinase N3 (PKN3) expression in vascular and lymphatic endothelial cells results in the inhibition of tumor progression and lymph node metastasis formation. The present study investigated whether combination therapy of small interfering RNA (siRNA) against PKN3 and doxorubicin (DXR) could increase therapeutic efficacy against liver and lung metastases. In vitro transfection of PKN3 siRNA into PKN3-positive MDA-MB-231, LLC, and Colon 26 cells and PKN3-negative MCF-7 cells did not inhibit cell growth and did not increase sensitivity to DXR. However, following in vivo treatment, PKN3 siRNA suppressed the growth of liver MDA-MB-231 and lung LLC and MCF-7 metastases, although combination therapy with DXR did not increase the therapeutic efficacy. By contrast, in liver MCF-7 metastases, PKN3 siRNA or DXR alone did not exhibit significant inhibition of tumor growth, but their combination significantly improved therapeutic efficacy. Treatment of liver MDA-MB-231 metastases with PKN3 siRNA induced a change in vasculature structure via suppression of PKN3 mRNA expression. PKN3 siRNA may induce antitumor effects in lung and liver metastases by suppression of PKN3 expression in stroma cells, such as endothelial cells. From these findings, PKN3 siRNA alone or in combination with DXR may reduce the tumor growth of liver and lung metastases regardless of PKN3 expression in tumor cells. PMID:29098022

  15. Therapy Talk: Analyzing Therapeutic Discourse

    Science.gov (United States)

    Leahy, Margaret M.

    2004-01-01

    Therapeutic discourse is the talk-in-interaction that represents the social practice between clinician and client. This article invites speech-language pathologists to apply their knowledge of language to analyzing therapy talk and to learn how talking practices shape clinical roles and identities. A range of qualitative research approaches,…

  16. Predictive markers of efficacy for an angiopoietin-2 targeting therapeutic in xenograft models.

    Directory of Open Access Journals (Sweden)

    Gallen Triana-Baltzer

    Full Text Available The clinical efficacy of anti-angiogenic therapies has been difficult to predict, and biomarkers that can predict responsiveness are sorely needed in this era of personalized medicine. CVX-060 is an angiopoietin-2 (Ang2 targeting therapeutic, consisting of two peptides that bind Ang2 with high affinity and specificity, covalently fused to a scaffold antibody. In order to optimize the use of this compound in the clinic the construction of a predictive model is described, based on the efficacy of CVX-060 in 13 cell line and 2 patient-derived xenograft models. Pretreatment size tumors from each of the models were profiled for the levels of 27 protein markers of angiogenesis, SNP haplotype in 5 angiogenesis genes, and somatic mutation status for 11 genes implicated in tumor growth and/or vascularization. CVX-060 efficacy was determined as tumor growth inhibition (TGI% at termination of each study. A predictive statistical model was constructed based on the correlation of these efficacy data with the marker profiles, and the model was subsequently tested by prospective analysis in 11 additional models. The results reveal a range of CVX-060 efficacy in xenograft models of diverse tissue types (0-64% TGI, median = 27% and define a subset of 3 proteins (Ang1, EGF, Emmprin, the levels of which may be predictive of TGI by Ang2 blockade. The direction of the associations is such that better efficacy correlates with high levels of target and low levels of compensatory/antagonizing molecules. This effort has revealed a set of candidate predictive markers for CVX-060 efficacy that will be further evaluated in ongoing clinical trials.

  17. Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

    Science.gov (United States)

    Bradbury, Allison M; Gray-Edwards, Heather L; Shirley, Jamie L; McCurdy, Victoria J; Colaco, Alexandria N; Randle, Ashley N; Christopherson, Pete W; Bird, Allison C; Johnson, Aime K; Wilson, Diane U; Hudson, Judith A; De Pompa, Nicholas L; Sorjonen, Donald C; Brunson, Brandon L; Jeyakumar, Mylvaganam; Platt, Frances M; Baker, Henry J; Cox, Nancy R; Sena-Esteves, Miguel; Martin, Douglas R

    2014-01-01

    The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated GM2 patients and those in future clinical trials. PMID:25284324

  18. Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

    Science.gov (United States)

    Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

    2007-01-01

    The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.

  19. Therapeutic efficacy of self-ligating brackets: A systematic review.

    Science.gov (United States)

    Dehbi, Hasnaa; Azaroual, Mohamed Faouzi; Zaoui, Fatima; Halimi, Abdelali; Benyahia, Hicham

    2017-09-01

    Over the last few years, the use of self-ligating brackets in orthodontics has progressed considerably. These systems have been the subject of numerous studies with good levels of evidence making it possible to evaluate their efficacy and efficiency compared to conventional brackets. The aim of this study was to evaluate the therapeutic efficacy of self-ligating brackets by means of a systematic review of the scientific literature. A systematic study was undertaken in the form of a recent search of the electronic Pubmed database, oriented by the use of several keywords combined by Boolean operators relating to the therapeutic efficacy of self-ligating brackets through the study of tooth alignment, space closure, expansion, treatment duration and degree of discomfort. The search was limited to randomized controlled studies, and two independent readers identified studies corresponding to the selection criteria. The chosen articles comprised 20 randomized controlled trials. The studies analyzed revealed the absence of significant differences between the two types of system on the basis of the clinical criteria adopted, thereby refuting the hypothesis of the superiority of self-ligating brackets over conventional systems. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

  20. Bee venom therapy: Potential mechanisms and therapeutic applications.

    Science.gov (United States)

    Zhang, Shuai; Liu, Yi; Ye, Yang; Wang, Xue-Rui; Lin, Li-Ting; Xiao, Ling-Yong; Zhou, Ping; Shi, Guang-Xia; Liu, Cun-Zhi

    2018-04-11

    Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

    Science.gov (United States)

    Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

    2016-02-01

    Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

  2. Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    John F. Flynn

    2009-01-01

    Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

  3. Therapeutic efficacy of nonsteroidal anti-inflammatory drug therapy versus exercise therapy in patients with chronic nonspecific low back pain: a prospective study.

    Science.gov (United States)

    Takahashi, Naoto; Omata, Jun-Ichi; Iwabuchi, Masumi; Fukuda, Hironari; Shirado, Osamu

    2017-04-28

    Therapy for chronic, nonspecific low back pain is mainly conservative: medication and/or exercise. Pharmacotherapy, however, has side effects, and the quantities of concomitant drugs in older persons require attention. Although exercise promises improved function, its use to alleviate pain is controversial. Thus, we compared the efficacy of pharmacotherapy versus exercise for treating chronic nonspecific low back pain. The pharmacotherapy group (n=18: 8 men, 10 women) were prescribed celecoxib monotherapy. The exercise group (n=22: 10 men, 12 women) undertook stretching exercises. Because of drop-outs, the NSAID group (n=15: 7 men, 8 women) and the exercise group (n =18: 8 men, 10 women) were finally analyzed. We applied a visual analog scale, Roland-Morris disability scores, and the 36-Item Short Form Health Survey. We used a paired t-test for within-group analyses and an unpaired t-test for between-group analyses. Pain relief was achieved after 3 months of pharmacotherapy or exercise. Quality of life improved only in the exercise group. Recovery outcomes for the two groups were not significantly different. Efficacy of exercise therapy for strictly defined low back pain was almost equivalent to that of pharmacotherapy and provided better quality of life.

  4. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

    Science.gov (United States)

    Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

    2018-01-01

    Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

  5. A pragmatic investigation into the effects of massage therapy on the self efficacy of multiple sclerosis clients.

    Science.gov (United States)

    Finch, Paul; Bessonnette, Susan

    2014-01-01

    This research was conducted to examine changes in self self-efficacy, (the perception/belief that one can competently cope with a challenging situation) in multiple sclerosis clients following a series of massage therapy treatments. This small practical trial investigated the effects of a pragmatic treatment protocol using a prospective randomized pretest posttest waitlist control design. Self-Efficacy scores were obtained before the first treatment, mid-treatment series, after the last treatment in the series, four weeks after the final treatment and again eight weeks after the final treatment had been received. The intervention involved a series of weekly one hour therapeutic massage treatments conducted over eight weeks and a subsequent eight week follow up period. All treatments were delivered by supervised student therapists in the final term of their two year massage therapy program. Self-Efficacy [SE] was the outcome for the study, measured using the Multiple Sclerosis Self-Efficacy survey [MSSE]. Descriptive statistics for SE scores were assessed and inferential analysis involved the testing of between group differences at each of the measurement points noted above. Statistically significant improvement in self-efficacy was noted between treatment (n = 8) and control (n = 7) groups at mid treatment series (t = 2.32; p massage therapy increases the self-efficacy of clients with multiple sclerosis, potentially resulting in a better overall adjustment to the disease and an improvement in psycho-emotional state. The increase in self-efficacy after 4 weeks of treatment suggests that positive response occurs more rapidly that was previously demonstrated. The improvement in self-efficacy endured 4 weeks after the end of the treatment series, which suggests that massage therapy may have longer term effects on self-efficacy that were not previously noted. Lack of inter group difference at the eight week follow up reinforces the notion that on-going treatment

  6. Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

    LENUS (Irish Health Repository)

    Byrne, A T

    2009-11-03

    Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.

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

    Science.gov (United States)

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

    2013-09-20

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

  8. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  9. Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

    Science.gov (United States)

    Niska, Jared A.; Shahbazian, Jonathan H.; Ramos, Romela Irene; Francis, Kevin P.; Bernthal, Nicholas M.

    2013-01-01

    Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects. PMID:23917317

  10. The Effectiveness of Cognitive-Behavioral Therapy on Alexithymia and Pain Self-Efficacy of Patients with Chronic Pain

    Directory of Open Access Journals (Sweden)

    Sara Saedi

    2016-11-01

    Full Text Available Chronic pain is one of the most common reasons for visit to primary medical centers. Evidences show that cognitive-behavioral therapy is the effective therapy in chronic pains. The present study evaluates the effectiveness of cognitive-behavioral therapy on alexithymia and pains self-efficacy of patients with chronic pain. For this purpose, in a quasi-experimental plan and pre-test and post-test kind with control group, 45 patients with chronic musculoskeletal pain who visited to the therapeutic-sanitary centers in Ahwaz city were selected by using the available sampling method and they were assigned randomly in two experimental and control groups. Groups were tested in terms of alexithymia and self-effectiveness of pain at first. Then behavioral-cognitive training was presented in the time of 8 sessions of 90 minutes to the group and after ending the training program and three month consistency period, both groups were tested in terms of alexithymia and self-efficacy of pain. analyzing data by multivariate covariance method showed that the behavioral-cognitive therapy has been effective on alexithymia and pain intensity of patients with chronic musculoskeletal pain and these effects remain on patients in the high amount in the consistency stage, too. According to the results, behavioral-cognitive therapy causes to increasing the self-efficacy of pain and reducing the alexithymia and harmful effects of pain to the least level by changing nonefficiency behaviors, correction of adverse cognitions and destructive emotions related to pain.

  11. Efficacy of oral moxifloxacin for aerobic vaginitis.

    Science.gov (United States)

    Wang, C; Han, C; Geng, N; Fan, A; Wang, Y; Yue, Y; Zhang, H; Xue, F

    2016-01-01

    The purpose of this study was to investigate the therapeutic efficacy of oral moxifloxacin for aerobic vaginitis (AV). We also identified factors that are associated with therapeutic efficacy. This prospective study enrolled general gynecological outpatients at Tianjin Medical University General Hospital between September 2012 and May 2014. Women diagnosed with AV (n = 102) were recruited. All enrolled women were treated with oral moxifloxacin, 400 mg once daily for 6 days (one course). Therapeutic efficacy was evaluated based on microscopic criteria, and cure rates were calculated. Women who were microscopically improved (but not cured) received a second course of therapy. Women classified with microscopic failure were treated using other strategies. Univariate and multivariate logistic regression analysis was used to identify factors that may be associated with a cure after one course of therapy. After one course of therapy, 65.7 % (67/102) of women were cured, 29.4 % (30/102) of women were improved (but not cured), 4.9 % (5/102) of women failed to respond to the therapy. After two courses of therapy, 85.3 % (87/102) of women were cured, 9.8 % (10/102) of women were improved, 4.9 % (5/102) of women failed to respond to the therapy, and clinical improvement was achieved in additional women. In the multivariate logistic regression analysis, women with a baseline vaginal pH value of vaginal pH value of ≥5.0 (OR, 3.503; 95 % CI, 1.278-9.601). Moxifloxacin is an effective therapeutic option for patients with AV. Most women with AV were cured with one course of moxifloxacin. For those with a higher vaginal pH value of ≥5.0 before treatment, two courses of therapy should be considered.

  12. Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

    Science.gov (United States)

    Warsame, Marian; Atta, Hoda; Klena, John D; Waqar, Butt Ahmed; Elmi, Hussein Haji; Jibril, Ali Mohamed; Hassan, Hassan Mohamed; Hassan, Abdullahi Mohamed

    2009-02-01

    In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia.

  13. Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value.

    Science.gov (United States)

    Laffey, John G; Matthay, Michael A

    2017-08-01

    On the basis of several preclinical studies, cell-based therapy has emerged as a potential new therapeutic for acute respiratory distress syndrome (ARDS). Of the various cell-based therapy options, mesenchymal stem/stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and noninfectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have antiinflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by up-regulating sodium-dependent alveolar fluid clearance. MSCs also have antimicrobial effects mediated by release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis. Phase 2a clinical trials to establish safety in ARDS are in progress, and two phase 1 trials did not report any serious adverse events. Several issues need further study, including: determining the optimal methods for large-scale production, reconstitution of cryopreserved cells for clinical use, defining cell potency assays, and determining the therapeutic potential of conditioned media derived from MSCs. Because ARDS is a heterogeneous syndrome, targeting MSCs to patients with ARDS with a more hyperinflammatory endotype may further enhance their potential for efficacy.

  14. Efficacy of low-level laser therapy on orofacial pain: A literature review

    Directory of Open Access Journals (Sweden)

    Haleh Zokaee

    2018-01-01

    Full Text Available Low-level laser therapy (LLLT is a therapeutic approach to treat orofacial pain using a 600–1000 nm laser with a <500 mW power. The efficacy of LLLT is due to the chemical reactions causing an anti-inflammatory and analgesic effect on the affected regions. The aim of this study is to review the effects of low-level laser application on orofacial pain in the English articles released since 2017. Our search keywords were 'low-level laser therapy, temporomandibular disease (TMD, mucositis and orofacial pain'. The most relevant papers were clinical trial, review and meta-analysis articles. 26 out of 243 searched articles were selected from PubMed, Google Scholar and Science Direct and reviewed. Most of the studies reported the positive role of LLLT on orofacial pain relief regardless of their variable procedures; however, the exact mechanism of action still remains unclear. Some studies indicated that LLLT has significantly reduced pain, reduceamount of clicking and both masseter and temporal muscles activityin TMD. As an overall result, it is concluded that LLLT can be served as a therapeutic method for myofascial pain, mucositis and temporomandibular joint disorders and this is due to its analgesic features.

  15. Comparison of Efficacy of Eye Movement, Desensitization and Reprocessing and Cognitive Behavioral Therapy Therapeutic Methods for Reducing Anxiety and Depression of Iranian Combatant Afflicted by Post Traumatic Stress Disorder

    Science.gov (United States)

    Narimani, M.; Sadeghieh Ahari, S.; Rajabi, S.

    This research aims to determine efficacy of two therapeutic methods and compare them; Eye Movement, Desensitization and Reprocessing (EMDR) and Cognitive Behavioral Therapy (CBT) for reduction of anxiety and depression of Iranian combatant afflicted with Post traumatic Stress Disorder (PTSD) after imposed war. Statistical population of current study includes combatants afflicted with PTSD that were hospitalized in Isar Hospital of Ardabil province or were inhabited in Ardabil. These persons were selected through simple random sampling and were randomly located in three groups. The method was extended test method and study design was multi-group test-retest. Used tools include hospital anxiety and depression scale. This survey showed that exercise of EMDR and CBT has caused significant reduction of anxiety and depression.

  16. Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles.

    Science.gov (United States)

    Peccate, Cécile; Mollard, Amédée; Le Hir, Maëva; Julien, Laura; McClorey, Graham; Jarmin, Susan; Le Heron, Anita; Dickson, George; Benkhelifa-Ziyyat, Sofia; Piétri-Rouxel, France; Wood, Matthew J; Voit, Thomas; Lorain, Stéphanie

    2016-08-15

    In preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro-dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Impact of aging and comorbidity on the efficacy of low-intensity shock wave therapy for erectile dysfunction.

    Science.gov (United States)

    Hisasue, Shin-ichi; China, Toshiyuki; Horiuchi, Akira; Kimura, Masaki; Saito, Keisuke; Isotani, Shuji; Ide, Hisamitsu; Muto, Satoru; Yamaguchi, Raizo; Horie, Shigeo

    2016-01-01

    To evaluate the efficacy of low-intensity shock wave therapy and to identify the predictive factors of its efficacy in Japanese patients with erectile dysfunction. The present study included 57 patients with erectile dysfunction who satisfied all the following conditions: more than 6-months history of erectile dysfunction, sexual health inventory for men score of ≤ 12 without phosphodiesterase type-5 inhibitor, erection hardness score grade 1 or 2, mean penile circumferential change by erectometer assessing sleep related erection of energy shock waves generator (ED1000; Medispec, Gaithersburg, MD, USA). A total of 12 shock wave treatments were applied. Sexual health inventory for men score, erection hardness score with or without phosphodiesterase type-5 inhibitor, and mean penile circumferential change were assessed at baseline, 1, 3 and 6 months after the termination of low-intensity shock wave therapy. Of 57 patients who were assigned for the low-intensity shock wave therapy trial, 56 patients were analyzed. Patients had a median age of 64 years. The sexual health inventory for men and erection hardness score (with and without phosphodiesterase type-5 inhibitor) were significantly increased (P wave therapy (P wave therapy seems to be an effective physical therapy for erectile dysfunction. Age and comorbidities are negative predictive factors of therapeutic response. © 2015 The Japanese Urological Association.

  18. The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is mediated by tumor-specific immunity.

    Directory of Open Access Journals (Sweden)

    Anne Kleijn

    Full Text Available The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy.

  19. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

    Science.gov (United States)

    Cataland, S R; Wu, H M

    2015-06-01

    Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

  1. The therapeutic use of doll therapy in dementia.

    Science.gov (United States)

    Mitchell, Gary; O'Donnell, Hugh

    Over the next 15 years, the number of people with dementia in the UK will increase significantly. There are clear limitations associated with the sole use of pharmacological interventions to address the cognitive decline and related problems that people with dementia and their carers will experience. As a result, health professionals, including nurses, need to consider the development and use of nonpharmacological therapies to help resolve the distress and decline in social function that people with dementia can experience. The use of doll therapy in dementia care appears to be increasing, even though there is limited empirical evidence to support its use and therapeutic effectiveness. It is suggested by advocates of doll therapy that its use can alleviate distress and promote comfort in some people with dementia. Despite these encouraging claims, the theoretical basis for the use of doll therapy in dementia is poorly understood and morally questionable. The purpose of this article is to provide healthcare professionals with a succinct overview of the theory behind the therapeutic use of dolls for people with dementia, a presentation and appraisal of the available empirical evidence and an appreciation of the potential ethical dilemmas that are involved.

  2. Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease.

    Directory of Open Access Journals (Sweden)

    John Marshall

    Full Text Available Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency in the activity of the lysosomal hydrolase α-galactosidase A (α-gal. This deficiency results in accumulation of the glycosphingolipid globotriaosylceramide (GL-3 in lysosomes. Endothelial cell storage of GL-3 frequently leads to kidney dysfunction, cardiac and cerebrovascular disease. The current treatment for Fabry disease is through infusions of recombinant α-gal (enzyme-replacement therapy; ERT. Although ERT can markedly reduce the lysosomal burden of GL-3 in endothelial cells, variability is seen in the clearance from several other cell types. This suggests that alternative and adjuvant therapies may be desirable. Use of glucosylceramide synthase inhibitors to abate the biosynthesis of glycosphingolipids (substrate reduction therapy, SRT has been shown to be effective at reducing substrate levels in the related glycosphingolipidosis, Gaucher disease. Here, we show that such an inhibitor (eliglustat tartrate, Genz-112638 was effective at lowering GL-3 accumulation in a mouse model of Fabry disease. Relative efficacy of SRT and ERT at reducing GL-3 levels in Fabry mouse tissues differed with SRT being more effective in the kidney, and ERT more efficacious in the heart and liver. Combination therapy with ERT and SRT provided the most complete clearance of GL-3 from all the tissues. Furthermore, treatment normalized urine volume and uromodulin levels and significantly delayed the loss of a nociceptive response. The differential efficacies of SRT and ERT in the different tissues indicate that the combination approach is both additive and complementary suggesting the possibility of an improved therapeutic paradigm in the management of Fabry disease.

  3. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

    Science.gov (United States)

    Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

    2015-01-01

    Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  4. Therapeutic drug monitoring of aminoglycosides in neonates

    NARCIS (Netherlands)

    Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

    2009-01-01

    The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to

  5. Therapeutic efficacy of natural prostaglandin in the treatment of pyometra in bitches

    Directory of Open Access Journals (Sweden)

    Basanti Jena

    2013-12-01

    Full Text Available Aim: The current study was done to study the therapeutic effect of natural prostaglandin in treatment of canine pyometra. Materials and Methods: Seven bitches were treated with natural PGF2 á i.e. dinoprost tromethamine at the dose rate of 100 μg/kg body weight subcutaneously once daily for 7 days with supportive therapies. The physiological, haematological and biochemical parameters were studied before (0th day and after treatment (8th day. Therapeutic efficacy was assessed in terms of return of abnormal parameters to either normal or near normal value as compared to the untreated control group, intensity of side effects and post treatment reproductive status. Results: All physiological, haematological and biochemical parameters in the seven treated bitches returned to normal range at the end of treatment. The intensity of side effects was quite severe in the treatment group. Six bitches came to estrus within 2 months of treatment and out of them four conceived on subsequent mating. In rest three bitches there was recurrence of pyometra within 4 months of treatment. Conclusion: Though conception rate of recovered bitches is decreased when compared with that of normal healthy bitches still this treatment protocol can be used successfully in treatment of canine pyometra to conserve the breeding capability of bitches. [Vet World 2013; 6(6.000: 295-299

  6. Therapeutic Efficacy Of Cotecxin (R) alone and Its Combination with ...

    African Journals Online (AJOL)

    The therapeutic efficacy of Cotecxin(R) (Dihydroartemisinin) alone and its combination with diminazene aceturate (Berenil(R)) was studied in rats infected with Federe strain of Trypanosoma brucei brucei. Fifty healthy adult albino rats of both sexes weighing between 100-180g used were divided into five groups (A-E) of 10 ...

  7. Therapeutic Efficacy of Meropenem for Treatment of Experimental Penicillin-Resistant Pneumococcal Meningitis

    Science.gov (United States)

    Kim, Shin-Woo; Jin, Joung Hwa; Kang, Soo Jung; Jung, Sook-In; Kim, Yeon-Sook; Kim, Choon-Kwan; Lee, Hyuck; Oh, Won Sup; Kim, Sungmin; Peck, Kyong Ran

    2004-01-01

    With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in arabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis. PMID:14966336

  8. Therapeutic Media: Treating PTSD with Virtual Reality Exposure Therapy

    Directory of Open Access Journals (Sweden)

    Kathrin Friedrich

    2016-09-01

    Full Text Available Applying head-mounted displays (HMDs and virtual reality scenarios in virtual reality exposure therapy (VRET promises to alleviate combat-related post-traumatic stress disorders (among others. Its basic premise is that, through virtual scenarios, patients may re-engage immersively with situations that provoke anxiety, thereby reducing fear and psychosomatic stress. In this context, HMDs and visualizations should be considered not merely as devices for entertainment purposes or tools for achieving pragmatic objectives but also as a means to instruct and guide patients’ imagination and visual perception in triggering traumatic experiences. Under what perceptual and therapeutic conditions is virtual therapy to be considered effective? Who is the “ideal” patient for such therapy regimes, both in terms of his/her therapeutic indications and his/her perceptual readiness to engage with VR scenarios? In short, how are “treatable” patients conceptualized by and within virtual therapy? From a media-theory perspective, this essay critically explores various aspects of the VRET application Bravemind in order to shed light on conditions of virtual exposure therapy and conceptions of subjectivity and traumatic experience that are embodied and replicated by such HMD-based technology.

  9. Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.

    Directory of Open Access Journals (Sweden)

    Cameron P Simmons

    2007-05-01

    Full Text Available New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs and tested their efficacy for prophylaxis and therapy in a murine model of infection.Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1 in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1. mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1.These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1

  10. Understanding Music's Therapeutic Efficacy with Implications for Why Music Matters

    Science.gov (United States)

    Thram, Diane

    2015-01-01

    In this essay, I focus on how attention to music's therapeutic efficacy is important to the praxial music education philosophy espoused by Elliott and Silverman. I note, despite the use of the term praxis from Aristotle's philosophy dating back to antiquity, there is no mention in Music Matters 2 of what historical evidence tells us about how…

  11. Design of therapeutic vaccines as a novel antibody therapy for cardiovascular diseases.

    Science.gov (United States)

    Nakagami, Hironori

    2017-09-01

    Vaccines are primarily used worldwide as a preventive medicine for infectious diseases and have recently been applied to cancer. We and others have developed therapeutic vaccines designed for cardiovascular diseases that are notably different from previous vaccines. In the case of cancer vaccines, a specific protein in cancer cells is a target antigen, and the activation of cytotoxic T cells (CTL) is required to kill and remove the antigen-presenting cancer cells. Our therapeutic vaccines work against hypertension by targeting angiotensin II (Ang II) as the antigen, which is an endogenous hormone. Therapeutic vaccines must avoid CTL activation and induce the blocking antibodies for Ang II. The goal of our therapeutic vaccine for cardiovascular diseases is to induce the specific antibody response toward the target protein without inducing T-cell or antibody-mediated inflammation through the careful selection of the target antigen, carrier protein and adjuvants. The goal of our therapeutic vaccine is similar to that of antibody therapy. Recently, multiple antibody-based drugs have been developed for cancer, immune-related diseases, and dyslipidemia, which are efficient but expensive. If the effect of a therapeutic vaccine is nearly equivalent to antibody therapy as an alternative approach, the lower medical cost and improvement in drug adherence can be advantages of therapeutic vaccines. In this review, we will describe our concept of therapeutic vaccines for cardiovascular diseases and the future directions of therapeutic vaccines as novel antibody therapies. Copyright © 2017. Published by Elsevier Ltd.

  12. Salmonella-mediated cancer therapy: Roles and potential

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Vu Hong [Dept. of Experimental TherapeuticsBeckman Research Institute of City of Hope, Duarte (United States); Min, Jung Joon [Dept. of Nuclear MedicineChonnam National University Medical School, Gwangju (Korea, Republic of)

    2017-06-15

    The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT.{sub 2}.

  13. Salmonella-mediated cancer therapy: Roles and potential

    International Nuclear Information System (INIS)

    Nguyen, Vu Hong; Min, Jung Joon

    2017-01-01

    The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT._2

  14. EVALUATION OF THE THERAPEUTIC EFFICACY OF HIGH-INTENSITY PULSED-PERIODIC LASER RADIATION (CLINICAL AND EXPERIMENTAL OBSERVATIONS

    Directory of Open Access Journals (Sweden)

    V. V. Sokolov

    2016-01-01

    Full Text Available From the experience of clinical observations, we have shown a high therapeutic effectiveness of the medical laser KULON-MED in: cosmetics, non-cancer inflammatory diseases of the gastrointestinal tract and cancer (cancer of the stomach and colon as at different wavelengths, and with different types of photosensitizers. In the area of anti-tumor photodynamic therapy (PDT, based on experimental studies, we have showed the high antitumor (sarcoma S‑37 effectiveness of the laser (with the inhibition of tumor growth of up to 100% for repetitively pulsed irradiation mode, and for mode fractionation doses laser radiation. In addition, significant differences are shown in the effectiveness of anticancer PDT methods in the application of high-intensity lasers, continuous and pulsed caused fundamental properties of laser radiation characteristics – time structure of the radiation pulses. Thus, for the first time we have shown that the time of high-intensity laser pulses structure significantly affects therapeutic efficacy laser system, and hence on the mechanisms of interaction of laser radiation with biological tissue.

  15. Report on the 1. research coordination meeting on 'Development of therapeutic radiopharmaceuticals based on 177Lu for radionuclide therapy'

    International Nuclear Information System (INIS)

    2006-01-01

    Radionuclide therapy (RNT) employing radiopharmaceuticals labelled with emitting radionuclides is fast emerging as an important part of nuclear medicine. Radionuclide therapy is effectively utilized for bone pain palliation, thus providing significant improvement in quality of life of patients suffering from pain resulting from bone metastasis. Targeting primary diseases by using specific carrier molecules labelled with radionuclides is also widely investigated and efficacious products have been emerging for the treatment of Lymphoma and Neuroendocrine tumours. In order to ensure the wider use of radiopharmaceuticals, it is essential to carefully consider the choice of radionuclides that together with the carrier molecules will give suitable pharmacokinetic properties and therapeutic efficacy. The criteria for the selection of a radionuclide for radiotherapy are suitable decay characteristics and amenable chemistry. However, the practical considerations in selecting a radionuclide for targeted therapy are availability in high radionuclidic purity as well as high specific activity and low production cost and comfortable delivery logistics. 177 Lu is one of the isotopes emerging as a clear choice for therapy. Worldwide, the isotope is under investigation for approximately 30 different clinical applications, including treatment of colon cancer, metastatic bone cancer, non-Hodgkin's lymphoma, and lung cancer. 177 Lu decays with a half-life of 6.71 d by emission of particles with E max of 497 keV (78.6%), 384 keV (9.1%) and 176 keV (12.2%). It also emits photons of 113 keV (6.4%) and 208 keV (11%), that are ideally suited for imaging the in-vivo localization and dosimetric calculations applying a gamma camera. The physical half-life of 177 Lu is comparable to that of 131 I, the most widely used therapeutic radionuclide. The long halflife of 177 Lu provides logistic advantage for production, QA/QC of the products as well as feasibility to supply the products to places

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

    Directory of Open Access Journals (Sweden)

    Xi Lin

    2017-11-01

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

  17. Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges.

    Science.gov (United States)

    Köhler, Stephan; Guhn, Anne; Betzler, Felix; Stiglmayr, Christian; Brakemeier, Eva-Lotta; Sterzer, Philipp

    2017-01-01

    In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT) by so-called "third-wave" strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to "classical CBT," some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a) acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT), (b) the concept of "limited reparenting" as used in Schema Therapy (ST), and (c) disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP). On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies.

  18. Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Stephan Köhler

    2017-11-01

    Full Text Available In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT by so-called “third-wave” strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to “classical CBT,” some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT, (b the concept of “limited reparenting” as used in Schema Therapy (ST, and (c disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP. On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies.

  19. Efficacy and safety of statins and exercise combination therapy compared to statin monotherapy in patients with dyslipidaemia: A systematic review and meta-analysis.

    Science.gov (United States)

    Gui, Ya-Jun; Liao, Cai-Xiu; Liu, Qiong; Guo, Yuan; Yang, Tao; Chen, Jing-Yuan; Wang, Ya-Ting; Hu, Jia-Hui; Xu, Dan-Yan

    2017-06-01

    Background Statin treatment in association with physical exercise can substantially reduce mortality in dyslipidaemic individuals. However, the available data to compare the efficacy and safety of statins and exercise combination therapy with statin monotherapy are limited. Design Systematic review and meta-analysis. Methods We systematically searched PubMed, Embase and the Cochrane Library from database inception until December 2016. We included randomised and non-randomised studies that compared the efficacy and safety of statins and exercise combination therapy with statin monotherapy in patients with dyslipidaemia. Standardised mean differences were calculated and pooled by means of fixed effects models. The risk of bias and heterogeneity among trials was also assessed. Seven articles were assessed in terms of the efficacy of therapy and 13 from the viewpoint of therapeutic safety. Results In terms of efficacy, statins and exercise combination decreased the incidence of diabetes mellitus, improved insulin sensitivity and inflammation, but caused no change in lipid profile compared to statins alone. In terms of safety, statins and exercise combination increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced myopathy, chronic exercise training prior to statin treatment could counteract statin-induced adverse effects in skeletal muscle. Conclusion Statins and exercise combination therapy is more effective than statin monotherapy in terms of insulin sensitivity, inflammation and exercise capacity. The small number of studies warrants the need for more randomised controlled trials evaluating the efficacy and safety of combination therapy.

  20. Efficacy and safety of infliximab induction therapy in Crohn's Disease in Central Europe - a Hungarian nationwide observational study

    Directory of Open Access Journals (Sweden)

    Simon László

    2009-09-01

    Full Text Available Abstract Background Infliximab (IFX has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's disease (CD, with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary. Methods During a 6-year-period, beginning in 2000, a total of 363 CD patients were treated with IFX as induction therapy (5 mg/kg IFX infusions given at week 0, 2 and 6 at eleven centers in Hungary in this observational study. Data analysis included patient demographics, important disease parameters and the outcome of IFX induction therapy. Results Three hundred and sixty three patients (183 women and 180 men were treated with IFX since 2000. Mean age was 33.5 ± 11.2 years and the mean duration of disease was 6.7 ± 6.1 years. The population included 114 patients (31.4% with therapy-refractory CD, 195 patients (53.7% with fistulas, 16 patients (4.4% with both therapy-refractory CD and fistulas, and 26 patients (7.2% with steroid dependent CD. Overall response rate was 86.2% (313/363. A higher response rate was observed in patients with shorter disease duration (p = 0.05, OR:0.54, 95%CI:0.29-0.99 and concomitant immunosuppressant therapy (p = 0.05, OR: 2.03, 95%CI:0.165-0.596. Concomitant steroid treatment did not enhance the efficacy of IFX induction therapy. Adverse events included 34 allergic reactions (9.4%, 17 delayed type hypersensitivity (4.7%, 16 infections (4.4%, and 3 malignancies (0.8%. Conclusion IFX was safe and effective treatment in this cohort of Hungarian CD patients. Based on our experience co-administration of immunosuppressant therapy is suggested in patients receiving IFX induction therapy. However, concomitant steroid treatment did not enhanced the efficacy of IFX induction therapy.

  1. Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

    Directory of Open Access Journals (Sweden)

    Xie S

    2011-10-01

    Full Text Available Shuyu Xie1,*, Baoliang Pan1,*, Baoxin Shi2, Zhuangzhi Zhang2, Xu Zhang2, Ming Wang1, Wenzhong Zhou11Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2Veterinary Research Institute, Xinjiang Academy of Animal Science, Xinjiang, People’s Republic of China *These authors contributed equally to this study Abstract: Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and -11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91

  2. Therapeutic approaches for celiac disease

    Science.gov (United States)

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  3. Music therapy career aptitude and generalized self-efficacy in music therapy students.

    Science.gov (United States)

    Lim, Hayoung A; Befi, Cathy M

    2014-01-01

    While the Music Therapy Career Aptitude Test (MTCAT) provides a measure of student aptitude, measures of perceived self-efficacy may provide additional information about a students' suitability for a music therapy career. As a first step in determining whether future studies examining combined scores from the MTCAT and the Generalized Self-Efficacy (GSE) scale would be useful to help predict academic success in music therapy, we explored the internal reliability of these two measures in a sample of undergraduate students, and the relationship (concurrent validity) of the measures to one another. Eighty undergraduate music therapy students (14 male; 66 female) completed the MTCAT and GSE. To determine internal reliability we conducted tests of normality and calculated Cronbach's Coefficient Alpha for each measure. Pearson correlation coefficients were calculated to ascertain the strength of the relationship between the MTCAT and GSE. MTCAT scores were normally distributed and had high internal consistency (Cronbach's α = 0.706). GSE scores were not normally distributed, but had high internal consistency (Cronbach's α = 0.748). The correlation coefficient analysis revealed that MTCAT and GSE scores were moderately correlated ((r = 0.426, p music therapy students; however, a more complete picture of student suitability for music therapy may be determined by administering the GSE alongside the MTCAT. Future studies are needed to determine whether combined MTCAT and GSE scores can be used to predict student success in an undergraduate music therapy program. © the American Music Therapy Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Efficacy of transdiagnostic cognitive behaviour therapy for anxiety disorders

    DEFF Research Database (Denmark)

    Reinholt, Nina; Krogh, Jesper

    2014-01-01

    Transdiagnostic approaches to cognitive behaviour therapy (TCBT) of anxiety disorders have drawn increasing interest and empirical testing over the past decade. In this paper, we review evidence of the overall efficacy of TCBT for anxiety disorders, as well as TCBT efficacy compared with wait......-list, treatment-as-usual, and diagnosis-specific cognitive behaviour therapy (CBT) controls. A total of 11 studies reporting 12 trials (n = 1933) were included in the systematic review. Results from the meta-analysis of 11 trials suggest that TCBT was generally associated with positive outcome; TCBT patients did...

  5. Therapeutic efficacy of cyclic home elemental enteral alimentation in Crohn's disease: Japanese cooperative Crohn's disease study.

    Science.gov (United States)

    Matsueda, K; Shoda, R; Takazoe, M; Hiwatashi, N; Bamba, T; Kobayashi, K; Saito, T; Terano, A; Yao, T

    1995-11-01

    Crohn's disease (CD) often flares up and requires frequent hospitalization and/or surgery. Cyclic home elemental enteral alimentation (C-HEEA) was developed to prevent flare-up of CD and to minimize patient hospitalization. However, its therapeutic efficacy has not been studied in a large patient population. Therefore, questionnaires were sent to members of the Inflammatory Bowel Disease (IBD) Research Group of Japan to evaluate the therapeutic efficacy of C-HEEA and to define the factors that may affect the efficacy of the treatment. Data for 410 patients (C-HEEA-treated n = 322; drug-treated n = 88) were collected from 29 institutions and analysis showed the following results. The cumulative remission and non-hospitalization rates of the C-HEEA treated group were significantly higher than the rates of the drug-treated group in all patients and in those with ileitis and ileo-colitis (P < 0.0001, P < 0.001, and P < 0.01, respectively), but no significant difference was noted in patients with colitis. Cumulative remission and non-hospitalization rates were also influenced by the daily calorie content of the elemental diet (ED); more than 1200 kcal of the ED per day was found to be more effective than lower amounts to maintain remission and to prevent hospitalization. The therapeutic efficacy of C-HEEA was shown to be superior to that of drug treatment in patients with CD with ileal involvement, and it is suggested that more than 1200kcal per day should be supplied by the ED to enhance its therapeutic efficacy.

  6. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, Karan [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia); Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M. [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Atkins, Gerald J., E-mail: gerald.atkins@adelaide.edu.au [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Losic, Dusan, E-mail: dusan.losic@adelaide.edu.au [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia)

    2016-12-01

    There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements. - Highlights: • Ti wire with titania nanotubes (TNTs) are proposed as ‘in-bone’ therapeutic implants. • 3D cell culture model is used to confirm therapeutic efficacy of drug releasing implants. Osteoblasts migrated and firmly attached to the TNTs and the micro-scale cracks. • Tailorable drug loading from few nanograms to several hundred

  7. IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

    Science.gov (United States)

    Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

    2017-11-01

    The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  8. Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

    Science.gov (United States)

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

    Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Applications of Nanotechnology in Bladder Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jong-Wei Hsu

    2012-01-01

    Full Text Available Effective therapies can prevent superficial bladder cancer from developing into muscle-invasive stage or more severe stages which require radical cystectomy and negatively affect life quality. In terms of therapeutic approaches against superficial bladder cancer, intravesical (regional therapy has several advantages over oral (systemic therapy. Though urologists can directly deliver drugs to bladder lesions by intravesical instillation after transurethral resection, the efficacy of conventional drug delivery is usually low due to the bladder permeability barrier and bladder periodical discharge. Nanoparticles have been well developed as pharmaceutical carriers. By their versatile properties, nanoparticles can greatly improve the interactions between urothelium and drugs and also enhance the penetration of drugs into urothelium with lesions, which dramatically improves therapeutic efficacy. In this review, we discuss the advances of nanotechnology in bladder cancer therapy by different types of nanoparticles with different encapsulating materials.

  10. Efficacy of postexposure therapy against glanders in mice.

    Science.gov (United States)

    Waag, David M

    2015-04-01

    Burkholderia mallei, the causative agent of glanders, is a CDC Tier 1 Select Agent for which there is no preventive vaccine and antibiotic therapy is difficult. In this study, we show that a combination of vaccination using killed cellular vaccine and therapy using moxifloxacin, azithromycin, or sulfamethoxazole-trimethoprim can protect BALB/c mice from lethal infection even when given 5 days after infectious challenge. Vaccination only, or antibiotic therapy only, was not efficacious. Although antibiotics evaluated experimentally can protect when given before or 1 day after challenge, this time course is not realistic in the cases of natural infection or biological attack, when the patient seeks treatment after symptoms develop or after a biological attack has been confirmed and the agent has been identified. Antibiotics can be efficacious after a prolonged interval between exposure and treatment, but only if the animals were previously vaccinated. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

    Science.gov (United States)

    Cohan, Stanley

    2016-01-01

    Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

  12. Neoadjuvant Therapy in Patients with Pancreatic Cancer: A Disappointing Therapeutic Approach?

    International Nuclear Information System (INIS)

    Zimmermann, Carolin; Folprecht, Gunnar; Zips, Daniel; Pilarsky, Christian; Saeger, Hans Detlev; Grutzmann, Robert

    2011-01-01

    Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed

  13. Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

    Directory of Open Access Journals (Sweden)

    Mario Gimona

    2017-06-01

    Full Text Available Extracellular vesicles (EVs derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

  14. Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev; Ahmad, Shamim; Berrong, Zuzana; Okoev, Grigori; Matevosyan, Adelaida; Razavi, Ghazaleh Shoja E; Petit, Robert; Gupta, Seema; Mkrtichyan, Mikayel; Khleif, Samir N

    2017-08-15

    We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4 + and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment. Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model. We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations. We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model. We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals. We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4 + and CD8 + T cells along with a decrease of inhibitory cells. To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy. We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall

  15. A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug.

    Science.gov (United States)

    Li, Jingwen; Lyv, Zhonglin; Li, Yanli; Liu, Huan; Wang, Jinkui; Zhan, Wenjun; Chen, Hong; Chen, Huabing; Li, Xinming

    2015-05-01

    Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Efficacy of secondary isoniazid preventive therapy among ...

    African Journals Online (AJOL)

    Objective. To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among goldminers working in South Africa. Design. An observational study. Methods. The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort had received secondary preventive ...

  17. Cognitive-behavioral therapy for body dysmorphic disorder: a review of its efficacy

    Science.gov (United States)

    Prazeres, Angélica M; Nascimento, Antônio L; Fontenelle, Leonardo F

    2013-01-01

    The aim of this study was to review the efficacy of different methods of cognitive and/or behavioral therapies used to treat body dysmorphic disorder. We evaluated all case series, open studies, controlled trials, and meta-analyses of cognitive and/or behavioral treatment approaches to body dysmorphic disorder published up to July 2012, identified through a search in the PubMed/Medline, PsycINFO, ISI Web of Knowledge, and Scopus databases. Our findings indicate that individual and group cognitive behavioral therapies are superior to waiting list for the treatment of body dysmorphic disorder. While the efficacy of cognitive therapy is supported by one controlled trial, utility of behavioral therapy is suggested by one open study and one controlled relapse prevention follow-up study. There is a pressing need to conduct head-to-head studies, with appropriate, active, control treatment groups, in order to examine further the efficacy of cognitive and/or behavioral therapies for body dysmorphic disorder. PMID:23467711

  18. Medical Therapy of Acromegaly

    Directory of Open Access Journals (Sweden)

    U. Plöckinger

    2012-01-01

    Full Text Available This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs, dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

  19. Predicting and influencing voice therapy adherence using social-cognitive factors and mobile video.

    Science.gov (United States)

    van Leer, Eva; Connor, Nadine P

    2015-05-01

    Patient adherence to voice therapy is an established challenge. The purpose of this study was (a) to examine whether adherence to treatment could be predicted from three social-cognitive factors measured at treatment onset: self-efficacy, goal commitment, and the therapeutic alliance, and (b) to test whether the provision of clinician, self-, and peer model mobile treatment videos on MP4 players would influence the same triad of social cognitive factors and the adherence behavior of patients. Forty adults with adducted hyperfunction with and without benign lesions were prospectively randomized to either 4 sessions of voice therapy enhanced by MP4 support or without MP4 support. Adherence between sessions was assessed through self-report. Social cognitive factors and voice outcomes were assessed at the beginning and end of therapy. Utility of MP4 support was assessed via interviews. Self-efficacy and the therapeutic alliance predicted a significant amount of adherence variance. MP4 support significantly increased generalization, self-efficacy for generalization, and the therapeutic alliance. An interaction effect demonstrated that MP4 support was particularly effective for patients who started therapy with poor self-efficacy for generalization. Adherence may be predicted and influenced via social-cognitive means. Mobile technology can extend therapy to extraclinical settings.

  20. Efficacy of Helicobacter pylori eradication therapies in Korea: A systematic review and network meta-analysis.

    Science.gov (United States)

    Jung, Yoon Suk; Park, Chan Hyuk; Park, Jung Ho; Nam, Eunwoo; Lee, Hang Lak

    2017-08-01

    The efficacy of Helicobacter pylori eradication regimens may depend on the country where the studies were performed because of the difference in antibiotic resistance. We aimed to analyze the efficacy of H. pylori eradication regimens in Korea where clarithromycin resistance rate is high. We searched for all relevant randomized controlled trials published until November 2016 that investigated the efficacy of H. pylori eradication therapies in Korea. A network meta-analysis was performed to calculate the direct and indirect estimates of efficacy among the eradication regimens. Forty-three studies were identified through a systematic review, of which 34 studies, published since 2005, were included in the meta-analysis. Among 21 included regimens, quinolone-containing sequential therapy for 14 days (ST-Q-14) showed the highest eradication rate (91.4% [95% confidence interval [CI], 86.9%-94.4%] in the intention-to-treat [ITT] analysis). The eradication rate of the conventional triple therapy for 7 days, standard sequential therapy for 10 days, hybrid therapy for 10-14 days, and concomitant therapy for 10-14 days was 71.1% (95% CI, 68.3%-73.7%), 76.2% (95% CI, 72.8%-79.3%), 79.4% (95% CI, 75.5%-82.8%), and 78.3% (95% CI, 75.3%-80.9%), respectively, in the ITT analysis. In the network meta-analysis, ST-Q-14 showed a better comparative efficacy than the conventional triple therapy, standard sequential therapy, hybrid therapy, and concomitant therapy. In addition, tolerability of ST-Q-14 was comparable to those regimens. In Korea, ST-Q-14 showed the highest efficacy in terms of eradication and a comparable tolerability, compared to the results reported for the conventional triple therapy, standard sequential therapy, hybrid therapy, and concomitant therapy. © 2017 John Wiley & Sons Ltd.

  1. Therapeutic efficacy and mechanism of action of ethamsylate, a long-standing hemostatic agent.

    Science.gov (United States)

    Garay, Ricardo P; Chiavaroli, Carlo; Hannaert, Patrick

    2006-01-01

    Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. This review covers more than 40 years of intensive clinical and fundamental research with ethamsylate. First, we summarize the large medical literature concerning its clinical efficacy. Of these, well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding. Second, we review the numerous investigations performed to elucidate the mechanism of action of ethamsylate. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. Recent studies showed that ethamsylate promotes P-selectin-dependent, platelet adhesive mechanisms. Finally, we compare ethamsylate with other recent hemostatic agents. It is suggested that the place of ethamsylate as a hemostatic agent is that of a mild but well-tolerated drug, particularly useful in dysfunctional uterine bleeding when contraception is not needed.

  2. The Therapeutic Relationship and Cognitive Behavioural Therapy: A Case Study of an Adolescent Girl With Depression

    Directory of Open Access Journals (Sweden)

    Cheryl Joy Easterbrook

    2017-02-01

    Full Text Available The therapeutic relationship in Cognitive Behavioural Therapy (CBT has been argued to play an essential role in positive outcomes in therapy. However, it is described as necessary and yet, secondary to technique, often receiving little attention in the training of CBT therapists. This case study explores a trainee psychologist’s experience of finding difficulty in feeling authentic and the application of CBT techniques with her client. This difficulty informed the research question; what is the value of the therapeutic relationship in CBT? A hermeneutic approach with a strong emphasis on phenomenology, is used to explore the therapeutic process and the therapeutic relationship that developed between therapist and client. Qualitative descriptions of 11 sessions are divided into themes, these are discussed in relation to what happened in therapy, and are then discussed further regarding discovery and process into the therapeutic relationship. Conclusions from this case study could possibly reveal the value of the therapeutic relationship when working from a CBT approach, and how it seemed to enable the client to achieve her goal in therapy.

  3. Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chen-Yu; Oborn, Bradley M.; Guatelli, Susanna; Allen, Barry J. [Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia); Illawarra Cancer Care Centre, Wollongong, New South Wales 2522, Australia and Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia)

    2012-03-15

    Purpose: Metastatic melanoma lesions experienced marked regression after systemic targeted alpha therapy in a phase 1 clinical trial. This unexpected response was ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor regression is achieved by killing endothelial cells (ECs) in tumor capillaries and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT by building up the testing Monte Carlo microdosimetric models. Methods: Geant4 was adapted to simulate the spatial nonuniform distribution of the alpha emitter {sup 213}Bi. The intraluminal model was designed to simulate the background dose to normal tissue capillary ECs from the nontargeted activity in the blood. The perivascular model calculates the EC dose from the activity bound to the perivascular cancer cells. The key parameters are the probability of an alpha particle traversing an EC nucleus, the energy deposition, the lineal energy transfer, and the specific energy. These results were then applied to interpret the clinical trial. Cell survival rate and therapeutic gain were determined. Results: The specific energy for an alpha particle hitting an EC nucleus in the intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the average probability of traversal in these models is 2.7% and 1.1%, the mean specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that the source distribution has a significant impact on the dose. Using the melanoma clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be 3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a maximum therapeutic gain of about 180 and validate the TAVAT concept. Conclusions: TAVAT can deliver a cytotoxic dose to tumor capillaries without being toxic to normal tissue capillaries.

  4. Comparing the therapeutic efficacies of third-generation cephalosporins and broader-spectrum β-lactams as appropriate empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia: a propensity score matched analysis.

    Science.gov (United States)

    Lee, Chung-Hsun; Hsieh, Chih-Chia; Hong, Ming-Yuan; Hung, Yuan-Pin; Ko, Wen-Chien; Lee, Ching-Chi

    2017-05-01

    In this study, the therapeutic efficacy of third-generation cephalosporins (3GCs) was compared with that of broader-spectrum β-lactams (BSBLs) [fourth-generation cephalosporins (4GCs) and carbapenems] as empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia. Compared with those in the 3GC group (n = 477), a significantly higher proportion of patients in the BSBL group (n = 141) had initial presentation with severe sepsis or septic shock, critical illness (Pitt bacteraemia score ≥4) at bacteraemia onset and fatal co-morbidities (McCabe classification). For propensity score matching, 318 of the 477 patients in the 3GC group were matched with 106 patients in the BSBL group with the closest propensity scores on the basis of five independent predictors of 28-day mortality. After appropriate matching, no significant differences were observed in major baseline characteristics between the 3GC and BSBL groups in terms of causative micro-organism, bacteraemia severity, major source of bacteraemia, major co-morbidities and severity of co-morbidity. Consequently, the early clinical failure rate (12.9% vs. 12.3%; P = 0.87), bacteraemia severity (Pitt bacteraemia score ≥4; 4.6% vs. 8.2%; P = 0.17) at Day 3, and 3-day (3.8% vs. 7.5%; P = 0.11) and 28-day (13.2% vs. 17.0%; P = 0.33) crude mortality rates between the two groups were similar. These data suggest that the efficacy of 3GCs is similar to that of 4GCs or carbapenems when used as empirical antimicrobial therapy for community-onset Enterobacteriaceae bacteraemia. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  5. Therapeutic efficacy of different Hemodialysis prescriptions in canine azotemia

    Directory of Open Access Journals (Sweden)

    Ekta Atul Thakkar

    2014-12-01

    Full Text Available Aim: The aim was to determine therapeutic efficacy of different Hemodialysis prescriptions in canine azotemia. Materials and Methods: Patients (n=9 with acute onset of renal dysfunction or chronic patients with superimposed acute factor (component or patients with known chronic nature of the disease were dialyzed with Fresenius 4008S hemodialysis machine after jugular catheterization. Patients were randomly divided into two groups, one group (n=3 was dialyzed every day and second (n=4 was dialyzed on alternate days. The patients were evaluated for following parameters to compare the efficacy of the dialysis prescription: Urea reduction ratio (URR, creatinine reduction ratio (CRR, Kt/V, time averaged concentration of urea (TAC urea. Result and Discussion: Increasing both dialysis frequency and duration is the superior dialysis schedule. Patient dialyzed every day with total processed blood volume 1.79 L/Kg for 4 h 26 min/session had the lowest TAC of 36.82 mg/dl, thereby was considered it as a better prescription.

  6. Therapeutic Effects of Extinction Learning as a Model of Exposure Therapy in Rats

    Science.gov (United States)

    Fucich, Elizabeth A; Paredes, Denisse; Morilak, David A

    2016-01-01

    Current treatments for stress-related psychiatric disorders, such as depression and posttraumatic stress disorder (PTSD), are inadequate. Cognitive behavioral psychotherapies, including exposure therapy, are an alternative to pharmacotherapy, but the neurobiological mechanisms are unknown. Preclinical models demonstrating therapeutic effects of behavioral interventions are required to investigate such mechanisms. Exposure therapy bears similarity to extinction learning. Thus, we investigated the therapeutic effects of extinction learning as a behavioral intervention to model exposure therapy in rats, testing its effectiveness in reversing chronic stress-induced deficits in cognitive flexibility and coping behavior that resemble dimensions of depression and PTSD. Rats were fear-conditioned by pairing a tone with footshock, and then exposed to chronic unpredictable stress (CUS) that induces deficits in cognitive set-shifting and active coping behavior. They then received an extinction learning session as a therapeutic intervention by repeated exposure to the tone with no shock. Effects on cognitive flexibility and coping behavior were assessed 24 h later on the attentional set-shifting test or shock-probe defensive burying test, respectively. Extinction reversed the CUS-induced deficits in cognitive flexibility and coping behavior, and increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex (mPFC) of stress-compromised rats, suggesting a role for activity-dependent protein synthesis in the therapeutic effect. Inhibiting protein synthesis by microinjecting anisomycin into mPFC blocked the therapeutic effect of extinction on cognitive flexibility. These results demonstrate the utility of extinction as a model by which to study mechanisms underlying exposure therapy, and suggest these mechanisms involve protein synthesis in the mPFC, the further study of which may identify novel therapeutic targets. PMID:27417516

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

    Science.gov (United States)

    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 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.

  8. [Relationship experiences and therapeutic outcome in inpatient psychotherapy].

    Science.gov (United States)

    Sammet, Isa; Staats, Herrmann; Schauenburg, Henning

    2004-01-01

    Inpatient psychotherapy includes the patient's manifold contacts with different therapists, nurses and fellow patients. The present study investigated the association between these multiple relationships and therapy outcome. Pre-post measures of symptom load (Brief Symptom Inventory), interpersonal problems (IIP) and self-efficacy (SEB) were used to define three groups with positive (N=129), unchanged (N=44) or negative (N=40) outcome. These groups were compared 1) by their alliance with an individual therapist, their relationship to the therapeutic team, their experience of cohesion and climate concerning fellow patients in the ward (measured weekly by the "Stationserfahrungsbogen" SEB), and 2) by their differences in mean correlations between the courses of relationship experiences and symptom load. Cohesion and relationship to the therapeutic team were not associated with therapy outcome. Therapeutic alliance with the individual therapist and climate among fellow patients turned out to be moderate indicators of the therapeutic outcome. It is recommended to include these process parameters systematically into the process diagnostics of inpatient psychotherapy.

  9. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  10. Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects.

    Directory of Open Access Journals (Sweden)

    Laura S Stone

    Full Text Available Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α2-adrenergic receptors (α2ARs. Analgesics acting at α2ARs and opioid receptors (ORs frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α2AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C. Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic

  11. The Efficacy of Cardiac Anti-miR-208a Therapy Is Stress Dependent

    NARCIS (Netherlands)

    Eding, Joep E C; Demkes, Charlotte J; Lynch, Joshua M; Seto, Anita G; Montgomery, Rusty L; Semus, Hillary M; Jackson, Aimee L; Isabelle, Marc; Chimenti, Stefano; van Rooij, Eva

    2017-01-01

    MicroRNAs (miRNAs) are important regulators of biology and disease. Recent animal efficacy studies validate the therapeutic benefit of miRNA modulation and underscore the therapeutic value of miRNA-targeting oligonucleotides. However, whether disease conditions (stress) influence the pharmacological

  12. Efficacy of supplemental anti-inflammatory therapy with fenspiride in chronic obstructive and nonobstructive bronchitis.

    Science.gov (United States)

    Volkova, L I; Budkova, A A; Filonova, N N; Khristolyubova, E I; Kutuzova, E B; Koroleva, N V; Radzivil, T T; Aminova, Z R; Chuchalin, A G

    2005-01-01

    The objective of this randomised, nonblind study was to assess the efficacy of fenspiride as complementary anti-inflammatory therapy in combination with ipratropium bromide in patients with chronic bronchitis (CB). A comparison was made with ipratropium bromide alone, the generally accepted standard therapy for CB. The study population comprised 20 patients with chronic obstructive bronchitis (COB) and 60 patients without signs of obstruction. Fifty-one males (64%) and 29 females (36%) aged from 25 to 65 years were studied over a 6-month treatment period. Combined therapy with fenspiride (160 mg/day) and ipratropium bromide (160 mug/day) was prescribed to 39 patients (28 with CB and 11 with COB) for 6 months, and monotherapy with ipratropium bromide (160 microg/day) was prescribed for 41 patients (32 with CB and nine with COB). The combined therapy group had a reduced intensity of dyspnoea, improvements in sputum nature and quantity of exudation, and a reduced intensity of coughing. The monotherapy group showed reductions in sputum exudation and cough intensity. Improvements in lung respiratory function were observed in both groups, but were greater in the combined therapy group of patients. Reduced cytosis, percentage and absolute content of neutrophils, and absolute content of lymphocytes and eosinophils in induced sputum were observed with CB patients in the combined therapy group. A reduced content of lymphocytes and an increase in macrophages were observed with CB patients in the monotherapy group. A significant decline in tumour necrosis factor (TNF)-alpha content in sputum was observed with both therapeutic regimens, although a statistically significant decline in serum TNFalpha (10.85 ng/L to 5.58 ng/L; p = 0.03) and reduced interleukin-8 in sputum (311.94 ng/L to 122.02 ng/L; p = 0.027) were observed with patients given combined therapy. The study showed greater efficacy of long-term treatment with fenspiride and ipratropium bromide compared with

  13. Efficacy of Low Level Laser Therapy After Hand Flexor Tendon Repair

    Science.gov (United States)

    Ayad, K. E.; El Gohary, H. M.; Abd Elrahman, M.; Abd El Mejeed, S. F.; Bekheet, A. B.

    2009-09-01

    Flexor tendon injury is a common problem requiring suturing repair followed by early postoperative mobilization. Muscle atrophy, joint stiffness, osteoarthritis, infection, skin necrosis, ulceration of joint cartilage and tendocutaneous adhesion are familiar complications produced by prolonged immobilization of surgically repaired tendon ruptures. The purpose of this study was to clarify the importance of low level laser therapy after hand flexor tendon repair in zone II. Thirty patients aging between 20 and 40 years were divided into two groups. Patients in group A (n = 15) received a conventional therapeutic exercise program while patients in group B (n = 15) received low level laser therapy combined with the same therapeutic exercise program. The results showed a statistically significant increase in total active motion of the proximal and distal interphalangeal joints as well as maximum hand grip strength at three weeks and three months postoperative, but improvement was more significant in group B. It was concluded that the combination of low level laser therapy and early therapeutic exercises was more effective than therapeutic exercises alone in improving total active motion of proximal and distal interphalangeal joints and hand grip strength after hand flexor tendon repair.

  14. Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

    Directory of Open Access Journals (Sweden)

    Yuya Yoshimoto

    Full Text Available PURPOSE: There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL activity. METHODS AND MATERIALS: C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD was defined as the time (in days for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. RESULTS: In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days and prolonged median survival time (MST to 59 days (versus 28 days in the non-irradiated group. CD8(+ cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days. Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days, while anti-FR4 and anti-GITR antibodies did not affect efficacy. CONCLUSIONS: Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4

  15. Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model

    Science.gov (United States)

    Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

    2014-01-01

    Purpose There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. Methods and Materials C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. Results In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Conclusions Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a

  16. The efficacy of cognitive behavioral therapy for Chinese people: A meta-analysis.

    Science.gov (United States)

    Ng, Ting Kin; Wong, Daniel Fu Keung

    2018-07-01

    Over the past decade, cognitive behavioral therapy has been applied to an increasingly wider range of disorders and problems in Chinese societies. However, no meta-analysis has been conducted to synthesize the studies on cognitive behavioral therapy for Chinese clients. The purpose of this meta-analytic study was to examine the overall efficacy of cognitive behavioral therapy for Chinese people. A literature search was conducted using electronic databases, including Web of Science, PsycINFO and PubMed. Pooled mean effect sizes were calculated using the random-effects model. The literature search identified 55 studies with 6763 Chinese participants. The overall short-term effect of cognitive behavioral therapy on the primary outcome was medium in size. Effect sizes were medium for anxiety, depression/well-being and caregiving stress and small for psychotic symptoms and addictive behaviors. The effects of cognitive behavioral therapy on process variables, dysfunctional thoughts and coping, were in the small range. The overall longer-term effect of cognitive behavioral therapy on the primary outcome was medium in size. Moderator analyses showed that the short-term effect was stronger for culturally adapted cognitive behavioral therapy than for unadapted cognitive behavioral therapy. Type of primary outcome, type of control group, recruitment method, study design, the format of delivery and region were found to moderate the efficacy of cognitive behavioral therapy. The findings of this study provide evidence for the overall efficacy of cognitive behavioral therapy for Chinese people and the benefit of cultural adaptation of cognitive behavioral therapy to Chinese culture.

  17. Report on the 1. research coordination meeting on 'Development of therapeutic radiopharmaceuticals based on {sup 177}Lu for radionuclide therapy'

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    Radionuclide therapy (RNT) employing radiopharmaceuticals labelled with emitting radionuclides is fast emerging as an important part of nuclear medicine. Radionuclide therapy is effectively utilized for bone pain palliation, thus providing significant improvement in quality of life of patients suffering from pain resulting from bone metastasis. Targeting primary diseases by using specific carrier molecules labelled with radionuclides is also widely investigated and efficacious products have been emerging for the treatment of Lymphoma and Neuroendocrine tumours. In order to ensure the wider use of radiopharmaceuticals, it is essential to carefully consider the choice of radionuclides that together with the carrier molecules will give suitable pharmacokinetic properties and therapeutic efficacy. The criteria for the selection of a radionuclide for radiotherapy are suitable decay characteristics and amenable chemistry. However, the practical considerations in selecting a radionuclide for targeted therapy are availability in high radionuclidic purity as well as high specific activity and low production cost and comfortable delivery logistics. {sup 177}Lu is one of the isotopes emerging as a clear choice for therapy. Worldwide, the isotope is under investigation for approximately 30 different clinical applications, including treatment of colon cancer, metastatic bone cancer, non-Hodgkin's lymphoma, and lung cancer. {sup 177}Lu decays with a half-life of 6.71 d by emission of particles with E{sub max} of 497 keV (78.6%), 384 keV (9.1%) and 176 keV (12.2%). It also emits photons of 113 keV (6.4%) and 208 keV (11%), that are ideally suited for imaging the in-vivo localization and dosimetric calculations applying a gamma camera. The physical half-life of {sup 177}Lu is comparable to that of {sup 131}I, the most widely used therapeutic radionuclide. The long halflife of {sup 177}Lu provides logistic advantage for production, QA/QC of the products as well as feasibility to

  18. Shangri-La revisited: an exploration of therapeutic efficacy among intentional communities.

    Science.gov (United States)

    Francis, T L

    1992-04-01

    Field and literature surveys were employed to explore the therapeutic efficacy of a reportedly common set of social structures found among some Intentional Communities (ICs). Substance misuse served as an example of social problems plausibly related to the examined social structures, which included: (1) meditative practices, (2) progressive education, (3) holistic health practices, (4) nutritional diet, (5) open policy making, (6) equally or equitably shared resources, (7) integrating membership processes, and (8) environmental concern. The field survey identified and examined 11 such ICs, and the literature exploration concerning the structures found that they appear to be therapeutic. Future research should focus on refining the study of structural and antecedent variables and on finding relationships between these variables to communities in the larger society.

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  20. Therapeutic enhancement of protective immunity during experimental leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Senad Divanovic

    2011-09-01

    Full Text Available Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+ T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx, a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+ T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

  1. Therapeutic Songwriting in Music Therapy Part I

    DEFF Research Database (Denmark)

    Baker, Felicity; Wigram, Tony; Stott, Dave

    2008-01-01

    Songwriting as therapeutic intervention has received increasing attention in the field of music therapy over the past decade however much of the publications focus on clinical outcomes rather than methods of practice. This paper, part of a two-part research report into trends in the clinical...... practice of songwriting, aims to describe the most frequently employed goal areas across a range of clinical populations and compare these findings with the published literature. Responses to a 21-question on-line survey were obtained from 477 professional music therapists practicing in 29 countries which...... of songwriting clinical practice and the frequency with which songwriting is employed in practice. The data highlights that songwriting is frequently employed in developmental disability and ASD practice, with reports on songwriting with these diagnostic groups being underrepresented in the music therapy...

  2. pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

    Science.gov (United States)

    Feng, Qianhua; Zhang, Wanxia; Yang, Xuemei; Li, Yuzhen; Hao, Yongwei; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

    2018-03-01

    Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO 2 generation and HMME release with spatial/temporal resolution. Afterward, the CO 2 bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO 2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Therapeutic efficacy of uterine arterial embolization for intractable uterine hemorrhage

    International Nuclear Information System (INIS)

    Liu Lang; Lu Lianwei; Ke Mengjia; Zhao Ru'en; Zeng Shaolan

    2010-01-01

    Objective: To evaluate the therapeutic efficacy of uterine arterial embolization (UAE) for intractable uterine hemorrhage. Methods: 16 patients with intractable uterine hemorrhage underwent bilateral UAE after failed conventional conservative treatment. Results: Uterine hemorrhage ceased within 12 hours in 15 patients (93.8%) after bilateral super-selective UAE. Internal iliac artery embolization was performed on one patient (6.2%) and hysterectomy was eventually carried out because of recurrent hemorrhage. Conclusion: UAE is a rapid and effective treatment method obviating hysterectomy for intractable uterine hemorrhage. (authors)

  4. Gestalt Therapy and the Therapeutic Presence of Fritz Perls: An Interview with Claudio Naranjo

    Directory of Open Access Journals (Sweden)

    Iván Ramírez Calderón

    2011-01-01

    Full Text Available As exceptional witness and participant in the origin and development of the Gestalt therapy, Claudio Naranjo considers in this interview the cha- racteristics of this form of therapy, doing so from his work and his personal encounter with the man and the therapeutic figure of Fritz Perls. In the interview the experiential base and the therapeutic change elements are established, along with the therapeutic attitude, and the holistic conception of the person; also, the contrasts among academic psychology, the spiritual dimension of human beings, and the therapist’s intuition in the help rela- tionship are highlighted.

  5. The effectiveness of drama therapy on preparation for diagnostic and therapeutic procedures in children suffering from cancer

    Directory of Open Access Journals (Sweden)

    Ľubica Ilievová

    2015-10-01

    Full Text Available Introduction: The integral part of the treatment of pediatric oncological patients is a range of diagnostic and therapeutic procedures. These procedures are often associated with the fear and anxiety of the suffering child. We investigated whether a psychological preparation through drama therapy and the therapeutic puppet may reduce the anxiety related to diagnostic and therapeutic procedures in the preschool or early school children suffering from cancer.Methods: Twenty consecutive pediatric patients of preschool and early school age, with the diagnosis of lymphoblastic leukemia, were included in the study. The patients were alternatingly assigned to experimental or control group, and subjected or not subjected to drama therapy, respectively. We measured the changes in heart rate, blood pressure and respiratory rate as indicators of anxiety and fear, before and after the diagnostic or therapeutic procedures.Results: Heart rate, blood pressure, and respiratory rate in pediatric oncological patients before and after the diagnostic or therapeutic procedure were significantly lower in the experimental group of patients.Conclusion: Our results show that psychological preparation using drama therapy and therapeutic puppet reduced the fear and anxiety related to diagnostic or therapeutic procedures in pediatric oncological patients.Key words: drama therapy; therapeutic puppet; children; oncology; psychology 

  6. Loss of Efficacy to Spinal Cord Stimulator Therapy: Clinical Evidence and Possible Causes.

    Science.gov (United States)

    Aiudi, Christopher M; Dunn, Roger Y; Burns, Sara M; Roth, Sarah A; Opalacz, Arissa; Zhang, Yi; Chen, Lucy; Mao, Jianren; Ahmed, Shihab U

    2017-11-01

    Although spinal cord stimulation (SCS) therapy has been shown to be efficacious in various pain conditions, the ability for SCS therapy to maintain long-term efficacy has been questioned. The purpose of this study was to investigate whether a loss of efficacy (LOE) phenomenon exists with SCS therapy and to investigate if this phenomenon is more apparent in any specific patient population. A retrospective, observation chart review was conducted to evaluate the patient response to SCS therapy over time. Massachusetts General Hospital, Boston, Massachusetts. Patients who received a SCS at the Massachusetts General Hospital, between January 1, 2002 and December 31, 2012, were invited to participate. A total of 62 patients were included in this study. Various models were created to analyze pain score changes over time using 2-tailed statistical analysis. Additionally, one-way ANOVA and Pearson's chi-square tests were used to determine if certain patient characteristics were associated with LOE. Compared to the visual analog scale (VAS) score at one month after device implantation, pain scores increased 1.95 points after 2 years (95% CI: 1.06 to 2.84, P = patient characteristic that helped predict LOE. However, patients who have significant baseline response to therapy may be more likely to experience LOE. Spinal cord stimulation, chronic pain, retrospective study, low frequency electrical stimulation, efficacy, chronic pain therapy.

  7. Cognitive-behavioral therapy for body dysmorphic disorder: a review of its efficacy

    Directory of Open Access Journals (Sweden)

    Prazeres AM

    2013-02-01

    Full Text Available Angélica M Prazeres,1 Antônio L Nascimento,1 Leonardo F Fontenelle1,21Anxiety and Depression Research Program, Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 2Department of Psychiatry and Mental Health, Universidade Federal Fluminense, Hospital Universitário Antonio Pedro, Niterói, BrazilAbstract: The aim of this study was to review the efficacy of different methods of cognitive and/or behavioral therapies used to treat body dysmorphic disorder. We evaluated all case series, open studies, controlled trials, and meta-analyses of cognitive and/or behavioral treatment approaches to body dysmorphic disorder published up to July 2012, identified through a search in the PubMed/Medline, PsycINFO, ISI Web of Knowledge, and Scopus databases. Our findings indicate that individual and group cognitive behavioral therapies are superior to waiting list for the treatment of body dysmorphic disorder. While the efficacy of cognitive therapy is supported by one controlled trial, utility of behavioral therapy is suggested by one open study and one controlled relapse prevention follow-up study. There is a pressing need to conduct head-to-head studies, with appropriate, active, control treatment groups, in order to examine further the efficacy of cognitive and/or behavioral therapies for body dysmorphic disorder.Keywords: dysmorphophobia, behavioral therapy, cognitive therapy, literature review

  8. Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

    Science.gov (United States)

    Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

    2016-07-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells

  9. Efficacy of pentavalent antimoniate intralesional infiltration therapy for cutaneous leishmaniasis: A systematic review.

    Directory of Open Access Journals (Sweden)

    Nayara Castelano Brito

    15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4-92.4% when compared with IL-Sbv alone (53.3%, 95%IC 46.1-66%, OR: 3.14 (95%CI 1.1-8.9, p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66-85%. In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49-73% versus 82% (95%CI 70-89%.By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates.Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications.

  10. Comparing the Effectiveness of Cognitive Behavioral Therapy and Hypnosis Therapy Pain Self-Efficacy and Pain Severity in Girls with Primary Dysmenorrhea

    OpenAIRE

    F Farshbaf Manei Sefat; A Abolghasemi; U Barahmand; N Hajloo

    2017-01-01

    ABSTRACT   Background & aim: Menstruation as an important issue in adolescence and menstrual pain is a common problem in adolescents. Regarding the relationship between pain severity and  pain self-efficacy, this study aimed to investigate and compare the efficacy of cognitive-behavioral therapy and hypnosis therapy on pain and pain self-efficacy in girls with primary dysmenorrhea.   Methods: The method of research is Quasi experimental and research design is pretes...

  11. Efficacy of music therapy in the neuropsychiatric symptoms of dementia: systematic review

    Directory of Open Access Journals (Sweden)

    Mariângela Aparecida Rezende Aleixo

    Full Text Available ABSTRACT Objective A large number of psychosocial interventions in dementia are based on music activities and music therapy interventions. We aim at assessing the efficacy of music therapy in the neuropsychiatric symptoms of people with dementia. Methods This systematic review is according to the methodology suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched for articles in PubMed, Web of Knowledge Cross Search, Cochrane Library, Scopus and Lilacs/Bireme databases published from 2005 to 2016. The search keywords included “early onset” and “late onset” combined with “dementia”, “Alzheimer”, “vascular dementia”, “mixed dementia”, “frontotemporal dementia”, “neuropsychiatric symptoms”, “behavioral disturbances”, “behavioral and psychological symptoms of dementia” and “music therapy”. The studies were categorized according to its efficacy on the decline of neuropsychiatric symptoms and improvement of cognitive function, quality of life and well-being. Results We selected 12 out of 257 papers. Music therapy interventions were applied individually or in group setting, using active or receptive technique. In general, studies indicated the efficacy of music therapy on the decline of depression, agitation and anxiety. There were heterogeneity of interventions, methodological design and instruments of evaluation among the studies. Conclusions Although there are reports of the efficacy of music therapy on the decline of neuropsychiatric symptoms of dementia, the area still needs randomized studies aimed at the solution of important methodological problems like the lack of standardized approaches.

  12. Therapeutic drug monitoring of infliximab : performance evaluation of three commercial ELISA kits

    NARCIS (Netherlands)

    Schmitz, E.M.H.; van de Kerkhof, D.; Hamann, D.; van Dongen, J.L.J.; Kuijper, P.H.M.; Brunsveld, L.; Scharnhorst, V.; Broeren, M.A.C.

    2016-01-01

    BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX, Remicade®) can aid to optimize therapy efficacy. Many assays are available for this purpose. However, a reference standard is lacking. Therefore, we evaluated the analytical performance, agreement and clinically relevant differences

  13. Antibiotic therapy versus appendicectomy in uncomplicated acute appendicitis in terms of efficacy

    International Nuclear Information System (INIS)

    Zaidi, M.A.; Nazeer, T.B.; Aziz, O.B.A.; Asad, T.; Dar, Z.S.

    2017-01-01

    Objective: To compare antibiotic therapy and appendectomy in uncomplicated acute appendicitis in terms of efficacy. Study Design: Randomized controlled trial. Place and Duration of Study: Surgical Ward Forward Treatment Centre (FTC), 5 Mountain Medical Battalion Forward Kahuta Azad Jammu Kashmir (AJK), from Oct 2011 to Mar 2013. Material and Methods: A total of 103 patients with clinical diagnosis of acute appendicitis (AA) were admitted during the duration of study and divided into two groups by consecutive sampling. The antibiotic group consisted of 51 patients who received intravenous antibiotics for 48 hours and oral antibiotics for another 8 days. The appendectomy group comprised of 52 patients who all underwent standard appendectomy. All the patients were followed up at 1 month and 1 year for assessing efficacy and post treatment complications. Results: The efficacy of antibiotic treatment is 90.625 percent as compared to appendectomy which was 88.46 percent (p=0.759) at 1 month follow up after treatment. At one year post treatment, the comparison between the efficacy of antibiotic therapy (71.87 percent) and appendectomy (87.14 percent) remains statistically insignificant (p=0.055). Conclusion: Antibiotic therapy is comparable to appendectomy in AA in terms of efficacy at 1 month and 1 year post treatment. (author)

  14. Efficacy of chemotherapy after hormone therapy for hormone receptor-positive metastatic breast cancer.

    Science.gov (United States)

    Mori, Ryutaro; Nagao, Yasuko

    2014-01-01

    According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor-positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy-effective and hormone therapy-ineffective cases. Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2-positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy-ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy. The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of

  15. A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, Christina M., E-mail: wilhelmc@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Snider, Thomas H., E-mail: snidert@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Babin, Michael C., E-mail: babinm@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Jett, David A., E-mail: jettd@ninds.nih.gov [National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892 (United States); Platoff, Gennady E., E-mail: platoffg@niaid.nih.gov [National Institutes of Health/National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892 (United States); Yeung, David T., E-mail: dy70v@nih.gov [National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892 (United States)

    2014-12-15

    The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl{sub 2}, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. - Highlights: • First comprehensive evaluation of leading AChE oxime reactivators • All oximes are compared against current U.S. therapy 2-PAM Cl. • Relative therapeutic oxime efficacies against OP CWNA and pesticides • Contribution to more effective

  16. Cognitive Behavior Therapy: A Comparison of Group and Individual Formats.

    Science.gov (United States)

    Shaffer, Carolyn S.; And Others

    The relative efficacy of both group and individual cognitive behavior therapeutic approaches in treating anxiety and depression are evaluated and then compared to an interpersonal group therapy approach. The two major hypotheses are that group cognitive behavior therapy is at least as effective as individual cognitive behavior therapy, and that…

  17. Therapeutic orientations, professional efficacy, and burnout among substance abuse social workers in Israel.

    Science.gov (United States)

    Tartakovsky, Eugene; Kovardinsky, Slava

    2013-07-01

    This study investigates the therapeutic orientations of substance abuse social workers and the relationship between these orientations and burnout. Ninety-two social workers who provided outpatient treatment to people suffering from substance-related disorders in Israel participated in the study. The results obtained demonstrated that the substance abuse social workers adhere more to the psychodynamic and ecosystemic therapeutic orientations than to the cognitive-behavioral orientation. A greater adherence to the cognitive-behavioral orientation was associated with a higher sense of professional efficacy; a greater adherence to the psychodynamic orientation was associated with a higher level of exhaustion; and greater adherence to the ecosystemic orientation was associated with lower levels of exhaustion and cynicism. Female social workers reported lower levels of exhaustion and cynicism. The cognitive-behavioral orientation mediated the connection between the social workers' experience in the field of substance abuse and two dimensions of burnout-exhaustion and professional efficacy. Significance of the findings for improving the well-being of substance abuse social workers and for the advancement of psychosocial services is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Magnetic Seizure Therapy for Unipolar and Bipolar Depression: A Systematic Review

    OpenAIRE

    Cretaz, Eric; Brunoni, Andr? R.; Lafer, Beny

    2015-01-01

    Objective. Magnetic seizure therapy (MST) is a novel, experimental therapeutic intervention, which combines therapeutic aspects of electroconvulsive therapy (ECT) and transcranial magnetic stimulation, in order to achieve the efficacy of the former with the safety of the latter. MST might prove to be a valuable tool in the treatment of mood disorders, such as major depressive disorder (MDD) and bipolar disorder. Our aim is to r...

  19. Assessing delivery and quantifying efficacy of small interfering ribonucleic acid therapeutics in the skin using a dual-axis confocal microscope

    Science.gov (United States)

    Ra, Hyejun; Gonzalez-Gonzalez, Emilio; Smith, Bryan R.; Gambhir, Sanjiv S.; Kino, Gordon S.; Solgaard, Olav; Kaspar, Roger L.; Contag, Christopher H.

    2010-05-01

    Transgenic reporter mice and advances in imaging instrumentation are enabling real-time visualization of cellular mechanisms in living subjects and accelerating the development of novel therapies. Innovative confocal microscope designs are improving their utility for microscopic imaging of fluorescent reporters in living animals. We develop dual-axis confocal (DAC) microscopes for such in vivo studies and create mouse models where fluorescent proteins are expressed in the skin for the purpose of advancing skin therapeutics and transdermal delivery tools. Three-dimensional image volumes, through the different skin compartments of the epidermis and dermis, can be acquired in several seconds with the DAC microscope in living mice, and are comparable to histologic analyses of reporter protein expression patterns in skin sections. Intravital imaging with the DAC microscope further enables visualization of green fluorescent protein (GFP) reporter gene expression in the skin over time, and quantification of transdermal delivery of small interfering RNA (siRNA) and therapeutic efficacy. Visualization of transdermal delivery of nucleic acids will play an important role in the development of innovative strategies for treating skin pathologies.

  20. Psychometric Properties of an Instrument Derived from the Intentional Relationship Model: The SelfEfficacy for Recognizing Clients’ Interpersonal Characteristics (N-SERIC

    Directory of Open Access Journals (Sweden)

    Victoria C. Ritter

    2018-04-01

    Full Text Available Background: The Intentional Relationship Model conceptualizes the therapeutic use of self in occupational therapy. To increase motivation for and success in establishing therapeutic relationships, therapists need self-efficacy for using the self in therapeutic practice. However, attempts to combine this model with self-efficacy theory are rare, and instruments by which to measure self-efficacy for therapeutic use of self are in a developing stage. This study aimed to examine the factor structure and internal consistency of the Norwegian Self-Efficacy for Recognizing Interpersonal Characteristics (N-SERIC. Methods: Occupational therapy students (n = 100 from two education programs completed the instrument and sociodemographic information. The factor structure was examined with Principal Components Analysis (PCA, and internal consistency was assessed with Cronbach’s α and inter-item correlations. Results: The PCA revealed that all N-SERIC items belonged to the same latent factor, with factor loadings ranging between 0.75 and 0.89. The internal consistency of the scale items was high (Cronbach’s α = 0.96. Conclusions: The N-SERIC scale is unidimensional and the items have very high internal consistency. Thus, the scale sum score can be useful for occupational therapy research and audits focusing on interpersonal aspects of practice.

  1. 99mTc-HYNIC-Annexin A5 in Oncology: Evaluating Efficacy of Anti-Cancer Therapies

    International Nuclear Information System (INIS)

    Schaper, Frédéric L.W.V.J.; Reutelingsperger, Chris P.

    2013-01-01

    Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT). Structural changes, if present, become apparent 1–2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99m Tc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1–4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome-based medicine, applicable to all cancer patients

  2. Promoting Efficacy Research on Functional Analytic Psychotherapy

    Science.gov (United States)

    Maitland, Daniel W. M.; Gaynor, Scott T.

    2012-01-01

    Functional Analytic Psychotherapy (FAP) is a form of therapy grounded in behavioral principles that utilizes therapist reactions to shape target behavior. Despite a growing literature base, there is a paucity of research to establish the efficacy of FAP. As a general approach to psychotherapy, and how the therapeutic relationship produces change,…

  3. PUVA therapy is preferable to UVB phototherapy in the management of HIV-associated dermatoses

    Energy Technology Data Exchange (ETDEWEB)

    Morison, W.L. [Johns Hopkins Univ., Baltimore, MD (United States)

    1996-08-01

    Both methoxsalen plus UVA (PUVA) therapy and UVB phototherapy are commonly used in the management of human immunodeficiency virus-associated dermatoses but UVB phototherapy appears to be the preferred treatment. There are several considerations, in particular therapeutic efficacy and therapeutic profile, which suggest that PUVA therapy might be more effective. This needs to be established in clinical trials. (Author).

  4. Therapeutic efficacy and toxicity of {sup 225}Ac-labelled vs. {sup 213}Bi-labelled tumour-homing peptides in a preclinical mouse model of peritoneal carcinomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Essler, Markus; Gaertner, Florian C.; Blechert, Birgit; Senekowitsch-Schmidtke, Reingard; Seidl, Christof [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Neff, Frauke [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-04-15

    Targeted delivery of alpha-particle-emitting radionuclides is a promising novel option in cancer therapy. We generated stable conjugates of the vascular tumour-homing peptide F3 both with {sup 225}Ac and {sup 213}Bi that specifically bind to nucleolin on the surface of proliferating tumour cells. The aim of our study was to determine the therapeutic efficacy of {sup 225}Ac-DOTA-F3 in comparison with that of {sup 213}Bi-DTPA-F3. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were determined via clonogenic assays. The therapeutic efficacy of both constructs was assayed by repeated treatment of mice bearing intraperitoneal MDA-MB-435 xenograft tumours. Therapy was monitored by bioluminescence imaging. Nephrotoxic effects were analysed by histology. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were 53 kBq/ml and 67 Bq/ml, respectively. The median survival of control mice treated with phosphate-buffered saline was 60 days after intraperitoneal inoculation of 1 x 10{sup 7} MDA-MB-435 cells. Therapy with 6 x 1.85 kBq of {sup 225}Ac-DOTA-F3 or 6 x 1.85 MBq of {sup 213}Bi-DTPA-F3 prolonged median survival to 95 days and 97 days, respectively. While F3 labelled with short-lived {sup 213}Bi (t{sub 1/2} 46 min) reduced the tumour mass at early time-points up to 30 days after treatment, the antitumour effect of {sup 225}Ac-DOTA-F3 (t{sub 1/2} 10 days) increased at later time-points. The difference in the fraction of necrotic cells after treatment with {sup 225}Ac-DOTA-F3 (43%) and with {sup 213}Bi-DTPA-F3 (36%) was not significant. Though histological analysis of kidney samples revealed acute tubular necrosis and tubular oedema in 10-30% of animals after treatment with {sup 225}Ac-DOTA-F3 or {sup 213}Bi-DTPA-F3, protein casts were negligible (2%), indicating only minor damage to the kidney. Therapy with both {sup 225}Ac-DOTA-F3 and {sup 213}Bi-DTPA-F3 increased survival of mice with peritoneal carcinomatosis. Mild renal toxicity of both

  5. Therapeutic Inertia in the New Landscape of Multiple Sclerosis Care

    Directory of Open Access Journals (Sweden)

    Gustavo Saposnik

    2018-03-01

    Full Text Available The landscape of multiple sclerosis (MS treatment is constantly changing. Significant heterogeneity exists in the efficacy and risks associated with these therapies. Therefore, clinicians have the challenge to tailor treatment based on several factors (disease activity level, risk of progression, individual patient preferences and characteristics, personal expertise, etc., to identify the optimal balance between safety and efficacy. However, most clinicians have limited education in decision-making and formal training in risk management. Together, these factors may lead to therapeutic inertia (TI; defined as the absence of treatment initiation or intensification when therapeutic goals are unmet. TI may lead to suboptimal treatments choices, worse clinical outcomes, and more disability. This article provides a succinct overview on factors influencing TI in MS care.

  6. Targeting PEPT1: a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy.

    Science.gov (United States)

    Gong, Yanxia; Wu, Xiang; Wang, Tao; Zhao, Jia; Liu, Xi; Yao, Zhi; Zhang, Qingyu; Jian, Xu

    2017-06-20

    Proton coupled oligopeptide transporter 1 (PEPT1) is a member of the peptide transporter superfamily and plays important role in the absorption of oligopeptide and peptidomimetic drugs. Our previous research verified that PEPT1 expressed specifically in human Hepatocellular carcinoma (HCC) tissue and cell lines and showed potential transport activity to be a new candidate of the tumor therapeutic target. In this study, we aim to explore the feasibility of a novel tumor target therapeutic strategy: Targeting PEPT1 to improve the antitumor efficacy of Doxorubicin in human HCC therapy. First, Doxorubicin was conjugated with Glycylglycylglycine (Gly-Gly-Gly) - a tripeptide which was known as the substrate of PEPT1 and characterized by HPLC and MS successfully. Doxorubicin-tripeptide conjugate was then observed to clarify the target delivery by PEPT1 and the antitumor effect on human hepatocarcinoma in vivo and in vitro. Furthermore, the improvement of the toxic and side effect of Doxorubicin after conjugation was also evaluated by some biochemical tests. Our results reveal that targeting PEPT1 may contribute to the efficient delivery of Doxorubicin to hepatocarcinoma cells and the reduction of drug toxicity. PEPT1 has the prospect to be a novel target of HCC therapy.

  7. Efficacy of six weeks infrared radiation therapy on chronic low back ...

    African Journals Online (AJOL)

    Background: Infrared radiation therapy is a modality widely used in Physiotherapy for the management of pain. The objective of this study was to determine the efficacy of six weeks infrared radiation therapy on pain intensity and functional disability index in subjects suffering from non- specific low back pain. Methods: The ...

  8. Aging and stem cell therapy: AMPK as an applicable pharmacological target for rejuvenation of aged stem cells and achieving higher efficacy in stem cell therapy.

    Science.gov (United States)

    Khorraminejad-Shirazi, Mohammadhossein; Farahmandnia, Mohammad; Kardeh, Bahareh; Estedlal, Alireza; Kardeh, Sina; Monabati, Ahmad

    2017-10-19

    In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy. By utilizing an effective therapeutic intervention for aged stem cells, stem cell therapy can become more promising for future application. mTORC1 inhibition is a practical approach to preserve the stem cell pool. In this article, we review the dynamic interaction between sirtuin (silent mating type information regulation 2 homolog) 1, AMPK, and mTORC1. We propose that using AMPK activators such as 5-aminoimidazole-4-carboxamide ribonucleotide, A769662, metformin, and oxidized nicotinamide adenine dinucleotide (NAD + ) are practical ways to be employed for achieving better optimized results in stem cell-based transplantation therapies. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  9. The Efficacy of Danshen Injection as Adjunctive Therapy in Treating Angina Pectoris: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shao, Huikai; Li, Mengsi; Chen, Fuchao; Chen, Lianghua; Jiang, Zhengjin; Zhao, Lingguo

    2018-04-01

    During the last 40 years, Danshen injection has been widely used as an adjunctive therapy for angina pectoris in China, but its efficacy is not yet well defined. The objective of this study was to verify the efficacy of Danshen injection as adjunctive therapy in treating angina pectoris. The major databases including PubMed, Cochrane Library, Sino-Med, Medline, Embase, Google Scholar, China National Knowledge Infrastructure, Wanfang Databases, Chinese Scientific Journal Database, Chinese Biomedical Literature Database and the Chinese Science Citation Database were systematically searched for the published randomised controlled trials (RCTs) on Danshen injection until April 2016. Meta-analysis was conducted on the primary outcomes (i.e., the improvements in symptoms and electrocardiography (ECG)). The quality of the included RCTs was evaluated with the M scoring system (the refined Jadad scale). Based on the quality, year of publication and sample size of RCTs, sensitivity analysis and subgroup analysis were performed in this study. Ten RCTs, including 944 anginal patients, were identified in this meta-analysis. Compared with using antianginal agents (β-blockers, calcium antagonists, nitrates, etc.) alone, Danshen injection combined with antianginal agents had a better therapeutic effect in symptom improvement (odds ratio [OR], 3.66; 95% confidence interval [CI]: 2.50-5.36) and in ECG improvement (OR, 3.25; 95% CI: 1.74-6.08). This study showed that Danshen injection as adjunctive therapy seemed to be more effective than antianginal agents alone in treating angina pectoris. However, more evidence is needed to accurately evaluate the efficacy of Danshen injection because of the low methodological quality of the included RCTs. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  10. 99mTc-HYNIC-Annexin A5 in Oncology: Evaluating Efficacy of Anti-Cancer Therapies

    Directory of Open Access Journals (Sweden)

    Chris P. Reutelingsperger

    2013-05-01

    Full Text Available Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT. Structural changes, if present, become apparent 1–2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99mTc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1–4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome-based medicine, applicable to all cancer patients.

  11. The Therapeutic Relationship in Cognitive-Behavioral Therapy and Pharmacotherapy for Anxious Youth

    Science.gov (United States)

    Cummings, Colleen M.; Caporino, Nicole E.; Settipani, Cara A.; Read, Kendra L.; Compton, Scott N.; March, John; Sherrill, Joel; Piacentini, John; McCracken, James; Walkup, John; Ginsburg, Golda; Albano, Anne Marie; Rynn, Moira; Birmaher, Boris; Sakolsky, Dara; Gosch, Elizabeth; Keeton, Courtney; Kendall, Philip C.

    2014-01-01

    Objective Examine the therapeutic relationship with cognitive-behavioral therapists and with pharmacotherapists for youth from the Child/Adolescent Anxiety Multimodal Study (CAMS; Walkup et al., 2008). The therapeutic relationship was examined in relation to treatment outcomes. Method Participants were 488 youth (ages 7-17; 50% male) randomized to cognitive-behavioral therapy (CBT; Coping cat), pharmacotherapy (SRT; sertraline), their combination, or pill placebo. Participants met DSM-IV criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. The therapeutic relationship was assessed by youth-report at weeks 6 and 12 of treatment using the Child's Perception of Therapeutic Relationship scale. Outcome measures (Pediatric Anxiety Rating Scale; Clinical Global Impressions Scales) were completed by Independent Evaluators blind to condition. Results For youth who received CBT only, a stronger therapeutic relationship predicted positive treatment outcome. In contrast, the therapeutic relationship did not predict outcome for youth receiving sertraline, combined treatment, or placebo. Conclusions A therapeutic relationship may be important for anxious youth who receive CBT alone. PMID:23750468

  12. Qualitative Study of the Therapeutic Relationship in Speech and Language Therapy: Perspectives of Adults with Acquired Communication and Swallowing Disorders

    Science.gov (United States)

    Fourie, Robert J.

    2009-01-01

    Background: Considerations of the negotiated therapeutic relationship in speech and language therapy are somewhat scarce, with specific therapeutic factors generally framed from psycholinguistic, behavioural, or neurological perspectives. Aims: To explore the therapeutic relationship in speech and language therapy, focusing on the personal…

  13. Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

    Directory of Open Access Journals (Sweden)

    Thomas L. Chenevert

    2002-10-01

    Full Text Available The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator of treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a non-volumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.

  14. Male emotional intimacy: how therapeutic men's groups can enhance couples therapy.

    Science.gov (United States)

    Garfield, Robert

    2010-03-01

    Men's difficulty with emotional intimacy is a problem that therapists regularly encounter in working with heterosexual couples in therapy. The first part of this article describes historical and cultural factors that contribute to this dilemma in men's marriages and same-sex friendships. Therapeutic men's groups can provide a corrective experience for men, helping them to develop emotional intimacy skills while augmenting their work in couples therapy. A model for such groups is presented, including guidelines for referral, screening, and collaboration with other therapists. Our therapeutic approach encourages relationship-based learning through direct emotional expression and supportive feedback. We emphasize the development of friendship skills, core attributes of friendship (connection, communication, commitment, and cooperation) that contribute to emotional intimacy in men's relationships. Case examples are included to illustrate how this model works in clinical practice, as well as specific suggestions for further study that could lead to a more evidence-based practice.

  15. Therapeutic Silencing of Bcl-2 by Systemically Administered siRNA Nanotherapeutics Inhibits Tumor Growth by Autophagy and Apoptosis and Enhances the Efficacy of Chemotherapy in Orthotopic Xenograft Models of ER (− and ER (+ Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ibrahim Tekedereli

    2013-01-01

    Full Text Available Bcl-2 is overexpressed in about a half of human cancers and 50–70% of breast cancer patients, thereby conferring resistance to conventional therapies and making it an excellent therapeutic target. Small interfering RNA (siRNA offers novel and powerful tools for specific gene silencing and molecularly targeted therapy. Here, we show that therapeutic silencing of Bcl-2 by systemically administered nanoliposomal (NL-Bcl-2 siRNA (0.15 mg siRNA/kg, intravenous twice a week leads to significant antitumor activity and suppression of growth in both estrogen receptor-negative (ER(− MDA-MB-231 and ER-positive (+ MCF7 breast tumors in orthotopic xenograft models (P < 0.05. A single intravenous injection of NL-Bcl-2-siRNA provided robust and persistent silencing of the target gene expression in xenograft tumors. NL-Bcl-2-siRNA treatment significantly increased the efficacy of chemotherapy when combined with doxorubicin in both MDA-MB-231 and MCF-7 animal models (P < 0.05. NL-Bcl-2-siRNA treatment-induced apoptosis and autophagic cell death, and inhibited cyclin D1, HIF1α and Src/Fak signaling in tumors. In conclusion, our data provide the first evidence that in vivo therapeutic targeting Bcl-2 by systemically administered nanoliposomal-siRNA significantly inhibits growth of both ER(− and ER(+ breast tumors and enhances the efficacy of chemotherapy, suggesting that therapeutic silencing of Bcl-2 by siRNA is a viable approach in breast cancers.

  16. Therapeutic benefits of Nanoparticles in Stroke

    Directory of Open Access Journals (Sweden)

    Stavros ePanagiotou

    2015-05-01

    Full Text Available Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy. The delivery of many potentially therapeutic neuroprotectants and diagnostic compounds to the brain is restricted by the blood-brain barrier (BBB. Nanoparticles (NPs, which can readily cross the BBB without compromising its integrity, have immense applications in the treatment of ischemic stroke. In this review, potential uses of NPs will be summarized for the treatment of ischemic stroke. Additionally, an overview of targeted NPs will be provided, which could be used in the diagnosis of stroke. Finally, the potential limitations of using NPs in medical applications will be mentioned. Since the use of NPs in stroke therapy is now emerging and is still in development, this review is far from comprehensive or conclusive. Instead, examples of NPs and their current use will be provided, as well as the potentials of NPs in an effort to meet the high demand of new therapies in stroke.

  17. Therapeutic efficacy of bipolar radiofrequency thermotherapy for patients with chronic prostatitis: a retrospective analysis of 26 cases.

    Science.gov (United States)

    Lim, Ju Young; Shim, Seung Bum; Yoo, Dong Hoon; Park, Young Woong; Kim, Jong Yeon; Noh, Joon Hwa

    2012-07-01

    Chronic prostatitis (CP) does not yet have a universally successful therapy. Alternative treatments including thermotherapy have been adopted in the multimodal management of pain and voiding dysfunction. We retrospectively analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for patients who were unsatisfied with conventional medication for CP. A retrospective study between October 2009 and September 2010 of 26 patients who were under 50 years old and diagnosed with CP (National Institutes of Health [NIH]-category III) was performed. Twenty patients were diagnosed with inflammatory CP (NIH-category IIIa) and the rest with noninflammatory CP (NIH-category IIIb). We used the Tempro system at an intraprostatic temperature of 55℃ for 50 minutes with a medium heating rate. All patients also completed the NIH-Chronic Prostatitis Symptom Index (CPSI) before and after treatment. In the patients diagnosed with CP, the mean serum prostate-specific antigen (PSA) level was 0.9±0.3 ng/ml, the prostate volume was 27.1±5.5 g, and the average score for all 3 domains on the NIH-CPSI significantly decreased. The total scores decreased from 19.8±7.1 to 11.1±7.0, the pain domain decreased from 8.6±3.1 to 4.8±3.1, the voiding symptom domain decreased from 5.1±1.8 to 2.9±1.8, and the effect on the quality of life decreased from 6.1±2.2 to 3.4±2.2 (pthermotherapy for patients with CP intractable to conventional medication can provide significant improvement in the NIH-CPSI. Large, randomized controlled trials will also be required to confirm the efficacy of this therapy.

  18. Quality of life, treatment satisfaction and efficacy of non-biological systemic therapies in patients with plaque psoriasis: study protocol for a prospective observational study.

    Science.gov (United States)

    Fink, Christine; Schank, Timo E; Trenkler, Nina; Uhlmann, Lorenz; Schäkel, Knut

    2017-06-30

    Psoriasis vulgaris often leads to a significant impaired quality of life and dissatisfaction with the existing therapeutic approaches. However, patients' quality of life and treatment satisfaction are of utmost importance, since it is positively related to therapy adherence and encourages patient's compliance. The study described herein evaluates the quality of life, treatment satisfaction and efficacy during the initial 6 months of treatment with a non-biological systemic agent in a real-life clinical setting. This observational study compares quality of life, treatment satisfaction and the efficacy of non-biological systemic therapy between 60 patients suffering from plaque psoriasis receiving the non-biological systemic therapies with apremilast, methotrexate and fumaric acid esters. Ethics approval was provided by the ethics committee of the medical faculty of the University of Heidelberg. Ethics approval number is S-298/2015. The design and the final results of the study will be published and made available to the public. German Clinical Trial Register (DRKS): DRKS00008721 (https://www.germanctr.de/). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

    DEFF Research Database (Denmark)

    Gustafsson, Anna M E; Bäck, Tom; Elgqvist, Jörgen

    2012-01-01

    The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.......The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model....

  20. Biomarkers of Therapeutic Response in the IL-23 Pathway in Inflammatory Bowel Disease

    OpenAIRE

    Cayatte, Corinne; Joyce-Shaikh, Barbara; Vega, Felix; Boniface, Katia; Grein, Jeffrey; Murphy, Erin; Blumenschein, Wendy M; Chen, Smiley; Malinao, Maria-Christina; Basham, Beth; Pierce, Robert H; Bowman, Edward P; McKenzie, Brent S; Elson, Charles O; Faubion, William A

    2012-01-01

    OBJECTIVES: Interleukin-23 (IL-23) has emerged as a new therapeutic target for the treatment of inflammatory bowel disease (IBD). As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD). METHODS: Candidate IL-23 biomarkers, downstream of IL-23 signaling, were identified using shotgun proteomic analysis of feces and colon lavages obtained from a short-...

  1. Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

    International Nuclear Information System (INIS)

    Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

    2007-01-01

    years. New potential therapeutic agents for OPI poisoning include: glycopyrrolate as anticholinergic; organophosphorous hydrolases, butyrilcholinesterases and sodium bicarbonate which degrade OPI and accelerate AChE reactivation; reversible anticholinesterases for reduction of AChE reinchibition; NMDA antagonist as neuroprotectors. Authors from Maryland have proposed the usage of IL-1 Rp antagonists in acute OPI intoxication, a new, original approach to therapy which deserves to be elucidated. For now pharmaceutical industries do not show satisfying initiative in developing new therapeutic agents and antidotes for OPI poisoning. However, randomized, controlled clinical studies, for the beginning with the agents which are in clinical practice, would elucidate their clinical efficacy, reduce the number of lethal pesticide poisonings in developing countries and provide information of special importance for the army and medical service. (author)

  2. Early Therapeutic Alliance and Treatment Outcome in Individual and Family Therapy for Adolescent Behavior Problems

    Science.gov (United States)

    Hogue, Aaron; Dauber, Sarah; Stambaugh, Leyla Faw; Cecero, John J.; Liddle, Howard A.

    2006-01-01

    The impact of early therapeutic alliance was examined in 100 clients receiving either individual cognitive-behavioral therapy (CBT) or family therapy for adolescent substance abuse. Observational ratings of adolescent alliance in CBT and adolescent and parent alliance in family therapy were used to predict treatment retention (in CBT only) and…

  3. Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

    Science.gov (United States)

    Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-05-01

    Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (˜141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

  4. Radionuclides for therapeutic applications: Biological and medical aspects (present status, development and expectations)

    International Nuclear Information System (INIS)

    Wambersie, A.; Gahbauer, R.A.

    2002-01-01

    Different multidisciplinary therapeutic strategies and technical approaches are used today in cancer therapy. Among the techniques involving ionizing radiation, therapeutic applications of radioactive nuclides deserve a particular interest ; some clinical indications are well established, while several others are now being investigated, and some of them are promising. The efficacy of radionuclides in therapy often depends on technical factors such as specific activity, purity, chemical presentation, availability, etc. These factors are closely related, at least partly, to the production methods. This justifies the organization of the present Consultant's meeting by the IAEA. Brief information on cancer, its socio-economic aspects, and some data concerning cure rate are presented first

  5. Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12.

    Science.gov (United States)

    Bozeman, Erica N; He, Sara; Shafizadeh, Yalda; Selvaraj, Periasamy

    2016-01-01

    Immunotherapeutic approaches have emerged as promising strategies to treat various cancers, including breast cancer. A single approach, however, is unlikely to effectively combat the complex, immune evasive strategies found within the tumor microenvironment, thus novel, effective combination treatments must be explored. In this study, we investigated the efficacy of a combination therapy consisting of PD-L1 immune checkpoint blockade and whole cell vaccination in a HER-2 positive mouse model of breast cancer. We demonstrate that tumorigenicity is completely abrogated when adjuvanted with immune stimulatory molecules (ISMs) B7-1 and a cell-surface anchored (GPI) form of IL-12 or GM-CSF. Irradiated cellular vaccines expressing the combination of adjuvants B7-1 and GPI-IL-12 completely inhibited tumor formation which was correlative with robust HER-2 specific CTL activity. However, in a therapeutic setting, both cellular vaccination and PD-L1 blockade induced only 10-20% tumor regression when administered alone but resulted in 50% tumor regression as a combination therapy. This protection was significantly hindered following CD4 or CD8 depletion indicating the essential role played by cellular immunity. Collectively, these pre-clinical studies provide a strong rationale for further investigation into the efficacy of combination therapy with tumor cell vaccines adjuvanted with membrane-anchored ISMs along with PD-L1 blockade for the treatment of breast cancer.

  6. Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    Full Text Available Multiple sclerosis (MS, characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE, a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.

  7. Therapeutic peptides for cancer therapy. Part I - peptide inhibitors of signal transduction cascades.

    Science.gov (United States)

    Bidwell, Gene L; Raucher, Drazen

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that inhibit signal transduction cascades are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Given our current knowledge of protein sequences, structures and interaction interfaces, therapeutic peptides that inhibit interactions of interest are easily designed. These peptides are advantageous because they are highly specific for the interaction of interest, and they are much more easily developed than small molecule inhibitors of the same interactions. The main hurdle to application of peptides for cancer therapy is their poor pharmacokinetic and biodistribution parameters. Therefore, successful development of peptide delivery vectors could potentially make possible the use of this new and very promising class of anticancer agents.

  8. Therapeutic efficacy of Artemether/Lumefantrine (Coartem® against Plasmodium falciparum in Kersa, South West Ethiopia

    Directory of Open Access Journals (Sweden)

    Animut Abebe

    2010-01-01

    Full Text Available Abstract Background Artemether/Lumefantrine (Coartem® has been used as a first-line treatment for uncomplicated Plasmodium falciparum infection since 2004 in Ethiopia. In the present study the therapeutic efficacy of artemether/lumefantrine for the treatment of uncomplicated P. falciparum infection at Kersa, Jima zone, South-west Ethiopia, has been assessed. Methods A 28 day therapeutic efficacy study was conducted between November 2007 and January 2008, in accordance with the 2003 WHO guidelines. Outcomes were classified as early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF and adequate clinical and parasitological response (ACPR. Results 90 patients were enrolled and completed the 28 day follow-up period after treatment with artemether/lumefantrine. Cure rate was very high, 96.3%, with 95% CI of 0.897-0.992 (PCR uncorrected. Age-stratified data showed adequate clinical and parasitological response (ACPR to be 100% for children under 5 and 97.4% and 87.3% for children aged 5-14, and adults, respectively. There was no early treatment failure (ETF in all age groups. Fever was significantly cleared on day 3 (P 0.05. No major side effect was observed in the study except the occurrence of mouth ulcers in 7% of the patients. Conclusions The current study proved the excellent therapeutic efficacy of artemether/lumefantrine in the study area and the value of using it. However, the proper dispensing and absorption of the drug need to be emphasized in order to utilize the drug for a longer period of time. This study recommends further study on the toxicity of the drug with particular emphasis on the development of oral ulcers in children.

  9. Narrative Financial Therapy: Integrating a Financial Planning Approach with Therapeutic Theory

    Directory of Open Access Journals (Sweden)

    Megan A. McCoy

    2014-03-01

    Full Text Available The article serves as one of the first attempts to develop an integrated theoretical approach to financial therapy that can be used by practitioners from multiple disciplines. The presented approach integrates the components of the six-step financial planning process with components of empirically-supported therapeutic methods. This integration provides the foundation for a manualized approach to financial therapy, shaped by the writings of narrative theorists and select cognitive-behavioral interventions that can be used both by mental health and financial professionals.

  10. Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

    Science.gov (United States)

    Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

    2015-01-01

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

  11. Efficacy of therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    1998-01-01

    The following topics are discussed: (i) 131 I therapy of thyrotoxicosis; (ii) 131 I therapy of differentiated thyroid carcinoma; (iii) 32 P therapy of myeloproliferative disease; (iv) 131 MIBG therapy of neural crest tumors; (v) radiolabelled peptides in neuroendocrine tumors; (vi) radioimmunotherapy; (vii) palliative bone therapy of painful skeletal metastases; (viii) radiosynoviorthesis; (ix) alternative approaches; (x) side effects and long-term effects

  12. Molecular targeting of gene therapy and radiotherapy

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Kufe, D.W.; Advani, S.J.; Roizman, B.

    2001-01-01

    The full promise of gene therapy has been limited by the lack of specificity of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. In this paper we review our studies investigating two modifications of gene therapy combined with radiotherapy. The first investigations described include studies of radiation inducible gene therapy. In this paradigm, radio-inducible DNA sequences from the CarG elements of the Egr-1 promoter are cloned upstream of a cDNA encoding TNFa. The therapeutic gene (TNFa) is induced by radiation within the tumor microenvironment. In the second paradigm, genetically engineered herpes simplex virus (HSV-1) is induced by ionizing radiation to proliferate within the tumor volume. These modifications of radiotherapy and gene therapy may enhance the efficacy of both treatments

  13. [Clinical efficacy of Viagra with behavior therapy against premature ejaculation].

    Science.gov (United States)

    Tang, Wenhao; Ma, Lulin; Zhao, Lianming; Liu, Yuqing; Chen, Zhenwen

    2004-05-01

    To study the efficacy of Viagra combined with behavior therapy against premature ejaculation (PE). Sixty PE patients were divided into two groups randomly: control group (behavior therapy alone) and the group of Viagra combined with behavior therapy. Intra-vaginal ejaculation latency time (IELT) and the coitus satisfaction of the patient and the partner were recorded before and after treatment. The IELTs of the two groups were 0.80 +/- 0.20 and 0.73 +/- 0.24 minutes respectively before treatment, and 1.82 +/- 0.54 and 3.63 +/- 0.55 minutes respectively after treatment. As for IELT and satisfaction degree, Viagra produced better result than behavior therapy. During this clinical trial, Viagra combined with behavior therapy prolonged IELT, which suggests that Viagra may be helpful for the treatment of premature ejaculation.

  14. Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

    Science.gov (United States)

    Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

    2013-05-01

    Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

  15. The roles of safety and compliance in determining effectiveness of topical therapy for psoriasis.

    Science.gov (United States)

    Stein Gold, Linda; Corvari, Linda

    2007-01-01

    Topical therapies are the mainstays of treatment for most patients with psoriasis because they relieve symptoms and reduce the size and severity of lesions. The effectiveness of a therapeutic intervention is a function of drug efficacy (determined by randomized clinical trial results) and patient safety and compliance. Alterations in any parameter can have a substantial influence on clinical outcomes. However, topical agents can be associated with unwanted and potentially toxic side effects that make physicians reluctant to prescribe them, and patients intentionally discontinue treatment with these topical agents. To maximize effectiveness and improve patient safety, physicians may prescribe medications in combination, sequential, or rotational therapeutic regimens. This treatment strategy has the potential to improve the overall efficacy and safety of topical therapy; however, the effectiveness of this method may be compromised because the complexity of the therapeutic regimen may decrease patient compliance. Newer topical therapies that have a convenient once-daily dosing schedule are needed and will have important implications for patient compliance.

  16. Interpersonal Circumplex Profiles Of Persistent Depression: Goals, Self-Efficacy, Problems, And Effects Of Group Therapy.

    Science.gov (United States)

    Locke, Kenneth D; Sayegh, Liliane; Penberthy, J Kim; Weber, Charlotte; Haentjens, Katherine; Turecki, Gustavo

    2017-06-01

    We assessed severely and persistently depressed patients' interpersonal self-efficacy, problems, and goals, plus changes in interpersonal functioning and depression during 20 weeks of group therapy. Outpatients (32 female, 26 male, mean age = 45 years) completed interpersonal circumplex measures of goals, efficacy, and problems before completing 20 weeks of manualized group therapy, during which we regularly assessed depression and interpersonal style. Compared to normative samples, patients lacked interpersonal agency, including less self-efficacy for expressive/assertive actions; stronger motives to avoid conflict, scorn, and humiliation; and more problems with being too submissive, inhibited, and accommodating. Behavioral Activation and especially Cognitive Behavioral Analysis System of Psychotherapy interventions produced improvements in depression and interpersonal agency, with increases in "agentic and communal" efficacy predicting subsequent decreases in depression. While severely and persistently depressed patients were prone to express maladaptive interpersonal dispositions, over the course of group therapy, they showed increasingly agentic and beneficial patterns of cognitions, motives, and behaviors. © 2016 Wiley Periodicals, Inc.

  17. Oligonucleotide-based theranostic nanoparticles in cancer therapy

    Science.gov (United States)

    Shahbazi, Reza; Ozpolat, Bulent; Ulubayram, Kezban

    2016-01-01

    Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics. PMID:27102380

  18. Correlation between paclitaxel Tc > 0.05 and its therapeutic efficacy and severe toxicities in ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Shuyao Zhang

    2016-01-01

    Conclusion: These results indicated that the PTX Tc > 0.05 correlated with therapeutic efficacy and drug toxicity. Therefore, monitoring the PTX Tc > 0.05 other than blood concentration of PTX is necessary to optimize individual treatment.

  19. Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

    Science.gov (United States)

    Chen, Kuan-Ju

    Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

  20. Predictors of change in music therapy with children and adolescents: The role of therapeutic techniques

    DEFF Research Database (Denmark)

    Gold, Christian; Wigram, Tony; Voracek, Martin

    2006-01-01

    and burdens on their social environment showed greater improvement when music therapy was limited to discipline-specific music therapy techniques and did not include other media such as play therapy elements. The findings indicate the importance of being aware about a therapy method's specific strengths......  Music therapy has been shown to be efficacious in experimental studies. However, there is little empirical research knowledge about what elements of music therapy influence its effectiveness in clinical practice. Children and adolescents with psychopathology (N = 75) were assessed before...

  1. The Impact of Rational Emotive Behavior Therapy on Teacher Efficacy and Student Achievement

    Science.gov (United States)

    Warren, Jeffrey M.

    2010-01-01

    This literature review explores the potential impact of Rational Emotive Behavior Therapy (REBT) on teacher efficacy and student achievement. Research conducted to date, focusing on increasing teacher efficacy and student achievement, has produced mixed results. Teachers continue to think, emote, and behave in unhelpful ways. REBT appears to…

  2. A review of technology-assisted self-help and minimal contact therapies for drug and alcohol abuse and smoking addiction: is human contact necessary for therapeutic efficacy?

    Science.gov (United States)

    Newman, Michelle G; Szkodny, Lauren E; Llera, Sandra J; Przeworski, Amy

    2011-02-01

    Technology-based self-help and minimal contact therapies have been proposed as effective and low-cost interventions for addictive disorders, such as nicotine, alcohol, and drug abuse and addiction. The present article reviews the literature published before 2010 on computerized treatments for drug and alcohol abuse and dependence and smoking addiction. Treatment studies are examined by disorder as well as amount of therapist contact, ranging from self-administered therapy and predominantly self-help interventions to minimal contact therapy where the therapist is actively involved in treatment but to a lesser degree than traditional therapy and predominantly therapist-administered treatments involving regular contact with a therapist for a typical number of sessions. In the treatment of substance use and abuse it is concluded that self-administered and predominantly self-help computer-based cognitive and behavioral interventions are efficacious, but some therapist contact is important for greater and more sustained reductions in addictive behavior. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  4. Is phage therapy acceptable in the immunocompromised host?

    Science.gov (United States)

    Borysowski, Jan; Górski, Andrzej

    2008-09-01

    Over the last decade, bacteriophages (bacterial viruses) have emerged as the major alternative to antibiotics in the treatment of antibiotic-resistant infections. While a considerable body of evidence has accumulated for the efficacy and safety of phage therapy in immunocompetent patients, data remain relatively scarce regarding its use in the immunocompromised host. To our knowledge, the present article is the first to summarize all findings, of both experimental and clinical studies, that may be relevant to the employment of phage therapy in immunocompromised patients. The available data suggest that bacteriophages could also be an efficacious and safe therapeutic modality in such patients.

  5. A Feedback-Controlled Mandibular Positioner Identifies Individuals With Sleep Apnea Who Will Respond to Oral Appliance Therapy.

    Science.gov (United States)

    Remmers, John E; Topor, Zbigniew; Grosse, Joshua; Vranjes, Nikola; Mosca, Erin V; Brant, Rollin; Bruehlmann, Sabina; Charkhandeh, Shouresh; Zareian Jahromi, Seyed Abdolali

    2017-07-15

    Mandibular protruding oral appliances represent a potentially important therapy for obstructive sleep apnea (OSA). However, their clinical utility is limited by a less-than-ideal efficacy rate and uncertainty regarding an efficacious mandibular position, pointing to the need for a tool to assist in delivery of the therapy. The current study assesses the ability to prospectively identify therapeutic responders and determine an efficacious mandibular position. Individuals (n = 202) with OSA participated in a blinded, 2-part investigation. A system for identifying therapeutic responders was developed in part 1 (n = 149); the predictive accuracy of this system was prospectively evaluated on a new population in part 2 (n = 53). Each participant underwent a 2-night, in-home feedback-controlled mandibular positioner (FCMP) test, followed by treatment with a custom oral appliance and an outcome study with the oral appliance in place. A machine learning classification system was trained to predict therapeutic outcome on data obtained from FCMP studies on part 1 participants. The accuracy of this trained system was then evaluated on part 2 participants by examining the agreement between prospectively predicted outcome and observed outcome. A predicted efficacious mandibular position was derived from each FCMP study. Predictive accuracy was as follows: sensitivity 85%; specificity 93%; positive predictive value 97%; and negative predictive value 72%. Of participants correctly predicted to respond to therapy, the predicted mandibular protrusive position proved efficacious in 86% of cases. An unattended, in-home FCMP test prospectively identifies individuals with OSA who will respond to oral appliance therapy and provides an efficacious mandibular position. The trial that this study reports on is registered on www.clinicaltrials.gov, ID NCT03011762, study name: Feasibility and Predictive Accuracy of an In-Home Computer Controlled Mandibular Positioner in Identifying Favourable

  6. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

    Directory of Open Access Journals (Sweden)

    Robert H E Friesen

    2010-02-01

    Full Text Available The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.

  8. [50 years of hepatology - from therapeutic nihilism to targeted therapies].

    Science.gov (United States)

    Manns, Michael P

    2013-04-01

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

  9. Graphene-based platforms for cancer therapeutics

    Science.gov (United States)

    Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

    2016-01-01

    Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management. PMID:26769305

  10. Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer.

    Science.gov (United States)

    Salaam, Amanee D; Hwang, Patrick T J; Poonawalla, Aliza; Green, Hadiyah N; Jun, Ho-wook; Dean, Derrick

    2014-10-24

    Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer (HRPC). To improve the efficacy of doxorubicin (DOX) for treating chemoresistant disease, the feasibility of using nanodiamond (ND) particles was investigated. Utilizing the pH responsive properties of ND, a novel protocol for complexing NDs and DOX was developed using a pH 8.5 coupling buffer. The DOX loading efficiency, loading on the NDs, and pH responsive release characteristics were determined utilizing UV-Visible spectroscopy. The effects of the ND-DOX on HRPC cell line PC3 were evaluated with MTS and live/dead cell viability assays. ND-DOX displayed exceptional loading efficiency (95.7%) and drug loading on NDs (23.9 wt%) with optimal release at pH 4 (80%). In comparison to treatment with DOX alone, cell death significantly increased when cells were treated with ND-DOX complexes demonstrating a 50% improvement in DOX efficacy. Of the tested treatments, ND-DOX with 2.4 μg mL(-1) DOX exhibited superior efficacy (60% cell death). ND-DOX with 1.2 μg mL(-1) DOX achieved 42% cell death, which was comparable to cell death in response to 2.4 μg mL(-1) of free DOX, suggesting that NDs aid in decreasing the DOX dose necessary to achieve a chemotherapeutic efficacy. Due to its enhanced efficacy, ND-DOX can be used to successfully treat HRPC and potentially decrease the clinical side effects of DOX.

  11. Strategies for combinational cancer therapies

    International Nuclear Information System (INIS)

    Khleif, Samir

    2014-01-01

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

  12. Efficacy of Cognitive Behavioral Group Therapy (CBGT) among children with anxiety disorders

    OpenAIRE

    Nilgun Ongider-Gregory; Burak Baykara

    2015-01-01

    Objective: It was aimed to investigate efficacy of Cognitive behavioral group therapy (CBGT) in childhood anxiety disorders by pre and post therapy. Method: Trial sample was obtained from an university outpatient child psychiatry clinic. Therapy group (n=12) was selected from children and their parents whom was diagnosed as DSM-IV childhood anxiety disorder. And comparation group (n=12) was selected from children and their parents whom was in the waiting list. The total sample includes...

  13. Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies

    Science.gov (United States)

    Scarfe, Lauren; Brillant, Nathalie; Kumar, J. Dinesh; Ali, Noura; Alrumayh, Ahmed; Amali, Mohammed; Barbellion, Stephane; Jones, Vendula; Niemeijer, Marije; Potdevin, Sophie; Roussignol, Gautier; Vaganov, Anatoly; Barbaric, Ivana; Barrow, Michael; Burton, Neal C.; Connell, John; Dazzi, Francesco; Edsbagge, Josefina; French, Neil S.; Holder, Julie; Hutchinson, Claire; Jones, David R.; Kalber, Tammy; Lovatt, Cerys; Lythgoe, Mark F.; Patel, Sara; Patrick, P. Stephen; Piner, Jacqueline; Reinhardt, Jens; Ricci, Emanuelle; Sidaway, James; Stacey, Glyn N.; Starkey Lewis, Philip J.; Sullivan, Gareth; Taylor, Arthur; Wilm, Bettina; Poptani, Harish; Murray, Patricia; Goldring, Chris E. P.; Park, B. Kevin

    2017-10-01

    Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies. To facilitate clinical translation, non-invasive in vivo imaging technologies that enable careful evaluation and characterisation of the administered cells and their effects on host tissues are critically required to evaluate their safety and efficacy in relevant preclinical models. This article reviews the most common imaging technologies available and how they can be applied to regenerative medicine research. We cover details of how each technology works, which cell labels are most appropriate for different applications, and the value of multi-modal imaging approaches to gain a comprehensive understanding of the responses to cell therapy in vivo.

  14. Theranostic Imaging of Cancer Gene Therapy.

    Science.gov (United States)

    Sekar, Thillai V; Paulmurugan, Ramasamy

    2016-01-01

    Gene-directed enzyme prodrug therapy (GDEPT) is a promising therapeutic approach for treating cancers of various phenotypes. This strategy is independent of various other chemotherapeutic drugs used for treating cancers where the drugs are mainly designed to target endogenous cellular mechanisms, which are different in various cancer subtypes. In GDEPT an external enzyme, which is different from the cellular proteins, is expressed to convert the injected prodrug in to a toxic metabolite, that normally kill cancer cells express this protein. Theranostic imaging is an approach used to directly monitor the expression of these gene therapy enzymes while evaluating therapeutic effect. We recently developed a dual-GDEPT system where we combined mutant human herpes simplex thymidine kinase (HSV1sr39TK) and E. coli nitroreductase (NTR) enzyme, to improve therapeutic efficiency of cancer gene therapy by simultaneously injecting two prodrugs at a lower dose. In this approach we use two different prodrugs such as ganciclovir (GCV) and CB1954 to target two different cellular mechanisms to kill cancer cells. The developed dual GDEPT system was highly efficacious than that of either of the system used independently. In this chapter, we describe the complete protocol involved for in vitro and in vivo imaging of therapeutic cancer gene therapy evaluation.

  15. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  16. Development and efficacy of music therapy techniques within palliative care.

    Science.gov (United States)

    Clements-Cortés, Amy

    2016-05-01

    Music therapy is increasingly becoming an intervention used in palliative care settings around the globe. While the specialty of palliative care music therapy is relatively young having emerged in the late 1980s, there is a strong and growing body of evidence demonstrating its efficacy in assisting a variety of issues common at end-of-life. There are multiple music therapy techniques that are implemented with clients in palliative care and they can be categorized in four broad areas: receptive, creative, recreative and combined. These techniques will be presented with respect to their development by clinicians as supported by the descriptive and research literature. Information is also provided on the use of music therapy in facilitating the grieving and bereavement process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The efficacy of cognitive-behavioral therapy for eating disorders: A systematic review and meta-analysis.

    Science.gov (United States)

    Linardon, Jake; Wade, Tracey D; de la Piedad Garcia, Xochitl; Brennan, Leah

    2017-11-01

    This meta-analysis examined the efficacy of cognitive-behavioral therapy (CBT) for eating disorders. Randomized controlled trials of CBT were searched. Seventy-nine trials were included. Therapist-led CBT was more efficacious than inactive (wait-lists) and active (any psychotherapy) comparisons in individuals with bulimia nervosa and binge eating disorder. Therapist-led CBT was most efficacious when manualized CBT-BN or its enhanced version was delivered. No significant differences were observed between therapist-led CBT for bulimia nervosa and binge eating disorder and antidepressants at posttreatment. CBT was also directly compared to other specific psychological interventions, and therapist-led CBT resulted in greater reductions in behavioral and cognitive symptoms than interpersonal psychotherapy at posttreatment. At follow-up, CBT outperformed interpersonal psychotherapy only on cognitive symptoms. CBT for binge eating disorder also resulted in greater reductions in behavioral symptoms than behavioral weight loss interventions. There was no evidence that CBT was more efficacious than behavior therapy or nonspecific supportive therapies. CBT is efficacious for eating disorders. Although CBT was equally efficacious to certain psychological treatments, the fact that CBT outperformed all active psychological comparisons and interpersonal psychotherapy specifically, offers some support for the specificity of psychological treatments for eating disorders. Conclusions from this study are hampered by the fact that many trials were of poor quality. Higher quality RCTs are essential. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke; Kajikawa, Shu-hei [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Uesato, Shin-ichi [Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680 (Japan); Watanabe, Kazushi [Proubase Technology Inc., Kanagawa 211-0063 (Japan); Tanimura, Susumu [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Koji, Takehiko [Department of Histology and Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kohno, Michiaki, E-mail: kohnom@nagasaki-u.ac.jp [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Proubase Technology Inc., Kanagawa 211-0063 (Japan); Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501 (Japan)

    2013-04-19

    Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.

  19. Mindfulness-based stress reduction and cognitive behavioral therapy for chronic low back pain: similar effects on mindfulness, catastrophizing, self-efficacy, and acceptance in a randomized controlled trial.

    Science.gov (United States)

    Turner, Judith A; Anderson, Melissa L; Balderson, Benjamin H; Cook, Andrea J; Sherman, Karen J; Cherkin, Daniel C

    2016-11-01

    Cognitive behavioral therapy (CBT) is believed to improve chronic pain problems by decreasing patient catastrophizing and increasing patient self-efficacy for managing pain. Mindfulness-based stress reduction (MBSR) is believed to benefit patients with chronic pain by increasing mindfulness and pain acceptance. However, little is known about how these therapeutic mechanism variables relate to each other or whether they are differentially impacted by MBSR vs CBT. In a randomized controlled trial comparing MBSR, CBT, and usual care (UC) for adults aged 20 to 70 years with chronic low back pain (N = 342), we examined (1) baseline relationships among measures of catastrophizing, self-efficacy, acceptance, and mindfulness and (2) changes on these measures in the 3 treatment groups. At baseline, catastrophizing was associated negatively with self-efficacy, acceptance, and 3 aspects of mindfulness (nonreactivity, nonjudging, and acting with awareness; all P values pain.

  20. Engineering Specificity and Function of Therapeutic Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Jenny L. McGovern

    2017-11-01

    Full Text Available Adoptive therapy with polyclonal regulatory T cells (Tregs has shown efficacy in suppressing detrimental immune responses in experimental models of autoimmunity and transplantation. The lack of specificity is a potential limitation of Treg therapy, as studies in mice have demonstrated that specificity can enhance the therapeutic potency of Treg. We will discuss that vectors encoding T cell receptors or chimeric antigen receptors provide an efficient gene-transfer platform to reliably produce Tregs of defined antigen specificity, thus overcoming the considerable difficulties of isolating low-frequency, antigen-specific cells that may be present in the natural Treg repertoire. The recent observations that Tregs can polarize into distinct lineages similar to the Th1, Th2, and Th17 subsets described for conventional T helper cells raise the possibility that Th1-, Th2-, and Th17-driven pathology may require matching Treg subsets for optimal therapeutic efficacy. In the future, genetic engineering may serve not only to enforce FoxP3 expression and a stable Treg phenotype but it may also enable the expression of particular transcription factors that drive differentiation into defined Treg subsets. Together, established and recently developed gene transfer and editing tools provide exciting opportunities to produce tailor-made antigen-specific Treg products with defined functional activities.

  1. Electroconvulsive Therapy Intervention for Parkinson's Disease.

    Science.gov (United States)

    Narang, Puneet; Glowacki, Anna; Lippmann, Steven

    2015-01-01

    Electroconvulsive therapy is an established means to improve function in a variety of psychiatric and neurologic conditions, particularly for patients who remain treatment-refractory. Parkinson's disease is a neurodegenerative disorder that sometimes does not respond well to conventional pharmacotherapies. Reports have indicated that electroconvulsive therapy may be an effective and safe treatment for those patients with Parkinson's disease who are not optimally responding to first-line treatments. Despite these reports, however, electroconvulsive therapy is not often used by clinicians in patients with treatment-resistant Parkinson's disease, perhaps due to stigma, lack of knowledge regarding its safety and efficacy, and/or inability to predict the duration of therapeutic benefit. Our objective was to determine if the available literature on ECT supports it as a safe and effective treatment option in patients with treatment-refractory Parkinson's disease. Motoric improvement induced by electroconvulsive therapy has been documented for decades in persons with Parkinson's disease. Efficacy and safety are reported following electroconvulsive therapy in people with Parkinson's disease who have sub-optimal response to medicines or experience the "on/off" phenomenon to L-dopa. Electroconvulsive therapy is an effective option for acute and maintenance treatment of Parkinson's disease in select patients. Inability to predict how long the beneficial effects of ECT therapy will last in patients with Parkinson's disease may be a reason why this treatment is underutilized by clinicians. More research is warranted to clarify parameters for application and duration of therapeutic benefit in individuals with difficult-to-treat Parkinson's disease.

  2. The Efficacy of Dog Assisted Therapy in Detained Drug Users: A Pilot Study in an Italian Attenuated Custody Institute.

    Science.gov (United States)

    Contalbrigo, Laura; De Santis, Marta; Toson, Marica; Montanaro, Maria; Farina, Luca; Costa, Aldo; Nava, Felice Alfonso

    2017-06-24

    Drug addiction is a major care and safety challenge in prison context. Nowadays, rehabilitation and specific therapeutic programs are suggested to improve health and well-being of inmates during their detention time and to reduce substance abuse relapse after release from prison. Among these programs, several studies reported the benefits for inmates coming from animal assisted interventions. In this pilot controlled study, we investigated the efficacy of a dog assisted therapy program addressed to 22 drug addicted male inmates housed in an attenuated custody institute in Italy. The study lasted six months, the treated group (12 inmates) was involved once a week for one hour in 20 dog assisted therapy sessions, whereas the control group (10 inmates) followed the standard rehabilitation program. One week before the beginning and one week after the end of the sessions, all inmates involved were submitted to symptom checklist-90-revised and Kennedy axis V. Inmates involved in the dog assisted therapy sessions significantly improved their social skills, reducing craving, anxiety and depression symptoms compared to the control group. Despite the limitation due to the small number of inmates enrolled and to the absence of follow up, we found these results encouraging to the use of dog assisted therapy as co-therapy in drug addicted inmates rehabilitation programs, and we claim the need of more extensive study on this subject.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

  4. Development of CAR T cells designed to improve antitumor efficacy and safety

    OpenAIRE

    Jaspers, Janneke E.; Brentjens, Renier J.

    2017-01-01

    Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how ...

  5. How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms

    Science.gov (United States)

    Singh, Amit; Kar, Sujita Kumar

    2017-01-01

    Electroconvulsive therapy (ECT) is a time tested treatment modality for the management of various psychiatric disorders. There have been a lot of modifications in the techniques of delivering ECT over decades. Despite lots of criticisms encountered, ECT has still been used commonly in clinical practice due to its safety and efficacy. Research evidences found multiple neuro-biological mechanisms for the therapeutic effect of ECT. ECT brings about various neuro-physiological as well as neuro-chemical changes in the macro- and micro-environment of the brain. Diverse changes involving expression of genes, functional connectivity, neurochemicals, permeability of blood-brain-barrier, alteration in immune system has been suggested to be responsible for the therapeutic effects of ECT. This article reviews different neurobiological mechanisms responsible for the therapeutic efficacy of ECT. PMID:28783929

  6. Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy

    Directory of Open Access Journals (Sweden)

    C Shivaprasad

    2015-01-01

    Full Text Available Introduction: Data from several studies suggest that pretreatment with antithyroid drugs (ATD before 131 I increases the risk of treatment failure. This effect has been demonstrated more consistently with propylthiouracil than with carbimazole (CMZ or methimazole (MMI. Men with Graves′ disease (GD have a lower rate of remission with 131 I compared to women and the impact of long-term ATD pretreatment on the success of 131 I is unknown. The objective of our study was to compare the efficacy of fixed doses of radioiodine between patients with and without long-term CMZ pretreatment. Materials and Methods: We performed a retrospective study on 335 male patients with GD treated with 131 I from 1998 to 2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients received 131 I without pretreatment. We compared the success rate of a single dose of 131 I, between patients with and without long-term CMZ pretreatment. Results: The success rate of a single dose of 131 I was significantly higher in patients without pretreatment than in patients who were pretreated with CMZ (91.4% vs. 82.3%, P = 0.01. The rate of hypothyroidism in the first 6 months after 131 I therapy was significantly higher in patients without pretreatment (55.1% vs. 44.6%, P = 0.05. There was also a trend for higher cumulative rate of hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%. Conclusion: Male patients with Graves′ hyperthyroidism pretreated with CMZ have lower efficacy with 131I therapy compared to nonpretreated patients. CMZ pretreatment given for a prolonged period reduces the efficacy of 131 I therapy.

  7. Cupping Therapy May be Harmful for Eczema: A PubMed Search

    Science.gov (United States)

    Hon, Kam Lun E.; Luk, David Chi Kong; Leong, Kin Fon; Leung, Alexander K. C.

    2013-01-01

    Eczema is a common childhood atopic condition and treatment is with emollients, topical corticosteroids, and avoidance of possible triggers. S. aureus colonization is a common complication. As there is no immediate cure, many parents seek alternative therapies that claim unproven therapeutic efficacy. We report a girl with long history of treatment noncompliance. After practicing a long period of dietary avoidance and supplementation, the grandparents took her to an alternative medicine practitioner. Following cupping therapy and acupuncture, the child developed blistering and oozing over her back the next day, which rapidly evolved to two large irregular-edge deep ulcers. She was treated with intravenous antibiotics and received multidisciplinary supportive intervention. Using search words of  “cupping,” “eczema,” and “atopic dermatitis,” only two reports were found on PubMed. Therapeutic efficacy was claimed but not scientifically documented in these reports. Childhood eczema is an eminently treatable atopic disease. Extreme alternative therapy seems not to be efficacious and may even be associated with serious undesirable sequelae. Physicians should be aware of various alternative treatment modalities and be prepared to offer evidence-based advice to the patients with eczema and their families. PMID:24282650

  8. Cupping Therapy May be Harmful for Eczema: A PubMed Search

    Directory of Open Access Journals (Sweden)

    Kam Lun E. Hon

    2013-01-01

    Full Text Available Eczema is a common childhood atopic condition and treatment is with emollients, topical corticosteroids, and avoidance of possible triggers. S. aureus colonization is a common complication. As there is no immediate cure, many parents seek alternative therapies that claim unproven therapeutic efficacy. We report a girl with long history of treatment noncompliance. After practicing a long period of dietary avoidance and supplementation, the grandparents took her to an alternative medicine practitioner. Following cupping therapy and acupuncture, the child developed blistering and oozing over her back the next day, which rapidly evolved to two large irregular-edge deep ulcers. She was treated with intravenous antibiotics and received multidisciplinary supportive intervention. Using search words of  “cupping,” “eczema,” and “atopic dermatitis,” only two reports were found on PubMed. Therapeutic efficacy was claimed but not scientifically documented in these reports. Childhood eczema is an eminently treatable atopic disease. Extreme alternative therapy seems not to be efficacious and may even be associated with serious undesirable sequelae. Physicians should be aware of various alternative treatment modalities and be prepared to offer evidence-based advice to the patients with eczema and their families.

  9. A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

    Directory of Open Access Journals (Sweden)

    Peter Jonas Grahn

    2014-06-01

    Full Text Available Current strategies for optimizing deep brain stimulation (DBS therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS.Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a smart neuroprosthetic system for treatment of neurologic and

  10. Difficulties in the therapeutic relationship in cognitive-behavioral therapy. M. Linehan's dialectical behavior therapy in work with borderline personality disorder.

    OpenAIRE

    Monika Romanowska

    2015-01-01

    According to popular opinions therapeutic relationship doesn't play a significant role in cognitive-behavioral therapy. Furthermore it is frequently assumed that cognitive therapist doesn't pay attention to processes taking place during the session, focuses solely on a realization of an earlier planned protocol and convinces patient to rational thinking minimizing the role of emotions. Contrary to this beliefs CBT therapists often focus on a therapeutic relationship and use it in a process of...

  11. The Efficacy of Metacognitive Therapy for Anxiety and Depression

    DEFF Research Database (Denmark)

    Normann, Nicoline; van Emmerik, Arnold A.P.; Morina, Nexhmedin

    2014-01-01

    effective than both waitlist control groups (between-group Hedges’ g = 1.81) as well as cognitive behavior therapy (CBT; between-group Hedges’ g = 0.97). Conclusions: Results suggest that MCT is effective in treating disorders of anxiety and depression and is supe- rior compared to waitlist control groups......Background: Metacognitive therapy (MCT) is a relatively new approach to treat- ing mental disorders. The aim of the current meta-analysis was to examine the efficacy of MCT in patients with mental disorders. Method: A comprehensive literature search revealed 16 published as well as unpublished...... and CBT, although the latter finding should be interpreted with caution. The implications of these findings are limited by small sample sizes and few active control conditions. Future studies should include larger sample sizes and also include comparisons of MCT with other empirically supported therapies....

  12. The efficacy of surfactant replacement therapy in the growth restricted preterm infant: what is the evidence?

    Directory of Open Access Journals (Sweden)

    Atul eMalhotra

    2014-10-01

    Full Text Available Background: Surfactant replacement therapy (SRT is an integral part of management of preterm surfactant deficiency (respiratory distress syndrome, RDS. Its role in the management of RDS has been extensively studied. However its efficacy in the management of lung disease in preterm infants born with intrauterine growth restriction (IUGR has not been systematically studied.Objective: To evaluate the efficacy of exogenous surfactant replacement therapy in the management of preterm IUGR lung disease. Methods: A systematic search of all available randomised clinical trials (RCT of surfactant replacement therapy in preterm IUGR infants was done according to the standard Cochrane collaboration search strategy. Neonatal respiratory outcomes were compared between the preterm IUGR and appropriately-grown for gestational age (AGA preterm infant populations in eligible studies. Results: No study was identified which evaluated the efficacy or responsiveness of exogenous surfactant replacement therapy in preterm IUGR infants as compared to preterm AGA infants. The only study identified through the search strategy used small for gestational age (SGA; defined as less than 10th centile for birth weight as a proxy for IUGR. The RCT evaluated the efficacy or responsiveness of SRT in preterm SGA group as compared to AGA infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary air leaks and days on the ventilator did not differ between both groups. However, the requirement for prolonged nasal CPAP (p< 0.001, supplemental oxygen therapy (p <0.01 and the incidence of bronchopulmonary dysplasia at 28 days and 36 weeks (both p<0.01 was greater in SGA infants. Discussion: There is currently insufficient data available to evaluate the efficacy of SRT in preterm IUGR lung disease. A variety of research strategies will be needed to enhance our understanding of the role and rationale for use of surfactant replacement therapy in preterm

  13. An updated review of the efficacy of cupping therapy.

    Science.gov (United States)

    Cao, Huijuan; Li, Xun; Liu, Jianping

    2012-01-01

    Since 1950, traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy. Six databases were searched for articles published through 2010. RCTs on cupping therapy for various diseases were included. Studies on cupping therapy combined with other TCM treatments versus non-TCM therapies were excluded. 135 RCTs published from 1992 through 2010 were identified. The studies were generally of low methodological quality. Diseases for which cupping therapy was commonly applied were herpes zoster, facial paralysis (Bell palsy), cough and dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was used in most trials, followed by retained cupping, moving cupping, and flash cupping. Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis. No serious adverse effects were reported in the trials. Numerous RCTs on cupping therapy have been conducted and published during the past decades. This review showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted.

  14. An Updated Review of the Efficacy of Cupping Therapy

    Science.gov (United States)

    Cao, Huijuan; Li, Xun; Liu, Jianping

    2012-01-01

    Background Since 1950, traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy. Method Six databases were searched for articles published through 2010. RCTs on cupping therapy for various diseases were included. Studies on cupping therapy combined with other TCM treatments versus non-TCM therapies were excluded. Results 135 RCTs published from 1992 through 2010 were identified. The studies were generally of low methodological quality. Diseases for which cupping therapy was commonly applied were herpes zoster, facial paralysis (Bell palsy), cough and dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was used in most trials, followed by retained cupping, moving cupping, and flash cupping. Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis. No serious adverse effects were reported in the trials. Conclusions Numerous RCTs on cupping therapy have been conducted and published during the past decades. This review showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted. PMID:22389674

  15. An updated review of the efficacy of cupping therapy.

    Directory of Open Access Journals (Sweden)

    Huijuan Cao

    Full Text Available BACKGROUND: Since 1950, traditional Chinese medicine (TCM cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs to evaluate the therapeutic effect of cupping therapy. METHOD: Six databases were searched for articles published through 2010. RCTs on cupping therapy for various diseases were included. Studies on cupping therapy combined with other TCM treatments versus non-TCM therapies were excluded. RESULTS: 135 RCTs published from 1992 through 2010 were identified. The studies were generally of low methodological quality. Diseases for which cupping therapy was commonly applied were herpes zoster, facial paralysis (Bell palsy, cough and dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was used in most trials, followed by retained cupping, moving cupping, and flash cupping. Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis. No serious adverse effects were reported in the trials. CONCLUSIONS: Numerous RCTs on cupping therapy have been conducted and published during the past decades. This review showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted.

  16. Effects of music therapy on drug avoidance self-efficacy in patients on a detoxification unit: a three-group randomized effectiveness study.

    Science.gov (United States)

    Silverman, Michael J

    2014-01-01

    Self-efficacy is a component of Bandura's social cognitive theory and can lead to abstinence and a reduction of relapse potential for people who have substance abuse disorders. To date, no music therapy researcher has utilized this theoretical model to address abstinence and reduce the likelihood of relapse in people who have addictions. The purpose of this study was to determine the effects of music therapy on drug avoidance self-efficacy in a randomized three-group wait-list control design with patients on a detoxification unit. Participants (N = 131) were cluster randomized to one of three single-session conditions: music therapy, verbal therapy, or wait-list control. Music therapy participants received a group lyric analysis intervention, verbal therapy participants received a group talk therapy session, and wait-list control participants eventually received a group recreational music therapy intervention. Although there was no significant between-group difference in drug avoidance self-efficacy, participants in the music therapy condition tended to have the highest mean drug avoidance self-efficacy scores. Posttest written comments supported the use of both music therapy and verbal therapy sessions. Two music therapy participants specifically noted that their initial skepticism had dissipated after receiving music therapy. Despite a lack of significant differences, the theoretical support of self-efficacy for substance abuse rehabilitation suggests that this may be an area of continued clinical focus and empirical investigation. Clinical anecdotes, limitations of the study, and suggestions for future research are provided.

  17. Advances in gene therapy of myocardial ischemia and the monitoring with molecular imaging

    International Nuclear Information System (INIS)

    Zhang Guopeng; Zhang Yongxue

    2008-01-01

    Cardiovascular diseases are harmful for people. Recent advances in understanding the molecular basis of cardiovascular diseases, together with some studies of the gene therapy on cardiovascular disorders, have offered possibilities for new treatments. Gene therapies have demonstrated potential usefulness in treating myocardial ischemia. Therefore, the monitoring of the expression of therapy gene and therapeutic efficacy has become an important issue. (authors)

  18. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy

    DEFF Research Database (Denmark)

    Battelino, T; Conget, I; Olsen, B

    2012-01-01

    The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes.......The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes....

  19. Do ABO blood group antigens hamper the therapeutic efficacy of mesenchymal stromal cells?

    Science.gov (United States)

    Moll, Guido; Hult, Annika; von Bahr, Lena; Alm, Jessica J; Heldring, Nina; Hamad, Osama A; Stenbeck-Funke, Lillemor; Larsson, Stella; Teramura, Yuji; Roelofs, Helene; Nilsson, Bo; Fibbe, Willem E; Olsson, Martin L; Le Blanc, Katarina

    2014-01-01

    Investigation into predictors for treatment outcome is essential to improve the clinical efficacy of therapeutic multipotent mesenchymal stromal cells (MSCs). We therefore studied the possible harmful impact of immunogenic ABO blood groups antigens - genetically governed antigenic determinants - at all given steps of MSC-therapy, from cell isolation and preparation for clinical use, to final recipient outcome. We found that clinical MSCs do not inherently express or upregulate ABO blood group antigens after inflammatory challenge or in vitro differentiation. Although antigen adsorption from standard culture supplements was minimal, MSCs adsorbed small quantities of ABO antigen from fresh human AB plasma (ABP), dependent on antigen concentration and adsorption time. Compared to cells washed in non-immunogenic human serum albumin (HSA), MSCs washed with ABP elicited stronger blood responses after exposure to blood from healthy O donors in vitro, containing high titers of ABO antibodies. Clinical evaluation of hematopoietic stem cell transplant (HSCT) recipients found only very low titers of anti-A/B agglutination in these strongly immunocompromised patients at the time of MSC treatment. Patient analysis revealed a trend for lower clinical response in blood group O recipients treated with ABP-exposed MSC products, but not with HSA-exposed products. We conclude, that clinical grade MSCs are ABO-neutral, but the ABP used for washing and infusion of MSCs can contaminate the cells with immunogenic ABO substance and should therefore be substituted by non-immunogenic HSA, particularly when cells are given to immunocompentent individuals.

  20. Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

    Science.gov (United States)

    Shen, Chunhong; Zhang, Bijun; Liu, Zhirong; Tang, Yelei; Zhang, Yinxi; Wang, Shan; Guo, Yi; Ding, Yao; Wang, Shuang; Ding, Meiping

    2017-10-01

    The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Creativity and improvisation as therapeutic tools within music therapy.

    Science.gov (United States)

    Tomaino, Concetta M

    2013-11-01

    The neuroscience of creativity and music improvisation is a fascinating topic and one with strong implications for clinical music therapy. Music therapists are trained to use musical improvisation as a means to bring their clients into deeper therapeutic relationship as well as free up any inhibitions or limitations that may block recovery. Could recent fMRI studies of jazz musicians showing areas of brain activation during music improvisation provide a new framework to understand underlying mechanisms at work with neurologically impaired individuals? © 2013 New York Academy of Sciences.

  2. Treatment of obsessive morbid jealousy with cognitive analytic therapy: An adjudicated hermeneutic single-case efficacy design evaluation.

    Science.gov (United States)

    Curling, Louise; Kellett, Stephen; Totterdell, Peter; Parry, Glenys; Hardy, Gillian; Berry, Katherine

    2018-03-01

    The evidence base for the treatment of morbid jealousy with integrative therapies is thin. This study explored the efficacy of cognitive analytic therapy (CAT). An adjudicated hermeneutic single-case efficacy design evaluated the cognitive analytic treatment of a patient meeting diagnostic criteria for obsessive morbid jealousy. A rich case record was developed using a matrix of nomothetic and ideographic quantitative and qualitative outcomes. This record was then debated by sceptic and affirmative research teams. Experienced psychotherapy researchers acted as judges, assessed the original case record, and heard the affirmative-versus-sceptic debate. Judges pronounced an opinion regarding the efficacy of the therapy. The efficacy of CAT was supported by all three judges. Each ruled that change had occurred due to the action of the therapy, beyond any level of reasonable doubt. This research demonstrates the potential usefulness of CAT in treating morbid jealousy and suggests that CAT is conceptually well suited. Suggestions for future clinical and research directions are provided. The relational approach of CAT makes it a suitable therapy for morbid jealousy. The narrative reformulation component of CAT appears to facilitate early change in chronic jealousy patterns. It is helpful for therapists during sessions to use CAT theory to diagrammatically spell out the patterns maintaining jealousy. © 2017 The British Psychological Society.

  3. Efficacy of topical latanoprost versus minoxidil and betamethasone valerate on the treatment of alopecia areata.

    Science.gov (United States)

    El-Ashmawy, Amal Ahmad; El-Maadawy, Iman Hamed; El-Maghraby, Gamal Mohamed

    2018-02-01

    Alopecia areata (AA) is one of the most common causes of localized hair loss. There is no universally proven therapy that induces and sustains remission of hair growth in AA. To compare the efficacy and safety of topical latanoprost, minoxidil and betamethasone valerate on hair growth in patients with AA. Hundred patients with AA classified into five groups of 20 treated with: Group I, latanoprost 0.1% lotion; Group II, minoxidil 5% lotion; Group III, betamethasone valerate 0.1% solution; Group IV, combination of latanoprost lotion and betamethasone valerate solution and Group V, a vehicle lotion control group. There was a statistically significant improvement in all therapeutic groups when compared with control group and reduction of severity of alopecia tool score of scalp and beard before and after treatment for all therapeutic groups. Latanoprost, minoxidil and betamethasone valerate are effective and safe in the treatment of patchy AA. The use of latanoprost added to the therapeutic efficacy of topical betamethasone valerate in the treatment of AA and could be an effective adjunctive topical therapy for AA.

  4. Efficacy and mechanisms of behavioral therapy components for insomnia coexisting with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Kapella, Mary C; Herdegen, James J; Laghi, Franco; Steffen, Alana D; Carley, David W

    2016-05-23

    and substantive departure from the usual insomnia therapy, namely by testing traditional CBT-I with education to enhance outcomes. The work proposed in aims 1 and 2 will provide systematic evidence of the efficacy and mechanisms of components of a novel approach to insomnia comorbid with COPD. Such results are highly likely to provide new approaches for preventive and therapeutic interventions for insomnia and fatigue in COPD. ClinicalTrials.gov Identifier: NCT01973647 . Registered on 22 October 2013.

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

    Science.gov (United States)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

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

  6. Use of polyclonal/monoclonal antibody therapies in transplantation.

    Science.gov (United States)

    Yeung, Melissa Y; Gabardi, Steven; Sayegh, Mohamed H

    2017-03-01

    For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation. Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection. It also provides examples of promising novel mAb therapies, and discusses the potential for future mAb development in transplantation. Expert opinion: The broad capability of antibodies, in parallel with our growing ability to synthetically modulate them, offers exciting opportunities to develop better biologic therapeutics. In order to do so, we must further our understanding about the basic biology underlying allograft rejection, and gain better appreciation of how characteristics of therapeutic antibodies affect their efficacy.

  7. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

    Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

  8. Efficacy and Safety of Combined Oral and Enema Therapy Using Polyethylene Glycol 3350-Electrolyte for Disimpaction in Pediatric Constipation.

    Science.gov (United States)

    Yoo, Taeyeon; Bae, Sun Hwan

    2017-12-01

    We evaluated the efficacy and safety of combined oral and enema therapy using polyethylene glycol (PEG) 3350 with electrolyte solution for disimpaction in hospitalized children. We retrospectively studied 28 children having functional constipation who received inpatient treatment between 2008 and 2016. The amount of oral PEG 3350 electrolyte solution administered was 50-70 mL/kg/d (PEG 3350, 3-4.1 g/kg/d), and an enema solution was administered 1-2 times a day as a single dose of 15-25 mL/kg (PEG 3350, 0.975-1.625 g/kg/d). A colon transit time (CTT) test based on the Metcalf protocol was performed in some patients. Administration of oral and enema doses of PEG 3350 electrolyte solution showed 2.1±0.3 times and 2.9±0.4 times, respectively. After disimpaction, the frequency of defecation increased from 2.2±0.3 per week to once a day (1.1±0.1 per day). The number of patients who complained of abdominal pain was reduced from 15 (53.6%) to 4 (14.3%). Before hospitalization, nine patients underwent a CTT test, and 5 of 9 patients (55.6%) were classified as belonging to a group showing abnormalities. And in some patients, mild adverse effects were noted. We examined electrolytes and osmolality before and after disimpaction in 16 of 28 patients, and no abnormalities were noted. In terms of therapeutic efficacy and safety, combined oral and enema therapy using high-dose PEG 3350 with electrolytes is considered superior to conventional oral monotherapy or combined oral and enema therapy on an outpatient basis.

  9. A Qualitative Exploration of Therapeutic Relationships from the Perspective of Six Children Receiving Speech-Language Therapy

    Science.gov (United States)

    Fourie, Robert; Crowley, Niamh; Oliviera, Ana

    2011-01-01

    Although some studies have explored the adult therapeutic relationship in speech-language pathology, few, if any, have examined it with regard to children. This study aimed to explore the therapeutic relationship in pediatric speech and language therapy, focusing on the child's experience. Accordingly, the study was qualitative and involved the…

  10. Liposome based radiosensitizer cancer therapy

    DEFF Research Database (Denmark)

    Pourhassan, Houman

    Liposome-encapsulated chemotherapeutics have been used in the treatment of a variety of cancers and are feasible for use as mono-therapeutics as well as for combination therapy in conjunction with other modalities. Despite widespread use of liposomal drugs in cancer patient care, insufficient drug...... biomolecules. By modulating the liposomal membrane, liposomes can become sensitive towards enzymatically-driven destabilization and/or functionalization, thereby allowing control of the release of encapsulated therapeutics within the diseased tissue upon intrinsic stimulation from tumor-associated enzymes...... in tumor-bearing mice.The safety and efficacy of sPLA2-sensitive liposomal L-OHP was assessed in sPLA2-deficient FaDu hypopharyngeal squamous cell carcinoma and sPLA2-expressing Colo205 colorectal adenocarcinoma. Also, the feasibility of multimodal cancer therapy employing L-OHP encapsulated in MMP...

  11. Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure

    NARCIS (Netherlands)

    Dickinson, Brent A; Semus, Hillary M; Montgomery, Rusty L; Stack, Christianna; Latimer, Paul A; Lewton, Steven M; Lynch, Joshua M; Hullinger, Thomas G; Seto, Anita G; van Rooij, Eva

    AIMS: Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in

  12. Therapeutic Change in Group Therapy For Interpersonal Trauma: A Relational Framework for Research and Clinical Practice.

    Science.gov (United States)

    Chouliara, Zoë; Karatzias, Thanos; Gullone, Angela; Ferguson, Sandra; Cosgrove, Katie; Burke Draucker, Claire

    2017-04-01

    Our understanding of therapeutic change processes in group therapy for complex interpersonal trauma has been limited. The present study aimed at addressing this gap by developing a framework of therapeutic change in this field from a survivor and therapist perspective. This is a qualitative study, which utilized semistructured individual interviews. Transcripts were analyzed using interpretative phenomenological analysis (IPA) to identify recurrent themes. A final sample of n = 16 patients and n = 5 facilitators completed the interview. Main change processes identified by survivors were as follows: self versus others, trust versus threat, confrontation versus avoidance, and "patching up" versus true healing. Therapeutic processes identified by therapist facilitators included managing group dynamics, unpredictability and uncertainty, and process versus content. The proposed framework explains therapeutic change in group therapy in relational terms, that is, therapeutic dissonance, the dynamic interaction of self and experience as well as building empathic trusting relations. The importance of managing dissonance to aid personally meaningful recovery was highlighted. These findings have implications for the usefulness of relational and person-centered approaches to clinical practice in the area of interpersonal and complex trauma, especially in the early identification, prevention, and management of dropouts.

  13. Clinical efficacy of implementing Bio Immune(G)ene MEDicine in the treatment of chronic asthma with the objective of reducing or removing effectively corticosteroid therapy: A novel approach and promising results.

    Science.gov (United States)

    Glady, Gilbert

    2018-06-01

    Asthma is one of the diseases that demonstrates a wide range of variation in its clinical expression, in addition to an important heterogeneity in the pathophysiological mechanisms present in each case. The ever-increasing knowledge of the molecular signalling routes and the development of the Bio Immune(G)ene Medicine [BI(G)MED] therapy in line with this knowledge has revealed a whole novel potential set of self-regulation biological molecules, that may be used to promote the physiological immunogenic self-regulation mechanisms and re-establish the homeostatic balance at a genomic, proteomic and cellular level. The aim of the present study is to demonstrate that the sublingual use of a therapeutic protocol based on BI(G)MED regulatory BIMUREGs in the treatment of chronic asthma may reduce or suppress corticosteroid therapy and avoid its harmful side effects which some patients suffer when using this treatment on a long-term basis. The clinical efficacy of BI(G)MED for chronic asthma was evaluated through a multi-centre study carried out in 2016 implementing a 6-month BI(G)MED treatment protocol for Bronchial Asthma. A total of 61 patients from private medical centres and of European countries including Germany, Austria, France, Belgium and Spain participated. The manuscript describes in detail the clinical efficacy of Bio Immune(G)ene regulatory BI(G)MED treatment protocol that allows the reduction or total removal of the corticosteroid dose in patients with chronic asthma. No adverse reactions were observed. The BI(G)MED regulatory therapy brings novel therapeutic possibilities as an effective and safe treatment of chronic asthma. BI(G)MED was demonstrated to significantly reduce asthma severity when parameter compositions were all analysed by categorical outcomes. Therefore, it is considered a good therapeutic alternative for patients who respond poorly to steroids.

  14. Adverse events and therapeutic efficacy associated with TACE for hepatocellular carcinoma with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension

    International Nuclear Information System (INIS)

    Araki, Takuji; Okada, Taiki; Kimura, Kazufumi; Sawada, Eiichi; Sano, Katushiro; Araki, Tsutomu

    2012-01-01

    The aim of this study was to evaluate the short-term adverse events and therapeutic efficacy of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension. Of patients who underwent TACE for unresectable HCCs in 2009 and 2010, twenty-nine and twenty-seven patients underwent TACE using cisplatin-lipiodol suspension (C-LS) and miriplatin-lipiodol suspension (M-LS), respectively. Adverse events of fever, pain, nausea, anorexia, elevation of aspartate aminotransferase (AST), total bilirubin, creatinine and a decrease in platelet count were evaluated by the National Cancer Institute Common Toxicity Criteria Ver.4. to compare the C-LS and M-LS groups. The short-term therapeutic efficacy of both groups was evaluated by the treatment effect (TE) on the CT images three months after TACE according to the General Rules for the Clinical and Pathological Study of Primary Liver Cancer (the 5th edition, Revised Version). With regard to the adverse events, the M-LS group had significantly less fever and anorexia than the C-LS group. No critical adverse events were observed in either group. The therapeutic efficacy was not significantly different between the groups. TACE with M-LS had fewer adverse events than TACE with C-LS, but neither TACE led to any critical adverse events. The short-term therapeutic efficacy of TACE with M-LS was equivalent to that of TACE with C-LS. (author)

  15. Gene Therapy With Regulatory T Cells: A Beneficial Alliance

    Directory of Open Access Journals (Sweden)

    Moanaro Biswas

    2018-03-01

    Full Text Available Gene therapy aims to replace a defective or a deficient protein at therapeutic or curative levels. Improved vector designs have enhanced safety, efficacy, and delivery, with potential for lasting treatment. However, innate and adaptive immune responses to the viral vector and transgene product remain obstacles to the establishment of therapeutic efficacy. It is widely accepted that endogenous regulatory T cells (Tregs are critical for tolerance induction to the transgene product and in some cases the viral vector. There are two basic strategies to harness the suppressive ability of Tregs: in vivo induction of adaptive Tregs specific to the introduced gene product and concurrent administration of autologous, ex vivo expanded Tregs. The latter may be polyclonal or engineered to direct specificity to the therapeutic antigen. Recent clinical trials have advanced adoptive immunotherapy with Tregs for the treatment of autoimmune disease and in patients receiving cell transplants. Here, we highlight the potential benefit of combining gene therapy with Treg adoptive transfer to achieve a sustained transgene expression. Furthermore, techniques to engineer antigen-specific Treg cell populations, either through reprogramming conventional CD4+ T cells or transferring T cell receptors with known specificity into polyclonal Tregs, are promising in preclinical studies. Thus, based upon these observations and the successful use of chimeric (IgG-based antigen receptors (CARs in antigen-specific effector T cells, different types of CAR-Tregs could be added to the repertoire of inhibitory modalities to suppress immune responses to therapeutic cargos of gene therapy vectors. The diverse approaches to harness the ability of Tregs to suppress unwanted immune responses to gene therapy and their perspectives are reviewed in this article.

  16. High-Throughput Cancer Cell Sphere Formation for Characterizing the Efficacy of Photo Dynamic Therapy in 3D Cell Cultures

    Science.gov (United States)

    Chen, Yu-Chih; Lou, Xia; Zhang, Zhixiong; Ingram, Patrick; Yoon, Euisik

    2015-07-01

    Photodynamic therapy (PDT), wherein light sensitive non-toxic agents are locally and selectively activated using light, has emerged as an appealing alternative to traditional cancer chemotherapy. Yet to date, PDT efficacy has been mostly characterized using 2D cultures. Compared to 2D cultures, 3D sphere culture generates unique spatial distributions of nutrients and oxygen for the cells that better mimics the in-vivo conditions. Using a novel polyHEMA (non-adherent polymer) fabrication process, we developed a microfluidic sphere formation platform that can (1) generate 1,024 uniform (size variation successfully characterized the different responses in 2D and 3D cell culture to PDT. Furthermore, we investigated the treatment resistance effect in cancer cells induced by tumor associated fibroblasts (CAF). Although the CAFs can enhance the resistance to traditional chemotherapy agents, no significant difference in PDT was observed. The preliminary results suggest that the PDT can be an attractive alternative cancer therapy, which is less affected by the therapeutic resistance induced by cancer associated cells.

  17. Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: jayjeong@chonbuk.ac.k [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of)

    2011-01-15

    Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.

  18. Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

    Science.gov (United States)

    Patel, Ravi Mangal; Denning, Patricia Wei

    2013-01-01

    Synopsis Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. In addition, prebiotics and postbiotics may be potential alternatives or adjunctive therapies to the administration of live microorganisms, although studies demonstrating their clinical efficacy in preventing NEC are lacking. This review summarizes the current evidence regarding the use of probiotics, prebiotics and postbiotics in the preterm infant, including its therapeutic role in preventing NEC. PMID:23415261

  19. Determining efficacy of breast cancer therapy by PET imaging of HER2 mRNA

    International Nuclear Information System (INIS)

    Paudyal, Bishnuhari; Zhang, Kaijun; Chen, Chang-Po; Wampole, Matthew E.; Mehta, Neil; Mitchell, Edith P.; Gray, Brian D.; Mattis, Jeffrey A.; Pak, Koon Y.; Thakur, Mathew L.; Wickstrom, Eric

    2013-01-01

    Introduction: Monitoring the effectiveness of therapy early and accurately continues to be challenging. We hypothesize that determination of Human Epidermal Growth Factor Receptor 2 (HER2) mRNA in malignant breast cancer (BC) cells by positron emission tomography (PET) imaging, before and after treatment, would reflect therapeutic efficacy. Method: WT4340, a peptide nucleic acid (PNA) 12-mer complementary to HER2 mRNA was synthesized together with -CSKC, a cyclic peptide, which facilitated internalization of the PNA via IGFR expressed on BC cells, and DOTA that chelated Cu-64. Mice (n = 8) with BT474 ER +/HER2+ human BC received doxorubicin (DOX, 1.5 mg/kg) i.p. once a week for six weeks. Mice (n = 8) without DOX served as controls. All mice were PET imaged with F-18-FDG and 48 h later with Cu-64-WT4340. PET imaging were performed before and 72 h after each treatment. Standardized uptake values (SUVs) were determined and percent change calculated. Animal body weight (BW) and tumor volume (TV) were measured. Results: SUVs for Cu-64-WT4340 after DOX treatment declined by 54% ± 17% after the second dose, 41% ± 15% after the fourth dose, and 29% ± 7% after the sixth dose, compared with 42% ± 22%, 31% ± 18%, and 13% ± 9% (p < 0.05) for F-18-FDG. In untreated mice, the corresponding percent SUVs for Cu-64-WT4340 were 145% ± 82%, 165% ± 39%, and 212% ± 105% of pretreatment SUV, compared with 108% ± 28%, 151% ± 8%, and 152% ± 35.5%, (p < 0.08) for F-18-FDG. TV in mice after second dose was 114.15% ± 61.83%, compared with 144.7% ± 64.4% for control mice. BW of DOX-treated mice was 103.4% ± 7.6% of pretreatment, vs. 100.1% ± 4.3% for control mice. Conclusion: Therapeutic efficacy was apparent sooner by molecular PET imaging than by determination of reduction in TV

  20. The significance of the host inflammatory response on the therapeutic efficacy of cell therapies utilising human adult stem cells

    International Nuclear Information System (INIS)

    Navarro, Melba; Pu, Fanrong; Hunt, John A.

    2012-01-01

    Controlling the fate of implanted hMSCs is one of the major drawbacks to be overcome to realize tissue engineering strategies. In particular, the effect of the inflammatory environment on hMSCs behaviour is poorly understood. Studying and mimicking the inflammatory process in vitro is a very complex and challenging task that involves multiple variables. This research addressed the questions using in vitro co-cultures of primary derived hMSCs together with human peripheral blood mononucleated cells (PBMCs); the latter are key agents in the inflammatory process. This work explored the in vitro phenotypic changes of hMSCs in co-culture direct contact with monocytes and lymphocytes isolated from blood using both basal and osteogenic medium. Our findings indicated that hMSCs maintained their undifferentiated phenotype and pluripotency despite the contact with PBMCs. Moreover, hMSCs demonstrated increased proliferation and were able to differentiate specifically down the osteogenic lineage pathway. Providing significant crucial evidence to support the hypothesis that inflammation and host defence mechanisms could be utilised rather than avoided and combated to provide for the successful therapeutic application of stem cell therapies.

  1. Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

    International Nuclear Information System (INIS)

    Tirkey, Bulbul; Bhushan, Bharat; Uday Kumar, S.; Gopinath, P.

    2017-01-01

    Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

  2. Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tirkey, Bulbul [Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Bhushan, Bharat; Uday Kumar, S. [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Gopinath, P., E-mail: pgopifnt@iitr.ernet.in [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India)

    2017-04-01

    Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

  3. EFFECT OF MUSIC THERAPY ON INTRINSIC MOTIVATION, PHYSICAL SELF EFFICACY AND PERFORMANCE OF FEMALE FOOTBALL PLAYERS

    OpenAIRE

    Mamta Sharma; Gagandeep Kaur

    2015-01-01

    Music therapy is increasingly used in sports for enhancing sport performance. It provides a mean of improving mental strength among sportspersons. The purpose of this study is to enhance intrinsic motivation, physical self-efficacy and performance of female football players through music therapy. For this purpose, twenty two female football players, in the age group of 21-26 were screened on the basis of their scores on Sport Motivation Scale and Physical Self-Efficacy Scale. Then, they were ...

  4. Stem Cell Therapy for Diabetic Erectile Dysfunction in Rats: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Mingchao Li

    Full Text Available Stem cell therapy is a novel method for the treatment of diabetic erectile dysfunction (ED. Many relative animal studies have been done to evaluate the efficacy of this therapy in rats.This meta-analysis was performed to compare the efficacy of different stem cell therapies, to evaluate the influential factors and to determine the optimal stem cell therapeutic strategy for diabetic ED.We searched the studies analyzing the efficacy of stem cell therapy for diabetic ED in rats published before September 30, 2015 in PubMed, Web of Science and EBSCO. A random effects meta-analysis was conducted to assess the outcomes of stem cell therapy. Subgroup analysis was also performed by separating these studies based on their different characteristics. Changes in the ratio of intracavernous pressure (ICP to mean arterial pressure (MAP and in the structure of the cavernous body were compared.10 studies with 302 rats were enrolled in this meta-analysis. Pooled analysis of these studies showed a beneficial effect of stem cell therapy in improving erectile function of diabetic rats (SMD 4.03, 95% CI = 3.22 to 4.84, P< 0.001. In the stem cell therapy group, both the smooth muscle and endothelium content were much more than those in control group. There was also significant increase in the expression of endothelial nitric oxide synthase (eNOS and neuronal nitric oxide synthase (nNOS, the ratio of smooth muscle to collagen, as well as the secretion of vascular endothelial growth factor (VEGF. Besides, apoptotic cells were reduced by stem cell treatment. The subgroup analysis indicated that modified stem cells were more effective than those without modification.Our results confirmed that stem cell therapy could apparently improve the erectile function of diabetic rats. Some specific modification, especially the gene modification with growth factors, could improve the efficacy of stem cell therapy. Stem cell therapy has potential to be an effective therapeutic

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

    Science.gov (United States)

    Romano, Michele; Negrini, Stefano

    2008-01-22

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

  6. Associations between therapy skills and patient experiences of change processes in cognitive behavioral therapy for psychosis.

    Science.gov (United States)

    Wittorf, Andreas; Jakobi-Malterre, Ute E; Beulen, Silke; Bechdolf, Andreas; Müller, Bernhard W; Sartory, Gudrun; Wagner, Michael; Wiedemann, Georg; Wölwer, Wolfgang; Herrlich, Jutta; Klingberg, Stefan

    2013-12-30

    Despite the promising findings in relation to the efficacy of cognitive behavioral therapy for psychosis (CBTp), little attention has been paid to the therapy skills necessary to deliver CBTp and to the influence of such skills on processes underlying therapeutic change. Our study investigated the associations between general and technical therapy skills and patient experiences of change processes in CBTp. The study sample consisted of 79 patients with psychotic disorders who had undergone CBTp. We randomly selected one tape-recorded therapy session from each of the cases. General and technical therapy skills were assessed by the Cognitive Therapy Scale for Psychosis. The Bern Post Session Report for Patients was applied to measure patient experiences of general change processes in the sense of Grawe's psychological therapy. General skills, such as feedback and understanding, explained 23% of the variance of patients' self-esteem experience, but up to 10% of the variance of mastery, clarification, and contentment experiences. The technical skill of guided discovery consistently showed negative associations with patients' alliance, contentment, and control experiences. The study points to the importance of general therapy skills for patient experiences of change processes in CBTp. Some technical skills, however, could detrimentally affect the therapeutic relationship. © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Differences and similarities in therapeutic mode use between occupational therapists and occupational therapy students in Norway.

    Science.gov (United States)

    Carstensen, Tove; Bonsaksen, Tore

    2017-11-01

    The Intentional Relationship Model (IRM) is a new model of the therapeutic relationship in occupational therapy practice. Two previous studies have focused on therapist communication style, or 'mode' use, but to date no group comparisons have been reported. To explore differences between occupational therapists and occupational therapy students with regard to their therapeutic mode use. The study had a cross-sectional design, and convenience samples consisting of occupational therapists (n = 109) and of second-year occupational therapy students (n = 96) were recruited. The Self-Assessment of Modes Questionnaire was the main data collection tool. Group differences were analysed with independent t-tests. The occupational therapists responded more within the collaborative and empathizing modes than the students did. The students responded more within the advocating and instructing modes than the occupational therapists did. There may be systematic differences between occupational therapists and students concerning their therapeutic mode use. Some modes, such as the collaborating and empathizing modes, may be viewed as requiring more experience, whereas other modes, such as the advocating mode may be related to more recent rehabilitation ideologies. These factors may contribute to explaining several of the group differences observed.

  8. Efficacy of magneto-laser therapy in the treatment of ureaplasma infection

    Directory of Open Access Journals (Sweden)

    N N Aliev

    2018-04-01

    Full Text Available Aim. To study clinical and epidemiological data in males and females with ureaplasma infection and to evaluate efficacy of magneto-laser therapy used as additional treatment of ureaplasma infection. Methods. 104 patients (94 men and 10 women with urogenital ureaplasma infection were observed. Patients were divided into two groups: a study group (n=55 that received standard and magneto-laser therapy, and a comparison group (n=49 that received only standard treatment. Polymerase chain reaction was used to investigate samples for Mycoplasma hominis, Ureaplasma parvum and urealyticum, and bacteriological study for Mycoplasma hominis and Ureaplasma spp. was additionally performed with determining their antibiotic susceptibility. Magnetic therapy was conducted with the use of Michelangelo device (Italy for 10 minutes to small pelvis area for 10 days. Results. As a result, 78 (82.9% males were diagnosed with uretritis, 52 (55.3% with prostatitis, 37 (39.3% with cystitis. In females monoinfection was more prevalent than in males (50.0% vs 40.4%. Ureaplasmosis predominantly affected subjects aged 20-29 (97.8% and 30-39 (86.0% years. In female group, patients aged 20-29 years prevailed, while in a male group - patients aged 30-39 years. In males, the association of Ureaplasma with Mycoplasma hominis (36.1% prevailed. Conclusion. Complex treatment of ureaplasma infection of urogenital tract including magneto-laser therapy demonstrated high clinical efficacy and allowed achieving clinical and laboratory cure of ureaplasma infection in 85.4% of cases.

  9. Therapy of the burnout syndrome.

    Science.gov (United States)

    Korczak, Dieter; Wastian, Monika; Schneider, Michael

    2012-01-01

    The prevalence, diagnostics and therapy of the burnout syndrome are increasingly discussed in the public. The unclear definition and diagnostics of the burnout syndrome are scientifically criticized. There are several therapies with unclear evidence for the treatment of burnout in existence. The health technology assessment (HTA) report deals with the question of usage and efficacy of different burnout therapies. For the years 2006 to 2011, a systematic literature research was done in 31 electronic databases (e.g. EMBASE, MEDLINE, PsycINFO). Important inclusion criteria are burnout, therapeutic intervention and treatment outcome. 17 studies meet the inclusion criteria and are regarded for the HTA report. The studies are very heterogeneous (sample size, type of intervention, measuring method, level of evidence). Due to their study design (e.g. four reviews, eight randomized controlled trials) the studies have a comparable high evidence: three times 1A, five times 1B, one time 2A, two times 2B and six times 4. 13 of the 17 studies are dealing with the efficacy of psychotherapy and psychosocial interventions for the reduction of burnout (partly in combination with other techniques). Cognitive behaviour therapy leads to the improvement of emotional exhaustion in the majority of the studies. The evidence is inconsistent for the efficacy of stress management and music therapy. Two studies regarding the efficacy of Qigong therapy do not deliver a distinct result. One study proves the efficacy of roots of Rhodiola rosea (evidence level 1B). Physical therapy is only in one study separately examined and does not show a better result than standard therapy. Despite the number of studies with high evidence the results for the efficacy of burnout therapies are preliminary and do have only limited reach. The authors of the studies complain about the low number of skilled studies for the therapy of burnout. Furthermore, they point to the insufficient evaluation of the therapy

  10. Therapeutic efficacy of hydro-kinesiotherapy Programs in lumbar spondylosis

    Directory of Open Access Journals (Sweden)

    Ana-Maria BOTEZAN

    2015-12-01

    Full Text Available Lumbar spondylarthrosis is a degenerative disease that affects the joint structures of the lumbar spine. In the course of time, numerous studies on the role of hydro-kinesiotherapy in the treatment of lumbar spondylosis have been conducted. The aim of this research is motivated by the significantly high number of patients with chronic pain in the lumbar spine due to lumbar spondylosis, as well as by the negative impact on their quality of life through the impairment of the activities of daily living. The prospective longitudinal study was carried out at the Clinical Rehabilitation Hospital Cluj-Napoca. The study included 35 patients with chronic low back pain and mobility limitation in the lumbar spine. The patients were assigned to two groups: the study group formed by 20 patients and the control group consisting of 15 patients aged between 40-70 years. The treatment of the patients included in the study was performed over a two week period and consisted of a hydro-kinesiotherapy program, for the patients of the study group, the duration of a treatment session being 40 minutes. Both the subjects of the study group and of the control group also benefited from sedative massage of the lumbosacral spine, kinesiotherapy, laser therapy of the lumbar spine. The patients were evaluated using Schober’s test, the Visual Analogue Scale, the Oswestry index. These evaluation methods were applied to the patients of both groups at the beginning of the rehabilitation programs and after two weeks. The results of the study demonstrated the therapeutic efficacy of the medical rehabilitation programs that included hydro-kinesiotherapy programs. The patients of both groups had improvements through a decrease of lumbar pain, an increase in lumbar spine mobility, as well as in the patients’ ability to organize themselves in the activities of daily living. However, the patients of the study group, with a hydro-kinesiotherapy program performed for two weeks, had

  11. Cumulative Childhood Trauma and Therapeutic Alliance: The Moderator Role of Attachment in Adult Patients Consulting in Sex Therapy.

    Science.gov (United States)

    Lafrenaye-Dugas, Anne-Julie; Godbout, Natacha; Hébert, Martine

    2018-03-05

    While it is documented that clients consulting in sex therapy tend to report high rates of childhood interpersonal traumas (e.g., physical, psychological and sexual abuse), which are associated to insecure attachment and poorer therapeutic alliance, the interrelations of these variables have not yet been evaluated in this specific population. This study examined the associations between attachment, cumulative trauma and therapeutic alliance in 278 sex therapy patients who filled out self-report questionnaires. Results revealed that avoidant attachment acted as a moderator between cumulative trauma and the agreement on tasks dimension of therapeutic alliance. Results suggests the relevance for sex therapists to investigate past traumas and current attachment representations to guide interventions and optimize treatment benefits.

  12. Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study.

    Science.gov (United States)

    Sambola, A; Ferreira-González, I; Angel, J; Alfonso, F; Maristany, J; Rodríguez, O; Bueno, H; López-Minguez, J R; Zueco, J; Fernández-Avilés, F; San Román, A; Prendergast, B; Mainar, V; García-Dorado, D; Tornos, P

    2009-09-01

    To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk. A prospective multicentre registry. In hospital, after discharge and follow-up by telephone call. 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included. Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk. In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

  13. Radiation therapy for metastatic spinal tumors

    International Nuclear Information System (INIS)

    Kida, Akio; Fukuda, Haruyuki; Taniguchi, Shuji; Sakai, Kazuaki

    2000-01-01

    The results of radiation therapy for metastatic spinal tumors were evaluated in terms of pain relief, improvement of neurological impairment, and survival. Between 1986 and 1995, 52 symptomatic patients with metastatic spinal tumors treated with radiation therapy were evaluated. The patients all received irradiation of megavoltage energy. Therapeutic efficacy was evaluated in terms of pain relief and improvement of neurological impairment. Pain relief was observed in 29 (61.7%) of 47 patients with pain. Therapy was effective for 17 (70.8%) of 24 patients without neurological impairment, and efficacy was detected in 12 (52.2%) of 23 patients with neurological impairment. Improvement of neurological symptoms was obtained in seven (25.0%) of 28 patients with neurological impairment. Radiation therapy was effective for pain relief in patients with metastatic spinal tumors. In patients with neurological impairment, less pain relief was observed than in those without impairment. Improvement of neurological impairment was restricted, but radiation therapy was thought to be effective in some cases in the early stage of neurological deterioration. Radiation therapy for metastatic spinal tumors contraindicated for surgery was considered effective for improvement of patients' activities of daily living. (author)

  14. Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trouette, R; Causse, N; Elkhadri, M; Caudry, M; Maire, J P; Houlard, J P; Racaldini, L; Demeaux, H

    1995-12-01

    Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

  15. Predictors of change in music therapy with children and adolescents: the role of therapeutic techniques.

    Science.gov (United States)

    Gold, Christian; Wigram, Tony; Voracek, Martin

    2007-12-01

    Music therapy has been shown to be efficacious in experimental studies. However, there is little empirical research knowledge about what elements of music therapy influence its effectiveness in clinical practice. Children and adolescents with psychopathology (N=75) were assessed before and after participating in individual music therapy with 1 out of 15 music therapists in the Vienna region. Relationships between outcomes (as evaluated by parents) and therapy contents (as reported by therapists) were examined using general linear modelling. Results indicated that clients' symptoms and burdens on their social environment showed greater improvement when music therapy was limited to discipline-specific music therapy techniques and did not include other media such as play therapy elements. The findings indicate the importance of being aware of a therapy method's specific strengths and limitations. More research on the indicated specific ingredients of music therapy intervention is needed.

  16. Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma.

    Science.gov (United States)

    Cancedda, S; Rohrer Bley, C; Aresu, L; Dacasto, M; Leone, V F; Pizzoni, S; Gracis, M; Marconato, L

    2016-12-01

    Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi-institutional trial was conducted to compare efficacy and safety of radiation therapy (RT) and RT with post-radiation temozolomide in dogs with chemotherapy-naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m -2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p = 0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post-radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to coarse fractionated RT. © 2014 John Wiley & Sons Ltd.

  17. Efficacy of functional electrical stimulation-biofeedback with sexual cognitive-behavioral therapy as treatment of vaginismus.

    Science.gov (United States)

    Seo, Ju Tae; Choe, Jin Ho; Lee, Won Sik; Kim, Kyung Hee

    2005-07-01

    To report 12 cases of vaginismus that were successfully treated with functional electrical stimulation (FES)-biofeedback with sexual cognitive-behavioral therapy (SCBT) to determine the efficacy of FES-biofeedback with SCBT as a standard therapy for vaginismus. Vaginismus is an involuntary spasm of the musculature of the outer third of the vagina that leads to impossible vaginal penetration, causing personal distress. Various therapeutic approaches, both physiologic and psychological, have been considered. Twelve women with vaginismus referred from a checkup outpatient clinic participated in this study. The patients enrolled in this study had vaginismus according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders. The patients were assessed before and after treatment with gynecologic examinations and structured interviews pertaining to sexual function and psychological adjustment. After the diagnosis of vaginismus, we conducted weekly pelvic floor muscle relaxation using FES-biofeedback. Once the patients became tolerable to vaginal manipulation, the eight-stage SCBT (eight-stage gradual desensitization described by Kaplan using vaginal self-dilation with fingers and vaginal probe insertion) was added for 8 weeks. After 8 weeks of treatment, all 12 couples had completed the program, had become tolerable to vaginal insertion of larger size probes, and could achieve satisfactory vaginal intercourse. FES-biofeedback with SCBT is an effective aid for patients with vaginismus to learn muscle control. Therefore, it may increase the success rate of treatment of vaginismus.

  18. Oncogenic Human Papillomavirus: Application of CRISPR/Cas9 Therapeutic Strategies for Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Shuai Zhen

    2017-12-01

    Full Text Available Oncogenic human papillomaviruses (HPVs cause different types of cancer especially cervical cancer. HPV-associated carcinogenesis provides a classical model system for clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 based cancer therapies since the viral oncogenes E6 and E7 are exclusively expressed in cancerous cells. Sequence-specific gene knockdown/knockout using CRISPR/Cas9 shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, CRISPR/Cas9-based targeting therapy requires further validation of its efficacy in vitro and in vivo to eliminate the potential off-target effects, necessitates verification of the delivery vehicles and the combinatory use of conventional therapies with CRISPR/Cas9 to ensure the feasibility and safety. In this review we discuss the potential of combining CRISPR/Cas9 with other treatment options as therapies for oncogenic HPVs-associated carcinogenesis. and present our assessment of the promising path to the development of CRISPR/Cas9 therapeutic strategies for clinical settings.

  19. Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting.

    Science.gov (United States)

    Layek, Buddhadev; Sadhukha, Tanmoy; Panyam, Jayanth; Prabha, Swayam

    2018-06-01

    Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUC lung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. ©2018 AACR . ©2018 American Association for Cancer Research.

  20. Therapeutic efficacy of rose oil: A comprehensive review of clinical evidence

    Directory of Open Access Journals (Sweden)

    Safieh Mohebitabar

    2017-04-01

    Full Text Available Objective: Rose oil is obtained from the petals of difference Rosa species especially Rosa centifolia L. and Rosa damascena Mill. Various pharmacological properties have been attributed to rose oil. The aim of the present study was to review the rose oil therapeutic effects which had been clinically evaluated in trial studies. Materials and Methods: Google scholar, PubMed, Cochrane Library, and Scopus were searched for human studies which have evaluated the therapeutic effects of rose oil and published in English language until August 2015. Results: Thirteen clinical trials (772 participants were included in this review. Rose oil was administered via inhalation or used topically. Most of the studies (five trials evaluated the analgesic effect of rose oil. Five studies evaluated the physiological relaxation effect of rose oil. Anti-depressant, psychological relaxation, improving sexual dysfunction, and anti-anxiety effects were the other clinical properties reported for rose oil. Conclusion: Numerous studies on the pharmacological properties of rose oil have been done in animals, but studies in humans are few.  In this study, it was observed that rose oil had physiological and psychological relaxation, analgesic and anti-anxiety effects. To obtain conclusive results on the efficacy and safety of rose oil, further clinical trials with larger sample size and better designation are required.

  1. Prevalence of Schistosoma mansoni infection and the therapeutic efficacy of praziquantel among school children in Manna District, Jimma Zone, southwest Ethiopia

    Directory of Open Access Journals (Sweden)

    Mitiku Bajiro

    2016-10-01

    Full Text Available Abstract Background Intestinal schistosomiasis is one of the neglected tropical parasitic diseases caused by Schistosoma mansoni. Currently, the control measures for the disease are mainly based on mass drug administration (MDA with praziquantel (PZQ targeting the school-age children. In Ethiopia, the potential foci for schistosomiasis and therapeutic efficacy of PZQ among school-age children remain poorly explored. Therefore, we determined both the prevalence and intensity of S. mansoni infection and the therapeutic efficacy of PZQ among school children in the Manna District (new foci for S. mansoni, Jimma Zone, southwest Ethiopia. Methods A cross-sectional study was conducted among the school children aged between 6 and 18 years in three primary schools in Manna district from March to April 2014. For diagnosis of S. mansoni, a single stool sample was obtained from each child and processed using single Kato Katz and examined under light microscopy. A questionnaire was used to collect demographic information of the school children participated in the study. School children excreting eggs of S. mansoni were administered with 40 mg/kg of PZQ and re-examined after three weeks post-treatment. The therapeutic efficacy of PZQ against S. mansoni was evaluated by means of cure rate and egg reduction rate. Results The overall prevalence of S. mansoni among the school children in the three primary schools in Manna District was 24.0 %. Higher prevalence was recorded for males 25.6 % (61/238 than for females 22.5 % (59/262. Majority (27.5 % of infection intensity was light with mean faecal egg count (FEC of 202 eggs per gram (EPG. The therapeutic efficacy of PZQ at a dose of 40 mg/kg was highly efficient (cure rate of 99.1 % and egg reduction rate of 99.9 % among the school children in the three primary schools in Manna District. Conclusions The school children in the three primary schools of Manna District, Jimma Zone were at moderate risk of the

  2. Blood pressure control with amlodipine add-on therapy in patients with hypertension and diabetes: results of the Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial.

    Science.gov (United States)

    Kloner, Robert A; Neutel, Joel; Roth, Eli M; Weiss, Robert; Weinberger, Myron H; Thakker, Kamlesh M; Schwartz, Brian; Shi, Harry; Gregg, Anne-Marie

    2008-11-01

    Attainment of blood pressure (BP) goals in patients with diabetes is critical both to reduce the risk of cardiovascular events and to delay the progression of renal disease. While therapeutic guidelines advise initial therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, monotherapy with these agents may not be sufficient to attain target BP. The ADHT (Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial) evaluated the efficacy and safety of adding amlodipine to the treatment regimen of patients with hypertension and diabetes who were already receiving either quinapril or losartan as monotherapy. ADHT was a double-blind, double-dummy, 22-week trial conducted in the US. After a washout period of 7-13 days, patients (aged 30-75 y) with hypertension and diabetes were randomized to receive quinapril 20 mg/day plus placebo or losartan 50 mg/day plus placebo for 4 weeks, titrated to 40 mg or 100 mg (if required), respectively, for an additional 4 weeks to achieve their BP goals (<130/80 mm Hg). At week 8, either amlodipine 5 mg/day or placebo was added for an additional 12 weeks, with titration to 10 mg at week 14 if the BP goal was not achieved. Efficacy of add-on therapy was evaluated in 411 patients (amlodipine 211, placebo 200). BP goal was reached by 27.5% of patients when amlodipine was added to quinapril or losartan monotherapy, compared with 12.5% when placebo was added (OR 2.73; 95% CI 1.61 to 4.64; p < 0.001). When added to quinapril or losartan monotherapy, amlodipine reduced BP by 8.1/5.4 mm Hg, compared with a 1.6/0.7 mm Hg decrease with add-on placebo (p < 0.001). Amlodipine, quinapril, and losartan were well tolerated. Amlodipine is safe and effective when added to quinapril or losartan monotherapy to help lower BP toward therapeutic targets in patients with hypertension and diabetes.

  3. What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

    Energy Technology Data Exchange (ETDEWEB)

    Gotthardt, M. [Radboud Univ. Nijmegen Medical Center, Nijmegen (Netherlands). Dept. of Nuclear Medicine; Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Rubner, C. [Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Bauhofer, A. [Philipps Univ., Marburg (DE). Inst. of Theoretical Surgery] (and others)

    2006-07-01

    Purpose: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. Patients, methods: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). Results: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n=143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n=44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p>0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76{+-}80.6 Gy versus 125.6{+-}46.3 Gy; p<0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2{+-}101.7 Gy versus 125.6{+-}46.3 Gy; p=0.0097). Conclusions: TcTUs-based determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm. (orig.)

  4. What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

    International Nuclear Information System (INIS)

    Gotthardt, M.; Philipps Univ., Marburg; Rubner, C.; Bauhofer, A.

    2006-01-01

    Purpose: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. Patients, methods: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). Results: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n=143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n=44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p>0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76±80.6 Gy versus 125.6±46.3 Gy; p<0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2±101.7 Gy versus 125.6±46.3 Gy; p=0.0097). Conclusions: TcTUs-based determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm. (orig.)

  5. The efficacy discussion of interventional therapy for advanced pancreatic carcinoma

    International Nuclear Information System (INIS)

    Song Tian; Yin Shimeng; Sun Rongyue; Shen Lan; Qian Yu

    2008-01-01

    Objective: To evaluate the efficacy of interventional therapy for advanced pancreatic carcinoma. Methods: 33 cases of advanced pancreatic carcinoma accepted interventional therapy from April 2005 were retrospectively analyzed. All patients were unoperable and accepted one or more times of celiac and superior mesenteric arterial chemotheraputics perfusion with dosage of 2:1. The embolization was further introduced with the addition of liver invasion. The repetition interval was kept at 6 weeks with no severe complications. Results: The one with follow-up CT imagings showed obvious decrease of the lesion size, together with release or disappearance of the sensation of abdominal pain and abdominal distention. The life span prolonged with average survival of 13 months, including the longest of 22 months and the life quality improved. Conclusions: The interventional therapy could be the first method of choice in the management of advanced pancreatic carcinoma. (authors)

  6. Molecular image guided radiation therapy-MIGRT in radiobioluminescence and nanoradioguidance

    International Nuclear Information System (INIS)

    Rao, V.L. Papineni

    2014-01-01

    Accurate dose delivery to malignant tissue in radiotherapy is essential for enhancing the treatment efficacy while minimizing morbidity of surrounding normal tissues. Advances in therapeutic strategies and diagnosis technologies along with our understanding of the biology of tumor response to radiation therapy have paved way to allow nearly 60% of current cancer patients to be treated with Radiation Therapy. The confluence of molecular imaging and nanotechnology fields are bridging physics and medicine and are quickly making strides in opening new avenues and therapeutic strategies that complement radiation therapy - with a distinct footprint in immunotherapy, adoptive cell therapy, and targeted chemotherapy. Incorporating optical imaging in radiation therapy in my laboratory, endogenous bioluminescence resulting from whole body irradiation in different organs, and in different animals, which is distinct from the Cherenkov radiation. The endogenous bioluminescence in response to irradiation is coined recently as radiobioluminescence. Thus with the necessity, the design, construction, and validation of Molecular Image Guided Radiation Therapy (MIGRT) instrumentation for preclinical theragnostics is carried out

  7. [Therapeutic massage on behavioral disturbances of elderly patients with dementia].

    Science.gov (United States)

    Barquilla Ávila, Carolina; Rodríguez-Mansilla, Juan

    2015-12-01

    To know the efficacy of therapeutic massage on behavioral disturbances of elderly patients with dementia. Literature review. The literature search was done in six scientific databases: PubMed, Cochrane Library Plus, PEDro, Dialnet, Scopus and CSIC, between 1983 and 2013. The search terms were "massage", "dementia", "therapy", "behavior disorders" and "Alzheimer". Of the 496 articles analyzed, 11 scientific articles have met the selection criteria. Inclusion criteria were: clinical trials, published in English or Spanish, which had analyzed the effects of massage therapy on altered behaviors in people with dementia. The variables were massage benefits, type of massage and massage lubricant. Their authors use different massage techniques (effleurage, pétrissage, pressures, frictions and kneading), obtain better conduct disorders (aggression, anxiety, agitation, and resistance to care) of elderly. The therapeutic massage can be a complementary treatment in the rehabilitation program for better behavior disorders. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  8. In vitro and in vivo photothermal cancer therapy using excited gold nanorod surface plasmons

    Science.gov (United States)

    Chen, Cheng-Lung; Liu, Bruce; Ou, Min-Nan; Chang, Fu-Hsiung; Lin, Win-Li; Chia, Chih-Ta; Chen, Yang-Yuan

    2013-03-01

    The application of heat to eliminate or restrain specific cancer cells is proposed as an encouraging approach in optimizing cancer therapy. This talk presents the in vitro and in vivo photothermal cancer therapy using photo-excited gold nanorods (Au NRs), and studies the impact of thermal heat on the necrosis of tumor tissue. The therapeutic efficacy in vivo was evaluated by analyzing tumor size change, vascular development, and histological images. The safety standard for the therapy process and administration of Au NRs were conducted to exclude side effects arising from the irradiation and materials. It is found that the smaller size of Au NRs exhibits better therapeutic efficacy due to their optical absorption efficiency and space distribution uniformity in the cell. The generation of local heating from excited Au NR surface plasmons is high enough to make the tumor tissue gradually develop to an eschar; resulting in a dramatic size decreases in these treated tumors.

  9. Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

    Science.gov (United States)

    Dukart, Juergen; Regen, Francesca; Kherif, Ferath; Colla, Michael; Bajbouj, Malek; Heuser, Isabella; Frackowiak, Richard S.; Draganski, Bogdan

    2014-01-01

    There remains much scientific, clinical, and ethical controversy concerning the use of electroconvulsive therapy (ECT) for psychiatric disorders stemming from a lack of information and knowledge about how such treatment might work, given its nonspecific and spatially unfocused nature. The mode of action of ECT has even been ascribed to a “barbaric” form of placebo effect. Here we show differential, highly specific, spatially distributed effects of ECT on regional brain structure in two populations: patients with unipolar or bipolar disorder. Unipolar and bipolar disorders respond differentially to ECT and the associated local brain-volume changes, which occur in areas previously associated with these diseases, correlate with symptom severity and the therapeutic effect. Our unique evidence shows that electrophysical therapeutic effects, although applied generally, take on regional significance through interactions with brain pathophysiology. PMID:24379394

  10. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial.

    Science.gov (United States)

    Firoozabadi, Mohammad Dehghani; Navabzadeh, Maryam; Roudsari, Mohammad Khodashenas; Zahmatkash, Mohsen

    2014-12-01

    Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients) and conventional treatment group (30 patients). An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months). Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6) and 32.6 (±12.7) years, respectively (P = 0.45). After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80), frequency of migraine attacks (P = 0.63) and duration of attacks per hours (P = 0.48) were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

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

    Science.gov (United States)

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

    2018-02-01

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

  12. WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

    Science.gov (United States)

    Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

    2017-04-01

    There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

  13. Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Wang, Xijun

    2014-04-01

    Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  15. Propensity score-matched analysis comparing the therapeutic efficacies of cefazolin and extended-spectrum cephalosporins as appropriate empirical therapy in adults with community-onset Escherichia coli, Klebsiella spp. and Proteus mirabilis bacteraemia.

    Science.gov (United States)

    Hsieh, Chih-Chia; Lee, Chung-Hsun; Hong, Ming-Yuan; Hung, Yuan-Pin; Lee, Nan-Yao; Ko, Wen-Chien; Lee, Ching-Chi

    2016-12-01

    In this study, the therapeutic efficacy of cefazolin was compared with that of extended-spectrum cephalosporins (ESCs) (cefotaxime, ceftriaxone and ceftazidime) as appropriate empirical therapy in adults with community-onset monomicrobial bacteraemia caused by Escherichia coli, Klebsiella spp. or Proteus mirabilis (EKP). Compared with cefazolin-treated patients (n = 135), significantly higher proportions of patients in the ESC treatment group (n = 456) had critical illness at bacteraemia onset (Pitt bacteraemia score ≥4) and fatal co-morbidities (McCabe classification). Of the 591 patients, 121 from each group were matched using propensity score matching (PSM) based on the following independent predictors of 28-day mortality: fatal co-morbidities (McCabe classification); Pitt bacteraemia score ≥4 at bacteraemia onset; initial syndrome of septic shock; and bacteraemia due to pneumonia. After appropriate PSM, no significant differences were observed in the early clinical failure rate (10.7% vs. 7.4%; P = 0.37), the proportion of critical illness (Pitt bacteraemia score ≥4) (0% vs. 0%; P = 1.00) and defervescence (52.6% vs. 42.6%; P = 0.13) on Day 3 between the cefazolin and ESC treatment groups. Similarly, no significant differences were observed in the mean of time to defervescence (4.1 days vs. 4.9 days; P = 0.15), late clinical failure rate (18.2% vs. 10.7%; P = 0.10) and 28-day crude mortality rate (0.8% vs. 3.3%; P = 0.37) between the two groups. These data suggest that the efficacy of cefazolin is similar to that of ESCs when used as appropriate empirical antimicrobial treatment for community-onset EKP bacteraemia. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  16. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

    2016-01-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...

  17. [Analysis of Therapeutic Regularities and Characteristics of Blood-letting Therapy for Acne Patients Based on Data Mining].

    Science.gov (United States)

    Du, Yu-zhu; Jia, Chun-sheng; Wang, Jian-ling; Shi, Jing; Zhang, Xiao-xu; Liu, Xin; Gang, Wei-juan

    2015-06-01

    To analyze the therapeutic regularities and characteristics of blood-letting therapy for acne in the past clinical practice by using data mining. Original papers about acne treated by pricking blood therapy were searched and screened from common databases as Chinese National Knowledge Infrastructure Database (CNKI), WanFang Data, SinoMed, Ovid, ScienceDirect, Socolar, SciFinder, Foreign Medical Journal Full-Text Service (FMJS) and PubMed using keywords of acne+bleeding therapy, acne+blood-letting, acne+ pricking blood, followed by establishing a data plateform to conduct a data mining using Online Analytical Processing (OLAP). A total of 230 original journal articles about acne treated by pricking blood therapy were collected. The included acne cases with wind-heat pattern were predoment, being 56 in frequency-times and acounting for 24. 78 %. In the treatment of acne, the therapeutic tool, three-edged needle was often used, being 168 in frequency and acounting for 71.79%. The frequently employed acupoints were those of the Governor Vessel and Bladder Meridian, such as Dazhui (GV 14) and back-shu points. When auricular points used for blood-letting, Erjian (EX-HN 6) and the Vena of the auricular back were most frequently selected. In addition to blood-letting, other therapies such as Chinese herbal medicines, filiform needles, and otopoint-pellet pressure were also used in combination, being 166 in items and constituting 72. 17%. Generally, blood-letting treatment was conducted once every three days (twice a week) or once every two days (three times a week) for about 20 sessions for each acne patient. Blood-letting therapy is effective in the treatment of acne. But if used in combination with other therapies, the therapeutic effect would be better.

  18. The Process of Change in Cognitive Therapy for Depression: Predictors of Early Inter-Session Symptom Gains

    OpenAIRE

    Strunk, Daniel R.; Brotman, Melissa A.; DeRubeis, Robert J.

    2010-01-01

    Although Cognitive Therapy for depression is an efficacious treatment, questions about the aspects of the therapy that are most critical to successful implementation remain. In a sample of 60 Cognitive Therapy patients with moderate to severe depression, we examined three aspects of therapists’ adherence to Cognitive Therapy techniques, the patients’ facilitation or inhibition of these techniques, and the therapeutic alliance as predictors of session-to-session symptom improvement across the ...

  19. Sensory integration dysfunction affects efficacy of speech therapy on children with functional articulation disorders

    Directory of Open Access Journals (Sweden)

    Tung LC

    2013-01-01

    Full Text Available Li-Chen Tung,1,# Chin-Kai Lin,2,# Ching-Lin Hsieh,3,4 Ching-Chi Chen,1 Chin-Tsan Huang,1 Chun-Hou Wang5,6 1Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, 2Program of Early Intervention, Department of Early Childhood Education, National Taichung University of Education, Taichung, 3School of Occupational Therapy, College of Medicine, National Taiwan University, Taipei, 4Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, 5School of Physical Therapy, College of Medical Science and Technology, Chung Shan Medical University, Taichung, 6Physical Therapy Room, Chung Shan Medical University Hospital, Taichung, Taiwan#These authors contributed equally Background: Articulation disorders in young children are due to defects occurring at a certain stage in sensory and motor development. Some children with functional articulation disorders may also have sensory integration dysfunction (SID. We hypothesized that speech therapy would be less efficacious in children with SID than in those without SID. Hence, the purpose of this study was to compare the efficacy of speech therapy in two groups of children with functional articulation disorders: those without and those with SID.Method: A total of 30 young children with functional articulation disorders were divided into two groups, the no-SID group (15 children and the SID group (15 children. The number of pronunciation mistakes was evaluated before and after speech therapy.Results: There were no statistically significant differences in age, sex, sibling order, education of parents, and pretest number of mistakes in pronunciation between the two groups (P > 0.05. The mean and standard deviation in the pre- and posttest number of mistakes in pronunciation were 10.5 ± 3.2 and 3.3 ± 3.3 in the no-SID group, and 10.1 ± 2.9 and 6.9 ± 3.5 in the SID group, respectively. Results showed great changes after speech therapy treatment (F

  20. A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

    Directory of Open Access Journals (Sweden)

    Lorf Thomas

    2010-04-01

    Full Text Available Abstract Background Immunosuppression with calcineurin inhibitors (CNI increases the risk of renal dysfunction after orthotopic liver transplantation (OLT. Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. Methods/Design A prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate, liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT, treatment failure, (i. e., re-introduction of CNI, incidence of adverse events, and mortality up to one year after OLT. Discussion This prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation of this phase III trial. Trial registration number NCT00890253 (clinicaltrials.gov

  1. Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Chien-Chih Ke

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

  2. Morphological functional criteria of neuroprotective therapy efficacy in glaucomatous optic neuropathy

    Directory of Open Access Journals (Sweden)

    Tszin Dan

    2015-01-01

    Full Text Available Electrophysiological tests may be used to detect early glaucomatous changes and glaucoma progression risk and to monitor treatment efficacy. Most important pathogenic aspects of glaucomatous process, pathogenesis and multifactorial nature of glaucomatous optic neuropathy are described. Major triggers of glaucomatous optic neuropathy are mechanical and vascular. Principles of neuroprotective therapy, neuroprotective drugs, and mechanisms of action of direct and indirect neuroprotective agents are presented. IOPcc is a basis for neuroprotective therapy selection and its efficacy monitoring. Amongst neuroprotective drugs, NMDA agonists, antioxidants, peptides, and calcium channel blockers are of special importance. Structural damage and functional deficiency (e.g., visual field loss in glaucoma and the most informative and accurate methods of their detection are characterized. Confocal laser microscopy, optical coherence tomography, and scanning laser polarimetry are compared. These techniques are used to study optic nerve head and retinal nerve fiber layer. They are proposed as diagnostic and monitoring tools for glaucoma, glaucoma suspicion, and ocular hypertension. The most sensitive and specific electrophysiological tests for glaucomatous optic neuropathy are pattern electroretinography, multfocal electroretinography, and multifocal visually evoked potentials. 

  3. Pretreatment with 5-Fluorouracil Cream Enhances the Efficacy of Daylight-mediated Photodynamic Therapy for Actinic Keratosis

    DEFF Research Database (Denmark)

    Nissen, Christoffer V; Heerfordt, Ida Marie; Wiegell, Stine R

    2017-01-01

    The efficacy of photodynamic therapy (PDT) with methyl aminolevulinate is reduced when treating actinic keratosis (AK) on the extremities in comparison with the face and scalp. Studies indicate that PDT efficacy can be improved by combining PDT with other treatment modalities. This randomized intra...

  4. The efficacy of maggot debridement therapy - a review of comparative clinical trials

    DEFF Research Database (Denmark)

    Zarchi, K.; Jemec, G.B.

    2012-01-01

    in a variety of ulcers. However, comparative clinical trials and in particular randomized controlled trials investigating the efficacy of MDT are sparse. A systematic search in the literature showed three randomized clinical trials and five non randomized studies evaluating the efficacy of sterile Lucilia......, including hydrocolloid, hydrogel and saline moistened gauze. However, the design of the studies was suboptimal, with important differences in the use of other therapies, such as compression, that may influence both debridement and healing between the compared groups, as well as inappropriately short follow...

  5. Stem cell therapy for ischemic heart diseases.

    Science.gov (United States)

    Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

    2017-01-01

    Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  6. Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression.

    Science.gov (United States)

    Renner, Fritz; Jarrett, Robin B; Vittengl, Jeffrey R; Barrett, Marna S; Clark, Lee Anna; Thase, Michael E

    2012-05-01

    The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remains unclear. We analyzed data of adult outpatients (N=523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16-20 sessions protocol (50-60 min each) of individual CT according to the treatment manual by Beck et al. (1979). We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d=.90), but interpersonal style did not change substantively during CT (communion d=.03; agency d=.14). High initial agency scores related negatively to the therapeutic alliance (β=-.12), whereas high initial communion scores related positively to the therapeutic alliance (β=.15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β=.13) and higher symptom levels throughout treatment (β=.10). All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression

    Science.gov (United States)

    Renner, Fritz; Jarrett, Robin B.; Vittengl, Jeffrey R.; Barrett, Marna S.; Clark, Lee Anna; Thase, Michael E.

    2012-01-01

    Background The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remain unclear. Methods We analyzed data of adult outpatients (N = 523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16–20 sessions protocol (50–60 minutes each) of individual CT according to the treatment manual by Beck et al. (1979). Results We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d = .90), but interpersonal style did not change substantively during CT (communion d = .03; agency d = .14). High initial agency scores related negatively to the therapeutic alliance (β = −.12), whereas high initial communion scores related positively to the therapeutic alliance (β = .15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β = .13) and higher symptom levels throughout treatment (β = .10). Limitations All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. Conclusions This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. PMID:22306232

  8. The therapeutic advantage of combination antihypertensive drug therapy using amlodipine and irbesartan in hypertensive patients: Analysis of the post-marketing survey data from PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; safety and efficacy in patients with hypertension) study.

    Science.gov (United States)

    Ishimitsu, Toshihiko; Fukuda, Hirofumi; Uchida, Masako; Ishibashi, Kazushi; Sato, Fusako; Nukui, Kazuhiko; Nagao, Munehiko

    2015-01-01

    Two-thirds of hypertensive patients need a combination antihypertensive therapy to achieve the target blood pressure (BP). The PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in paTieNts with hypERtension) study is a prospective specific clinical use survey examining the efficacy and safety of 12-week treatment with amlodipine (AML) and Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current analysis was performed as to the BP control, adverse reactions, and the effects on laboratory data in patients treated with the combination of AML and irbesartan (IRB), namely the patients added AML to already taking IRB (AML add-on group, n = 1202) and the patients added IRB to AML (IRB add-on group, n = 1050). Both study groups showed distinct decreases in office BP at 4 week (p 7 mg/dl. The incidence of adverse reactions was as few as 1.11% and there were no severe adverse reactions which hampered the continuation of combination therapy. In conclusion, combination antihypertensive therapy with AML and IRB effectively lowers BP without particular safety problems, reduces serum uric acid especially in patients with hyperuricemia and exhibits renoprotective effects in patients with chronic kidney disease.

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

    Directory of Open Access Journals (Sweden)

    Negrini Stefano

    2008-01-01

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

  10. Electroconvulsive therapy stimulus titration: Not all it seems.

    Science.gov (United States)

    Rosenman, Stephen J

    2018-05-01

    To examine the provenance and implications of seizure threshold titration in electroconvulsive therapy. Titration of seizure threshold has become a virtual standard for electroconvulsive therapy. It is justified as individualisation and optimisation of the balance between efficacy and unwanted effects. Present day threshold estimation is significantly different from the 1960 studies of Cronholm and Ottosson that are its usual justification. The present form of threshold estimation is unstable and too uncertain for valid optimisation or individualisation of dose. Threshold stimulation (lowest dose that produces a seizure) has proven therapeutically ineffective, and the multiples applied to threshold to attain efficacy have never been properly investigated or standardised. The therapeutic outcomes of threshold estimation (or its multiples) have not been separated from simple dose effects. Threshold estimation does not optimise dose due to its own uncertainties and the different short-term and long-term cognitive and memory effects. Potential harms of titration have not been examined. Seizure threshold titration in electroconvulsive therapy is not a proven technique of dose optimisation. It is widely held and practiced; its benefit and harmlessness assumed but unproven. It is a prematurely settled answer to an unsettled question that discourages further enquiry. It is an example of how practices, assumed scientific, enter medicine by obscure paths.

  11. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    Science.gov (United States)

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Evaluation of transcatheter arterial chemoembolization combined with radiofrequency capacitive heating on clinical therapeutic effect of metastatic carcinoma

    International Nuclear Information System (INIS)

    Chen Qianli; Ye Qiang; Gu Weizhong; Zhang Jiazhong; Tong Qiangang; Xi Shunfa

    2006-01-01

    Objective: To evaluate clinical therapeutic efficacy and adverse efficacy of transcatheter arterial chemoembolization (TACE) combined with radiofrequency capacitive heating (RCH) for metastatic hepatic carcinoma (MHC). Methods: Thirty-nine cases of MHC were enrolled in this study and divided into two groups: study group (n=19) and control group (n=20). Before therapy, the Karnofsky's score of the patients was all beyond 60. Results: The carcinoma growth rate of the study group was -(0.38±0.22), while that of the control group was -(0.13±0.25), showing significant statistical difference (P 0.05). Conclusion: The therapeutic effect of MHC can be further improved by the treatment of TACE combined with radiofrequency capacitive heating without increase of adverse side effects. (authors)

  13. Testosterone Replacement Therapy: Long-Term Safety and Efficacy

    Directory of Open Access Journals (Sweden)

    Giovanni Corona

    2017-08-01

    Full Text Available Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG or late-onset hypogonadism (LOH. The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T therapy (TTh. In addition, concerns related to cardiovascular (CV safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented.

  14. Occupational therapy consultation for case managers in community mental health: exploring strategies to improve job satisfaction and self-efficacy.

    Science.gov (United States)

    Chapleau, Ann; Seroczynski, A D; Meyers, Susan; Lamb, Kristen; Haynes, Susan

    2011-01-01

    The purpose of this study was 2-fold: (1) to examine to what extent case managers' job satisfaction and self-efficacy were impacted by the addition of an occupational therapy consultation model and (2) to identify factors that both positively and negatively impacted the occupational therapy consultation services. The study was conducted at a mental health community support program in a local homeless center. In a 2-year study, a mixed-methods design was used to study changes over time in job satisfaction and perceived self-efficacy among 14 case managers who received ongoing occupational therapy consultation. Job satisfaction and self-efficacy data were obtained using standardized questionnaires. Qualitative data related to factors impacting the consultation program were obtained using open-ended written questions, focus groups, and individual interviews. Statistically significant differences in job satisfaction and perceptions of self-efficacy were found 18 months into the study, when case managers were more actively seeking occupational therapy consultation services and were reporting improved client outcomes from occupational therapy intervention. In addition, themes related to both positive and negative factors impacting the occupational therapy consultation program were identified and provided useful data for development of future consultation services. IMPLICATION FOR CASE MANAGEMENT PRACTICE: Results suggest that ongoing training and professional support for case managers who are paraprofessionals and/or new to mental health practice may improve job satisfaction and efficacy. Occupational therapy consultation may be helpful in developing services for health promotion, including self-care management, cognitive assessments, activity-based programming, and home safety evaluation and modification. In addition, new graduates and paraprofessional case managers working with clients who are high utilizers of services may benefit from smaller caseloads and support

  15. Biofield Therapies: Helpful or Full of Hype? A Best Evidence Synthesis

    OpenAIRE

    Jain, Shamini; Mills, Paul J.

    2010-01-01

    Background Biofield therapies (such as Reiki, therapeutic touch, and healing touch) are complementary medicine modalities that remain controversial and are utilized by a significant number of patients, with little information regarding their efficacy. Purpose This systematic review examines 66 clinical studies with a variety of biofield therapies in different patient populations. Method We conducted a quality assessment as well as a best evidence synthesis approach to examine evidence for bio...

  16. Survival of lung cancer patients after combined therapy with hyperglycemia

    International Nuclear Information System (INIS)

    Zharkov, V.V.; Demidchik, Yu.E.; Khodina, T.V.

    1991-01-01

    The results of a randomized study of combined therapy of lung cancer patients including large field radiotherapy (total irradiation of 20 Gy, daily fractionation of 4 Gy) and induced hyperglycemia (22-23 mmol/1) are presented. The use of new variants of combined therapy was shown to increase significantly the survival of patients, however therapeutic efficacy was different depending on the time of hyperglycemia: wheter it was used before radiotherapy sessions of after their discontinuation

  17. Stem Cell Therapy and Breast Cancer Treatment: review of stem cell research and potential therapeutic impact against cardiotoxicities due to breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Thomas E. Sharp

    2014-11-01

    Full Text Available A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually lead to heart failure (HF. This cardiomyocyte toxicity can leave the breast cancer survivor with a probable diagnosis of dilated or restrictive cardiomyopathy (DCM or RCM. While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies. There is a need to develop novel therapeutics that can either prevent or reverse the cardiac injury caused by cancer therapeutics. These new therapeutics should promote the regeneration of lost or deteriorating myocardium. Over the last several decades the therapeutic potential of cell-based therapy has been investigated for HF patients. In this review we discuss the progress of preclinical and clinical stem cell research for the diseased heart and discuss the possibility of utilizing these novel therapies to combat cardiotoxicity observed in breast cancer survivors.

  18. Increasing the safety and efficacy of chimeric antigen receptor T cell therapy

    Directory of Open Access Journals (Sweden)

    Hua Li

    2017-04-01

    Full Text Available Abstract Chimeric antigen receptor (CAR T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or “on-target/off-tumor” toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal—curing cancer with high safety, high efficacy, and low cost.

  19. [Therapeutic efficacy of nootropil different doses in attention deficit hyperactivity disorder].

    Science.gov (United States)

    Zavadenko, N N; Suvorinova, S Iu

    2004-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is the most common cause of behavioral and learning problems in childhood. Therapeutic efficiency of nootropil (piracetam) in two different doses has been evaluated in the open control study of 80 children with ADHD, 70 boys and 10 girls, aged 6-11 years, being divided into 3 groups. Two groups received nootropil, as a monotherapy, for a month: 1st group (30 patients)--in the dosage of 70 mg/kg daily and 2nd group (30 patients)--40 mg/kg daily orally. The control group of 20 patients did not receive any treatment. All children were examined twice with one month interval. A procedure of assessment included of structured questionnaire to parents, neurological examination with scored evaluation of subtle signs and psychological testing. Nootropil therapy in ADHD children resulted in the improvement of behavioral characteristics, motor coordination as well as continuous, selective and divided attention. A response rate was 60% in patients received 70 mg/kg of nootropil and 43% for nootropil dosage of 40 mg/kg. The results of the study suggest more considerable positive therapeutic effects of nootropil higher dose on behavioral, motor and attention characteristics in children with ADHD.

  20. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

    Science.gov (United States)

    Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

    2015-05-01

    Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared

  1. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial

    Directory of Open Access Journals (Sweden)

    Mohammad Dehghani Firoozabadi

    2014-01-01

    Full Text Available Background: Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. Materials and Methods: This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients and conventional treatment group (30 patients. An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months. Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Results: Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6 and 32.6 (±12.7 years, respectively (P = 0.45. After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80, frequency of migraine attacks (P = 0.63 and duration of attacks per hours (P = 0.48 were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P < 0.001. Conclusion: There was no significant difference between cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

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

    Science.gov (United States)

    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.

  3. Structuring polymers for delivery of DNA-based therapeutics: updated insights.

    Science.gov (United States)

    Gupta, Madhu; Tiwari, Shailja; Vyas, Suresh

    2012-01-01

    Gene therapy offers greater opportunities for treating numerous incurable diseases from genetic disorders, infections, and cancer. However, development of appropriate delivery systems could be one of the most important factors to overcome numerous biological barriers for delivery of various therapeutic molecules. A number of nonviral polymer-mediated vectors have been developed for DNA delivery and offer the potential to surmount the associated problems of their viral counterpart. To address the concerns associated with safety issues, a wide range of polymeric vectors are available and have been utilized successfully to deliver their therapeutics in vivo. Today's research is mainly focused on the various natural or synthetic polymer-based delivery carriers that protect the DNA molecule from degradation, which offer specific targeting to the desired cells after systemic administration, have transfection efficiencies equivalent to virus-mediated gene delivery, and have long-term gene expression through sustained-release mechanisms. This review explores an updated overview of different nonviral polymeric delivery system for delivery of DNA-based therapeutics. These polymeric carriers have been evaluated in vitro and in vivo and are being utilized in various stages of clinical evaluation. Continued research and understanding of the principles of polymer-based gene delivery systems will enable us to develop new and efficient delivery systems for the delivery of DNA-based therapeutics to achieve the goal of efficacious and specific gene therapy for a vast array of clinical disorders as the therapeutic solutions of tomorrow.

  4. Ketogenic Diet Therapy in Infants: Efficacy and Tolerability.

    Science.gov (United States)

    Wirrell, Elaine; Eckert, Susan; Wong-Kisiel, Lily; Payne, Eric; Nickels, Katherine

    2018-05-01

    This study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. Infants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. Twenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital. Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1). Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. The ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  6. Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.

    Directory of Open Access Journals (Sweden)

    Pengfei Liu

    Full Text Available The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs in acute kidney injury (AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

  7. Efficacy of Creative Clay Work for Reducing Negative Mood: A Randomized Controlled Trial

    Science.gov (United States)

    Kimport, Elizabeth R.; Robbins, Steven J.

    2012-01-01

    Clay work has long been used in art therapy to achieve therapeutic goals. However, little empirical evidence exists to document the efficacy of such work. The present study randomly assigned 102 adult participants to one of four conditions following induction of a negative mood: (a) handling clay with instructions to create a pinch pot, (b)…

  8. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 2 new and emerging therapies and their efficacy. MS Neurology Group of the Australian and New Zealand Association of Neurologists.

    Science.gov (United States)

    Broadley, Simon A; Barnett, Michael H; Boggild, Mike; Brew, Bruce J; Butzkueven, Helmut; Heard, Robert; Hodgkinson, Suzanne; Kermode, Allan G; Lechner-Scott, Jeannette; Macdonell, Richard A L; Marriott, Mark; Mason, Deborah F; Parratt, John; Reddel, Stephen W; Shaw, Cameron P; Slee, Mark; Spies, Judith; Taylor, Bruce V; Carroll, William M; Kilpatrick, Trevor J; King, John; McCombe, Pamela A; Pollard, John D; Willoughby, Ernest

    2014-11-01

    In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  9. Therapeutic efficacy of different brands of albendazole against soil transmitted helminths among students of Mendera Elementary School, Jimma, Southwest Ethiopia.

    Science.gov (United States)

    Tefera, Ephrem; Belay, Tariku; Mekonnen, Seleshi Kebede; Zeynudin, Ahmed; Belachew, Tefera

    2015-01-01

    Different brands Albendazole are commercially available and the efficacious brand/s is/are required for effective control of STHs infection. Thus, this study is aimed at determining the therapeutic efficacy of different brands of albendazole against soil transmitted helminths among school children of Jimma town. A cross sectional survey for prevalence of geohelminths and a randomized trial for efficacy study of different brands of albendazole was conducted among students Mendera Elementary School from March 29 to April 29, 2010. Positive subjects were randomized into three treatment arms using lottery method. The collected stool samples were examined by the McMaster method. CRs were calculated using SPSS windows version 16 and ERRs were calculated using appropriate formula. Of the 715 school children who had their stools examined, 326 were positive for STHs with a prevalence rate of 45.6%. The cure rates (CR) for A. lumbricoides, T. trichiura and Hookworm were 99.4, 59.9 and 93.7%, respectively. Similarly, the egg reduction rates (ERR) were 97, 99.9 and 99.9% respectively. A statistical significant mean STH egg count difference were observed between pre and post-intervention study (p 0.05). All the three brands of Albendazole tested regardless of the brand type were therapeutically efficacious for Ascariasis, Trichuriasis and Hookworm infections irrespective of the infection status whether it was single or multiple.

  10. Research progress in combination therapy with pegylated interferon and nucleos(tide analogues in treatment of chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    YU Yiqi

    2015-09-01

    Full Text Available Current antiviral treatment strategy for chronic hepatitis B (CHB includes pegylated interferon (PEG-IFN and nucleos(tide analogues (NAs. Whether combination therapy with PEG-IFN and NAs improve therapeutic efficacy has become the key question regarding the antiviral therapy for CHB. This article reviews the recent progress in combination therapy for the management of CHB. The results indicate that the efficacy of simultaneous combination of PEG-IFN and NAs is not superior to that of PEG-IFN monotherapy in terms of HBeAg seroconversion and response after drug withdrawal. Sequential combination or switching therapy in PEG-IFN- or NAs-treated patients, as well as combination with immune cell therapy, is a promising treatment strategy.

  11. Efficacy of intense pulse light therapy and tripple combination cream versus intense pulse light therapy and tripple combination cream alone in epidermal melasma treatment

    International Nuclear Information System (INIS)

    Shakeeb, N.; Noor, S.M.; Paracha, M.M.; Ullah, G.

    2018-01-01

    Objective:To compare the efficacy of intense pulse light therapy (IPL) and triple combination cream (TCC) versus intense pulse light therapy and triple combination cream alone in epidermal melasma treatment, downgrading MASI score to more than 10. Study Design:Randomized controlled trial. Place and Duration of Study:Dermatology Department, Lady Reading Hospital, Peshawar, from August 2014 to January 2015. Methodology:Patients of 18-45 years were included in the study with Fitzpatrick skin type II-V. Sample of 96 patients was divided in to three groups of 32 each, through consecutive (non-probability) sampling method. Detailed history was taken, Woods Lamp Examination done, and melasma area and severity index (MASI) score was calculated. TCC had to be applied daily at night for two months by group A patients while group B was consigned for IPL therapy fortnightly, and those in group C were given both for two months. Efficacy was compared by recalculating MASI score at treatment end as well as at follow-up after 4 weeks, using Chi-square test with significance at p < 0.05. Results:Male and female patients were 10 (31.2%) and 22 (68.8%) in group A, 7 (21.9%) and 25 (78.1%) in group B, while in group C were 12 (37.5%) and 20 (62.5%). The average age was 28.70 +8.70 years. MASI score reduction was achieved in 22 (68.8%) patients in group A; whereas, in 20 (62.5%) and 30(93.8%) patients in group B and C, respectively. Efficacy-wise distribution was significant (p=0.009). Conclusion:Intense pulse light therapy and triple combination cream are more efficacious in epidermal melasma treatment than intense pulse light therapy and triple combination cream alone. (author)

  12. Efficacy of multiple anticancer therapies may depend on host immune response

    Directory of Open Access Journals (Sweden)

    Kritika Karri

    2017-06-01

    Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

  13. How does electroconvulsive therapy work?

    DEFF Research Database (Denmark)

    Bolwig, Tom G

    2011-01-01

    This article reviews 3 current theories of electroconvulsive therapy (ECT). One theory points to generalized seizures as essential for the therapeutic efficacy of ECT. Another theory highlights the normalization of neuroendocrine dysfunction in melancholic depression as a result of ECT. A third...... theory is based on recent findings of increased hippocampal neurogenesis and synaptogenesis in experimental animals given electroconvulsive seizures. Presently, the endocrine theory has the strongest foundation to explain the working mechanism of ECT....

  14. Efficacy of aquatic therapy for multiple sclerosis: a systematic review.

    Science.gov (United States)

    Corvillo, Iluminada; Varela, Enrique; Armijo, Francisco; Alvarez-Badillo, Antonio; Armijo, Onica; Maraver, Francisco

    2017-12-01

    Multiple sclerosis (MS) is a chronic, inflammatory, progressive, disabling autoimmune disease affecting the central nervous system. Symptoms and signs of MS vary widely and patients may lose their ability to walk. To date the benefits of aquatic therapy often used for rehabilitation in MS patients have not been reviewed. The aim of this study was to systematically review the current state of aquatic treatment for persons with MS (hydrotherapy, aquatic therapy, aquatic exercises, spa therapy) and to evaluate the scientific evidence supporting the benefits of this therapeutic option. The databases PubMed, Scopus, WoS and PEDro were searched to identify relevant reports published from January 1, 2011 to April 30, 2016. Of 306 articles identified, only 10 fulfilled the inclusion criteria: 5 randomized controlled, 2 simple randomized quasi-experimental, 1 semi-experimental, 1 blind controlled pilot and 1 pilot. Evidence that aquatic treatment improves quality of life in affected patients was very good in two studies, good in four, fair in two and weak in two.

  15. Complementary and Alternative Therapies for Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Natascia Brondino

    2015-01-01

    Full Text Available Background. Complementary and alternative medicine (CAM represents a popular therapeutic option for patients with autism spectrum disorder (ASD. Unfortunately, there is a paucity of data regarding the efficacy of CAM in ASD. The aim of the present systematic review is to investigate trials of CAM in ASD. Material and Methods. We searched the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CINAHL, Psychology and Behavioral Sciences Collection, Agricola, and Food Science Source. Results. Our literature search identified 2687 clinical publications. After the title/abstract screening, 139 publications were obtained for detailed evaluation. After detailed evaluation 67 studies were included, from hand search of references we retrieved 13 additional studies for a total of 80. Conclusion. There is no conclusive evidence supporting the efficacy of CAM therapies in ASD. Promising results are reported for music therapy, sensory integration therapy, acupuncture, and massage.

  16. Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.

    Science.gov (United States)

    Kremenchutzky, Marcelo; O'Connor, Paul; Hohlfeld, Reinhard; Zhang-Auberson, Lixin; von Rosenstiel, Philipp; Meng, Xiangyi; Grinspan, Augusto; Hashmonay, Ron; Kappos, Ludwig

    2014-05-01

    Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis. This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history. Annualized relapse rate and safety profile of treatment with fingolimod 0.5mg, 1.25mg, or placebo once-daily for 24 months were analyzed in 1272 relapsing multiple sclerosis patients, by subgroups based on disease-modifying therapy history (treatment-naive; prior interferon-β or glatiramer acetate), reason for discontinuation of prior disease-modifying therapy (unsatisfactory therapeutic response or adverse events), and prior disease-modifying therapy duration. Both fingolimod doses significantly reduced annualized relapse rate in patients that received prior interferon-β or glatiramer acetate, discontinued prior disease-modifying therapy owing to unsatisfactory therapeutic effect, were treatment-naive, or had prior disease-modifying therapy duration of >1-3 years (P≤0.0301 for all comparisons vs placebo). Fingolimod 1.25mg resulted in greater reductions in annualized relapse rate in patients that discontinued prior disease-modifying therapy for adverse events or had prior disease-modifying therapy duration of ≤1 year or >3 years (P≤0.0194 vs placebo). Fingolimod demonstrated similar efficacy in relapsing multiple sclerosis patients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Recent advances in (therapeutic protein drug development [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    H.A. Daniel Lagassé

    2017-02-01

    Full Text Available Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016.

  18. Potential mechanisms for cell-based gene therapy to treat HIV/AIDS.

    Science.gov (United States)

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-02-01

    An estimated 35 million people are infected with HIV worldwide. Anti-retroviral therapy (ART) has reduced the morbidity and mortality of HIV-infected patients but efficacy requires strict adherence and the treatment is not curative. Most importantly, the emergence of drug-resistant virus strains and drug toxicity can restrict the long-term therapeutic efficacy in some patients. Therefore, novel treatment strategies that permanently control or eliminate the virus and restore the damaged immune system are required. Gene therapy against HIV infection has been the topic of intense investigations for the last two decades because it can theoretically provide such a durable anti-HIV control. In this review we discuss two major gene therapy strategies to combat HIV. One approach aims to kill HIV-infected cells and the other is based on the protection of cells from HIV infection. We discuss the underlying molecular mechanisms for candidate approaches to permanently block HIV infection, including the latest strategies and future therapeutic applications. Hematopoietic stem cell-based gene therapy for HIV/AIDS may eventually become an alternative for standard ART and should ideally provide a functional cure in which the virus is durably controlled without medication. Recent results from preclinical research and early-stage clinical trials support the feasibility and safety of this novel strategy.

  19. Rationale for selecting antihistamine drugs for the therapy of chronic urticaria in terms of efficacy and safety

    Directory of Open Access Journals (Sweden)

    O. V. Skorokhodkina

    2014-01-01

    Full Text Available Goal of the study. To compare the efficacy of antihistamine drugs for the therapy of chronic urticaria taking into consideration their effect on the patients’ cognitive functions. Materials and methods. The study involved 178 patients with chronic urticaria who were divided into six groups taking second generation antihistamine drugs: Cetirizine (n = 38, Levocetirizine (n = 27, Fexofenadine (n=26, Ebastine (n = 33, Loratadine (n = 26 and Desloratadine (n = 28. The patients recorded dynamic changes in clinical symptoms of the disease (number of urticarial components, skin itching intensity, availability or absence of urticarial derniographism, angioedema signs and signs of the shortness of breath and reduced blood pressure in their individual diaries. Baseline signs of the patients’ cognitive condition and those recorded during the treatment were studied using the Kraepelin’s arithmetic test (modified by Schulte, I.M. Lushchikhina’s verbal and visual thinking assessment method and method for memorizing ten words. The control group comprised 31 subjects without chronic urticaria. Results of the study. Ebastine and Fexofenadine are the most efficient antihistamine drugs for the treatment of chronic urticaria. At the same time, they do not have any negative effect on the patients’ cognitive functions so they can be recommended for long-term treatment of chronic urticaria. In spite of its evident positive therapeutic effect, Cetirizine reduces mental alertness and deteriorates thinking in patients with chronic urticaria. Because of this, the drug must be prescribed with care for long-term administration to those patients whose professional activities demand increased attention concentration. Loratadine has a positive effect on the patients’ attention and thinking. However, taking into consideration its low efficacy, the drug can be prescribed as the basis therapy for the treatment of light forms of chronic urticaria.

  20. Therapeutic Alliance and Retention in Brief Strategic Family Therapy: A Mixed-Methods Study.

    Science.gov (United States)

    Sheehan, Alyson H; Friedlander, Myrna L

    2015-10-01

    We explored how the therapeutic alliance contributed to retention in Brief Strategic Family Therapy by analyzing videotapes of eight-first sessions in which four therapists worked with one family that stayed in treatment and one family that dropped out. Although behavioral exchange patterns between clients and therapists did not differ by retention status, positive therapist alliance-related behavior followed negative client alliance behavior somewhat more frequently in the retained cases. In the qualitative aspect of the study, four family therapy experts each viewed two randomly assigned sessions and commented on their quality without knowing the families' retention status. A qualitative analysis of the audiotaped commentaries revealed 18 alliance-related themes that were more characteristic of either the retained or the nonretained cases. © 2015 American Association for Marriage and Family Therapy.

  1. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  2. Gene therapy of cancer and development of therapeutic target gene

    International Nuclear Information System (INIS)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

  3. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

    Science.gov (United States)

    Taylor, Frederick; Levine, Laurence

    2010-01-01

    The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

  4. Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

    Science.gov (United States)

    Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

    2018-03-01

    Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  5. PREVALENCE OF GASTROINTESTINAL TRACT DISEASES AND EFFICACY OF ERADICATION THERAPY FOR H.PYLORI INFECTION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    I.A. Zhdanova

    2006-01-01

    Full Text Available Prevalence of upper gastrointestinal tract pathology and estimations of clinical and pharmacoeconomic efficacy of different algorithms of therapy for H. pyloria assosiated diseases in children dwelling in Krasnodar region are presented in this article.Key words: h. Pylori, prevalence, treatment, eradication therapy, children.

  6. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

    Directory of Open Access Journals (Sweden)

    Stefano Salmaso

    2013-01-01

    Full Text Available Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.

  7. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

    Science.gov (United States)

    Abbasalizadeh, Saeed; Baharvand, Hossein

    2013-12-01

    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

  8. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

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

  9. Network Meta-Analysis Comparing the Efficacy of Therapeutic Treatments for Bronchiolitis in Children.

    Science.gov (United States)

    Guo, Caili; Sun, Xiaomin; Wang, Xiaowen; Guo, Qing; Chen, Dan

    2018-01-01

    This study aims to compare placebo (PBO) and 7 therapeutic regimens-namely, bronchodilator agents (BAs), hypertonic saline (HS), BA ± HS, corticosteroids (CS), epinephrine (EP), EP ± CS, and EP ± HS-to determine the optimal bronchiolitis treatment. We plotted networks using the curative outcome of several studies and specified the relations among the experiments by using mean difference, standardized mean difference, and corresponding 95% credible interval. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each therapy on clinical severity score (CSS) and length of hospital stay (LHS). This network meta-analysis included 40 articles from 1995 to 2016 concerning the treatment of bronchiolitis in children. All 7 therapeutic regimens displayed no significant difference to PBO with regard to CSS in our study. Among the 7 therapies, BA performed better than CS. As for LHS, EP and EP ± HS had an advantage over PBO. Moreover, EP and EP ± HS were also more efficient than BA. The SUCRA results showed that EP ± CS is most effective, and EP ± HS is second most effective with regard to CSS. With regard to LHS, EP ± HS ranked first, EP ± CS ranked second, and EP ranked third. We recommend EP ± CS and EP ± HS as the first choice for bronchiolitis treatment in children because of their outstanding performance with regard to CSS and LHS. © 2017 American Society for Parenteral and Enteral Nutrition.

  10. Therapeutic efficacy and dosimetric aspects of Rhenium-188-HEDP in bone pain palliation

    International Nuclear Information System (INIS)

    Liepe, Knut

    2005-01-01

    Full text: Bone metastases are a frequent complication of cancer, occurring in up 70% of patients suffering from advanced breast or prostate cancer and often present with severe bone pain. In this purpose the radionuclide therapy is a useful option for cancer patients. Different radionuclides are described, such as 89 Sr, 32 P, 153 Sm-EDTMP, 186 Re-HEDP, 131 I-BDP3, 90 Y, 117mSn-DTPA, 188 Re-HEDP and 188 Re-DMSA. The most experiences are available for 89 Sr. An indication for the treatment are patients with osteoblastic metastases, bone pain, sufficient bone marrow function and at least of three bone metastases visualized in bone scan. A bisphosphonate therapy, a chemotherapy with lower bone marrow toxicity or a local field external beam radiotherapy represent no contraindications, especially because the reported synergistic effects to the systemic radionuclide therapy. In 33 treated patients (breast and prostate cancer) we investigated the effect of 188 Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function. There were an improvement on the Karnofsky performance scale from 74 7% to 85 9% 12 weeks after therapy (p= 0.001). The pain score showed a maximum decrease from 44 ± 18% to 27 ± 20% in the 3rd to the 8th week after therapy (p = .009) and 76% had a pain relief (20% were pain free). The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p = 0.021 and p = 0.094). In 105 investigated patients treated with different radionuclides ( 89 Sr, 153 Sm-EDTMP, 186 Re-HEDP, 188 Re-HEDP and 89 Sr in combination with chemotherapy) no different therapeutic efficacy of the treatments were observed. In dose calculation of 188 Re-HEDP a radiation dose of 3.83 ± 2.01 mGy/MBq (12.6 Gy for 3300 MBq) for bone metastases and 0.61 ± 0.21 mGy/MBq (2 Gy for 3300 MBq) were found. With the introducing of radionuclide treatments with chemotherapy and repeated treatments, the

  11. Gene Therapy Approaches to Hemoglobinopathies.

    Science.gov (United States)

    Ferrari, Giuliana; Cavazzana, Marina; Mavilio, Fulvio

    2017-10-01

    Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment. These hurdles need be addressed for gene therapy for hemoglobinopathies to become a clinical reality. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 8. Therapeutic and Educational Potential of Combining Cognitive Behavioural Therapy and Art – Qualitative Analysis of a Case Study

    Directory of Open Access Journals (Sweden)

    Růžička Michal

    2016-03-01

    Full Text Available Cognitive behavioural psychotherapy is, just like other psychotherapeutic systems, of an eclectic nature. Should a therapist be successful across a wide range of issues, he/she needs to be adaptable, flexible and eclectic in terms of the techniques applied. Eclectically oriented therapists use a wide range of interventions; however, they adhere to individual theoretical structures. The aim of the paper is to point out the application of a combination of artistic activities within the system of the Cognitive behavioural therapy. For this purpose the paper presents a qualitative analysis of two case studies. We formulated the following research questions. Can the methods of combining the cognitive behavioural therapy and art accelerate the course of therapy? Can the methods of combining the cognitive behavioural therapy and art be perceived by the client as effective? The phenomenon investigated in the case study is a functional analysis of a client’s case and subsequent application of therapeutic and educational techniques of the Cognitive behavioural therapy and art. In both case studies it was demonstrated that the involvement of therapeutic elements accelerated the course of therapy. The clients in the research sample assessed the therapy as beneficial.

  13. Therapeutic laryngoscopy during exercise: A novel non-surgical therapy for refractory EILO.

    Science.gov (United States)

    Olin, J Tod; Deardorff, Emily H; Fan, Elizabeth M; Johnston, Kristina L; Keever, Valerie L; Moore, Camille M; Bender, Bruce G

    2017-06-01

    Exercise-induced laryngeal obstruction (EILO) may affect as many as 6% of the adolescent population, with some patients experiencing symptoms refractory to conservative interventions. This report describes therapeutic laryngoscopy during exercise, a novel, non-surgical intervention that harnesses real-time laryngoscopy video as biofeedback to control laryngeal aperture during high-intensity exercise. Additionally, we quantitate patient-reported perceptions of procedure safety, tolerability, learning value, and effectiveness. Clinical EILO patients with symptoms refractory to conventional respiratory retraining and other therapies were referred for the procedure which features laryngoscopy video as biofeedback during serial physician-guided 1-min exercise sprints. We quantify perceptions of procedure safety, tolerability, learning value, and effectiveness through questionnaires offered to all patients as well as observers of the procedure. Forty-one patients and 37 parent observers were approached for feedback; 88% of patients and 95% of observers consented to participation. Patients and observers reported perceptions of safety and tolerability (81% and 86%, respectively), learning value (78% and 91%, respectively), and effectiveness (58% and 80%, respectively) with patient age predicting some responses. Seventy-five percent of patients noted that "Since the procedure, my breathing during exercise has improved," and 85% of this group noted that therapeutic laryngoscopy during exercise was "the most important therapy leading to my breathing improvement." The procedure also provided insight into the psychological experience of patients, a domain not clinically apparent prior to the procedure. Our data support further study of therapeutic laryngoscopy during exercise as a possible intervention for patients with refractory EILO. Pediatr Pulmonol. 2017;52:813-819. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  15. Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

    Science.gov (United States)

    Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

  16. Manual Therapy, Therapeutic Patient Education, and Therapeutic Exercise, an Effective Multimodal Treatment of Nonspecific Chronic Neck Pain: A Randomized Controlled Trial.

    Science.gov (United States)

    Beltran-Alacreu, Hector; López-de-Uralde-Villanueva, Ibai; Fernández-Carnero, Josué; La Touche, Roy

    2015-10-01

    The aim of this study was to determine the effectiveness of a multimodal treatment in the short and medium term for disability in nonspecific chronic neck pain. The design of this study is a single-blinded randomized controlled trial carried out in a university research laboratory. Forty-five patients between 18 and 65 yrs with nonspecific chronic neck pain were included in this study. Each patient was treated eight times over a 4-wk period. The sample was divided into three groups: control group, subjected to a protocol of manual therapy; experimental group 1, subjected to a protocol of manual therapy and therapeutic patient education; and experimental group 2, subjected to manual therapy, therapeutic patient education, and a therapeutic exercise protocol. Assessments were performed at baseline and at 4, 8, and 16 wks using the following measurements: the Neck Disability Index, the 11-item Tampa Scale of Kinesiophobia, the Fear Avoidance Beliefs Questionnaire, the Neck Flexor Muscle Endurance Test, and the Visual Analog Fatigue Scale. The nonparametric Kruskal-Wallis test for the Neck Disability Index showed statistically significant differences between baseline outcomes and all follow-up periods (P Kruskal-Wallis test, differences were found for the Visual Analog Fatigue Scale and the Neck Flexor Muscle Endurance Test in the follow-ups at 8 and 16 wks (P < 0.05). Analysis of variance for group × time interaction showed statistically significant changes (Tampa Scale of Kinesiophobia, F = 3.613, P = 0.005; Fear Avoidance Beliefs Questionnaire, F = 2.803, P = 0.022). Minimal detectable changes were obtained in both experimental groups for the 11-item Tampa Scale of Kinesiophobia but not in the control group. Differences between experimental groups and the control group were found in the short and medium term. A multimodal treatment is a good method for reducing disability in patients with nonspecific chronic neck pain in the short and medium term.

  17. Hyperbaric oxygen therapy for wound healing in diabetic rats: Varying efficacy after a clinically-based protocol

    NARCIS (Netherlands)

    J.W. van Neck (Han); B. Tuk (Bastiaan); E.M.G. Fijneman (Esther ); Redeker, J.J. (Jonathan J.); Talahatu, E.M. (Edwin M.); M. Tong (Miao)

    2017-01-01

    textabstractHyperbaric oxygen therapy (HBOT) is a clinical treatment in which a patient breathes pure oxygen for a limited period of time at an increased pressure. Although this therapy has been used for decades to assist wound healing, its efficacy for many conditions is unproven and its mechanism

  18. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies.

    Science.gov (United States)

    Panebianco, Concetta; Andriulli, Angelo; Pazienza, Valerio

    2018-05-22

    Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments.

  19. Skills use and common treatment processes in dialectical behaviour therapy for borderline personality disorder.

    Science.gov (United States)

    Barnicot, Kirsten; Gonzalez, Rafael; McCabe, Rosemarie; Priebe, Stefan

    2016-09-01

    Dialectical behaviour therapy (DBT) trains participants to use behavioural skills for managing their emotions. The study aimed to evaluate whether skills use is associated with positive treatment outcomes independently of treatment processes that are common across different therapeutic models. Use of the DBT skills and three common treatment processes (therapeutic alliance, treatment credibility and self-efficacy) were assessed every 2 months for a year in 70 individuals with borderline personality disorder receiving DBT. Mixed-multilevel modelling was used to determine the association of these factors with frequency of self-harm and with treatment dropout. Participants who used the skills less often at any timepoint were more likely to drop out of DBT in the subsequent two months, independently of their self-efficacy, therapeutic alliance or perceived treatment credibility. More frequent use of the DBT skills and higher self-efficacy were each independently associated with less frequent concurrent self-harm. Treatment credibility and the alliance were not independently associated with self-harm or treatment dropout. The skills use measure could not be applied to a control group who did not receive DBT. The sample size was insufficient for structural equation modelling. Practising the DBT skills and building an increased sense of self-efficacy may be important and partially independent treatment processes in dialectical behaviour therapy. However, the direction of the association between these variables and self-harm requires further evaluation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. SPECIFIC DISORDERS OF THE RESPIRATORY SYSTEM IN CYSTIC FIBROSIS. CLINICAL EFFICACY OF THERAPY WITH DORNASE ALFA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    T.V. Simanova

    2010-01-01

    Full Text Available The article is devoted to specific disorders of the respiratory system in cystic fibrosis. 64 patients with cystic fibrosis (CF aged 2 months to 32 years and residing in the Udmurtian Republic were studied. Epidemiological and genetic specifics of this disease in the mentioned region of the RF were examined. Clinical, X-ray, functional and microbiological studies of the CF patients’ respiratory system were conducted. It was found that genotype delF508 and chronic infection Pseudomonas aeruginosa, Staphylococcus aureus cause severe structural changes to the bronchopulmonary system more often. The obtained data suggest the advisability of identifying the groups of CF patients at the highest risk of severe respiratory system disorders in order to optimise therapeutic efforts. The article provides indicators of clinical efficacy of a dornase alfa therapy in CF children.Key words: cystic fibrosis, genotype, delF508 mutation, respiratory organs, pseudomonas aeruginosa infection, staphylococcal infection, respiratory function, mucolytic function, dornase alfa. (Pediatric Pharmacology. – 2010; 7(6:44-48

  1. Drug therapy for peripheral vestibular vertigo

    Directory of Open Access Journals (Sweden)

    L. M. Antonenko

    2017-01-01

    Full Text Available The choice of effective treatments for vestibular vertigo is one of the important problems, by taking into account the high prevalence of peripheral vestibular diseases. Different drugs, such as vestibular suppressants for the relief of acute vertigo attacks and vestibular compensation stimulants for rehabilitation treatment, are used to treat vestibular vertigo. Drug therapy in combination with vestibular exercises is effective in patients with vestibular neuronitis, Meniere's disease, so is that with therapeutic maneuvers in patients with benign paroxysmal positional vertigo. The high therapeutic efficacy and safety of betahistines permit their extensive use for the treatment of various vestibular disorders.

  2. How does electroconvulsive therapy work?

    DEFF Research Database (Denmark)

    Bolwig, Tom G

    2011-01-01

    This article reviews 3 current theories of electroconvulsive therapy (ECT). One theory points to generalized seizures as essential for the therapeutic efficacy of ECT. Another theory highlights the normalization of neuroendocrine dysfunction in melancholic depression as a result of ECT. A third t...... theory is based on recent findings of increased hippocampal neurogenesis and synaptogenesis in experimental animals given electroconvulsive seizures. Presently, the endocrine theory has the strongest foundation to explain the working mechanism of ECT....

  3. Research progress of therapeutic vaccines for treating chronic hepatitis B.

    Science.gov (United States)

    Li, Jianqiang; Bao, Mengru; Ge, Jun; Ren, Sulin; Zhou, Tong; Qi, Fengchun; Pu, Xiuying; Dou, Jia

    2017-05-04

    Hepatitis B virus (HBV) is a member of Hepadnavirus family, which leads to chronic infection in around 5% of patients with a high risk of developing liver cirrhosis, liver failure, and hepatocellular carcinoma. 1 Despite the availability of prophylactic vaccines against hepatitis B for over 3 decades, there are still more than 2 billion people have been infected and 240 million of them were chronic. Antiviral therapies currently used in the treatment of CHB (chronic hepatitis B) infection include peg-interferon, standard α-interferon and nucleos/tide analogs (NAs), but none of them can provide sustained control of viral replication. As an alternative strategy, therapeutic vaccines for CHB patients have been widely studied and showed some promising efficacies in dozens of preclinical and clinical trials. In this article, we review current research progress in several types of therapeutic vaccines for CHB treatment, including protein-based vaccines, DNA-based vaccines, live vector-based vaccines, peptide-based vaccines and cell-based therapies. These researches may provide some clues for developing new treatments in CHB infection.

  4. Therapy Processes and Outcomes of Psychological Interventions for Women Diagnosed with Gynecological Cancers: A Test of the Generic Process Model of Psychotherapy

    Science.gov (United States)

    Manne, Sharon; Winkel, Gary; Zaider, Talia; Rubin, Stephen; Hernandez, Enrique; Bergman, Cynthia

    2010-01-01

    Objective: Little attention has been paid to the role of nonspecific therapy processes in the efficacy of psychological interventions for individuals diagnosed with cancer. The goal of the current study was to examine the three constructs from the generic model of psychotherapy (GMP): therapeutic alliance, therapeutic realizations, and therapeutic…

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

    International Nuclear Information System (INIS)

    Bodei, L.; Kidd, M.; Modlin, I.M.; Severi, S.; Nicolini, S.; Paganelli, G.; Drozdov, I.; Kwekkeboom, D.J.; Krenning, E.P.; Baum, R.P.

    2016-01-01

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with 177 Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 18 FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ 2 = 27.4; p = 1.2 x 10 -7 ) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0.004) for predicting

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-15

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

  7. Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases.

    Science.gov (United States)

    Suen, Colin M; Mei, Shirley H J; Kugathasan, Lakshmi; Stewart, Duncan J

    2013-10-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety. © 2013 American Physiological Society. Compr Physiol 3:1749-1779, 2013.

  8. Optimization of ultrasound parameters of myocardial cavitation microlesions for therapeutic application.

    Science.gov (United States)

    Miller, Douglas L; Dou, Chunyan; Owens, Gabe E; Kripfgans, Oliver D

    2014-06-01

    Intermittent high intensity ultrasound scanning with contrast microbubbles can induce scattered cavitation microlesions in the myocardium, which may be of value for tissue reduction therapy. Anesthetized rats were treated in a heated water bath with 1.5 MHz focused ultrasound pulses, guided by an 8 MHz imaging transducer. The relative efficacy with 2 or 4 MPa pulses, 1:4 or 1:8 trigger intervals and 5 or 10 cycle pulses was explored in six groups. Electrocardiogram premature complexes (PCs) induced by the triggered pulse bursts were counted, and Evans blue stained cardiomyocyte scores (SCSs) were obtained. The increase from 2 to 4 MPa produced significant increases in PCs and SCSs and eliminated an anticipated decline in the rate of PC induction with time, which might hinder therapeutic efficacy. Increased intervals and pulse durations did not yield significant increases in the effects. The results suggest that cavitation microlesion production can be refined and potentially lead to a clinically robust therapeutic method. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  9. Corrective interpersonal experience in psychodrama group therapy: a comprehensive process analysis of significant therapeutic events.

    Science.gov (United States)

    McVea, Charmaine S; Gow, Kathryn; Lowe, Roger

    2011-07-01

    This study investigated the process of resolving painful emotional experience during psychodrama group therapy, by examining significant therapeutic events within seven psychodrama enactments. A comprehensive process analysis of four resolved and three not-resolved cases identified five meta-processes which were linked to in-session resolution. One was a readiness to engage in the therapeutic process, which was influenced by client characteristics and the client's experience of the group; and four were therapeutic events: (1) re-experiencing with insight; (2) activating resourcefulness; (3) social atom repair with emotional release; and (4) integration. A corrective interpersonal experience (social atom repair) healed the sense of fragmentation and interpersonal disconnection associated with unresolved emotional pain, and emotional release was therapeutically helpful when located within the enactment of this new role relationship. Protagonists who experienced resolution reported important improvements in interpersonal functioning and sense of self which they attributed to this experience.

  10. Deferasirox: appraisal of safety and efficacy in long-term therapy

    Directory of Open Access Journals (Sweden)

    Chaudhary P

    2013-08-01

    Full Text Available Preeti Chaudhary, Vinod PullarkatJane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USAAbstract: Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.Keywords: deferasirox, iron overload, thalassemia, sickle-cell disease, myelodysplastic syndrome

  11. Novel therapeutics for gastro-esophageal reflux symptoms.

    Science.gov (United States)

    Zerbib, Frank; Simon, Mireille

    2012-09-01

    Approximately 20-30% of patients with gastro-esophageal reflux symptoms report inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms involved are failure of the antireflux barrier (transient lower esophageal sphincter relaxations), high proximal extent of the refluxate, esophageal hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid reflux can be demonstrated in 40-50% of cases, suggesting that there is room for antireflux therapy in these patients. New antireflux compounds have been shown to decrease the occurrence of transient lower esophageal sphincter relaxations. The most promising classes of compounds are GABA type B agonists and metabotropic glutamate receptor 5 antagonists, which can reduce both reflux episodes and symptoms, but the development of these compounds has been abandoned for either safety issues or lack of efficacy. Esophageal hypersensitivity and impaired mucosal integrity may prove to be relevant therapeutic targets in the future.

  12. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

    Science.gov (United States)

    Geszke-Moritz, Małgorzata; Moritz, Michał

    2016-11-01

    This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

    2017-08-01

    Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

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

    Directory of Open Access Journals (Sweden)

    Mavroudi M

    2014-01-01

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

  15. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  16. Post-therapeutic recovery of serum interleukin-35 level might predict positive response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Huang, Zhen; Tong, Hongfei; Li, Yuan; Zhou, Haixia; Qian, Jiangchao; Wang, Juxiang; Ruan, Jichen

    2017-08-01

    The predictive value of interleukin-35 (IL-35) on efficacy of immunosuppressive therapy (IST) in aplastic anemia (AA) has not been well investigated. The aim of the study was to evaluate the association between serum IL-35 level and response to IST in pediatric AA. A total of 154 children with AA and 154 controls were included between January 2012 and December 2013. Blood and bone marrow fluid specimens were collected. Serum level of IL-35 was determined by enzyme-linked immunosorbent assay. Patients were treated with IST, and response to therapy was evaluated during 180-day follow-up period after starting therapy. Serum levels of IL-35 at admission decreased significantly in patients compared with that in controls (10.9 ± 5.5 pg ml -1 and 45.3 ± 8.8 pg ml -1 , p < 0.001). After starting IST, serum levels of IL-35 in patients recovered 30.7 ± 9.7 pg ml -1 in the first 28 days (p < 0.001). During the follow-up period, increased range of serum IL-35 level ≥30.7 pg ml -1 in the first 28 days was associated with effective response to therapy (odds ratio 7.97, 95% confidence interval 3.82-16.79). In addition, Fas/FasL protein expression in bone marrow mononuclear cells dropped significantly in the same group of patients in the first 28 days (p < 0.05). The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. Moreover, apoptosis might be involved in such a forecasting process.

  17. Host modulation therapeutics in periodontics: role as an adjunctive periodontal therapy.

    Science.gov (United States)

    Shinwari, Muhammad Saad; Tanwir, Farzeen; Hyder, Pakiza Raza; Bin Saeed, Muhammad Humza

    2014-09-01

    Host Modulation Therapy (HMT) is a treatment concept that reduces tissue destruction and stabilizes or even regenerates inflammatory tissue by modifying host response factors. It has been used for treating osteoporosis and arthritis for several decades. However, its use in dentistry has only been recently reported. The objective of this article is to present a review of the various literatures available on HMT and also its role as adjunct therapy in periodontics. For identifying studies for this review, a PUBMED search was carried out in 2013 for all articles published till December 2012. The search was restricted to English language publications only. Longitudinal prospective and retrospective studies were included in the search. The key words used were: Host Modulation Therapy; Sub antimicrobial dose doxycycline and Non-Surgical Periodontal Therapy. The main outcomes sought were host modulation therapeutics in periodontics. Exclusion criteria included cross sectional studies, short case series as well as studies with short follow-up periods. There is a paucity of literature on HMT in periodontics although the only drug approved by United States Food and Drug Administration (FDA) is a subantimicrobial dose of doxycycline (SDD) with highly predictable results as a host modulating agent in periodontal diseases and also an effective adjunctive therapy in various diseases of periodontium. However, more randomized controlled trials are needed to obtain clinical guidelines on the usage of other host modulating agents as adjunct as well as definite therapy for periodontal diseases. SDD is an effective adjunct therapy when used in dosage of 20mg twice daily for minimum 3 months duration in various periodontal diseases with predictable clinical outcomes. It is also recommended that future clinical research on anti cytokine drugs, chemically modified tetracycline and other HMT agents should be conducted so that new drugs are available with highly predictable results.

  18. The retinoids. A review of their clinical pharmacology and therapeutic use.

    Science.gov (United States)

    Orfanos, C E; Ehlert, R; Gollnick, H

    1987-10-01

    With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids

  19. Emerging pharmaceutical therapies for COPD

    Science.gov (United States)

    Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

    2017-01-01

    COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising. PMID:28790817

  20. Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

    Science.gov (United States)

    Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

    2017-10-01

    One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Efficacy of Parent-Child Interaction Therapy with Chinese ADHD Children: Randomized Controlled Trial

    Science.gov (United States)

    Leung, Cynthia; Tsang, Sandra; Ng, Gene S. H.; Choi, S. Y.

    2017-01-01

    Purpose: This study aimed to evaluate the efficacy of Parent-Child Interaction Therapy (PCIT) in Chinese children with attention-deficit/hyperactivity disorder (ADHD) or ADHD features. Methods: This study adopted a randomized controlled trial design without blinding. Participants were randomized into either the intervention group (n = 32) and…

  2. Characteristics of therapeutic alliance in musculoskeletal physiotherapy and occupational therapy practice: a scoping review of the literature.

    Science.gov (United States)

    Babatunde, Folarin; MacDermid, Joy; MacIntyre, Norma

    2017-05-30

    Most conventional treatment for musculoskeletal conditions continue to show moderate effects, prompting calls for ways to increase effectiveness, including drawing from strategies used across other health conditions. Therapeutic alliance refers to the relational processes at play in treatment which can act in combination or independently of specific interventions. Current evidence guiding the use of therapeutic alliance in health care arises largely from psychotherapy and medicine literature. The objective of this review was to map out the available literature on therapeutic alliance conceptual frameworks, themes, measures and determinants in musculoskeletal rehabilitation across physiotherapy and occupational therapy disciplines. A scoping review of the literature published in English since inception to July 2015 was conducted using Medline, EMBASE, PsychINFO, PEDro, SportDISCUS, AMED, OTSeeker, AMED and the grey literature. A key search term strategy was employed using "physiotherapy", "occupational therapy", "therapeutic alliance", and "musculoskeletal" to identify relevant studies. All searches were performed between December 2014 and July 2015 with an updated search on January 2017. Two investigators screened article title, abstract and full text review for articles meeting the inclusion criteria and extracted therapeutic alliance data and details of each study. One hundred and thirty articles met the inclusion criteria including quantitative (33%), qualitative (39%), mixed methods (7%) and reviews and discussions (23%) and most data came from the USA (23%). Randomized trials and systematic reviews were 4.6 and 2.3% respectively. Low back pain condition (22%) and primary care (30.7%) were the most reported condition and setting respectively. One theory, 9 frameworks, 26 models, 8 themes and 42 subthemes of therapeutic alliance were identified. Twenty-six measures were identified; the Working Alliance Inventory (WAI) was the most utilized measure (13%). Most of

  3. Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

    Directory of Open Access Journals (Sweden)

    Fuminori Sato

    2005-09-01

    Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

  4. Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

    DEFF Research Database (Denmark)

    Efe, Cumali; Hagström, Hannes; Ytting, Henriette

    2017-01-01

    BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate...

  5. The state of the art in therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Allen, B.J.

    2001-01-01

    Radionuclide therapy can be curative or palliative in intent, and local or systemic in administration. Current therapy relies of beta emitting radioisotopes and selective carriers for the treatment of advanced tumours. The next generation of therapeutics may be alpha emitting radionuclides for subclinical, micrometastatic disease. Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT has been tested by in vitro and in vivo studies many cancers. The first phase 1 clinical trial of TAT for leukaemia with Bi-213 has concluded at the Memorial Sloan Kettering Cancer Center, a phase 1 and 2 trial of intra-lesional TAT is ongoing at Duke University with At-211 labeled Mab against cystic glioma, and a phase 1 and 2 clinical trial for intra-lesional TAT with Bi-213 of subcutaneous secondary melanoma is underway at St George Hospital

  6. Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma

    OpenAIRE

    Bag?, Juli R.; Alfonso-Pecchio, Adolfo; Okolie, Onyi; Dumitru, Raluca; Rinkenbaugh, Amanda; Baldwin, Albert S.; Miller, C. Ryan; Magness, Scott T.; Hingtgen, Shawn D.

    2016-01-01

    Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced ap...

  7. Mesenchymal stem cell-based gene therapy: A promising therapeutic strategy.

    Science.gov (United States)

    Mohammadian, Mozhdeh; Abasi, Elham; Akbarzadeh, Abolfazl

    2016-08-01

    Mesenchymal stem cells (MSCs) are multipotent stromal cells that exist in bone marrow, fat, and so many other tissues, and can differentiate into a variety of cell types including osteoblasts, chondrocytes, and adipocytes, as well as myocytes and neurons. Moreover, they have great capacity for self-renewal while maintaining their multipotency. Their capacity for proliferation and differentiation, in addition to their immunomodulatory activity, makes them very promising candidates for cell-based regenerative medicine. Moreover, MSCs have the ability of mobilization to the site of damage; therefore, they can automatically migrate to the site of injury via their chemokine receptors following intravenous transplantation. In this respect, they can be applied for MSC-based gene therapy. In this new therapeutic method, genes of interest are introduced into MSCs via viral and non-viral-based methods that lead to transgene expression in them. Although stem cell-based gene therapy is a relatively new strategy, it lights a new hope for the treatment of a variety of genetic disorders. In the near future, MSCs can be of use in a vast number of clinical applications, because of their uncomplicated isolation, culture, and genetic manipulation. However, full consideration is still crucial before they are utilized for clinical trials, because the number of studies that signify the advantageous effects of MSC-based gene therapy are still limited.

  8. Therapeutic advancement of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Lu Kang

    2012-09-01

    Full Text Available Abstract Despite the combinations of chemotherapy with monoclonal antibodies have further improved response rates, chronic lymphocytic leukemia (CLL remains an incurable disease with an extremely variable course. This article reviews the ongoing clinical advances in the treatment of CLL in both previously untreated and relapsed disease and focuses on the benefit of different therapeutic strategies, the most effective therapy combinations and the potential activity of novel agents. Novel agents and combination therapies have been investigated by several studies in both the upfront and relapsed setting, particularly for patients with 17p deletion, TP53 mutation and fludarabine-refractory CLL. While these agents and combination therapies have improved initial response rates, ongoing studies are continued to determine and improve the efficacy and safety. Despite advancements in the treatment of CLL have led to high response rates, allogeneic hematopoietic stem cell transplantation (allo-HSCT remains the only curative option and reduced-intensity conditioning (RIC allo-HSCT must be strongly considered whenever feasible. As such, ongoing studies of these agents and other novel approaches in clinical development are needed to expand and improve treatment options for CLL patients.

  9. A comparative study of efficacy of emg bio-feedback and progressive muscular relaxation in tension headache.

    Science.gov (United States)

    Gada, M T

    1984-04-01

    The aim of the present study was to find out efficacy of frontalis EMG Biofeedback therapy, deep muscular relaxation therapy and compare the efficacy of both in cases of tension headache. During two week basal-data recording period all patients were taught deep muscular relaxation by Jacobson's technique. Simultaneously patients were instructed to keep headache diary. Headache diary yielded three different parameters a) number of headache-free days per week, b) peak headache intensity (or each week and c) average daily headache activity score per week. These parameters were used to find out therapeutic efficacy of each treatment. Patients were randomly divided in two groups. EMG Biofeedback group was given frontalis EMG feedback through EMG J 33 muscle trainer of Cyborg Corporation (U.S.A.). Patients in each group were given 20 sessions (two sessions per week); each session lasting 30 minutes. Patients were instructed to practice at least one 30 minute session of relaxation at home. The data were subjected to statistical calculation. The results indicate that frontalis EMG Biofeedback therapy and deep muscle relaxation therapy are significantly effective in cases of tension headache. Both treatments are equally effective. The findings are discussed in relation to Indian situation.

  10. Therapeutic efficacy of autologous platelet-rich plasma and polydeoxyribonucleotide on female pattern hair loss.

    Science.gov (United States)

    Lee, Si-Hyung; Zheng, Zhenlong; Kang, Jin-Soo; Kim, Do-Young; Oh, Sang Ho; Cho, Sung Bin

    2015-01-01

    Autologous platelet-rich plasma (PRP) exerts positive therapeutic effects on hair thickness and density in patients with pattern hair loss. The aim of our study was to evaluate the efficacy of intra-perifollicular autologous PRP and polydeoxyribonucleotide (PDRN) injections in treating female pattern hair loss (FPHL). Twenty FPHL patients were treated with a single session of PRP injection, followed by 12 sessions of PDRN intra-perifollicular injection, along the scalp at weekly intervals. Additionally, another 20 FPHL patients were treated with 12 sessions of PDRN injection only. Meanwhile, one half of the backs of two rabbits was injected with the PRP preparation, while the other half was injected with phosphate buffered saline as a control. Tissue samples from the rabbits were analyzed by real-time polymerase chain reaction and Western blotting. Compared with baseline values, patients treated with PRP and PDRN injections exhibited clinical improvement in mean hair counts (23.2 ± 15.5%; p hair thickness (16.8 ± 10.8%; p hair counts (17.9 ± 13.2%; p hair thickness (13.5 ± 10.7%; p hair thickness than treatment with PDRN therapy alone (p = 0.031), but not in hair counts (p > 0.05). The pilot animal study revealed significant up-regulation of WNT, platelet-derived growth factor, and fibroblast growth factor expression in rabbit skin treated with the PRP preparation, compared with control skin. In conclusion, intra-perifollicular injections of autologous PRP and/or PDRN generate improvements in hair thickness and density in FPHL patients. © 2014 by the Wound Healing Society.

  11. The Therapeutic Relationship as Predictor of Change in Music Therapy with Young Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Mössler, Karin; Gold, Christian; Aßmus, Jörg; Schumacher, Karin; Calvet, Claudine; Reimer, Silke; Iversen, Gun; Schmid, Wolfgang

    2017-09-21

    This study examined whether the therapeutic relationship in music therapy with children with Autism Spectrum Disorder predicts generalized changes in social skills. Participants (4-7 years, N = 48) were assessed at baseline, 5 and 12 months. The therapeutic relationship, as observed from session videos, and the generalized change in social skills, as judged by independent blinded assessors and parents, were evaluated using standardized tools (Assessment of the Quality of Relationship; ADOS; SRS). Linear mixed effect models showed significant interaction effects between the therapeutic relationship and several outcomes at 5 and 12 months. We found the music therapeutic relationship to be an important predictor of the development of social skills, as well as communication and language specifically.

  12. Heart failure—potential new targets for therapy

    Science.gov (United States)

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

    2016-01-01

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

  13. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    Science.gov (United States)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  14. Self care programs and multiple sclerosis: physical therapeutics treatment - literature review.

    Science.gov (United States)

    Demaille-Wlodyka, S; Donze, C; Givron, P; Gallien, P

    2011-03-01

    To clarify the therapeutic education program impact with multiple sclerosis patients, literature review. Highlight contents and efficacy. A non-systematic review on Medline, PubMed and Cochrane library databases from 1966 to 2010 using the following keywords: "multiple sclerosis", "self-care", "self-management" and specific symptoms keywords. Clinical trials and randomized clinical trials, as well as literature reviews published in English, French and German will be analyzed. Counseling is a part of the non-pharmacological management of chronic illnesses such as multiple sclerosis. Symptoms' diversity and the different clinical forms limit standardized programs of self-care management, applicable to patients. In the literature review, counseling programs have often low metrology. A behavior change with patients and medical staff could exist. To empower the patient, to reduce symptoms' impact and to improve treatment access are the aims of educational therapy. Therapeutic education program for multiple sclerosis patients could progress with their standardization and assessment, for each sign. To promote the educational therapy of multiple sclerosis patients, a specific training for medical staff, as specific financing are necessary. 2011 Elsevier Masson SAS. All rights reserved.

  15. Loco-regional therapy for liver cancer

    Directory of Open Access Journals (Sweden)

    YE Shenglong

    2013-01-01

    Full Text Available Loco-regional therapy, which uses imaging technologies to facilitate targeted delivery of therapeutic agents to cancers, has emerged as the most commonly used non-surgical treatment for primary liver cancer. Since the theory of loco-regional therapy was introduced, various strategies have been developed and successfully applied in clinic, including interventional radiology methods (mainly transarterial chemoembolization and local ablative methods (such as intratumoral ethanol injection, radiofrequency ablation, microwave coagulation, laser-induced thermal therapy, high-intensity focused ultrasound, and cryotherapy. TACE has been widely applied to treat inoperable liver cancers at intermediate and advanced stages, while the local ablative therapies have proven more suitable for small (<5 cm liver cancers. However, choosing the appropriate loco-regional therapy strategy should be carried out on an individual basis, considering the patient's particular disease condition and characteristics. To help guide such treatment decisions, this review highlights the principal indications, theory, techniques, and reported efficacies of the various loco-regional therapy strategies.

  16. Curcumin Nanomedicine: A Road to Cancer Therapeutics

    Science.gov (United States)

    Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.

    2013-01-01

    Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin’s limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics. PMID:23116309

  17. How do the features of mindfulness-based cognitive therapy contribute to positive therapeutic change? A meta-synthesis of qualitative studies.

    Science.gov (United States)

    Cairns, Victoria; Murray, Craig

    2015-05-01

    The exploration of Mindfulness-based Cognitive Therapy through qualitative investigation is a growing area of interest within current literature, providing valuable understanding of the process of change experienced by those engaging in this therapeutic approach. This meta-synthesis aims to gain a deeper understanding of how the features of Mindfulness-based Cognitive Therapy contribute to positive therapeutic change. Noblit and Hare's (1988) 7-step meta-ethnography method was conducted in order to synthesize the findings of seven qualitative studies. The process of reciprocal translation identified the following five major themes: i) Taking control through understanding, awareness and acceptance; ii) The impact of the group; (iii) Taking skills into everyday life; (iv) Feelings towards the self; (v) The role of expectations. The synthesis of translation identified the higher order concept of "The Mindfulness-based Cognitive Therapy Journey to Change", which depicts the complex interaction between the five themes in relation to how they contribute to positive therapeutic change. The findings are discussed in relation to previous research, theory and their implications for clinical practice.

  18. Colloidal silver nanoparticles improve anti-leukemic drug efficacy via amplification of oxidative stress.

    Science.gov (United States)

    Guo, Dawei; Zhang, Junren; Huang, Zhihai; Jiang, Shanxiang; Gu, Ning

    2015-02-01

    Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy. Copyright © 2015. Published by Elsevier B.V.

  19. Efficacy of Cognitive Rehabilitation Therapy on Poststroke Depression among Survivors of First Stroke Attack in Ibadan, Nigeria.

    Science.gov (United States)

    Olukolade, Olugbemi; Osinowo, Helen O

    2017-01-01

    Poststroke depression (PSD) is a common complication after stroke. There is no adequate treatment for PSD. This study examined efficacy of cognitive rehabilitation therapy (CRT) in the treatment of PSD among stroke survivors. An experimental design, 30 participants with poststroke depression were randomly assigned into 3 groups of cognitive rehabilitation therapy (CRT), psychoeducation (PE), and the control group (CG). CRT consisted of nine sessions with three-phased sessions focusing on activity stimulation, negative thoughts, and people contacts, PE consisted of nine sessions focusing on knowledge on stroke and poststroke depression, and the CG group was on the waiting list. The BDI scale was used for assessing PSD at posttest. There was a significant difference in the efficacy of CRT, PE, and the CG on PSD, with CRT-CG mean difference of -9.4 ± 3.11 and PE-CG 1.0 ± 3.83. Furthermore, stress was not a confounding variable on the efficacy of CRT. The type of therapy significantly influenced PSD at posttest, with the CRT having greater mean reduction to CG (-11.1 ± 3.1) than PE to the CG (3.0 ± 3.8). Cognitive rehabilitation therapy significantly reduced poststroke depression. Hence, it should be integrated as an adjunct treatment of poststroke depression.

  20. Novel therapies for malignant pleural mesothelioma.

    Science.gov (United States)

    Scherpereel, Arnaud; Wallyn, Frederic; Albelda, Steven M; Munck, Camille

    2018-03-01

    Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Contemporary Animal Models For Human Gene Therapy Applications.

    Science.gov (United States)

    Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

    2015-01-01

    Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

  2. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2007-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  3. [Music therapy and depression].

    Science.gov (United States)

    Van Assche, E; De Backer, J; Vermote, R

    2015-01-01

    Music therapy is a predominantly non-verbal psychotherapy based on music improvisation, embedded in a therapeutic relationship. This is the reason why music therapy is also used to treat depression. To examine the efficacy of music therapy and to report on the results of recent research into the value of music therapy as a treatment for depression. We reviewed the literature on recent research into music therapy and depression, reporting on the methods used and the results achieved, and we assessed the current position of music therapy for depression in the context of evidence-based scientific research. A wide variety of research methods was used to investigate the effects of using music therapy as a psychotherapy. Most studies focused usually on the added value that music therapy brings to the standard form of psychiatric treatment, when administered with or without psychopharmacological support. Music therapy produced particularly significant and favourable results when used to treat patients with depression. Current research into music therapy and depression points to a significant and persistent reduction in patients' symptoms and to improvements in their quality of life. However, further research is needed with regard to the best methods of illustrating the effects of music therapy.

  4. Pharmacological therapeutics targeting the secondary defects and downstream pathology of Duchenne muscular dystrophy

    Science.gov (United States)

    Spinazzola, Janelle M.; Kunkel, Louis M.

    2016-01-01

    Introduction Since the identification of the dystrophin gene in 1986, a cure for Duchenne muscular dystrophy (DMD) has yet to be discovered. Presently, there are a number of genetic-based therapies in development aimed at restoration and/or repair of the primary defect. However, growing understanding of the pathophysiological consequences of dystrophin absence has revealed several promising downstream targets for the development of therapeutics. Areas covered In this review, we discuss various strategies for DMD therapy targeting downstream consequences of dystrophin absence including loss of muscle mass, inflammation, fibrosis, calcium overload, oxidative stress, and ischemia. The rationale of each approach and the efficacy of drugs in preclinical and clinical studies are discussed. Expert opinion For the last 30 years, effective DMD drug therapy has been limited to corticosteroids, which are associated with a number of negative side effects. Our knowledge of the consequences of dystrophin absence that contribute to DMD pathology has revealed several potential therapeutic targets. Some of these approaches may have potential to improve or slow disease progression independently or in combination with genetic-based approaches. The applicability of these pharmacological therapies to DMD patients irrespective of their genetic mutation, as well as the potential benefits even for advanced stage patients warrants their continued investigation. PMID:28670506

  5. Prevention of depression and anxiety in adolescents: A randomized controlled trial testing the efficacy and mechanisms of Internet-based self-help problem-solving therapy

    Directory of Open Access Journals (Sweden)

    Schuurmans Josien

    2009-10-01

    Full Text Available Abstract Background Even though depression and anxiety are highly prevalent in adolescence, youngsters are not inclined to seek help in regular healthcare. Therapy through the Internet, however, has been found to appeal strongly to young people. The main aim of the present study is to examine the efficacy of preventive Internet-based guided self-help problem-solving therapy with adolescents reporting depressive and anxiety symptoms. A secondary objective is to test potential mediating and moderating variables in order to gain insight into how the intervention works and for whom it works best. Methods/design This study is a randomized controlled trial with an intervention condition group and a wait-list control group. The intervention condition group receives Internet-based self-help problem-solving therapy. Support is provided by a professional and delivered through email. Participants in the wait-list control group receive the intervention four months later. The study population consists of adolescents (12-18-year-olds from the general population who report mild to moderate depressive and/or anxiety symptoms and are willing to complete a self-help course. Primary outcomes are symptoms of depression and anxiety. Secondary outcomes are quality of life, social anxiety, and cost-effectiveness. The following variables are examined for their moderating role: demographics, motivation, treatment credibility and expectancy, externalizing behaviour, perceived social support from parents and friends, substance use, the experience of important life events, physical activity, the quality of the therapeutic alliance, and satisfaction. Mediator variables include problem-solving skills, worrying, mastery, and self-esteem. Data are collected at baseline and at 3 weeks, 5 weeks, 4 months, 8 months, and 12 months after baseline. Both intention-to-treat and completer analyses will be conducted. Discussion This study evaluates the efficacy and mechanisms of

  6. The Effect of Art Therapy on Cognitive Performance of Hispanic/Latino Older Adults

    Science.gov (United States)

    Alders, Amanda; Levine-Madori, Linda

    2010-01-01

    This article presents the results of a pilot study investigating the efficacy of art therapy to enhance cognitive performance in a sample of 24 elderly Hispanic/Latino members of a community center who participated in a weekly structured thematic therapeutic arts program. A 12-week, quasi-experimental, pretest/posttest, nonrandomized, controlled…

  7. The Effectiveness of Cognitive Behavioral Therapy on Increasing of Self-Efficacy and Improving of Addiction Symptoms among Drug Dependency Patients

    Directory of Open Access Journals (Sweden)

    Hamid Kamarzarin

    2012-08-01

    Full Text Available Introduction: The aim of this study was to determine the effectiveness of cognitive behavior therapy on increasing of self efficacy and improving of addiction symptoms among drug dependency patients. Method: For this purpose, 90 substance abusers were selected of private addiction center, Central Prison and drop in center by using of random sampling, and they were divided into two experimental (45 subjects and witness groups (45 subjects randomly. The members of experimental group were under 12 sessions of cognitive behavioral therapy by Carol method, and control group only have taken Methadone and other physical drugs. All participants at the beginning of research, during the study (after three months and three months after treatment completed self-efficacy questionnaire and Maudsley addiction profile (Map by a psychologist were assessed. The symptoms of addiction recovery and addiction treatment process. Results: Analysis of covariance indicated the treatment effectiveness and its maintenance on increasing of efficacy and reducing of the symptoms of Maudsley addiction profile. Conclusion: Cognitive behavior therapy is effective to increase self-efficacy and improve symptoms in substance abusers.

  8. Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

    Science.gov (United States)

    Marriott, James J; Miyasaki, Janis M; Gronseth, Gary; O'Connor, Paul W

    2010-05-04

    The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a "black box" warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in approximately 12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in approximately 0.4%, and leukemia occurs in approximately 0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking.

  9. The Therapeutic Alliance in Schema-Focused Therapy and Transference-Focused Psychotherapy for Borderline Personality Disorder

    Science.gov (United States)

    Spinhoven, Philip; Giesen-Bloo, Josephine; van Dyck, Richard; Kooiman, Kees; Arntz, Arnoud

    2007-01-01

    This study investigated the quality and development of the therapeutic alliance as a mediator of change in schema-focused therapy (SFT) and transference-focused psychotherapy (TFP) for borderline personality disorder. Seventy-eight patients were randomly allocated to 3 years of biweekly SFT or TFP. Scores of both therapists and patients for the…

  10. Effect of 131I therapy on outcomes of Graves' ophthalmopathy

    International Nuclear Information System (INIS)

    Wang Renfei; Tan Jian; Zhang Guizhi; Yin Liang

    2011-01-01

    Objective: To analyze the correlation between the therapeutic effect of Graves' hyperthyroidism and the outcomes of Graves' ophthalmopathy after 131 I therapy, and to explore the effect of 131 I treatment on turnout of Graves' ophthalmopathy. Methods: Six hundreds and fifty-two patients of Graves' disease accompanied with Graves' ophthalmopathy, received one-time 131 I treatment according to routine procedure. We recorded exophthalmometer readings, the signs and symptoms of eyes before therapy. Regular follow-up and appraisal of curative effect were carried out. Results: At least six months after 131 I therapy, the effective rate of Graves' hyperthyroidism and Graves' ophthalmopathy were 94.3% and 73.3% respectively. The total effective rate of hyperthyroidism with ophthalmopathy was 71.2%. There was a significant correlation between the prognosis of Graves' ophthalmopathy and therapeutic efficacy of hyperthyroidism (r=0.302, P 131 I therapy (χ 2 =0.296, P>0.05). Conclusions: The key to treat Graves' ophthalmopathy is the cure of Graves' hyperthyroidism through 131 I therapy. The timely diagnosis and replacement treatment of hypothyroidism can effectively avoid the aggravation of Graves' ophthalmopathy after 131 I therapy. (authors)

  11. THE EFFICACY AND SAFETY OF OXCARBAZEPINE AS ADD-ON THERAPY IN INTRACTABLE EPILEPSY IN CHILDREN

    OpenAIRE

    Azita TAVASSOLI; Mohammad GHOFRANI; Mohsen ROUZROKH; Eznollah AZARGASHB

    2010-01-01

    Objective1-3% of the population suffer from epilepsy. Up to 30% of them develop refractory epilepsy and their seizures occur more than once per month despite receiving at least 2 first line antiepileptic drugs. In  this group, more efficacious antiepileptics are needed. This study was undertaken to evaluate the efficacy and safety of Oxcarbazepine as an adjunction therapy in children with refractory epilepsy.Materials & MethodsFrom Feb 2004 until Sep 2006, 30 patients with refractory epilepsy...

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

    Directory of Open Access Journals (Sweden)

    A. Romeo

    2013-05-01

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

  13. [Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge].

    Science.gov (United States)

    Ďuďáková, Ľ; Kousal, B; Kolářová, H; Hlavatá, L; Lišková, P

    The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.Key words: gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease.

  14. Efficacy of long-term omalizumab therapy in patients with severe asthma.

    Science.gov (United States)

    Saji, Junko; Yamamoto, Takahito; Arai, Motonaka; Mineshita, Masamichi; Miyazawa, Teruomi

    2017-03-01

    The efficacy of omalizumab, an anti-immunoglobulin E (IgE) antibody, has been studied in patients with severe bronchial asthma. We conducted a study to evaluate, on the basis of both objective and subjective measures, the efficacy of omalizumab as a long-term therapy in patients with severe and persistent asthma. Omalizumab was administered subcutaneously every two or four weeks. The results of pulmonary function tests, Asthma Control Test (ACT) and Asthma Health Questionnaire (AHQ)-33 scores, the dosage of methylprednisolone during the 12-month treatment period, and the number of emergency visits prior to the start of treatment with omalizumab were compared in patients pre- and post-treatment with omalizumab. Fourteen patients were enrolled in the study between June 2010 and February 2012. Ten patients completed the study. With omalizumab treatment, there was no improvement in lung function; however, the number of emergency visits (19.3 before treatment vs. 1.2 after treatment, p=0.020) and the dosage of methylprednisolone (871.5mg before treatment vs. 119.0mg after treatment, p=0.046) decreased significantly. ACT and AHQ-33 scores at 16 weeks after treatment were significantly better than baseline scores. Four patients continued treatment with omalizumab for four years, and a reduction in their corticosteroid usage was noted. Long-term omalizumab therapy in our patients was found to significantly reduce corticosteroid usage and the number of emergency visits. Long-term omalizumab therapy was effective and might have potential to reduce the frequency of asthma exacerbations. The trial has not been registered because it is not an intervention study. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  15. Fermented dairy productsin children’ diet: Preventive and therapeutic possibilities of their use

    Directory of Open Access Journals (Sweden)

    M. K. Bekhtereva

    2017-01-01

    Full Text Available The article analyzes the preventive and therapeutic possibilities of using probiotic fermented dairy products (baby curds, yoghurts, biolacts in children with various pathological conditions. It outlines their effect in preventing respiratory and intestinal infections in children of different ages. Incorporation of probiotic strains with proven efficacy (including those as probiotic fermented dairy products into the combination treatment of pathological conditions associated with Helicobacter pylori is shown to significantly increase the efficiency of eradication therapy and to prevent the development antibiotic-associated diarrhea.

  16. The efficacy and safety of standardized allergen-removed Rhus verniciflua extract as maintenance therapy after first-line chemotherapy in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Lee, Jinsoo; Chae, Jean; Lee, Sookyung; Kim, Kyungsuk; Eo, Wankyu; Kim, Sehyun; Choi, Woncheol; Cheon, Seong Ha

    2013-01-01

    Chemotherapy improves the survival of patients with advanced non-small cell lung cancer (NSCLC), but tumor progression is often inevitable. Strategies are needed to improve the therapeutic efficacy of chemotherapy. Over recent years, there has been increasing interest in the role of maintenance therapy after first-line chemotherapy. We investigated the efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract (aRVS) as maintenance therapy in patients with non-progressive disease following first-line chemotherapy. We reviewed the medical records of 33 patients with advanced NSCLC, who started treatment with aRVS in a state of tumor regression or stable disease after completion of four or six cycles of induction chemotherapy at the Integrative Cancer Center, Kyung Hee University Hospital at Gangdong from June 2006 to April 2012. The primary objective of this study was progression-free survival (PFS) of aRVS as maintenance therapy. Secondary objectives included assessments of disease control rate (DCR), overall survival (OS), and the safety of aRVS treatment. The median PFS was 5.2 months with a 6- and 12-month PFS rate of 40.6% and 12.9%, respectively. The DCR was 93.9% and the median OS was 34.8 months. The overall survival rates at 12, 24, and 36 months were 84.2%, 76.7% and 49.9%, respectively. We observed no hematologic toxicity, nephrotoxicity, or hepatotoxicity during aRVS treatment. In conclusion, maintenance therapy with aRVS for patients with advanced NSCLC is well-tolerated and offers encouraging improved PFS and OS compared with historical controls. Our data provide further evidence that aRVS may be used beyond disease progression in this clinical setting.

  17. Therapeutic avenues for hereditary forms of retinal blindness.

    Science.gov (United States)

    Kannabiran, Chitra; Mariappan, Indumathi

    2018-03-01

    Hereditary retinal diseases, known as retinal degenerations or dystrophies, are a large group of inherited eye disorders resulting in irreversible visual loss and blindness. They develop due to mutations in one or more genes that lead to the death of the retinal photoreceptor cells. Till date, mutations in over 200 genes are known to be associated with all different forms of retinal disorders. The enormous genetic heterogeneity of this group of diseases has posedmany challenges in understanding the mechanisms of disease and in developing suitable therapies. Therapeutic avenues that are being investigated for these disorders include gene therapy to replace the defective gene, treatment with neurotrophic factors to stimulate the growth of photoreceptors, cell replacement therapy, and prosthetic devices that can capture light and transmit electrical signals through retinal neurons to the brain. Several of these are in process of human trials in patients, and have shown safety and efficacy of the treatment. A combination of approaches that involve both gene replacement and cell replacement may be required for optimum benefit.

  18. Towards the therapeutic use of vascular smooth muscle progenitor cells.

    Science.gov (United States)

    Merkulova-Rainon, Tatyana; Broquères-You, Dong; Kubis, Nathalie; Silvestre, Jean-Sébastien; Lévy, Bernard I

    2012-07-15

    Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

  19. The Efficacy of Parent-Child Interaction Therapy with Chinese Families: Randomized Controlled Trial

    Science.gov (United States)

    Leung, Cynthia; Tsang, Sandra; Sin, Tammy C. S.; Choi, Siu-yan

    2015-01-01

    Objective: This study aimed to examine the efficacy of the Parent-Child Interaction Therapy (PCIT) in Hong Kong Chinese families, using randomized controlled trial design. Methods: The participants included 111 Hong Kong Chinese parents with children aged 2--7 years old, who were randomized into the intervention group (n = 54) and control group (n…

  20. Reversibly extracellular pH controlled cellular uptake and photothermal therapy by PEGylated mixed-charge gold nanostars.

    Science.gov (United States)

    Wang, Shouju; Teng, Zhaogang; Huang, Peng; Liu, Dingbin; Liu, Ying; Tian, Ying; Sun, Jing; Li, Yanjun; Ju, Huangxian; Chen, Xiaoyuan; Lu, Guangming

    2015-04-17

    Shielding nanoparticles from nonspecific interactions with normal cells/tissues before they reach and after they leave tumors is crucial for the selective delivery of NPs into tumor cells. By utilizing the reversible protonation of weak electrolytic groups to pH changes, long-chain amine/carboxyl-terminated polyethylene glycol (PEG) decorated gold nanostars (GNSs) are designed, exhibiting reversible, significant, and sensitive response in cell affinity and therapeutic efficacy to the extracellular pH (pHe) gradient between normal tissues and tumors. This smart nanosystem shows good dispersity and unimpaired photothermal efficacy in complex bioenvironment at pH 6.4 and 7.4 even when their surface charge is neutral. One PEGylated mixed-charge GNSs with certain surface composition, GNS-N/C 4, exhibits high cell affinity and therapeutic efficacy at pH 6.4, and low affinity and almost "zero" damage to cells at pH 7.4. Remarkably, this significant and sensitive response in cell affinity and therapeutic efficacy is reversible as local pH alternated. In vivo, GNS-N/C 4 shows higher accumulation in tumors and improved photothermal therapeutic efficacy than pH-insensitive GNSs. This newly developed smart nanosystem, whose cell affinity reversibly transforms in response to pHe gradient with unimpaired biostability, provides a novel effective means of tumor-selective therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism.

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    H Akiko Popiel

    Full Text Available The polyglutamine (polyQ diseases such as Huntington's disease (HD, are neurodegenerative diseases caused by proteins with an expanded polyQ stretch, which misfold and aggregate, and eventually accumulate as inclusion bodies within neurons. Molecules that inhibit polyQ protein misfolding/aggregation, such as Polyglutamine Binding Peptide 1 (QBP1 and molecular chaperones, have been shown to exert therapeutic effects in vivo by crossing of transgenic animals. Towards developing a therapy using these aggregation inhibitors, we here investigated the effect of viral vector-mediated gene therapy using QBP1 and molecular chaperones on polyQ disease model mice. We found that injection of adeno-associated virus type 5 (AAV5 expressing QBP1 or Hsp40 into the striatum both dramatically suppresses inclusion body formation in the HD mouse R6/2. AAV5-Hsp40 injection also ameliorated the motor impairment and extended the lifespan of R6/2 mice. Unexpectedly, we found even in virus non-infected cells that AAV5-Hsp40 appreciably suppresses inclusion body formation, suggesting a non-cell autonomous therapeutic effect. We further show that Hsp40 inhibits secretion of the polyQ protein from cultured cells, implying that it inhibits the recently suggested cell-cell transmission of the polyQ protein. Our results demonstrate for the first time the therapeutic effect of Hsp40 gene therapy on the neurological phenotypes of polyQ disease mice.

  2. Therapeutic Effects of Horseback Riding Therapy on Gross Motor Function in Children with Cerebral Palsy: A Systematic Review

    Science.gov (United States)

    Whalen, Cara N.; Case-Smith, Jane

    2012-01-01

    Purpose: This systematic review examined the efficacy of hippotherapy or therapeutic horseback riding (THR) on motor outcomes in children with cerebral palsy (CP). Methods: Databases were searched for clinical trials of hippotherapy or THR for children with CP. Results: Nine articles were included in this review. Although the current level of…

  3. Similar Efficacy with Omalizumab in Chronic Idiopathic/Spontaneous Urticaria Despite Different Background Therapy.

    Science.gov (United States)

    Casale, Thomas B; Bernstein, Jonathan A; Maurer, Marcus; Saini, Sarbjit S; Trzaskoma, Benjamin; Chen, Hubert; Grattan, Clive E; Gimenéz-Arnau, Ana; Kaplan, Allen P; Rosén, Karin

    2015-01-01

    Data from the 3 omalizumab pivotal trials in patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) represent the largest database of patients reported to date with refractory disease (omalizumab, n = 733; placebo, n = 242). The objective of this study was to compare results from ASTERIA I and II, which included only approved doses of H1-antihistamine as background therapy based on regulatory authority requirements, to those from GLACIAL, which permitted higher doses of H1-antihistamines as well as other types of background therapy, in a post hoc analysis. Efficacy data from the placebo, omalizumab 150-mg, and omalizumab 300-mg treatment arms of ASTERIA I and II were pooled and analyzed (n = 162 and n = 160, respectively). The 300-mg treatment arm analyses were compared with the analysis of data from GLACIAL (n = 252) using analysis of covariance models. The key efficacy endpoint was change from baseline to week 12 in mean weekly itch severity score (ISS); other endpoints were also evaluated. Safety data were pooled from all 3 studies. Mean ISS was significantly reduced from baseline at week 12 in the pooled ASTERIA I and II omalizumab 150- and 300-mg treatment arms and in the GLACIAL omalizumab 300-mg arm. The weekly ISS reduction magnitude at week 12 was similar between the omalizumab 300-mg groups in the ASTERIA I and II pooled and GLACIAL studies. Similar treatment effect sizes were observed across multiple endpoints. Omalizumab was well tolerated and the adverse-event profile was similar regardless of background therapy for CIU/CSU. The overall safety profile was generally consistent with omalizumab therapy in allergic asthma. Omalizumab 300 mg was safe and effective in reducing CIU/CSU symptoms regardless of background therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shi J

    2013-07-01

    Full Text Available Jinjin Shi,* Rourou Ma,* Lei Wang, Jing Zhang, Ruiyuan Liu, Lulu Li, Yan Liu, Lin Hou, Xiaoyuan Yu, Jun Gao, Zhenzhong Zhang School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, People's Republic of China*These authors contributed equally to this workAbstract: 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.Keywords: photodynamic therapy, photothermal therapy, HA-derivatized carbon nanotubes, tumor targeting, synergistic effect, hematoporphyrin monomethyl ether

  5. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  6. Efficacy and effectiveness of mefloquine and artesunate combination therapy for uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon.

    Science.gov (United States)

    de Oliveira, Alexandre Macedo; Chavez, Jorge; de Leon, Gabriel Ponce; Durand, Salomon; Arrospide, Nancy; Roberts, Jacquelin; Cabezas, Cesar; Marquiño, Wilmer

    2011-09-01

    We evaluated the efficacy and effectiveness of mefloquine (MQ) plus artesunate (AS) to treat patients with uncomplicated malaria in the Peruvian Amazon Basin in April 2005-March 2006. Patients ≥ 1 year of age with fever (axillary temperature ≥ 37.5°C) or history of fever and Plasmodium falciparum monoinfection were included. Patients received antimalarial treatment with MQ (12.5 mg/kg/day for two days) and AS (4.0 mg/kg/day for three days) either by directly observed therapy or without directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed on the basis of clinical and parasitologic outcomes. Ninety-six patients were enrolled in each study group; nine patients were lost to follow-up. All patients, except for one in the observed group, demonstrated adequate clinical and parasitologic response; none had detectable parasitemia on day 3. The efficacy of MQ + AS efficacy was 98.9% (95% confidence interval = 94.1-100.0%) and the effectiveness was 100.0% (95% confidence interval = 95.9-100.0%). Our study shows that MQ + AS is highly efficacious in the Peruvian Amazon.

  7. Trials to optimize dosimetry for 153Sm-EDTMP therapy to improve therapeutic effects

    International Nuclear Information System (INIS)

    Riccabona, G.; Moncayo-Naveda, R.; Oberlandstaetter, M.; Donnemiller, E.; Kendler, D.

    2001-01-01

    In a trial to improve results of therapy with 153 Sm-EDTMP for pain control in patients with disseminated bone metastases dosimetric studies were performed. Out of 30 treated patients 8 were selected for the study at random (5 breast Ca., 3 prostate Ca.). Whole body retention (WBR) of 99m Tc-DPD and 99m Tc-EDTMP was compared with WBR of 153 Sm-EDTMP. Volume of metastases and regional 99 m Tc-phosphonate uptake were assessed by SPECT and conjugated whole body scan data after phantom studies. Effective half-life was estimated also. Clinically results of pain control, side effects and changes of in vitro parameters were followed after therapy for up to 8 months. Therapy was performed in these patients with 55,5 MBq/kg body weight. Results showed an identical pattern of radioactivity distribution on 99 Tc-phosphonate and 153 Sm-EDTMP posttherapy scans, WBR of tracers and therapeutic agent was similar. Tumour volumes were 151-652 mL, count ratios metastases/normal bone 1,72-2,41, so that 6-50% of applied 153 Sm-EDTMP were concentrated in bone lesions. This gave dose estimates of 2,8-13,7 Gy in metastases. Evaluation of clinical results showed that the majority of very good results were observed in patients receiving > 10 Gy (n=3) while with lower doses only 1/4 responded very well. 1 patient was lost to follow-up due to death in the first month after therapy. Moderate and transient myelodepression (platelets) was seen in 3/7 patients without relation to Gy applied. As obviously 153 Sm concentration is not homogenous in bone metastases it can be assumed, that in border zones between tumour and bone 30-40 Gy can be delivered when 10 Gy are calculated for the whole lesion, which would explain the satisfactory therapeutic effect in our study. The dosimetric approach to 153 Sm-EDTMP therapy could necessitate the application of higher amounts of 153 Sm-EDTMP to reach adequate radiation doses in lesions without necessarily increasing risk of myelodepression and with even

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

    Science.gov (United States)

    2017-10-01

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

  9. New perspectives on targeted therapy in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Coward JIG

    2015-02-01

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

  10. Pharmacogenetics approach to therapeutics.

    Science.gov (United States)

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

  11. Fluconazole in the therapy of Pityriasis versicolor

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    Poljački Mirjana N.

    2005-01-01

    Full Text Available The authors present the results of the systemic application of flukonazole in therapy of Pityriasis versicolor. It was arranged for the total number of 38 patients, 18 females and 20 males. The diagnosis of diseases was established on the base of the clinical examination, the native mycological examination and by the using of Wood lamps. The therapy was passed by the using of 300 mg flukonazole in a single dose, once weekly, during two weeks. The following period amounted to one week after the passed therapy. The therapeutic efficacy was assessed with regard to the clinical and mycological healing. The clinical efficacy was assessed semiquantitative on the base of increasing of the percentage rates of the total score of disease that was computed by collecting of the numeric values for every clinical argument typical for the disease, and the mycological efficacy on the base of the mycological findings and the fluorescence finding after lightening with the Wood's lamp. The controlling examinations were performed on day 0, 14 and 22. The results of investigations have shown that the complete clinical healing was achieved after two weeks of therapy in 94,74%, and the mycological healing in 92,11% patients. The rate of the mycological healing was evaluated after 1 week of following period equal to the rate of the clinical healing and it was also 94,74%. The undesirable effects of the drug applications weren't by any patient.

  12. Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies

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    Zhiqing Zhang

    2016-11-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection causes acquired immune deficiency syndrome (AIDS, a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

  13. Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial

    Directory of Open Access Journals (Sweden)

    Hengwei Jin

    2017-09-01

    Full Text Available Introduction: Brain arteriovenous malformations (BAVMs are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. Methods: This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety, and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy. Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula, volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS. Discussion: The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs. Keywords: Brain arteriovenous malformation, Clinical trial, Endovascular therapy, Gamma knife, Safety, Efficacy

  14. Identification of MALT1 as both a prognostic factor and a potential therapeutic target of regorafenib in cholangiocarcinoma patients.

    Science.gov (United States)

    Yeh, Chun-Nan; Chang, Yu-Chan; Su, Yeu; Shin-Shian Hsu, Dennis; Cheng, Chi-Tung; Wu, Ren-Chin; Chung, Yi-Hsiu; Chiang, Kun-Chun; Yeh, Ta-Sen; Lu, Meng-Lun; Liu, Chun-Yu; Mu-Hsin Chang, Peter; Chen, Ming-Han; Huang, Chi-Ying F; Hsiao, Michael; Chen, Ming-Huang

    2017-12-26

    Intrahepatic cholangiocarcinoma (CCA) is an aggressive cancer that lacks an effective targeted therapy. Here, we assessed the therapeutic efficacy of regorafenib in CCA, as well as elucidated its underlying mechanism. We first demonstrated that regorafenib not only inhibited growth but also induced apoptosis in human CCA cells. Subsequently, we used in silico approaches to identify MALT1 (Mucosa-associated lymphoid tissue protein 1), which plays an important role in activating NF-κB, as a potential target of regorafenib. Overexpression of Elk-1, but not Ets-1, in HuCCT1 cells markedly reduced their sensitivity to regorafenib, which might be attributed to a significant increase in MALT1 levels. Our results further demonstrated that this drug drastically inhibited MALT1 expression by suppressing the Raf/Erk/Elk-1 pathway. The efficacy of regorafenib in decreasing in vivo CCA growth was confirmed in animal models. Regorafenib efficacy was observed in two MALT1-positive CCA patients who failed to respond to several other lines of therapy. Finally, MALT1 was also identified as an independent poor prognostic factor for patients with intrahepatic CCA. In conclusion, our study identified MALT1 to be a downstream mediator of the Raf/Erk/Elk-1 pathway and suggested that MALT1 may be a new therapeutic target for successful treatment of CCA by regorafenib.

  15. Advances in Viral Vector-Based TRAIL Gene Therapy for Cancer

    International Nuclear Information System (INIS)

    Norian, Lyse A.; James, Britnie R.; Griffith, Thomas S.

    2011-01-01

    Numerous biologic approaches are being investigated as anti-cancer therapies in an attempt to induce tumor regression while circumventing the toxic side effects associated with standard chemo- or radiotherapies. Among these, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown particular promise in pre-clinical and early clinical trials, due to its preferential ability to induce apoptotic cell death in cancer cells and its minimal toxicity. One limitation of TRAIL use is the fact that many tumor types display an inherent resistance to TRAIL-induced apoptosis. To circumvent this problem, researchers have explored a number of strategies to optimize TRAIL delivery and to improve its efficacy via co-administration with other anti-cancer agents. In this review, we will focus on TRAIL-based gene therapy approaches for the treatment of malignancies. We will discuss the main viral vectors that are being used for TRAIL gene therapy and the strategies that are currently being attempted to improve the efficacy of TRAIL as an anti-cancer therapeutic

  16. Perceptions of Socratic and non-Socratic presentation of information in cognitive behaviour therapy.

    Science.gov (United States)

    Heiniger, Louise E; Clark, Gavin I; Egan, Sarah J

    2018-03-01

    Socratic Method is a style of inquiry used in cognitive behavioural therapy (CBT) that encourages clients to reflect on their problems and draw conclusions from newly-gained insights. However, assumptions about the superior efficacy of Socratic Method over non-Socratic (didactic) approaches remain largely untested. The aim of this study was to compare the perceived helpfulness of therapists' questions, autonomy supportiveness, likelihood of engaging in therapeutic tasks and preference for Socratic Method versus a didactic approach using a video analogue and ratings of lay observers. The mediating effects of therapeutic alliance and empathy were also examined. Participants (N = 144, mean age = 37, SD = 13) completed an online survey where they rated two videoed therapy analogues. Socratic Method had higher mean scores on perceived helpfulness of therapists' questions, autonomy supportiveness, and likelihood of engaging in therapeutic tasks and preference than didactic presentation. Perceived helpfulness and preference ratings were higher for Socratic Method after accounting for potential confounders. Perceived therapeutic alliance and empathy both mediated the effect of therapy condition on autonomy and engagement. The findings support the use of Socratic Method in CBT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Follow-up on thyroidal uptake after radioiodine therapy. How robust is the peri-therapeutic dosimetry?

    International Nuclear Information System (INIS)

    Eschner, Wolfgang; Kobe, Carsten; Schicha, Harald

    2011-01-01

    Radioiodine therapy (RIT) for benign thyroid diseases in Germany requires the patient to stay in a nuclear medicine therapy ward for at least 48 hours and the dose to the thyroid to be computed from activity measurements performed during that stay. A major part of the total dose will be delivered after the patient's discharge from the hospital and thus has to be predicted through extrapolation with the effective half-life measured peri-therapeutically. We performed repeated thyroid uptake measurements on patients up to five months post therapy to investigate post-therapeutic changes in their effective half-lives and examine the dosimetric consequences. 12 patients (4 m, 8 f; age 36 - 76 y; 4 Graves' disease, 4 toxic adenoma, 3 toxic goitre, 1 non-toxic goitre) underwent late uptake measurements (1 - 7 meas., 13 - 154 d post administration, median 54 d, performed with thyroid probe resp. whole body counter at lower activities). Doses calculated from late measurements were compared to those predicted at discharge; half-lives calculated from the late measurement closest to the median delay (54 d) were compared to those determined at time of discharge. A cross-calibration between activity calibrator, thyroid probe, and whole body counter over an activity range from 52 MBq down to 45 Bq revealed linearity to within 6%, which was considered sufficient. In 9 out of 12 patients the achieved dose was within the range predicted at discharge. Averaged deviation between achieved and predicted dose was 3.1 ± 2.2% (median 2.5%, range 0.7% - 7.2%). Averaged deviation between post- and peri-therapeutic half-lives was 5.1 ± 3.9% (median 3.5%, range 1.3% - 12.5%). For n=5 patients discharged after 3 days, averaged deviations were greater (dose 4.0%, half-life 5.6%) than for those patients (n = 7) who stayed in the hospital for a minimum of 4 days (dose 2.5%, half-life 4.8%). Excretion of iodine from the thyroid remains practically unchanged for at least two months after RIT. The

  18. Radiobiology of systemic radiation therapy.

    Science.gov (United States)

    Murray, David; McEwan, Alexander J

    2007-02-01

    Although systemic radionuclide therapy (SRT) is effective as a palliative therapy in patients with metastatic cancer, there has been limited success in expanding patterns of utilization and in bringing novel systemic radiotherapeutic agents to routine clinical use. Although there are many factors that contribute to this situation, we hypothesize that a better understanding of the radiobiology and mechanism of action of SRT will facilitate the development of future compounds and the future designs of prospective clinical trials. If these trials can be rationalized to the biological basis of the therapy, it is likely that the long-term outcome would be enhanced therapeutic efficacy. In this review, we provide perspectives of the current state of low-dose-rate (LDR) radiation research and offer linkages where appropriate with current clinical knowledge. These include the recently described phenomena of low-dose hyper-radiosensitivity-increased radioresistance (LDH-IRR), adaptive responses, and biological bystander effects. Each of these areas require a major reconsideration of existing models for radiation action and an understanding of how this knowledge will integrate into the evolution of clinical SRT practice. Validation of a role in vivo for both LDH-IRR and biological bystander effects in SRT would greatly impact the way we would assess therapeutic response to SRT, the design of clinical trials of novel SRT radiopharmaceuticals, and risk estimates for both therapeutic and diagnostic radiopharmaceuticals. We believe that the current state of research in LDR effects offers a major opportunity to the nuclear medicine community to address the basic science of clinical SRT practice, to use this new knowledge to expand the use and roles of SRT, and to facilitate the introduction of new therapeutic radiopharmaceuticals.

  19. Evidence of the efficacy for occupational therapy in different conditions: an overview of systematic reviews.

    NARCIS (Netherlands)

    Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Leemrijse, C.J.; Ende, C.H.M. van den

    2005-01-01

    OBJECTIVE: To summarize the research evidence available from systematic reviews of the efficacy of occupational therapy (OT) for practitioners, researchers, purchasing organizations and policy-makers. DATA SOURCE: The search for systematic reviews was conducted in PubMed and the Cochrane Library

  20. Therapeutic efficacy and microSPECT/CT imaging of {sup 188}Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-J.; Chang, C.-H.; Yu, C.-Y.; Chang, T.-J.; Chen, L.-C. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, M.-H. [National Health Research Institutes, Miaoli, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

    2010-01-15

    Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of {sup 188}Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ({sup 188}Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of {sup 188}Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of {sup 188}Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of {sup 188}Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of {sup 188}Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of {sup 188}Re-liposome and the synergistic effect of the combination radiochemotherapeutics of {sup 188}Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of

  1. Occupation and the relevance of primatology to occupational therapy.

    Science.gov (United States)

    Wood, W

    1993-06-01

    The adaptive functions of occupation during the phylogenetic history of the human species and the ontogenetic development of individual primates re examined through a review of relevant research of wild and captive nonhuman primates. This review suggests that the effectiveness of occupation as a therapeutic medium throughout life span development is fundamentally tied to humankind's phylogenetic history. It is accordingly argued that there is considerable justification to maintain occupational therapy's historical commitment to therapeutic occupation as the profession's primary treatment modality. To support this commitment, questions to guide practice and research are identified that emanate from the primate literature and that are highly germane to the therapeutic process in occupational therapy. These questions address: (a) the relationship between the press of the various environments in which occupational therapists practice and subsequent opportunities availed to patients for engagement in occupation; (b) the relationship between the extent to which patients are or are not empowered to exert real control over their use of time and their eventual development of disabling conditions; and (c) the therapeutic efficacy of occupation as compared with other treatment approaches that are not comparably holistic.

  2. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

    2012-03-27

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  3. Remodeling of Tumor Stroma and Response to Therapy

    International Nuclear Information System (INIS)

    Johansson, Anna; Ganss, Ruth

    2012-01-01

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

  4. Comparative evaluation of therapeutic efficacy of sulfadiazine-trimethoprim, oxytetracycline, enrofloxacin and florfenicol on Staphylococcus aureus-induced arthritis in broilers.

    Science.gov (United States)

    Mosleh, N; Shomali, T; Namazi, F; Marzban, M; Mohammadi, M; Boroojeni, A Motamedi

    2016-04-01

    Staphylococcus aureus is an important human and veterinary pathogen that causes economic loss in the poultry industry. This study aimed to compare therapeutic efficacy of 4 commonly used antibiotics in poultry on S. aureus-induced arthritis in broilers. Sixty broilers, 8 weeks of age, were assigned at random into 7 groups as follows: (1) negative control (n = 5); (2) vehicle control (n = 5); (3) sulfadiazine-trimethoprim, 250 ml/1000 l drinking water (n = 10); (4) oxytetracycline 20%, 1 mg/l drinking water (n = 10); (5) florfenicol 10%, 1/1000 v/v in drinking water (n = 10); (6) enrofloxacin 10%, 1/1000 v/v in drinking water (n = 10) and (7) positive control (n = 10). Birds in group 2 were injected with 1 ml of sterile TSB medium into the right tibiotarsal joint on d 0 while other birds (except group 1) were challenged with 1 ml of 1.2 × 10(10) CFU/ml suspension of S. aureus bacteria. Antibiotic therapy was started from d 4 post challenge and continued for 5 d. At the end, birds were weighed and clinical severity of arthritis was determined. After blood collection, birds were slaughtered and tibiotarsal and hip joints were evaluated grossly. The content of inflammatory exudates of tibiotarsal joint and the degree of femoral head necrosis were recorded. Mucin clot test and histopathological evaluation were performed on right tibiotarsal joint. Serum interleukin 6 was also assayed. Sulfadiazine-trimethoprim had higher therapeutic efficiency with regard to most of the assayed criteria, whereas none of the antibiotics significantly affected femoral head necrosis and body weight. These data will help clinicians to have better antibiotic choice in field conditions.

  5. The efficacy and tolerability of leflunomide (Arava® in therapy for psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available The paper gives data on differentiated disease-modifying anti-rheumatic therapy for psoriatic arthritis (PsA. When performing the therapy, account must be taken of the presence and magnitude of the major manifestations of this disease: the pattern of arthritis and spondylosis, the number of inflamed entheses, the number of swollen fingers or toes, the pattern of psoriasis in terms of its extent and stage, the presence and magnitude of systemic manifestations and the functional state of involved organs. There are data on the biological activity of leflunomide, its effect on the main manifestations of PsA with an analysis of its efficacy and tolerability, as well as the results of a comparative investigation of disease-modifying anti-rheumatic drugs used for the therapy of this disease.

  6. Efficacy of Cellular Therapy for Diabetic Foot Ulcer: A Meta-Analysis of Randomized Controlled Clinical Trials.

    Science.gov (United States)

    Zhang, Ye; Deng, Hong; Tang, Zhouping

    2017-12-01

    Diabetes mellitus is a widely spread chronic disease with growing incidence worldwide, and diabetic foot ulcer is one of the most serious complications of diabetes. Cellular therapy has shown promise in the management of diabetic foot ulcer in many preclinical experiments and clinical researches. Here, we performed a meta-analysis to evaluate the efficacy and safety of cellular therapy in the management of diabetic foot ulcer. We systematically searched PubMed, MEDLINE, EMBASE, and Cochrane Library databases from inception to May 2017 for randomized controlled trials assessing the efficacy of cellular therapy in diabetic foot ulcer, and a meta-analysis was conducted. A total of 6 randomized controlled clinical trials involving 241 individuals were included in this meta-analysis. The results suggested that cellular therapy could help accelerating the healing of diabetic foot ulcer, presented as higher ankle-brachial index (mean difference = 0.17, 95% confidence interval [CI] = 0.11 to 0.23), higher transcutaneous oxygen pressure (standardized mean difference [SMD] = 1.43; 95% CI, 1.09- to 1.78), higher ulcer healing rate (relative risk [RR] = 1.78; 95% CI, 1.41 to 2.25), higher amputation-free survival (RR = 1.25; 95% CI, 1.11 to 1.40), and lower scale of pain (SMD = -1.69; 95% CI, -2.05 to -1.33). Furthermore, cellular therapy seemed to be safe, with no serious complications and low risk of short-term slight complications. Cellular therapy could accelerate the rate of diabetic foot ulcer healing and may be more efficient than standard therapy for diabetic foot treatment.

  7. Three-phase Bone Scintigraphy Can Predict the Analgesic Efficacy of Ketamine Therapy in CRPS.

    Science.gov (United States)

    Sorel, Marc; Beatrix, Jacques-Christian; Locko, Blanche; Armessen, Catherine; Domec, Anne-Marie; Lecompte, Otilia; Boucheneb, Sofiane; Harache, Benoit; Robert, Jacques; Lefaucheur, Jean-Pascal

    2018-03-13

    The efficacy of ketamine in relieving complex regional pain syndrome (CRPS) lacks predictive factors. The value of three-phase bone scintigraphy (TPBS) was assessed or this purpose. TPBS was performed in 105 patients with unilateral, focal CRPS of type 1 before 5 days of ketamine infusions. Tracer uptake was measured in the region of interest concerned by CRPS and the contralateral homologous region. For the three scintigraphic phases (vascular, tissular, and bone phases), an asymmetry ratio of fixation was calculated between the affected and the unaffected sides (VPr, TPr, and BPr). Ketamine efficacy was assessed on pain intensity scores. Ketamine-induced pain relief did not correlate with VPr, TPr, and BPr, but with the ratios of these ratios: BPr/TPr (r=0.32, P=0.009), BPr/VPr (r=0.34, P=0.005), and TPr/VPr (r=0.23, P=0.02). The optimum cut-off value for predicting the response to ketamine therapy was >1.125 for BPr/TPr, >1.075 for BPr/VPr, and >0.935 for TPr/VPr. The combination of increased values of BPr/TPr, BPr/VPr, and TPr/VPr was extremely significantly associated with ketamine therapy outcome. The relative hyperfixation of the radioactive tracer in the limb region concerned by CRPS in phases 2 and 3 versus phase 1 of TPBS correlated positively to the analgesic efficacy of ketamine. This study shows for the first time the potential predictive value of TPBS regarding ketamine therapy outcome. In addition, these results suggest that the analgesic action of ketamine is not restricted to "central" mechanisms, but may also involve "peripheral" mechanisms related to tissue inflammation and bone remodeling.

  8. Efficacy of cupping therapy in patients with the fibromyalgia syndrome-a randomised placebo controlled trial

    OpenAIRE

    Lauche, Romy; Spitzer, Julia; Schwahn, Barbara; Ostermann, Thomas; Bernardy, Kathrin; Cramer, Holger; Dobos, Gustav; Langhorst, Jost

    2016-01-01

    This study aimed to test the efficacy of cupping therapy to improve symptoms and quality of life in patients diagnosed with the fibromyalgia syndrome. Participants were randomly assigned to cupping therapy, sham or usual care. Cupping was administered five times at twice weekly intervals on the upper and lower back. The primary outcome measure was pain intensity at day 18. Secondary outcomes included functional disability, quality of life, fatigue and sleep quality as well as pressure pain se...

  9. Music Therapy for Posttraumatic Stress in Adults: A Theoretical Review

    Science.gov (United States)

    Landis-Shack, Nora; Heinz, Adrienne J.; Bonn-Miller, Marcel O.

    2017-01-01

    Music therapy has been employed as a therapeutic intervention to facilitate healing across a variety of clinical populations. There is theoretical and empirical evidence to suggest that individuals with trauma exposure and Posttraumatic Stress Disorder (PTSD), a condition characterized by enduring symptoms of distressing memory intrusions, avoidance, emotional disturbance, and hyperarousal, may derive benefits from music therapy. The current narrative review describes the practice of music therapy and presents a theoretically-informed assessment and model of music therapy as a tool for addressing symptoms of PTSD. The review also presents key empirical studies that support the theoretical assessment. Social, cognitive, and neurobiological mechanisms (e.g., community building, emotion regulation, increased pleasure, anxiety reduction) that promote music therapy’s efficacy as an adjunctive treatment for individuals with posttraumatic stress are discussed. It is concluded that music therapy may be a useful therapeutic tool to reduce symptoms and improve functioning among individuals with trauma exposure and PTSD, though more rigorous empirical study is required. In addition, music therapy may help foster resilience and engage individuals who struggle with stigma associated with seeking professional help. Practical recommendations for incorporating music therapy into clinical practice are offered along with several suggestions for future research. PMID:29290641

  10. Effects of rational emotive behavior therapy for senior nursing students on coping strategies and self-efficacy.

    Science.gov (United States)

    Kim, Myung Ah; Kim, Jiyoung; Kim, Eun Jung

    2015-03-01

    Senior nursing students are faced with various types of stressful events such as taking the national licensure exam or finding employment. Such stress can generate maladaptive behaviors as well as physical and psychological symptoms. There is evidence supporting the use of rational emotive behavior therapy (REBT) for reducing disruptive behaviors and negative emotions as well as improving self-efficacy and stress-coping strategies. The purpose of this study is to examine the effects of rational emotive behavior therapy (REBT) on stress coping strategies and self-efficacy for senior nursing students. Thirty-four senior nursing students in a nursing college were assigned randomly to an experimental group (n=18) and a control group (n=16). The REBT program consisted of 8 sessions, and it was implemented for a 4-week period. Outcome measures assessed stress-coping strategies and self-efficacy before and after intervention. After intervention with REBT, the mean difference scores for self-efficacy (p=.032) were significantly higher in the experimental group than in the control group. However, the mean difference scores for seeking social support (p=.166), problem solving (p=.126), and avoidance (p=.154) in stress-coping strategies were not significantly different between the two groups. The results imply that group counseling based on REBT enhances the self-efficacy among senior nursing students before graduation. As regards stress coping strategies, a longer intervention period is suggested. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  12. Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy.

    Science.gov (United States)

    Hynynen, Kullervo; Jones, Ryan M

    2016-09-07

    Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

  13. Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

    Science.gov (United States)

    Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-02-12

    Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Endocrine therapy for breast cancer: Assessing an array of women's treatment experiences and perceptions, their perceived self-efficacy and nonadherence

    NARCIS (Netherlands)

    Wouters, Hans; Stiggelbout, Anne M.; Bouvy, Marcel L.; Maatman, Gemma A.; Van Geffen, Erica C.G.; Vree, Robbert; Nortier, Johan W.; Van Dijk, Liset

    2014-01-01

    Background Although adjuvant endocrine therapy effectively prevents breast cancer recurrence, nonadherence rates are substantial. We therefore examined associations of women's experiences and perceptions regarding the efficacy, side effects, and practical problems of endocrine therapy with

  15. Anti-B cell antibody therapies for inflammatory rheumatic diseases

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Jayne, David R W

    2014-01-01

    Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus...... and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies....

  16. Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.

    Science.gov (United States)

    Lee, Young Mok; Conlon, Thomas J; Specht, Andrew; Coleman, Kirsten E; Brown, Laurie M; Estrella, Ana M; Dambska, Monika; Dahlberg, Kathryn R; Weinstein, David A

    2018-05-25

    Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy. A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed. Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2-4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose. rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

  17. Associations between self-esteem, general self-efficacy and approaches to studying in occupational therapy students: A cross-sectional study

    OpenAIRE

    Bonsaksen, Tore; Sadeghi, Talieh; Thørrisen, Mikkel Magnus

    2017-01-01

    The aim of this study was to explore associations between self-esteem, general self-efficacy, and the deep, strategic, and surface approaches to studying. Norwegian occupational therapy students (n = 125) completed questionnaires measuring study approaches, self-esteem, and general self-efficacy. Regression analyses were used to explore the direct relationships between self-esteem, general self-efficacy and the approaches to studying, after controlling for age, gender, prior higher education,...

  18. Molecular Profiling to Optimize Treatment in Non-Small Cell Lung Cancer: A Review of Potential Molecular Targets for Radiation Therapy by the Translational Research Program of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Ausborn, Natalie L.; Le, Quynh Thu; Bradley, Jeffrey D.; Choy, Hak; Dicker, Adam P.; Saha, Debabrata; Simko, Jeff; Story, Michael D.; Torossian, Artour; Lu, Bo

    2012-01-01

    Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growth factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.

  19. Creation of Dystrophin Expressing Chimeric Cells of Myoblast Origin as a Novel Stem Cell Based Therapy for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Siemionow, M; Cwykiel, J; Heydemann, A; Garcia-Martinez, J; Siemionow, K; Szilagyi, E

    2018-04-01

    Over the past decade different stem cell (SC) based approaches were tested to treat Duchenne Muscular Dystrophy (DMD), a lethal X-linked disorder caused by mutations in dystrophin gene. Despite research efforts, there is no curative therapy for DMD. Allogeneic SC therapies aim to restore dystrophin in the affected muscles; however, they are challenged by rejection and limited engraftment. Thus, there is a need to develop new more efficacious SC therapies. Chimeric Cells (CC), created via ex vivo fusion of donor and recipient cells, represent a promising therapeutic option for tissue regeneration and Vascularized Composite Allotransplantation (VCA) due to tolerogenic properties that eliminate the need for lifelong immunosuppression. This proof of concept study tested feasibility of myoblast fusion for Dystrophin Expressing. Chimeric Cell (DEC) therapy through in vitro characterization and in vivo assessment of engraftment, survival, and efficacy in the mdx mouse model of DMD. Murine DEC were created via ex vivo fusion of normal (snj) and dystrophin-deficient (mdx) myoblasts using polyethylene glycol. Efficacy of myoblast fusion was confirmed by flow cytometry and dystrophin immunostaining, while proliferative and myogenic differentiation capacity of DEC were assessed in vitro. Therapeutic effect after DEC transplant (0.5 × 10 6 ) into the gastrocnemius muscle (GM) of mdx mice was assessed by muscle functional tests. At 30 days post-transplant dystrophin expression in GM of injected mdx mice increased to 37.27 ± 12.1% and correlated with improvement of muscle strength and function. Our study confirmed feasibility and efficacy of DEC therapy and represents a novel SC based approach for treatment of muscular dystrophies.

  20. Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

    International Nuclear Information System (INIS)

    Spaeth, Nicolas; Wyss, Matthias T.; Pahnke, Jens; Biollaz, Gregoire; Trachsel, Eveline; Drandarov, Konstantin; Treyer, Valerie; Weber, Bruno; Neri, Dario; Buck, Alfred

    2006-01-01

    Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. Methods: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ('small immunoprotein') was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Results: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm 3 . When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P 131 I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment

  1. A novel therapeutic approach for the treatment of central sleep apnea: The remedē® system

    International Nuclear Information System (INIS)

    Germany, Robin; Joseph, Susan; James, Kristofer; Kao, Andrew

    2014-01-01

    Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is associated with high morbidity and mortality. The disorder often is unrecognized due to the overlap of symptoms with those of the underlying cardiac disease. CSA can be easily diagnosed with a sleep study. Following optimization of all co-morbidities, the therapeutic approach available currently focuses on mask-based therapies which suffer from poor patient adherence. A new therapy, the remedē ® System, has been developed; it utilizes a transvenous, fully implantable system providing phrenic nerve stimulation intended to restore a more normal breathing pattern. The therapy demonstrated promising results based on an initial chronic study and a randomized trial is underway to further evaluate safety and efficacy of this novel system in patients with CSA

  2. The Clinical Efficacy of Autologous Platelet-Rich Plasma Combined with Ultra-Pulsed Fractional CO2 Laser Therapy for Facial Rejuvenation.

    Science.gov (United States)

    Hui, Qiang; Chang, Peng; Guo, Bingyu; Zhang, Yu; Tao, Kai

    2017-02-01

    Ultra-pulsed fractional CO 2 laser is an efficient, precise, and safe therapeutic intervention for skin refreshing, although accompanied with prolonged edema and erythema. In recent years, autologous platelet-rich plasma (PRP) has been proven to promote wound and soft tissue healing and collagen regeneration. To investigate whether the combination of PRP and ultra-pulsed fractional CO 2 laser had a synergistic effect on therapy for facial rejuvenation. Totally, 13 facial aging females were treated with ultra-pulsed fractional CO 2 laser. One side of the face was randomly selected as experimental group and injected with PRP, the other side acted as the control group and was injected with physiological saline at the same dose. Comprehensive assessment of clinical efficacy was performed by satisfaction scores, dermatologists' double-blind evaluation and the VISIA skin analysis system. After treatment for 3 months, subjective scores of facial wrinkles, skin texture, and skin elasticity were higher than that in the control group. Similarly, improvement of skin wrinkles, texture, and tightness in the experimental group was better compared with the control group. Additionally, the total duration of erythema, edema, and crusting was decreased, in the experimental group compared with the control group. PRP combined with ultra-pulsed fractional CO 2 laser had a synergistic effect on facial rejuvenation, shortening duration of side effects, and promoting better therapeutic effect.

  3. Extracorporeal shockwave therapy and therapeutic exercise for supraspinatus and biceps tendinopathies in 29 dogs.

    Science.gov (United States)

    Leeman, J J; Shaw, K K; Mison, M B; Perry, J A; Carr, A; Shultz, R

    2016-10-15

    Supraspinatus tendinopathy (ST) and biceps tendinopathy (BT) are common causes of forelimb lameness in large-breed dogs and have historically been treated with conservative management or surgery. Extracorporeal shockwave therapy (ESWT) and therapeutic exercise (TE) are thought to be treatment options for these conditions. The objectives of this study were to report the clinical presentations of dogs treated with ESWT for shoulder tendinopathies, to determine the association between shoulder lesion severity identified on ultrasonography or MRI and outcome, and to compare the outcomes of dogs treated with ESWT with and without TE. Medical records of 29 dogs diagnosed with shoulder tendinopathies and treated with ESWT were reviewed, and 24 dogs were diagnosed with either unilateral BT or BT and ST. None were found to have unilateral ST. Five dogs were diagnosed with bilateral disease. Eighty-five per cent of dogs had good or excellent outcomes determined by owner assessment 11-220 weeks after therapy. Outcomes were found to be better as tendon lesion severity increased (P=0.0497), regardless if ESWT was performed with or without TE (P=0.92). ESWT should be considered a safe primary therapeutic option for canine shoulder tendinopathies. Larger controlled prospective studies are needed to adequately assess these findings. British Veterinary Association.

  4. Investor Outlook: Gene Therapy Picking up Steam; At a Crossroads.

    Science.gov (United States)

    Schimmer, Joshua; Breazzano, Steven

    2016-09-01

    The gene therapy field continues to pick up steam with recent successes in a number of different therapeutic indications that highlight the potential for the platform. As the field continues to make progress, a growing data set of long-term safety and efficacy data will continue to define gene therapy's role, determining ultimately how widely it may be used beyond rare, serious diseases with high unmet needs. New technologies often take unanticipated twists and turns as patient exposure accumulates, and gene therapy may be no exception. That said, with many diseases that have no other treatment options beyond gene therapy and that present considerable morbidity and mortality, the field appears poised to withstand some minor and even major bumps in the road should they emerge.

  5. [Experimental validation of the efficacy of laser-magnetic therapy for chronic placental insufficiency].

    Science.gov (United States)

    Ordzhonikidze, N V; Filimonov, V G; Klimenko, P A; Kondrikov, N I; Akin'shina, V S; Berlin, Iu V

    1994-01-01

    A new pathogenetically based non-medicamentous method for correction of uteroplacental bloodflow disturbances has been developed on the model of chronic placental insufficiency in rats. A single 5 min laser-magnetic exposure on day 21 of normal pregnancy resulted in a vasodilating effect with reduction of the peripheral resistance in the uterine horn vessels and with improvement of their blood supply. A new LAMA laser magneto-therapeutic device was employed. Daily 5 min sessions of laser magnetic therapy administered to rats with chronic placental insufficiency from pregnancy days 15-16 to 21 normalized uterine horn contractility and resulted in positive morphofunctional changes in the components of the uterine horns and placenta, being associated with a noticeable improvement of fetal functions. Hence, laser magnetic therapy may be regarded as an effective non-drug method for therapy of chronic placental insufficiency.

  6. Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.

    Science.gov (United States)

    Oechslin, Frank; Piccardi, Philippe; Mancini, Stefano; Gabard, Jérôme; Moreillon, Philippe; Entenza, José M; Resch, Gregory; Que, Yok-Ai

    2017-03-01

    Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined. In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P 6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation). Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  7. Efficacy of On-Demand Therapy Using 20-mg Vonoprazan for Mild Reflux Esophagitis.

    Science.gov (United States)

    Umezawa, Mariko; Kawami, Noriyuki; Hoshino, Shintaro; Hoshikawa, Yoshimasa; Koizumi, Eriko; Takenouchi, Nana; Hanada, Yuriko; Kaise, Mitsuru; Iwakiri, Katsuhiko

    2018-01-01

    The study aimed to evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis (RE). On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 24 weeks using 30 patients with mild RE who were receiving maintenance therapy with proton pomp inhibitors (PPIs). The presence or absence of RE, degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin level before breakfast were examined before and after on-demand therapy. The number of tablets taken during the 24-week period was also noted. One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. Remission was maintained in 25 (86.2%) of the 29 patients (all 10 [100%] Los Angeles classification grade A patients and 15 (78.9%) of the 19 grade B patients). However, 4 grade B patients exhibited grade B relapse. There were no differences in the degree of overall satisfaction, score of symptoms or the gastrin level between PPI and on-demand therapies. The number of vonoprazan tablets taken during the observation period was 33 tablets (median)/24 weeks. On-demand therapy using 20-mg vonoprazan tablets is an effective alternative maintenance therapy for mild RE. © 2018 S. Karger AG, Basel.

  8. Therapeutic Strategy for Chronic Headache in Children

    Directory of Open Access Journals (Sweden)

    H.O. Lezhenko

    2016-05-01

    Full Text Available The therapeutic efficacy of a combined homeopathic preparation Cefavora, which consists of alcoholic extracts of Ginkgo biloba, hawthorn (Crataegus and white mistletoe (Viscum album, has been studied in the treatment of chronic tension-type headache in children. It has been shown that alongside with elimination of headache manifestations, the use of homeopathic medicine has contributed to the normalization of adaptive mechanisms of autonomic regulation in children indicating its high therapeutic efficacy.

  9. Efficacy of extracorporeal shock wave therapy in the treatment of lateral epicondylitis.

    Science.gov (United States)

    Bayram, Korhan; Yesil, Hilal; Dogan, Erdal

    2014-01-01

    Lateral epicondylitis is one of the widely seen lesions of the arm characterized by pain localized over lateral epicondyle which is the insertion site of the wrist extensors, and extensor muscles of the forearm. It is easy to diagnose lateral epicondylitis but treatment involves some inherent drawbacks. Conservative management includes non-steroidal anti-inflammatory drugs, ultrasound therapy, steroid injections, functional bracing, laser therapy and extracorporeal shock wave therapy, however none of these modalities have been shown to be really effective based on evidence-based data. Our study is aimed to determine the efficacy of extracorporeal shock wave therapy (ESWT) therapy in the treatment of lateral epicondylitis. A total of 12 patients with the diagnosis of lateral epicondylitis were included in the study and 3 sessions of ESWT were applied (1 session per week). Maximum grip strength and pain scores were assessed before and at 1. month after the treatment. Spesific tests for lateral epicondylitis were utilized and Turkish version of the Patient Rated Tennis Elbow Evaluation (PRTEE-T) questionnaire was administered and data obtained were analyzed. Visual analog scale (VAS) scores were significantly lower (plateral epicondyilitis was found to be effective on reducing pain, and improving functional activities and quality of life.

  10. Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia

    Directory of Open Access Journals (Sweden)

    Svetel Marina

    2007-01-01

    Full Text Available Background/Aim. Spasmodic dysphonia (DS is a disabling speech disturbance appearing as the consequence of dystonic vocal folds contraction. Its intermittent appearance in the laryngeal muscles causes vocal function discontinuation. The quality of life of these patients is significantly disturbed. Surgical and a medical therapy appear to be inadequate and unsuccessful ones of no steady improvement. It is the botulinum toxin therapy that proved to be highly efficacious one, with the established improvement in 80−100% of patients. The aim of our study was to evaluate the efficacy of botulinum toxin therapy in patients with SD and to show our preliminary results. Methods. The study included 10 patients with adductor spasmodic dysphonia. After diagnostic procedures, botulinum toxin was applied either in one or both vocal folds, in doses of 12−16 units each. In our study we applied indirect technique originally developed by Hočevar and Pirtošek. Perceptive voice and speech analysis was performed prior to and after the instillation of botuline toxin as per structured Scale of pathological characteristics of voice and speech appearing in the spasmodic dysphonia. Results. The majority of our patients experienced both subjective improvement and the improvement in the terms of the quality of life, Voice Henolicap Index − (VHI that was rated as rather significant one (t = 3.562; p = 0.006. Conclusion. Regardless unquestionable improvement of definite phonation, further function restitution requires individual vocal therapy and psychotherapy. Vocal therapy includes structural vocal techniques which reduce degree of vocal tension and rapid changes in the power and the height of voice. Further investigations are necessary for the scope of the definition of a standardized therapeutically procedure for spasmodic dysphonia treatment which comprises multidisciplinary approach in diagnosis, therapy and treatment efficacy evaluation.

  11. Antibacterial Efficacy of Polysaccharide Capped Silver Nanoparticles Is Not Compromised by AcrAB-TolC Efflux Pump

    Directory of Open Access Journals (Sweden)

    Mitali Mishra

    2018-05-01

    Full Text Available Antibacterial therapy is of paramount importance in treatment of several acute and chronic infectious diseases caused by pathogens. Over the years extensive use and misuse of antimicrobial agents has led to emergence of multidrug resistant (MDR and extensive drug resistant (XDR pathogens. This drastic escalation in resistant phenotype has limited the efficacy of available therapeutic options. Thus, the need of the hour is to look for alternative therapeutic approaches to mitigate healthcare concerns caused due to MDR bacterial infections. Nanoparticles have gathered much attention as potential candidates for antibacterial therapy. Equipped with advantages of, wide spectrum bactericidal activity at very low dosage, inhibitor of biofilm formation and ease of permeability, nanoparticles have been considered as leading therapeutic candidates to curtail infections resulting from MDR bacteria. However, substrate non-specificity of efflux pumps, particularly those belonging to resistance nodulation division super family, have been reported to reduce efficacy of many potent antibacterial therapeutic drugs. Previously, we had reported antibacterial activity of polysaccharide-capped silver nanoparticles (AgNPs toward MDR bacteria. We showed that AgNPs inhibits biofilm formation and alters expression of cytoskeletal proteins FtsZ and FtsA, with minimal cytotoxicity toward mammalian cells. In the present study, we report no reduction in antibacterial efficacy of silver nanoparticles in presence of AcrAB-TolC efflux pump proteins. Antibacterial tests were performed according to CLSI macrobroth dilution method, which revealed that both silver nanoparticles exhibited bactericidal activity at very low concentrations. Further, immunoblotting results indicated that both the nanoparticles modulate the transporter AcrB protein expression. However, expression of the membrane fusion protein AcrA did show a significant increase after exposure to AgNPs. Our results

  12. Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

    2017-08-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

  13. AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells.

    Science.gov (United States)

    Rafael, Diana; Gener, Petra; Andrade, Fernanda; Seras-Franzoso, Joaquin; Montero, Sara; Fernández, Yolanda; Hidalgo, Manuel; Arango, Diego; Sayós, Joan; Florindo, Helena F; Abasolo, Ibane; Schwartz, Simó; Videira, Mafalda

    2018-11-01

    Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible of sustaining the metastatic spread of the disease to distal organs and the progressive gain of resistance of advanced cancers, new anticancer therapies should be validated specifically for this subpopulation of cells. A new amphihilic-based gene delivery system that combines Pluronic ® F127 micelles with polyplexes spontaneously formed by electrostatic interaction between anionic siRNA and cationic polyethylenimine (PEI) 10K, was designed (PM). Resultant PM gather the requirements for an efficient and safe transport of siRNA in terms of its physicochemical characteristics, internalization capacity, toxicity profile and silencing efficacy. PM were loaded with a siRNA against AKT2, an important oncogene involved in breast cancer tumorigenesis, with a special role in CSC malignancy. Efficacy of siAKT2-PM was validated in CSC isolated from two breast cancer cell lines: MCF-7 and Triple Negative MDA-MB-231 corresponding to an aggressive subtype of breast cancer. In both cases, we observed significant reduction on cell invasion capacity and strong inhibition of mammosphere formation after treatment. These results prompt AKT2 inhibition as a powerful therapeutic target against CSC and pave the way to the appearance of more effective nanomedicine-based gene therapies aimed to prevent CSC-related tumor recurrence.

  14. Recent Advances in Monoclonal Antibody Therapies for Multiple Sclerosis

    Science.gov (United States)

    Stavropoulos, Nikolaos; Wittenberg, Nathan J.; Dasari, Harika; Abdelrahim, Murtada A.; Henley, John R.; Oh, Sang-Hyun; Warrington, Arthur E.; Rodriguez, Moses

    2016-01-01

    Introduction Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients. Areas Covered Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells. Expert Opinion Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside. PMID:26914737

  15. Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

  16. Treatment of ibuprofen intoxication in a dog via therapeutic plasma exchange.

    Science.gov (United States)

    Walton, Stuart; Ryan, Kirk A; Davis, Jennifer L; Acierno, Mark

    2017-07-01

    To describe the treatment of ibuprofen intoxication with therapeutic plasma exchange in a dog (TPE). A 13-year-old male neutered mixed breed dog presented after ingesting approximately 200 mg/kg of ibuprofen. Treatment consisted of supportive medical therapy with IV fluids, gastrointestinal protectants, antiemetics and prostaglandin analogs, and TPE. A cycle of TPE was performed over 180 minutes, achieving 1.5 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Ibuprofen concentrations were determined in the samples by high-pressure liquid chromatography. Post TPE, the dog was continued on supportive medical therapy and was discharged 96 hours after the overdose. This report describes the use of TPE as an adjunct for ibuprofen intoxication. An 85% reduction in plasma ibuprofen concentration occurred and recovery from a potentially lethal ingestion of ibuprofen was achieved with TPE and supportive care. TPE should be considered when presented with acute ibuprofen intoxication due to the rapid and efficacious nature of therapy. © Veterinary Emergency and Critical Care Society 2017.

  17. Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

    Science.gov (United States)

    Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

    2018-05-20

    This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic

  18. [Neoadjuvant therapy for esophageal cancer - indication and efficacy].

    Science.gov (United States)

    Kato, Ken; Hamaguchi, Tetsuya; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro

    2007-10-01

    Some approaches such as adjuvant chemotherapy, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been tried to improve the efficacy of treatment for resectable esophageal cancer patients. The usefullness of neoadjuvant chemotherapy, has remained a matter of controversy. However, there is a report from JCOG9907 in Japan that two courses of neoadjuvant 5-FU/CDDP improved the survival of esophageal squamous cell cancer patients. Neoadjuvant chemoradiotherapy has not had a consistent evaluation because of the varying results of each trial. But from the results of meta-analysis and CALGB9781, the neoadjuvant chemoradiotherapy called "trimodality therapy" has been a standard treatment in the United States. We should evaluate whether there would be similar effectiveness in Japan, where the histology and operative approach are different. Some approaches such as DNA microarray and proteomics, which can predict the treatment effect, are being tried.

  19. The therapeutic effect of three-dimensional conformal radiation therapy combined with conventional radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Liang Feng; Lu Zhonghong; Yao Zhijun; Cao Yongzhen

    2011-01-01

    Objective: To observe the therapeutic effect of three-dimensional conformal radiation therapy (3DCRT) for nasopharyngeal carcinoma (NPC). Methods: 78 patients with NPC was treated by radiation schedule in two phases. In the first phase, nasopharyngeal lesions and metastases of all patients were treated by three-dimensional conformal radiation therapy (3DCRT) with a fraction of 2-5 Gy daily, 5 day per weeks, total dose 30 Gy. The second phase T1N0 or parts of T2N0 patients were done by Conventional radiotherapy with total dose 55 Gy on two small lateral opposing fields + with total dose 50 Gy on neck on tangential field,adding a 3 cm block. Patients with lymph node metastasis were given 55 Gy on the dacio-neck field (After 40 Gy, two small lateral opposing fields were used to boost the primary tumor while the spinal cord shielded) + with total dose 55 Gy on lower neck on tangential field. The upper bound of designed therapeutic field was set to connect with lower bound of main therapeutic field. Results: Three months after treatment,the rate of CR, PR, SD, PD were 38.5%, 55.1%, 5.1%, 1.3%, Total effective rate (CR+PR) were 93.6%. The 1-year, 2-year, 3-year and 5-year local-regional control rates were 92.3%, 88.5%, 78.2%, 70.5%.The 1-year, 2-year , 3-year and 5-year overall survival rate were 96.2%, 89.7%, 83.3%, 71.8%. Appearing early radiation response is well tolerated and no obviously mouth difficulties and cranial nerve damage observed. Conclusion: Clinical result of early-course three-dimensional conformal radiation therapy (3DCRT) for nasopharyngeal carcinoma (NPC) is good. (authors)

  20. Radioiodine therapy in patients with Graves' disease and the effects of prior carbimazole therapy.

    Science.gov (United States)

    Karyampudi, Arun; Hamide, Abdoul; Halanaik, Dhanapathi; Sahoo, Jaya Prakash; Kamalanathan, Sadishkumar

    2014-09-01

    The use of radioiodine as the first line of treatment in Graves' disease is restricted in India because of its limited availability and an unrealistic risk perception associated with it. Additionally, the effectiveness of radioiodine ablation in Graves' disease is influenced by many factors. Prior medical antithyroid therapy is one such important factor. To analyze the efficacy of low dose radioiodine therapy (5 mCi) in treatment of naive patients of Graves' disease in comparison to that in which it was already primed with an antithyroid drug, carbimazole. A non-randomized, interventional study conducted in the Department of Medicine and Endocrinology of a tertiary care institute in South India. The study had two groups; Group A (36 treatment naive, uncomplicated Graves' disease patients) and B (34 Graves' disease patients on carbimazole prior to radioiodine therapy). Both groups had baseline clinical, biochemical evaluation and were reassessed at 3 and 6 months for evaluating the clinical status for possible documentation of cure. The cure rate was 61.1% in drug naive group and 58.8% in pretreated group at 6 months following radioiodine (P = 0.845). Higher baseline 999m technicium (99m Tc) uptake, male gender, BMI and higher baseline free thyroxine (fT4) level predicted treatment failure following radioiodine therapy. Administration of carbimazole prior to low dose radioiodine therapy does not alter the efficacy of radioiodine. Low fixed dose (5 mCi) of radioactive iodine may be a safe and effective primary therapeutic option in Graves' disease patients pretreated with antithyroid drugs.

  1. Using a partially randomized patient preference study design to evaluate the therapeutic effect of acupuncture and cupping therapy for fibromyalgia: study protocol for a partially randomized controlled trial.

    Science.gov (United States)

    Cao, Hui-Juan; Liu, Jian-Ping; Hu, Hui; Wang, Nissi S

    2014-07-10

    Conducting randomized controlled trials on traditional Chinese non-drug therapies has been limited by factors such as patient preference to specific treatment modality. The aim of this study is to investigate the feasibility of applying a partially randomized patient preference (PRPP) trial model in evaluating the efficacy of two types of traditional Chinese medicine therapies, acupuncture and cupping, for fibromyalgia while accounting for patients' preference of either therapeutic modality. This protocol was approved by the Institutional Ethics Committee of affiliated Dongfang Hospital, Beijing University of Chinese Medicine (approval number: 2013052104-2). One hundred participants with fibromyalgia will be included in this study. Diagnosis of fibromyalgia will be based on the American College of Rheumatology criteria. Before treatment, participants will be interviewed for their preference toward acupuncture or cupping therapy. Fifty participants with no preference will be randomly assigned to one of the two groups and another 50 participants with strong preference to either acupuncture or cupping will receive what they choose. For acupuncture and cupping therapy, the main acupoints used will be tender points (Ashi). Treatment will be three times a week for 5 consecutive weeks with a follow-up period of 12 weeks. Outcome measures will be qualitative (patient expectation and satisfaction) and quantitative (pain intensity, quality of life, depression assessment). NCT01869712 (in clinicaltrials.gov, on 22nd May 2013).

  2. Insulin gene therapy for type 1 diabetes mellitus.

    Science.gov (United States)

    Handorf, Andrew M; Sollinger, Hans W; Alam, Tausif

    2015-04-01

    Type 1 diabetes mellitus is an autoimmune disease resulting from the destruction of pancreatic β cells. Current treatments for patients with type 1 diabetes mellitus include daily insulin injections or whole pancreas transplant, each of which are associated with profound drawbacks. Insulin gene therapy, which has shown great efficacy in correcting hyperglycemia in animal models, holds great promise as an alternative strategy to treat type 1 diabetes mellitus in humans. Insulin gene therapy refers to the targeted expression of insulin in non-β cells, with hepatocytes emerging as the primary therapeutic target. In this review, we present an overview of the current state of insulin gene therapy to treat type 1 diabetes mellitus, including the need for an alternative therapy, important features dictating the success of the therapy, and current obstacles preventing the translation of this treatment option to a clinical setting. In so doing, we hope to shed light on insulin gene therapy as a viable option to treat type 1 diabetes mellitus.

  3. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

    Directory of Open Access Journals (Sweden)

    Daniela Rodrigues

    2016-01-01

    Full Text Available Colorectal cancer (CRC is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy.

  4. A COMPARATIVE STUDY OF EFFICACY OF EMG BIO-FEEDBACK AND PROGRESSIVE MUSCULAR RELAXATION IN TENSION HEADACHE1

    Science.gov (United States)

    Gada, M.T.

    1984-01-01

    SUMMARY The aim of the present study was to find out efficacy of frontalis EMG Biofeedback therapy, deep muscular relaxation therapy and compare the efficacy of both in cases of tension headache. During two week basal-data recording period all patients were taught deep muscular relaxation by Jacobson′s technique. Simultaneously patients were instructed to keep headache diary. Headache diary yielded three different parameters a) number of headache-free days per week, b) peak headache intensity (or each week and c) average daily headache activity score per week. These parameters were used to find out therapeutic efficacy of each treatment. Patients were randomly divided in two groups. EMG Biofeedback group was given frontalis EMG feedback through EMG J 33 muscle trainer of Cyborg Corporation (U.S.A.). Patients in each group were given 20 sessions (two sessions per week); each session lasting 30 minutes. Patients were instructed to practice at least one 30 minute session of relaxation at home. The data were subjected to statistical calculation. The results indicate that frontalis EMG Biofeedback therapy and deep muscle relaxation therapy are significantly effective in cases of tension headache. Both treatments are equally effective. The findings are discussed in relation to Indian situation. PMID:21965970

  5. Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria

    DEFF Research Database (Denmark)

    Abacassamo, F; Enosse, S; Aponte, J J

    2004-01-01

    This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of......% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up....

  6. Comparing and contrasting therapeutic effects of cognitive-behavior therapy for older adults suffering from insomnia with short and long objective sleep duration.

    Science.gov (United States)

    Lovato, Nicole; Lack, Leon; Kennaway, David J

    2016-06-01

    This study evaluated the efficacy of a brief group-based program of cognitive-behavior therapy for insomnia (CBTi) for older adults suffering from chronic insomnia with short objective sleep relative to those with long sleep duration. Ninety-one adults (male = 43, mean age = 63.34, standard deviation (SD) = 6.41) with sleep maintenance insomnia were selected from a community-based sample. The participants were classified as short sleepers (SS; treatment program of CBTi (N = 30 SS; N = 33 LS) or to a wait-list control condition (N = 9 SS, N = 19 LS). One-week sleep diaries, actigraphy, and a comprehensive battery of questionnaires were used to evaluate the efficacy of CBTi for those with short objective sleep relative to those with long sleep duration. Outcome measures were taken at pretreatment, posttreatment, and a 3-month follow-up. CBTi produced robust and durable improvements in quality of sleep, including reduced wake after sleep onset and improved sleep efficiency. Participants reported a reduction of scores on the Insomnia Severity Index, Flinders Fatigue Scale, Epworth Sleepiness Scale, Daytime Feeling and Functioning Scale, Sleep Anticipatory Anxiety Questionnaire, the Dysfunctional Beliefs and Attitudes about Sleep Scale, and gains on the Sleep Self-Efficacy Scale. All improvements were significant relative to their respective SS or LS wait-list group. The benefits of CBTi were comparable with those who had short and long objective sleep before the treatment. Older adults suffering from chronic insomnia with short objective sleep received comparable therapeutic benefits following CBTi relative to those with long objective sleep duration. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Radiation Therapy for Neovascular Age-related Macular Degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  8. [A comparative evaluation of the efficacy of magneto- and laser therapy in patients with osteoarthrosis deformans].

    Science.gov (United States)

    Selivonenko, V G; Syvolap, V D; Porada, L V; Medvedeva, V N; Boev, S S; Morozov, A I; Slin'ko, V G; Berest, S M; Garbuz, L N; Sholokh, S G

    1997-01-01

    A comparative evaluation of efficacy of magneto- and laser therapy was carried out in 82 patients with osteoarthrosis deformans. The magnetic field and laser irradiation dispelled the pain syndrome and synovitis manifestations. It is recommendable that the multiple-modality therapy of patients with osteoarthrosis deformans should involve magneto- and laser therapy (15 to 20 procedures per one course) that improve results of the treatment being received and allow the time of hospitalization to be reduced at an average by 5 bed-days. Laser appeared to be a very effective mode of treatment. No unfavourable side effects were recordable.

  9. Improvement of disfiguring skin conditions by laser therapy

    OpenAIRE

    van Drooge, A.M.

    2014-01-01

    Since their introduction in dermatology, lasers became a welcome addition to the therapeutic armentarium for disfiguring skin conditions. In this thesis, we evaluated laser therapy for the treatment of scars, of benign dermal tumours, and of port-wine stains. For scars, many different laser devices have been proposed. In this thesis, we performed a review that showed the pulsed dye laser most effective in hypertrophic scars. We did not find enough evidence for the efficacy of ablative fractio...

  10. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  11. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    Science.gov (United States)

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

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

  12. Child versus family cognitive-behavioral therapy in clinically anxious youth : An efficacy and partial effectiveness study

    NARCIS (Netherlands)

    Bodden, Denise H. M.; Bogels, Susan M.; Nauta, Maaike H.; De Haan, Else; Ringrose, Jaap; Appelboom, Carla; Brinkman, Andries G.; Appelboom-Geerts, Karen C. M. M. J.

    2008-01-01

    Objective: The efficacy and partial effectiveness of child-focused versus family-focused cognitive-behavioral therapy (CBT) for clinically anxious youths was evaluated, in particular in relation to parental anxiety disorders and child's age. Method: Clinically referred children with anxiety

  13. Child Versus Family Cognitive-Behavioral Therapy in Clinically Anxious Youth: An Efficacy and Partial Effectiveness Study

    NARCIS (Netherlands)

    Bodden, D.H.M.; Bögels, S.M.; Nauta, M.H.; Haan, E. de; Ringrose, J.; Appelboom, C.; Brinkman, A.G.; Appelboom-Geerts, K.C.M.M.J.

    2008-01-01

    Objective: The efficacy and partial effectiveness of child-focused versus family-focused cognitive-behavioral therapy (CBT) for clinically anxious youths was evaluated, in particular in relation to parental anxiety disorders and child's age. Method: Clinically referred children with anxiety

  14. Recombinant proteins in therapeutics: haemophilia treatment as an example

    Directory of Open Access Journals (Sweden)

    Liras Antonio

    2008-04-01

    Full Text Available Abstract One of the most spectacular advances in the history of scientific knowledge was the discovery of deoxyribonucleic acid (DNA by Watson and Crick in 1953. This enabled certain proteins to be prepared in this way for their therapeutic use in clinical practice. Today, in the first decade of the 21st century, hundreds of therapeutic proteins have been produced recombinantly and about 50 of them have been approved for clinical use. Because of the specific procedure used for obtaining these products, which is based on expressing a atherapeutica gene from a fragment of DNA in a cell to produce a functional protein that is free from any human or animal component, they are especially acleana and thus the therapy of choice for many current diseases. The immediate question is: why are recombinant products not used more extensively given their high efficacy and maximum safety? In short, we are faced with an interesting but also unfortunate paradox of pharmacology that greater progress in therapeutic procedures is not always associated with greater introduction of those resources that are safest, for the simple reason that they are more costly.

  15. The efficacy of levofloxacin-based triple therapy for first-line Helicobacter pylori eradication

    Directory of Open Access Journals (Sweden)

    Yusuf Aydın

    2011-06-01

    Full Text Available Standard triple therapy composed of a proton pump inhibitor, clarithromycin and amoxicillin has been widely preferred for H. pylori eradication in Turkey and World. Alternative therapies are currently under investigation because of an increase in clarithromycin resistance. The aim of this study was to evaluate the efficacy of a levoflox-acin-containing triple therapy.Materials and methods: The study was carried out in 81 H. pylori-infected patients (52 female, 29 male with nonul-cer dyspepsia. The mean age was found 46.3 ± 13.9. Treatment was indicated with lansoprazol 30 mg b.d., amoxicil-lin 1 g b.d., and levofloxacin 500 mg daily for 7 days. H. pylori status was rechecked by (14C urea breath test 6-8 weeks after the end of therapy.Results: Totally 81 patients could complete the treatment and follow-up protocol. Effectiveness was 68%. The distrib-tions of age, gender and smoking were similar between eradicated and non-eradicated groups (p > 0.05.Conclusion: Seven-day levofloxacin based triple therapy is not very effective in the first-line treatment of H. pylori in-fection. The new treatment modalities should be investigated.

  16. Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects.

    Science.gov (United States)

    Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

    2016-09-20

    To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).

  17. Gestalt therapy and cognitive therapy--contrasts or complementarities?

    Science.gov (United States)

    Tønnesvang, Jan; Sommer, Ulla; Hammink, James; Sonne, Mikael

    2010-12-01

    The article investigates the relationship between crucial concepts and understandings in gestalt therapy and cognitive therapy aiming at discussing if and how they can be mutually enriching when considered as complementary parts in a more encompassing integrative therapeutic approach. It is argued that gestalt therapy, defined as a field-theoretical approach to the study of gestalt formation process, can complement the schema-based understanding and practice in cognitive therapy. The clinical benefits from a complementary view of the two approaches will be a wider scope of awareness toward individual and contextual aspects of therapeutic change processes, toward different levels of memory involved in these processes, and toward the relationship between basic needs, sensation and cognition in therapeutic work. Further, a dialogue between the two approaches will pave the way for addressing the connection between fundamental awareness work in gestalt therapy and the tendency within cognitive therapy toward incorporating mindfulness as a therapeutic tool. In the conclusion of the article, additional complementary points between the two approaches are outlined. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  18. ANTI-B-CELL THERAPY AT IMMUNE INFLAMMATORY RHEUMATIC DISEASES: EFFICACY AND TOLERABILITY IN 229 PATIENTS

    Directory of Open Access Journals (Sweden)

    L. P. Ananieva

    2014-01-01

    Full Text Available Objective: to assess the efficacy and tolerability of Rituximab treatment in patients with serious immune inflammatory rheumatic diseases (IRD like systemic lupus erythematosus (SLE, systemic sclerosis (SS, systemic vasculitis (SV, Sjogren syndrome (SjS, dermatomyositis/polymyositis (DM/PM.Subjects and methods. The clinical efficacy has been analyzed in 229 patients with IRD: SLE (n=97, SV (n=50, SS (n=40, SjS (n=23 and DM/PM (n=19. Rituximab treatment was accompanied by administration of glucocorticoids and/or immunosuppressive drugs. Most patients demonstrated resistance to or low tolerability of standard therapy. Efficacy of treatment was analyzed in each group with the criteria relevant for each disease. To compare clinical response to the treatment between the groups we used gradations accepted by international registries: complete (good response, partial response, no response. Average duration of monitoring comprised 72 (1–288 weeks after the first introduction of Rituximab. Average Rituximab dose administered to patients over the period of monitoring was low and varied from 1.6±0.84 in DM/PM to 3.1±1.75 in SV. About 80% of patients received one or two courses of Rituximab except for patients with SS (half of them received three and more courses.Results. «Complete response» was observed in 50.6%, «partial response» – in 35% of patients. Rituximab courses provided positive dynamics in clinical scores and allowed to reduce supportive dose of glucocorticoids and to lower the dose or withdraw of immune-stimulating drugs. Multiple Rituximab courses provided stable and longlasting effect. Recurrences were observed less frequently, whereas efficacy of the therapy increased during a year and longer. Occurrence of adverse events and mortality rate were comparable to data of other national Rituximab registries.Conclusion. The results of the study may prove administration of Rituximab in patients with resistance to standard

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Insufficient scientific evidence for efficacy of widely used electrotherapy, laser therapy, and ultrasound treatment in physiotherapy

    NARCIS (Netherlands)

    Bouter, L M

    2000-01-01

    The Dutch Health Council recently published a report on the efficacy of electrotherapy, laser therapy and ultrasound treatment for musculoskeletal disorders. The assessment was based on three systematic reviews, including 169 randomized clinical trials, and focused on a best-evidence synthesis.