Radiofrequency ablation of liver cancer: early evaluation of therapeutic response with contrast-enhanced ultrasonography

International Nuclear Information System (INIS)

Choi, Dong Gil; Lim, Hyo K.; Lee, Won Jae; Kim, Seung Hoon; Kim, Min Ju; Kim, Seung Kwon; Jang, Kyung Mi; Lee, Ji Yeon; Lim, Jae Hoon

2004-01-01

The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation

Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD

Directory of Open Access Journals (Sweden)

Bhat Venkataramana

2011-04-01

Full Text Available Abstract Background The desired (therapeutic and undesired (side effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. Methods One hundred and fifty-seven children with ADHD (6-12 years were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose, each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents and teachers (CGI-Teachers, while side effects were assessed using the Barkley Side Effects Rating Scale (SERS. Results The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p Conclusion The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

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Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

2008-11-01

Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.

Therapeutic Assessment in Psychological Triage Using the PAI.

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Brown, Joshua D; Morey, Leslie C

2016-01-01

This case illustrates the utility of incorporating therapeutic assessment in a triage context that typically involves a focus on gathering information. A man referred to our clinic by a local mental health center was seen by our assessment team for a triage that includes the administration of a single psychological test, the Personality Assessment Inventory (PAI). Although this triage must rapidly gather information to determine client suitability and treatment assignment, we still attempt to work with clients to collaboratively develop goals for this assessment that include addressing questions that are central concerns for the clients. In this case, the test results suggested a severe disorder that accounted for many phenomena that he had been experiencing but had apparently been reluctant to share. The information gathered led to a referral to a different treatment program that could provide pharmacological and more intensive forms of treatment. However, the collaborative bond formed between the assessor and the client during this triage was sufficiently strong that it was our assessor to whom the client turned in a subsequent crisis precipitated by a symptomatic exacerbation. This case illustrates complementary information gathering and therapeutic goals of assessment even in the context of a brief assessment.

The advantages and challenges of using FDG PET/CT for response assessment in melanoma in the era of targeted agents and immunotherapy

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Wong, Annie N.M.; McArthur, Grant A. [The Peter MacCallum Cancer Centre, Cancer Medicine, Melbourne (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Hofman, Michael S. [The Peter MacCallum Cancer Centre, Cancer Imaging, Melbourne, VIC (Australia); Hicks, Rodney J. [The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); The Peter MacCallum Cancer Centre, Cancer Imaging, Melbourne, VIC (Australia)

2017-08-15

The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably. In this review, we discuss the mode of action of these emerging therapies and their toxicities to provide a framework for the use of FDG PET/CT in therapeutic response assessment. We propose that the greatest utility of PET in assessment of response to agents that abrogate signalling related to BRAF mutation is for early assessment of resistance, while in anti-CTLA4 therapy, immunological flare can compromise early assessment of response but can identify potentially life-threatening autoimmune reactions. For anti-PD1/PDL1 therapy, the role of FDG PET/CT is more akin to its use in other solid malignancies undergoing treatment with conventional chemotherapy. However, further research is required to optimise the timing of scans and response criteria in this disease. (orig.)

The advantages and challenges of using FDG PET/CT for response assessment in melanoma in the era of targeted agents and immunotherapy

International Nuclear Information System (INIS)

Wong, Annie N.M.; McArthur, Grant A.; Hofman, Michael S.; Hicks, Rodney J.

2017-01-01

The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably. In this review, we discuss the mode of action of these emerging therapies and their toxicities to provide a framework for the use of FDG PET/CT in therapeutic response assessment. We propose that the greatest utility of PET in assessment of response to agents that abrogate signalling related to BRAF mutation is for early assessment of resistance, while in anti-CTLA4 therapy, immunological flare can compromise early assessment of response but can identify potentially life-threatening autoimmune reactions. For anti-PD1/PDL1 therapy, the role of FDG PET/CT is more akin to its use in other solid malignancies undergoing treatment with conventional chemotherapy. However, further research is required to optimise the timing of scans and response criteria in this disease. (orig.)

Dual-energy CT in assessing therapeutic response to radiofrequency ablation of renal cell carcinomas

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Park, Sung Yoon; Kim, Chan Kyo, E-mail: chankyokim@skku.edu; Park, Byung Kwan

2014-02-15

Purpose: To investigate the utility of dual-energy (DE) CT using virtual noncontrast (VNC) and iodine overlay (IO) images to assess therapeutic response to radiofrequency ablation (RFA) for renal cell carcinomas (RCCs). Materials and methods: In this institutional review board-approved study (with waiver of informed consent), 47 patients with RCCs that underwent DECT after RFA were enrolled in this study. DECT protocols included true noncontrast (TNC), linearly blended DE corticomedullary and late nephrographic phase imaging. Two types of VNC and IO images were derived from corticomedullary and late nephrographic phases, respectively. To predict local tumor progression at RFA site, linearly blended and IO images were analyzed both qualitatively and quantitatively. Contrast-to-noise ratios (CNR) of renal cortex-to-RFA zones were calculated. The overall imaging quality of VNC images was compared with TNC images. Results: The IO images from corticomedullary and late nephrographic phases showed excellent diagnostic performance (each sensitivity 100% and each specificity 91.5%) for predicting local tumor progression. The degree of enhancement of local tumor progression was not significantly different between linearly blended and IO images (P > 0.05). The mean CT numbers were not significantly different between TNC and VNC images (P > 0.05). In renal cortex-to-RFA site, CNR between linearly blended and IO images was not significantly different (P > 0.05). The VNC imaging quality from the two phases was given a good rating. Conclusion: VNC and IO images from DECT may allow acceptable diagnostic performance with less radiation exposure as a follow-up imaging tool after RFA for RCC, compared to the linearly blended CT images.

Dual-energy CT in assessing therapeutic response to radiofrequency ablation of renal cell carcinomas

International Nuclear Information System (INIS)

Park, Sung Yoon; Kim, Chan Kyo; Park, Byung Kwan

2014-01-01

Purpose: To investigate the utility of dual-energy (DE) CT using virtual noncontrast (VNC) and iodine overlay (IO) images to assess therapeutic response to radiofrequency ablation (RFA) for renal cell carcinomas (RCCs). Materials and methods: In this institutional review board-approved study (with waiver of informed consent), 47 patients with RCCs that underwent DECT after RFA were enrolled in this study. DECT protocols included true noncontrast (TNC), linearly blended DE corticomedullary and late nephrographic phase imaging. Two types of VNC and IO images were derived from corticomedullary and late nephrographic phases, respectively. To predict local tumor progression at RFA site, linearly blended and IO images were analyzed both qualitatively and quantitatively. Contrast-to-noise ratios (CNR) of renal cortex-to-RFA zones were calculated. The overall imaging quality of VNC images was compared with TNC images. Results: The IO images from corticomedullary and late nephrographic phases showed excellent diagnostic performance (each sensitivity 100% and each specificity 91.5%) for predicting local tumor progression. The degree of enhancement of local tumor progression was not significantly different between linearly blended and IO images (P > 0.05). The mean CT numbers were not significantly different between TNC and VNC images (P > 0.05). In renal cortex-to-RFA site, CNR between linearly blended and IO images was not significantly different (P > 0.05). The VNC imaging quality from the two phases was given a good rating. Conclusion: VNC and IO images from DECT may allow acceptable diagnostic performance with less radiation exposure as a follow-up imaging tool after RFA for RCC, compared to the linearly blended CT images

Dual-energy CT in assessing therapeutic response to radiofrequency ablation of renal cell carcinomas.

Science.gov (United States)

Park, Sung Yoon; Kim, Chan Kyo; Park, Byung Kwan

2014-02-01

To investigate the utility of dual-energy (DE) CT using virtual noncontrast (VNC) and iodine overlay (IO) images to assess therapeutic response to radiofrequency ablation (RFA) for renal cell carcinomas (RCCs). In this institutional review board-approved study (with waiver of informed consent), 47 patients with RCCs that underwent DECT after RFA were enrolled in this study. DECT protocols included true noncontrast (TNC), linearly blended DE corticomedullary and late nephrographic phase imaging. Two types of VNC and IO images were derived from corticomedullary and late nephrographic phases, respectively. To predict local tumor progression at RFA site, linearly blended and IO images were analyzed both qualitatively and quantitatively. Contrast-to-noise ratios (CNR) of renal cortex-to-RFA zones were calculated. The overall imaging quality of VNC images was compared with TNC images. The IO images from corticomedullary and late nephrographic phases showed excellent diagnostic performance (each sensitivity 100% and each specificity 91.5%) for predicting local tumor progression. The degree of enhancement of local tumor progression was not significantly different between linearly blended and IO images (P>0.05). The mean CT numbers were not significantly different between TNC and VNC images (P>0.05). In renal cortex-to-RFA site, CNR between linearly blended and IO images was not significantly different (P>0.05). The VNC imaging quality from the two phases was given a good rating. VNC and IO images from DECT may allow acceptable diagnostic performance with less radiation exposure as a follow-up imaging tool after RFA for RCC, compared to the linearly blended CT images. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

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Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

2014-12-01

This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Therapeutic action and the analyst's responsibility.

Science.gov (United States)

Greenberg, Jay

2015-02-01

Models of the psychoanalytic situation can usefully be thought of as fictions. Viewed this way, the models can be understood as narrative structures that shape what we are able to see and how we are able to think about what happens between us and our analysands. Theories of therapeutic action are elements of what can be called a "controlling fiction," mediating between these theories and our very real responsibilities, both to our preferred method and to a suffering patient. This venture into comparative psychoanalysis is illustrated by a discussion of published case material. © 2015 by the American Psychoanalytic Association.

Tofacitinib Suppresses Antibody Responses to Protein Therapeutics in Murine Hosts1

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Onda, Masanori; Ghoreschi, Kamran; Steward-Tharp, Scott; Thomas, Craig; O’Shea, John J.; Pastan, Ira H.; FitzGerald, David J.

2014-01-01

Immunogenicity remains the ‘Achilles’ heel’ of protein-based therapeutics. Anti-drug antibodies produced in response to protein therapeutics can severely limit both the safety and efficacy of this expanding class of agent. Here we report that monotherapy of mice with tofacitinib (the Janus kinase inhibitor) quells antibody responses to an immunotoxin derived from the bacterial protein, Pseudomonas exotoxin A, as well as to the model antigen, keyhole limpet hemocyanin. Thousandfold reductions in IgG1 titers to both antigens were observed 21 days post-immunization. In fact, suppression was evident for all IgG isotypes and IgM. A reduction in IgG3 production was also noted with a thymus-independent type II antigen. Mechanistic investigations revealed that tofacitinib treatment led to reduced numbers of CD127+ pro-B cells. Furthermore, we observed fewer germinal center B cells and the impaired formation of germinal centers of mice treated with tofacitinib. Since normal immunoglobulin levels were still present during the tofacitinib treatment, this agent specifically reduced anti-drug antibodies, thus preserving the potential efficacy of biological therapeutics, including those that are used as cancer therapeutics. PMID:24890727

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

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Thomas L. Chenevert; Charles R. Meyer; Bradford A. Moffat; Alnawaz Rehemtulla; Suresh K. Mukherji; Stephen S. Gebarski; Douglas J. Quint; Patricia L. Robertson; Theodore S. Lawrence; Larry Junck; Jeremy M. G. Taylor; Timothy D. Johnson; Qian Dong; Karin M. Muraszko; James A. Brunberg

2002-01-01

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 ...

Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

International Nuclear Information System (INIS)

Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

2014-01-01

Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

Energy Technology Data Exchange (ETDEWEB)

Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

2014-07-01

Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

Therapeutic Assessment of Complex Trauma: A Single-Case Time-Series Study.

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Tarocchi, Anna; Aschieri, Filippo; Fantini, Francesca; Smith, Justin D

2013-06-01

The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including establishing a safe therapeutic environment, reprocessing the trauma, constructing a new narrative, and managing emotional dysregulation. Therapeutic Assessment (TA) is a semistructured, brief intervention that uses psychological testing to promote positive change. The case study of Kelly, a middle-aged woman with a history of repeated interpersonal trauma, illustrates delivery of the TA model for CPTSD. Results of this single-case time-series experiment indicate statistically significant symptom improvement as a result of participating in TA. We discuss the implications of these findings for assessing and treating trauma-related concerns, such as CPTSD.

Modeling Composite Assessment Data Using Item Response Theory

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Ueckert, Sebastian

2018-01-01

Composite assessments aim to combine different aspects of a disease in a single score and are utilized in a variety of therapeutic areas. The data arising from these evaluations are inherently discrete with distinct statistical properties. This tutorial presents the framework of the item response theory (IRT) for the analysis of this data type in a pharmacometric context. The article considers both conceptual (terms and assumptions) and practical questions (modeling software, data requirements, and model building). PMID:29493119

Inpatient Therapeutic Assessment With Narcissistic Personality Disorder.

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Hinrichs, Jon

2016-01-01

Growing evidence supporting the effectiveness of Collaborative/Therapeutic Assessment (C/TA) has led clinicians and researchers to apply C/TA to a variety of clinical populations and treatment settings. This case example presents a C/TA inpatient adaptation illustrated with narcissistic personality disorder. After a brief overview of salient concepts, I provide a detailed account of the clinical interview, test interpretation paired with diagnostic considerations specific to narcissism, planned intervention, and discussion of assessment results. Throughout the case study, I attempt to demonstrate defining features of C/TA, inpatient adaptations, and clinical techniques that encourage meaningful engagement with a "hard to reach" personality.

Potential Bedside Utility of the Clock-Drawing Test in Evaluating Rapid Therapeutic Response in the Natural Course of Schizophrenia: A Preliminary Study.

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Ransing, Ramdas Sarjerao; Khairkar, Praveen Homdeorao; Mishra, Kshirod; Sakekar, Gajanan

2017-01-01

The Clock-Drawing Test (CDT) is a brief, relatively time-efficient, easy to administer at bedside, and well-proven cognitive screening test that assesses a broad range of cognitive abilities in stroke, delirium, and dementia. However, challenges of comprehensive therapeutic outcome evaluations in schizophrenia can also be potentially overcome using CDT. The authors aimed to measure the therapeutic outcome using CDT in 101 schizophrenia patients, irrespective of their diagnostic subtypes. A repeated measures analysis of variance found that improvements on CDT and the Positive and Negative Syndrome Scale were closely correlated, reflecting critical information about therapeutic response measures in schizophrenia.

Therapeutic Touch in the Management of Responsive Behavior in Patients With Dementia.

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Kumarappah, Ananthavalli; Senderovich, Helen

2016-01-01

Patients with dementia experience various behavioral symptoms in the course of their illnesses, which greatly affect their quality of life. Current treatment modalities are not always effective, and, thus, nonpharmacological approaches are the preferred first-line therapy for managing such symptoms. They generally address the basic needs of the person with dementia and provide humane care, often producing noticeable improvements in symptoms. Thus, such therapies should precede pharmacological interventions. The following literature review of 5 publications from 2010 to 2015 evaluates the use of therapeutic touch (TT) in the management of responsive behavior in patients with dementia. The results of the review suggest that TT may be beneficial in reducing agitation in individuals with dementia; however, further research is needed to assess the use of TT.

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

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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

Response assessment in metronomic chemotherapy: RECIST or PERCIST?

International Nuclear Information System (INIS)

Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Puranik, Ameya; Banavali, Shripad; Rangarajan, Venkatesh

2014-01-01

Metronomic chemotherapy (MC) is a novel therapeutic variation for resistant cancers, wherein chemotherapeutic drugs are administrated in low doses with no prolonged drug-free break. It lessens the level of toxicity, is better tolerated and enhances the quality of life. This retrospective analysis was undertaken to evaluate whether anatomical (computed tomography [CT]) or functional (positron emission tomography [PET]) imaging be used for response assessment in patients on MC. A total of 16 males and 27 females with age range of 12-83 years on MC who underwent PET/CT were assessed by new response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST 1.0). Concordance between RECIST 1.1 and PERCIST was seen in 32 (75%) patients. There was discordance in 11 (25%) patients. In patients with discordance, the results were confirmed by follow-up imaging. PET upstaged the disease in 81% of patients (9/11) and down-staged the disease in 19% of patients (2/11). Metabolic response accurately identified the disease status as assessed by clinical or imaging follow-up. Alteration in morphology takes time to manifest, which is demonstrated by CT or magnetic resonance; whereas in MC which brings about tumor dormancy, assessing metabolic response by PET would be more appropriate. MC is usually given in palliative setting but in few cases complete metabolic response was demonstrated in our study. In such a scenario this form of treatment has the potential to become an adjunct mode of treatment in some tumors. This needs to be evaluated with larger, homogenous patient population in a prospective mode

Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses.

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Gonzalez-Rey, Elena; Chorny, Alejo; Del Moral, Raimundo G; Varela, Nieves; Delgado, Mario

2007-05-01

Rheumatoid arthritis is a chronic autoimmune disease of unknown aetiology characterised by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. To propose a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions. DBA/1J mice with collagen-induced arthritis were treated with cortistatin after the onset of disease, and the clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of various inflammatory mediators (cytokines and chemokines) in joints and serum. T helper cell type 1 (Th1)-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies. Cortistatin treatment significantly reduced the severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction in the two deleterious components of the disease-that is, the Th1-driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as interleukin 10 and transforming growth factor beta1. Cortistatin exerted its effects on synovial cells through both somatostatin and ghrelin receptors, showing a higher effect than both peptides protecting against experimental arthritis. This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.

Therapeutic response to benzodiazepine in panic disorder subtypes

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Alexandre Martins Valença

Full Text Available CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day, compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001 and decrease in anxiety (p = 0.024. In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

Treatment of chronic myeloid leukemia: assessing risk, monitoring response, and optimizing outcome.

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Shanmuganathan, Naranie; Hiwase, Devendra Keshaorao; Ross, David Morrall

2017-12-01

Over the past two decades, tyrosine kinase inhibitors have become the foundation of chronic myeloid leukemia (CML) treatment. The choice between imatinib and newer tyrosine kinase inhibitors (TKIs) needs to be balanced against the known toxicity and efficacy data for each drug, the therapeutic goal being to maximize molecular response assessed by BCR-ABL RQ-PCR assay. There is accumulating evidence that the early achievement of molecular targets is a strong predictor of superior long-term outcomes. Early response assessment provides the opportunity to intervene early with the aim of ensuring an optimal response. Failure to achieve milestones or loss of response can have diverse causes. We describe how clinical and laboratory monitoring can be used to ensure that each patient is achieving an optimal response and, in patients who do not reach optimal response milestones, how the monitoring results can be used to detect resistance and understand its origins.

The therapeutic use of the relaxation response in stress-related diseases.

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Esch, Tobias; Fricchione, Gregory L; Stefano, George B

2003-02-01

The objective of this work was to investigate a possible (therapeutic) connection between the relaxation response (RR) and stress-related diseases. Further, common underlying molecular mechanisms and autoregulatory pathways were examined. For the question of (patho)physiology and significance of RR techniques in the treatment of stress-related diseases, we analyzed peer-reviewed references only. The RR has been shown to be an appropriate and relevant therapeutic tool to counteract several stress-related disease processes and certain health-restrictions, particularly in certain immunological, cardiovascular, and neurodegenerative diseases/mental disorders. Further, common underlying molecular mechanisms may exist that represent a connection between the stress response, pathophysiological findings in stress-related diseases, and physiological changes/autoregulatory pathways described in the RR. Here, constitutive or low-output nitric oxide (NO) production may be involved in a protective or ameliorating context, whereas inducible, high-output NO release may facilitate detrimental disease processes. In mild or early disease states, a high degree of biological and physiological flexibility may still be possible (dynamic balance). Here, the therapeutic use of RR techniques may be considered particularly relevant, and the observable (beneficial) effects may be exerted via activation of constitutive NO pathways. RR techniques, regularly part of professional stress management or mind/body medical settings, represent an important tool to be added to therapeutic strategies dealing with stress-related diseases. Moreover, as part of 'healthy' life-style modifications, they may serve primary (or secondary) prevention. Further studies are necessary to elucidate the complex physiology underlying the RR and its impact upon stress-related disease states.

FDG PET/CT for therapeutic response monitoring in multi-site non-respiratory tuberculosis

International Nuclear Information System (INIS)

Geng Tian; Yong Xiao; Bin Chen; Jun Xia; Hong Guan; Qunyi Deng

2010-01-01

Background: Tuberculosis (TB) can produce positive signals during 18 F-fluorodeoxyglucose positron emission/computed tomography (FDG PET/CT) scanning. Until now, there has been no better method than clinical assessment to evaluate the therapeutic response of non-respiratory TB (NRTB). Purpose: To retrospectively assess the ability of FDG PET/CT to evaluate the response to anti-TB treatment in patients with NRTB. Material and Methods: Three patients with multi-site NRTB underwent repeat PET/CT scans during anti-TB treatment. Changes in maximal standard uptake value (SUVmax) of the TB lesions on PET/CT images were analyzed between two scans. Initial PET/CT scans were performed before the start of anti-TB treatment, and later scans were performed after completion of the treatment. Results: Patient 1, a 63-year-old female, and patient 2, a 50-year-old male, were diagnosed as multi-site NRTB by biopsy. Patient 3, a 37-year-old male was diagnosed clinically. These patients demonstrated multiple FDG-avid lesions in whole body on initial PET/CT images. The highest SUVmax of patient 1, 2, and 3 were 13.6, 17.7, and 13.9 separately. After completion of the treatment, all positive signals of patient 1, 2, and 3 decreased to undetectable value on repeated PET/CT scans with intervals of 318 days, 258 days, and 182 days separately. Conclusion: FDG PET/CT scan may be useful for monitoring responses to anti-TB treatment in patients with NRTB

Comparison of therapeutic response of keloids and hypertrophic scars to cryotherapy plus intralesional steroid and bleomycin tattoo

Directory of Open Access Journals (Sweden)

Farahnaz Fatemi

2005-01-01

Full Text Available Keloids and hypertrophic scars are abnormal responses of body to skin injuries. Overproduction of compacted fibrous tissue is the basic cause of these lesions. In this study the result of treatment of these skin conditions with bleomycin tattoo are compared with cryotherapy and triamcinolone injection. This study involved 45 patients with hypertrophic scar or keloid. Patients were divided into two groups consecutively. Group A (23 patients was treated with bleomycin tattoo and the group B with cryotherapy and triamcinolone injection. There were four therapeutic sessions one month apart. All patients were followedup for three month after the end of treatment .The therapeutic response was determined as reduction of lesion size or flattening relative to initial size. Therapeutic response was 88.3±14% in group A and 67.4 ±22.5% in group B (p<0.001. In group A 69%, but in group B only 49% of patients were asymptomatic after the end of treatment. In group A there was no relation between therapeutic response and lesion size (p=0.58 but in group B lesions those were smaller (<100mm2 had better therapeutic response than larger ones (p=0.007. It was concluded that bleomycin tattoo is more effective in treatment of hypertrophic scar and keloid than traditional treatment, cryotherapy plus triamcinolone injection especially in larger ones.

Professional responsibility in elder law: a synthesis of preventive law and therapeutic jurisprudence.

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Stolle, D P

1996-01-01

This article focuses on the professional responsibilities that a lawyer owes to older clients. Specifically, this article proposes that when working with older clients, lawyers have a responsibility to ensure that their clients have the capacity to manage their own affairs and to ensure their clients' legal, financial, and personal interests are protected in case of sudden future incapacity. Furthermore, a lawyer working with older clients has a responsibility to remain cognizant of the realities of ageing without giving in to the falsities of senior citizen stereotypes. Through an integration of Therapeutic Jurisprudence and Preventive Law, a proactive, client-centered, four-stage framework for advancing therapeutic goals through preventive lawyering is developed. The framework is then applied to a model lawyer/client interaction typical of elder practice. The advantages and limitations of the four-stage framework are discussed.

Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI.

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Nelson, Sarah J

2011-07-01

MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low-grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12-15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium-enhancing lesion on T(1) -weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T(2) lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti-angiogenic and anti

Meta-Analysis of Psychological Assessment as a Therapeutic Intervention

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Poston, John M.; Hanson, William E.

2010-01-01

This study entails the use of meta-analytic techniques to calculate and analyze 18 independent and 52 nonindependent effect sizes across 17 published studies of psychological assessment as a therapeutic intervention. In this sample of studies, which involves 1,496 participants, a significant overall Cohen's d effect size of 0.423 (95% CI [0.321,…

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

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Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

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

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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.

Trace levels of innate immune response modulating impurities (IIRMIs synergize to break tolerance to therapeutic proteins.

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Daniela Verthelyi

Full Text Available Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

Trace levels of innate immune response modulating impurities (IIRMIs) synergize to break tolerance to therapeutic proteins.

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Verthelyi, Daniela; Wang, Vivian

2010-12-22

Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs) that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS) and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st) dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

78 FR 9702 - Draft Guidance for Industry on Immunogenicity Assessment for Therapeutic Protein Products...

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2013-02-11

... approach in both the preclinical and clinical phases of the development of therapeutic protein products to... you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency... entitled ``Immunogenicity Assessment for Therapeutic Protein Products.'' The purpose of this document is to...

Diagnostic accuracy of contrast-enhanced ultrasound in assessing the therapeutic response to radio frequency ablation for liver tumors: systematic review and meta-analysis.

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Xuan, Min; Zhou, Fengsheng; Ding, Yan; Zhu, Qiaoying; Dong, Ji; Zhou, Hao; Cheng, Jun; Jiang, Xiao; Wu, Pengxi

2018-04-01

To review the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) used to detect residual or recurrent liver tumors after radiofrequency ablation (RFA). This technique uses contrast-enhanced computer tomography or/and contrast-enhanced magnetic resonance imaging as the gold standard of investigation. MEDLINE, EMBASE, and COCHRANE were systematically searched for all potentially eligible studies comparing CEUS with the reference standard that follows RFA. Risk of bias and applicability concerns were addressed by adopting the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled point estimates for sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios (DOR) with 95% CI were computed before plotting the sROC (summary receiver operating characteristic) curve. Meta-regression and subgroup analysis were used to identify the source of the heterogeneity that was detected. Publication bias was evaluated using Deeks' funnel plot asymmetry test. Ten eligible studies on 1162 lesions that occurred between 2001 and 2016 were included in the final analysis. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable. The pooled sensitivity and specificity of CEUS in detecting residual or recurrent liver tumors had the following values: 0.90 (95% CI 0.85-0.94) and 1.00 (95% CI 0.99-1.00), respectively. Overall DOR was 420.10 (95% CI 142.30-1240.20). The sources of heterogeneity could not be precisely identified by meta-regression or subgroup analysis. No evidence of publication bias was found. This study confirmed that CEUS exhibits high sensitivity and specificity in assessing therapeutic responses to RFA for liver tumors.

[Clinical features and therapeutic response of our anti-SRP positive patients with myositis].

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Botos, Balázs; Nagy-Vincze, Melinda; Dankó, Katalin

2017-09-01

Idiopathic inflammatory myopathies are a group of clinically heterogeneous diseases, which have been classified by myositis specific antibodies recently. The anti-SRP positive subset of this group is characterized by more severe clinical prognosis than other myositis specific antibody positive types. Our goal was to compare 16 anti-SRP positive patients in the Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen with 16 antibody negative ones. Muscle strength validated in both groups by the manual muscle test proved to be significantly decreased both before and after therapy (χ 2 = 0.006 and 0.019) in the anti-SRP positive group. Muscle-specific inflammatory laboratory parameters showed significant difference only in case of LDH-levels after therapy. Both groups showed good clinical response to first line steroid treatment, yet the significantly higher rate of second line administration suggests worse therapeutic response of the antibody positive group. Based on these facts we determined poor clinical prognosis and therapeutic response of the anti-SRP positive group. Orv Hetil. 2017; 158(35): 1382-1389.

Family Traditions, Cultural Values, and the Clinician's Countertransference: Therapeutic Assessment of a Young Sicilian Woman.

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Fantini, Francesca

2016-01-01

Despite recent advances in models and instruments to understand the role of a client's cultural background, clinical psychologists are not immune to implicit cultural biases that are potentially damaging to the therapeutic alliance. In this article, I present a Therapeutic Assessment with a young Sicilian woman conducted in a university-based student clinic in Italy. During the assessment, I assumed that because we were both Italians, my client shared my perspective (northern Italian) about family and individual values, which resulted in a therapeutic impasse when I responded on the basis of my individual and culturally shaped view of interpersonal and family relationships without appreciating important differences between my own and my client's microcultures. To overcome the impasse, I had to openly acknowledge such differences and reorient myself to my client's goals. I discuss the core processes involved in such a repair in the context of a cross-cultural psychological assessment.

The therapeutic factor inventory-8: Using item response theory to create a brief scale for continuous process monitoring for group psychotherapy.

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Tasca, Giorgio A; Cabrera, Christine; Kristjansson, Elizabeth; MacNair-Semands, Rebecca; Joyce, Anthony S; Ogrodniczuk, John S

2016-01-01

We tested a very brief version of the 23-item Therapeutic Factors Inventory-Short Form (TFI-S), and describe the use of Item Response Theory (IRT) for the purpose of developing short and reliable scales for group psychotherapy. Group therapy patients (N = 578) completed the TFI-S on one occasion, and their data were used for the IRT analysis. Of those, 304 completed the TFI-S and other measures on more than one occasion to assess sensitivity to change, concurrent, and predictive validity of the brief version. Results suggest that the new TFI-8 is a brief, reliable, and valid measure of a higher-order group therapeutic factor. The TFI-8 may be used for continuous process measurement and feedback to improve the functioning of therapy groups.

Alignment of learning objectives and assessments in therapeutics courses to foster higher-order thinking.

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FitzPatrick, Beverly; Hawboldt, John; Doyle, Daniel; Genge, Terri

2015-02-17

To determine whether national educational outcomes, course objectives, and classroom assessments for 2 therapeutics courses were aligned for curricular content and cognitive processes, and if they included higher-order thinking. Document analysis and student focus groups were used. Outcomes, objectives, and assessment tasks were matched for specific therapeutics content and cognitive processes. Anderson and Krathwohl's Taxonomy was used to define higher-order thinking. Students discussed whether assessments tested objectives and described their thinking when responding to assessments. There were 7 outcomes, 31 objectives, and 412 assessment tasks. The alignment for content and cognitive processes was not satisfactory. Twelve students participated in the focus groups. Students thought more short-answer questions than multiple choice questions matched the objectives for content and required higher-order thinking. The alignment analysis provided data that could be used to reveal and strengthen the enacted curriculum and improve student learning.

Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy.

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Sabir, Adeel; Schor-Bardach, Rachel; Wilcox, Carol J; Rahmanuddin, Syed; Atkins, Michael B; Kruskal, Jonathan B; Signoretti, Sabina; Raptopoulos, Vassilios D; Goldberg, S Nahum

2008-07-01

The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

The chicken TH1 response: potential therapeutic applications of ChIFN-γ.

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Guo, Pengju; Thomas, Jesse D; Bruce, Matthew P; Hinton, Tracey M; Bean, Andrew G D; Lowenthal, John W

2013-11-01

The outcomes of viral infections are costly in terms of human and animal health and welfare worldwide. The observed increase in the virulence of some viruses and failure of many vaccines to stop these infections has lead to the apparent need to develop new anti-viral strategies. One approach to dealing with viral infection may be to employ the therapeutic administration of recombinant cytokines to act as 'immune boosters' to assist in augmenting the host response to virus. With this in mind, a greater understanding of the immune response, particularly cell mediated T-helper-1 (TH1) type responses, is imperative to the development of new anti-viral and vaccination strategies. Following the release of the chicken genome, a number of TH1-type cytokines have been identified, including chicken interleukin-12 (ChIL-12), ChIL-18 and interferon-γ ChIFN-γ), highlighting the nature of the TH1-type response in this non-mammalian vertebrate. To date a detailed analysis of the in vivo biological function of these cytokines has been somewhat hampered by access to large scale production techniques. This review describes the role of TH-1 cytokines in immune responses to viruses and explores their potential use in enhancing anti-viral treatment strategies in chickens. Furthermore, this review focuses on the example of ChIFN-γ treatment of Chicken Anemia Virus (CAV) infection. CAV causes amongst other things thymocyte depletion and thymus atrophy, as well as immunosuppression in chickens. However, due to vaccination, clinical disease appears less often, nevertheless, the subclinical form of the disease is often associated with secondary complicating infections due to an immunocompromised state. Since CAV-induced immunosuppression can cause a marked decrease in the immune response against other pathogens, understanding this aspect of the disease is critically important, as well as providing insights into developing new control approaches. With increasing emphasis on developing

Using therapeutic assessment to explore emotional constriction: a creative professional in crisis

NARCIS (Netherlands)

Kamphuis, J.H.; de Saeger, H.; Finn, S.E.; Fischer, C.T.; Handler, L.

2012-01-01

A guide to conducting Collaborative/Therapeutic Assessment to promote client growth Mental health professionals are increasingly enthusiastic about and ready to use psychological test data, research, and theory in life-relevant ways to improve diagnosis, client care, and treatment outcomes. With

Therapeutic responses in systematic targeted alpha therapy trial for melanoma

International Nuclear Information System (INIS)

Raja, C.; Rizvi, S.M.A.; Song, E.Y.; Graham, P.; Kearsley, J.H.; Goldsmith, H.; Bosserhoff, A.; Morgenstern, A.; Apostolidis, C.; Reisfeld, R.

2006-01-01

Full text: The therapeutic response of melanoma patients after systemic alpha therapy has been investigated in an open-labeled Phase 1 dose escalation study to establish the effective dose of alpha-immunoconjugate 2l3 Bi-cDTPA-9.2.27 mAb (AIC). The tools used to investigate the effects were physical examination; the images of the tumours, pathology comparisons over 12 weeks; CT comparisons and changes in tumour marker over 8 weeks. The physical examination indicated varied tumour responses. One patient showed complete response at 12 weeks post-TAT, with 20 of 21 tumours completely regressing, the last reduced by 80%. The tumour beds were biopsied for staining; S l OO was negative and no viable cells were observed. Most patients showed stable disease at 2 weeks. In one patient the CT comparison of 8 weeks with baseline showed marked reduction in three lung lesions. At least 4/21 patients showed partial response at 4 to 8 weeks and the same number showed stable disease. The disease progressed in 7 patients. The tumour marker melanoma inhibitory activity protein (MIA) showed reductions over 8 weeks, and was consistent with observations in most patients. Complete and partial responses were observed in systemic TAT for stage IV melanoma, but there was no dose-response relationship

Evaluation of the therapeutic response to donepezil in patients with dat by 3DSRT

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Shigeaki Higashiyama; Terue Okamura; Koichi Koyama Yuichi Inoue; Joji kawabe; Kenji Torii; Susumu Shiomi; Hiroshi Hashimoto; Hisanori Akiyama; Kouki Inoue; Nobuo Kiriike

2004-01-01

Purpose: Alzheimer's disease (AD) is characterized by progressive impairment of memory and cognitive function associated with loss of presynaptic cholinergic function. It has recently been hypothesized that cholinergic agents such as cholinesterase inhibitors or cholinergic agonists may have the potential to improve these symptoms. One such compound is donepezil hydrochloride (Donepezil), which acts by blocking acetylcholinesterase and butyl cholinesterase, which hydoryze acetylcholine. In the diagnosis of AD, brain perfusion scintigraphy is an objective of visualization of brain perfusion. Up to the present, AD has been diagnosed objectively and quantitatively using brain perfusion single photon emission tomography (SPECT). In a quantitative evaluation of therapeutic response of Donepezil in AD, for comparison with regional cerebral blood flow (rCBF) in various lesions before and after treatment, uptake in various cerebral regions of interests (ROIs), such as the frontal lobes, temporo-occipital lobes, parietal lobes and cerebellar hemispheres, were used to be measured, The aim of this study was to investigate the accuratelity of therapeutic response of three-dimensional stereotaxic ROI template (3DSRT), fully automated ROI analysis software, which can objectively estimate rCBF in patients undergoing Donepezil therapy. We compare the effect of therapeutic response of three-dimensional stereotactic surface projections (3D-SSP). 3D-SSP is an image-processing and statistical program allowing pixel-by-pixel analysis of cerebral perfusion, provides a reliable and objective means of evaluation of severity of AD. On 3D-SSP images, we assessed the extent of abnormal region in each segment (rate of coordinates with a Z-value exceeding the.threshold value, of all coordinates within a segment) Methods: Twenty-one patients (15 females, 6 males;age range, 66-83 years old; mean age=69.4 years) diagnosed with AD according to the Diagnostic and Statistical Manual of Mental

Homeopathy as Boundary Object and Distributed Therapeutic Agency. A Discussion on the Homeopathic Placebo Response.

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Rughiniş, Cosima; Ciocănel, Alexandra; Vasile, Sorina

2017-09-27

We discuss homeopathy's placebo effect as the result of a distributed therapeutic agency involving humans, objects, and texts. Homeopathy has been involved in controversies for centuries, and the dispute whether it is therapy or quackery is as lively as ever. Still, homeopathy has retained significant popularity and acceptance within the medical establishment. We bracket the issue of biochemical effectiveness of homeopathic remedies as we only discuss homeopathy's potential to elicit a placebo response within its therapeutic alliance, in virtue of its social, symbolic, and material features. The review is based on literature discussing homeopathic effectiveness, including historical, biographical, sociological, and epistemological perspectives. We build upon research that clarifies the therapeutic relationship, examining its activities and meanings for practitioners and patients. Previous analyses discussing homeopathy's placebo effect stress the importance of the individualized consultation that functions as psychotherapy and generates empathy and hope. We enlarge the discussion, highlighting homeopathy's distributed therapeutic agency across humans, texts, and materials. The historical evolution of homeopathy in relation to biomedicine and science is important to understand its institutional integration into mainstream medicine and its appeal to scientifically minded doctors. Anecdotes of healing and the message of no-harm encourage patients to try homeopathy and hope for the best. The esthetics and ritual of remedies, coupled with computers' scientific legitimacy and time-saving power constitute a material infrastructure of therapeutic persuasion. Through its relation with biomedicine, its doctrine, consultation design, and treatment rituals, homeopathy offers a powerful medium to elicit a placebo response in a therapeutic alliance. By virtue of its proximity and radical difference from the scientific and biomedical enterprises, its material and textual

Quantitative methods in electroencephalography to access therapeutic response.

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Diniz, Roseane Costa; Fontenele, Andrea Martins Melo; Carmo, Luiza Helena Araújo do; Ribeiro, Aurea Celeste da Costa; Sales, Fábio Henrique Silva; Monteiro, Sally Cristina Moutinho; Sousa, Ana Karoline Ferreira de Castro

2016-07-01

Pharmacometrics or Quantitative Pharmacology aims to quantitatively analyze the interaction between drugs and patients whose tripod: pharmacokinetics, pharmacodynamics and disease monitoring to identify variability in drug response. Being the subject of central interest in the training of pharmacists, this work was out with a view to promoting this idea on methods to access the therapeutic response of drugs with central action. This paper discusses quantitative methods (Fast Fourier Transform, Magnitude Square Coherence, Conditional Entropy, Generalised Linear semi-canonical Correlation Analysis, Statistical Parametric Network and Mutual Information Function) used to evaluate the EEG signals obtained after administration regimen of drugs, the main findings and their clinical relevance, pointing it as a contribution to construction of different pharmaceutical practice. Peter Anderer et. al in 2000 showed the effect of 20mg of buspirone in 20 healthy subjects after 1, 2, 4, 6 and 8h after oral ingestion of the drug. The areas of increased power of the theta frequency occurred mainly in the temporo-occipital - parietal region. It has been shown by Sampaio et al., 2007 that the use of bromazepam, which allows the release of GABA (gamma amino butyric acid), an inhibitory neurotransmitter of the central nervous system could theoretically promote dissociation of cortical functional areas, a decrease of functional connectivity, a decrease of cognitive functions by means of smaller coherence (electrophysiological magnitude measured from the EEG by software) values. Ahmad Khodayari-Rostamabad et al. in 2015 talk that such a measure could be a useful clinical tool potentially to assess adverse effects of opioids and hence give rise to treatment guidelines. There was the relation between changes in pain intensity and brain sources (at maximum activity locations) during remifentanil infusion despite its potent analgesic effect. The statement of mathematical and computational

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

Directory of Open Access Journals (Sweden)

Castellote José

2011-07-01

Full Text Available Abstract Background Acute liver injury (ALI induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8 and of 10 per million paracetamol users-year (95% CI 4.3-19.4. Conclusions Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.

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Nagaraju, Kanneboyina; Ghimbovschi, Svetlana; Rayavarapu, Sree; Phadke, Aditi; Rider, Lisa G; Hoffman, Eric P; Miller, Frederick W

2016-09-01

To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19(+) B cells and CD68(+) macrophages in responders. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. Published by Oxford University Press on behalf British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the US.

A novel approach to assess the treatment response using Gaussian random field in PET

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Wang, Mengdie [Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China and Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Guo, Ning [Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Hu, Guangshu; Zhang, Hui, E-mail: hzhang@mail.tsinghua.edu.cn, E-mail: li.quanzheng@mgh.harvard.edu [Department of Biomedical Engineering, Tsinghua University, Beijing 100084 (China); El Fakhri, Georges; Li, Quanzheng, E-mail: hzhang@mail.tsinghua.edu.cn, E-mail: li.quanzheng@mgh.harvard.edu [Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 and Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115 (United States)

2016-02-15

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response

Evaluation of the effect of transcytolemmal water exchange analysis for therapeutic response assessment using DCE-MRI: a comparison study.

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Wang, Chunhao; Subashi, Ergys; Liang, Xiao; Yin, Fang-Fang; Chang, Zheng

2016-07-07

This study compares the shutter-speed (SS) and the Tofts models as used in assessing therapeutic response in a longitudinal DCE-MRI experiment. Sixteen nu/nu mice with implanted colorectal adenocarcinoma cell line (LS-174T) were randomly assigned into treatment/control groups (n  =  8/group) and received bevacizumab/saline twice weekly (Day1/Day4/Day8). All mice were scanned at one pre- (Day0) and two post-treatment (Day2/Day9) time points using a high spatiotemporal resolution DCE-MRI pulse sequence. The CA extravasation rate constant [Formula: see text] from the Tofts/SS model and the mean intracellular water residence time [Formula: see text] from the SS model were analyzed. A biological subvolume (BV) within the tumor was identified based on the [Formula: see text] intensity distribution, and the SS model parameters within the BV ([Formula: see text] and [Formula: see text]) were analyzed. It is found that [Formula: see text] and [Formula: see text] have a similar spatial distribution in the tumor volume. The Bayesian information criterion results show that the SS model was a better fit for all scans. At Day9, the treatment group had significantly higher tumor mean [Formula: see text] (p  =  0.021), [Formula: see text] (p  =  0.021) and [Formula: see text] (p  = 0.045). When BV from transcytolemmal water exchange analysis was adopted, the treatment group had higher mean [Formula: see text] at both Day2 (p  =  0.038) and Day9 (p  =  0.007). Additionally, at Day9, the treatment group had higher mean [Formula: see text] (p  =  0.045) and higher [Formula: see text] spatial heterogeneity indices (Rényi dimensions) d 1 (p  = 0.010) and d 2 (p  = 0.021). When mean [Formula: see text] and its coefficient of variation (CV) were used to separate treatment/control group samples using supporting vector machine, the accuracy of treatment/control classification was 68.8% at Day2 and 87.5% at Day9; in contrast, the

Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

International Nuclear Information System (INIS)

Speight, E.L.; Farr, P.M.

1994-01-01

In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease. (author)

Therapeutic Assessment of Complex Trauma: A Single-Case Time-Series Study

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Tarocchi, Anna; Aschieri, Filippo; Fantini, Francesca; Smith, Justin D.

2013-01-01

The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including es...

Assessment of the Therapeutic Effect of Total Glucosides of Peony for Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analysis

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Yongsong Cai

2016-01-01

Full Text Available Juvenile idiopathic arthritis (JIA is the most common rheumatic disease in children; some clinical trials have reported the effects of total glucosides of peony (TGP in the treatment of JIA. However, no systematic review has yet been conducted. In this study, we assessed the efficacy and safety in patients with JIA enrolled in randomized controlled trials (RCTs of TGP. We extracted data for studies searched from 8 electronic databases that were searched and also evaluated the methodological quality of the included studies. We assessed the following outcome measures: overall response rate, pain, tender joint count (TJC, swollen joint count (SJC, duration of morning stiffness (DMS, grip strength (GS, rheumatoid factor (RF, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and adverse effects (AEs in short term (4–8 weeks, intermediate term (9–26 weeks, and long term (>26 weeks. The final analysis showed that TGP acted as a unique nonbiologic disease-modifying antirheumatic drug (nonbiologic DMARD, and its therapeutic effects were safe and efficacious for the treatment of JIA with few AEs. However, more high-quality RCTs are needed to confirm these therapeutic effects.

Assessment of the Therapeutic Effect of Total Glucosides of Peony for Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analysis

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Cai, Yongsong; Yuan, Qiling; Xu, Ke; Zhu, Jialin; Li, Yuanbo; Wu, Xiaoqing; Yang, Le

2016-01-01

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children; some clinical trials have reported the effects of total glucosides of peony (TGP) in the treatment of JIA. However, no systematic review has yet been conducted. In this study, we assessed the efficacy and safety in patients with JIA enrolled in randomized controlled trials (RCTs) of TGP. We extracted data for studies searched from 8 electronic databases that were searched and also evaluated the methodological quality of the included studies. We assessed the following outcome measures: overall response rate, pain, tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness (DMS), grip strength (GS), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse effects (AEs) in short term (4–8 weeks), intermediate term (9–26 weeks), and long term (>26 weeks). The final analysis showed that TGP acted as a unique nonbiologic disease-modifying antirheumatic drug (nonbiologic DMARD), and its therapeutic effects were safe and efficacious for the treatment of JIA with few AEs. However, more high-quality RCTs are needed to confirm these therapeutic effects. PMID:27525026

Use of positron emission tomography for staging, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour

International Nuclear Information System (INIS)

Misch, Daniel; Steffen, Ingo G.; Furth, Christian; Stoever, Brigitte; Amthauer, Holger; Denecke, Timm; Schoenberger, Stefan; Voelker, Thomas; Henze, Guenter; Hautzel, Hubertus

2008-01-01

To evaluate FDG-PET for staging, grading, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour (WT). In this study, 23 FDG-PET examinations in 12 paediatric patients (female, n=5; male, n=7; age, 1-19 years) with WT (primary, n=9; relapsed, n=3) were analysed. All patients were examined with conventional imaging methods (CIM) according to the SIOP2001/GPOH trial protocol. Additionally, FDG-PET/PET-CT was performed for staging (n = 12), preoperative response assessment (n=6) and posttherapeutic evaluation (n=5). Imaging results of FDG-PET and CIM were analysed regarding the accuracy in tumour visualisation, impact on therapeutic management and preoperative response assessment, with clinical follow-up and histopathology as the standard of reference. FDG-PET and CIM showed concordant results for staging of primary WT, whereas FDG-PET was superior in 1/3 cases with recurrent WT. Concerning histological differentiation, one case with anaplastic WT had an standard uptake value (SUV) of 12.3, which was remarkably higher than the average SUV in the eight cases with intermediate risk histology. No parameter analysed for PET or CIM was reliably predictive for histological regression or clinical outcome. After completion of therapy, FDG-PET was superior to CIM in 2/5 cases in detecting residual disease with therapeutic relevance. FDG-PET does not provide additional information to the traditional imaging work-up for staging WT patients, preoperative response assessment and clinical outcome. FDG-PET was advantageous in ruling out residual disease after completion of first line treatment and in pretherapeutic staging of relapse patients. Furthermore, there seems to be a good correlation of initial SUV and histological differentiation. (orig.)

Prognosis and therapeutic response according to the world health organization histological classification in advanced thymoma

International Nuclear Information System (INIS)

Tagawa, Tetsuzo; Kometani, Takuro; Yamazaki, Koji

2011-01-01

The clinical efficacy of the World Health Organization (WHO) classification of thymoma has been reported to be a prognostic factor for patients with thymomas. This study focuses on the relationship between the therapeutic response and the WHO histological classification in patients with advanced thymoma. A retrospective review was performed on 22 patients with Masaoka stage III and IV thymoma treated from 1975 to 2007. There were 1, 1, 7, 3, and 10 patients with WHO histological subtypes A, AB, B1, B2, and B3, respectively. Surgery was performed on 10 patients. There were 2 complete resections, 2 incomplete resections, and 6 exploratory thoracotomies. Of 18 patients with unresectable tumors, 8, 5, and 5 were treated with radiotherapy, chemotherapy, and chemoradiotherapy as the initial therapy, respectively. The response rate in 9 patients with type A-B2 was significantly better than that in 9 patients with type B3 regardless of treatment modality (100% vs 11.1%, P=0.0001). Only the WHO classification was significantly associated with survival, with type B3 having a worse prognosis than A-B2 (P=0.01). Type B3 thymoma showed a lower response rate to treatments and thus shorter survival. The WHO classification is a good predictive factor for therapeutic response in advanced thymoma. (author)

The Role of Doppler Ultrasound in Assessing the Therapeutic Response in Advanced Breast Cancer

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Jamal Eyvazi-Ziaei

2018-01-01

Full Text Available Background and Objectives: Breast cancer is one of the most common cancers in Iran, which neo-adjuvant chemotherapy used to treat in advanced types to reduce tumor burden. The aim of this study was to evaluate the ultrasound scales of patients with advanced disease, using two common treatment methods include TACs (Taxotere, Adriamycin, and Cyclophosphamide and AC (Adriamycin, Cyclophosphamide. Material and Methods: Clinical examination and Doppler ultrasound were performed before and after treatment. Before and after the treatment, the size of the primary tumor and tumor vascularization, and the ultrasound Resistivity Index (RI, Pulsality Index (PI, Peak Systolic Velocity (PSV and the condition of the anterior lymph nodes, and the effect of two different therapies were investigated in response to treatment. The SPSS statistical software 17.0 was used to evaluate the relationship between the variables with 95% confidence interval, and P≤ 0.05. Results: The mean age of the patients was 48.90 (±10.58 SD years. From these, 8 were postmenopausal and 9 were menopausal, and in 3 cases the situation was unknown. There was significant difference between the PSV levels of the main breast mass, pre and post chemotherapy (P=0.004. Changes in other indexes of breast mass and axillary mass were not statistical significant. Conclusion: Color Doppler ultrasonography seems to be a promising alternative as an independent and complementary tool, to assess the response to treatment of breast masses to primary medical treatment in advanced breast cancers.

Potential immunological markers for diagnosis and therapeutic assessment of toxocariasis

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Guita Rubinsky-Elefant

2011-04-01

Full Text Available In human toxocariasis, there are few approaches using immunological markers for diagnosis and therapeutic assessment. An immunoblot (IB assay using excretory-secretory Toxocara canis antigen was standardized for monitoring IgG, IgE and IgA antibodies in 27 children with toxocariasis (23 visceral, three mixed visceral and ocular, and one ocular form for 22-116 months after chemotherapy. IB sensitivity was 100% for IgG antibodies to bands of molecular weight 29-38, 48-54, 95-116, 121-162, >205 kDa, 80.8% for IgE to 29-38, 48-54, 95-121, > 205 kDa, and 65.4% for IgA to 29-38, 48-54, 81-93 kDa. Candidates for diagnostic markers should be IgG antibodies to bands of low molecular weight (29-38 and 48-54 kDa. One group of patients presented the same antibody reactivity to all bands throughout the follow-up study; in the other group, antibodies decayed partially or completely to some or all bands, but these changes were not correlated with time after chemotherapy. Candidates for monitoring patients after chemotherapy may be IgG antibodies to > 205 kDa fractions, IgA to 29-38, 48-54, 81-93 kDa and IgE to 95-121 kDa. Further identification of antigen epitopes related to these markers will allow the development of sensitive and specific immunoassays for the diagnosis and therapeutic assessment of toxocariasis.

Maximum likelihood estimation of dose-response parameters for therapeutic operating characteristic (TOC) analysis of carcinoma of the nasopharynx

International Nuclear Information System (INIS)

Metz, C.E.; Tokars, R.P.; Kronman, H.B.; Griem, M.L.

1982-01-01

A Therapeutic Operating Characteristic (TOC) curve for radiation therapy plots, for all possible treatment doses, the probability of tumor ablation as a function of the probability of radiation-induced complication. Application of this analysis to actual therapeutic situation requires that dose-response curves for ablation and for complication be estimated from clinical data. We describe an approach in which ''maximum likelihood estimates'' of these dose-response curves are made, and we apply this approach to data collected on responses to radiotherapy for carcinoma of the nasopharynx. TOC curves constructed from the estimated dose-response curves are subject to moderately large uncertainties because of the limitations of available data.These TOC curves suggest, however, that treatment doses greater than 1800 rem may substantially increase the probability of tumor ablation with little increase in the risk of radiation-induced cervical myelopathy, especially for T1 and T2 tumors

Therapeutic Assessment for Preadolescent Boys with Oppositional Defiant Disorder: A Replicated Single-Case Time-Series Design

Science.gov (United States)

Smith, Justin D.; Handler, Leonard; Nash, Michael R.

2010-01-01

The Therapeutic Assessment (TA) model is a relatively new treatment approach that fuses assessment and psychotherapy. The study examines the efficacy of this model with preadolescent boys with oppositional defiant disorder and their families. A replicated single-case time-series design with daily measures is used to assess the effects of TA and to…

Therapeutic assessment with an adolescent: choosing connections over substances.

Science.gov (United States)

Austin, Cynthia A; Krumholz, Lauren S; Tharinger, Deborah J

2012-01-01

This case study provides an in-depth example of a comprehensive therapeutic assessment with an adolescent (TA-A) and his parents. The TA-A addressed parental concerns about their son's drug experimentation as well as the adolescent's own private questions about his distinctiveness from others, all set against a backdrop of ongoing parental conflict and poor communication. The TA-A process and how it is specifically tailored to balance the needs of adolescents and their parents is discussed. Subsequently, each step of TA-A is illustrated through the case study. Research findings at the conclusion of the assessment and at follow-up indicated significant decreases in internalizing symptomology and school problems, increases in self-esteem and self-reliance, and improved family functioning as reported by the adolescent. At follow-up, the father spoke of developing a more assertive parenting approach and successful follow-through on recommendations. This case study provides a template for clinicians interested in conducting TA-A.

ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

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Miao Yun

Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

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Robert A. Mitchell

2016-01-01

Full Text Available Background. Infliximab (IFX therapeutic drug monitoring (TDM allows for objective decision making in patients with inflammatory bowel disease (IBD and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67% and 2 (83% had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P=0.098. Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.

Human cervical cancer: therapeutic response assessment by innovative molecular strategies

International Nuclear Information System (INIS)

Nagarajan, Bala

2016-01-01

In Asia-Pacific region, the incidence of cancer of uterine cervix is high. Cancer is a multiple disease of multiple etiologies that has bearing on gene alteration that end result in abnormal cell dysfunction. We address the process interfacing infection, inflammation and oxidative damage that would lead to identify markers - to help improve patient management and bench to bedside. Radiation causes cell damage through production of reactive oxygen species. Radiation-induced DNA strand break is the primary mode of cell death. However, a secondary form of damage includes base modification or DNA adducts that are lethal on accumulation at higher levels. We analyzed polar and lipophilic adducts and found that the levels of adducts formed were independent of severity of disease status. 8 oxodG could be used as a marker to reflect patients potential to fix the lesion and response to radiation therapy. There was an increase in adduct levels in post treatment samples when compared to pre-RT, indicating radiation-induced DNA damage. Patients divided into two groups, high and low adduct formers, tend to show interindividual differences to fix the lesion that could be used to delineate radio-resistant or non-responding tumors. We have also looked at inflammatory cytokines, both by immunocytochemistry and m-RNA by RT-PCR through therapy, and generated definitive data that augur well with treatment response. The bottom line approach is prognostication and stratification. (author)

Therapeutic outcomes, assessments, risk factors and mitigation efforts of immunogenicity of therapeutic protein products.

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Yin, Liusong; Chen, Xiaoying; Vicini, Paolo; Rup, Bonita; Hickling, Timothy P

2015-06-01

Therapeutic protein products (TPPs) are of considerable value in the treatment of a variety of diseases, including cancer, hemophilia, and autoimmune diseases. The success of TPP mainly results from prolonged half-life, increased target specificity and decreased intrinsic toxicity compared with small molecule drugs. However, unwanted immune responses against TPP, such as generation of anti-drug antibody, can impact both drug efficacy and patient safety, which has led to requirements for increased monitoring in regulatory studies and clinical practice, termination of drug development, or even withdrawal of marketed products. We present an overview of current knowledge on immunogenicity of TPP and its impact on efficacy and safety. We also discuss methods for measurement and prediction of immunogenicity and review both product-related and patient-related risk factors that affect its development, and efforts that may be taken to mitigate it. Lastly, we discuss gaps in knowledge and technology and what is needed to fill these. Copyright © 2015 Elsevier Inc. All rights reserved.

The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents

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Julia A. Tree

2014-01-01

Full Text Available Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of “omic” technologies (next generation sequencing, DNA, and protein microarrays for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.

Impact of household food insecurity on the nutritional status and the response to therapeutic feeding of people living with human immunodeficiency virus

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Bahwere P

2011-12-01

Full Text Available Paluku Bahwere1,2,*, Hedwig Deconinck3,*, Theresa Banda1,*, Angella Mtimuni1,*, Steve Collins1,* 1Valid International, Oxford, United Kingdom; 2Center of Research in Epidemiology, Biostatistics, and Clinical Research, School of Public Health, Free University of Brussels, Brussels, Belgium; 3Save the Children, Westport, CT, USA *These authors contributed equally to this workBackground: The role of household food security (HFS in the occurrence of wasting and the response to food-based intervention in people living with human immunodeficiency virus (PLHIV, especially adults, is still controversial and needs investigation.Methods: Face-to-face interviews to collect data for Coping Strategies Index score and Dietary Diversity Score estimation were conducted during a noncontrolled and nonrandomized study assessing the effectiveness of ready-to-use therapeutic food in the treatment of wasting in adults with HIV. Coping Strategies Index score and Dietary Diversity Score were used to determine HFS, and the participants and tertiles of Coping Strategies Index score were used to categorize HFS.Results: The study showed that most participants were from food insecure households at admission, only 2.7% (5/187 ate food from six different food groups the day before enrolment, and 93% (180/194 were applying forms of coping strategy. Acute malnutrition was rare among <5-year-old children from participants’ households, but the average (standard deviation mid-upper arm circumference of other adults in the same households were 272.7 (42.1 mm, 254.8 (33.8 mm, and 249.8 (31.7 mm for those from the best, middle, and worst tertile of HFS, respectively (P = 0.021. Median weight gain was lower in participants from the worst HFS tertile than in those from the other two tertiles combined during therapeutic feeding phase (0.0 [–2.1 to 2.6] kg versus 1.9 [–1.7 to 6.0] kg; P = 0.052 and after ready-to-use therapeutic food discontinuation (–1.9 [–5.2 to 4.2] kg

ErbB polymorphisms: Insights and implications for response to targeted cancer therapeutics

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Moulay A Alaoui-Jamali

2015-02-01

Full Text Available Advances in high-throughput genomic-scanning have expanded the repertory of genetic variations in DNA sequences encoding ErbB tyrosine kinase receptors in humans, including single nucleotide polymorphisms (SNPs, polymorphic repetitive elements, microsatellite variations, small-scale insertions and deletions. The ErbB family members: EGFR, ErbB2, ErbB3 and ErbB4 receptors are established as drivers of many aspects of tumor initiation and progression to metastasis. This knowledge has provided rationales for the development of an arsenal of anti-ErbB therapeutics, ranging from small molecule kinase inhibitors to monoclonal antibodies. Anti-ErbB agents are becoming the cornerstone therapeutics for the management of cancers that overexpress hyperactive variants of ErbB receptors, in particular ErbB2-positive breast cancer and non-small cell lung carcinomas. However, their clinical benefit has been limited to a subset of patients due to a wide heterogeneity in drug response despite the expression of the ErbB targets, attributed to intrinsic (primary and to acquired (secondary resistance. Somatic mutations in ErbB tyrosine kinase domains have been extensively investigated in preclinical and clinical setting as determinants for either high sensitivity or resistance to anti-ErbB therapeutics. In contrast, only scant information is available on the impact of SNPs, which are widespread in genes encoding ErbB receptors, on receptor structure and activity, and their predictive values for drug susceptibility. This review aims to briefly update polymorphic variations in genes encoding ErbB receptors based on recent advances in deep sequencing technologies, and to address challenging issues for a better understanding of the functional impact of single versus combined SNPs in ErbB genes to receptor topology, receptor-drug interaction, and drug susceptibility. The potential of exploiting SNPs in the era of stratified targeted therapeutics is discussed.

The use of Deauville criteria in follow-up assessment of response to therapy in extra-nodal Non-Hodgkin's lymphoma

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Manar Hussein Abdel-Sattar

2018-03-01

Full Text Available Objective: Our aim was evaluate the role the PET/CT in the assessment of response to therapy in patients with Non-Hodgkin extra-nodal lymphoma: in particular, a five-point scale (Deauville criteria, which can be employed for early- and late-therapeutic response assessment. Methods: Sixty patients with pathologically confirmed Non-Hodgkin lymphoma (NHL were enrolled in this prospective study. All patients underwent the following PET/CT examinations: initial PET/CT for staging, interim PET/CT and end of treatment PET/CT. Response assessment was done using new Cheson’s guidelines and five-point scale (Deauville criteria. Results: All patients were evaluated for response to therapy in the early interim, followed by late interim, as well as end treatment assessment for the overall response. We found good concordance of response assessment according to the Deauville criteria classification with International Harmonization Project (IHP classification. After early interim 48/60 patients had concordant designations (91.7%, 83.3%, 70%, and 33.3% and 12 patients had discordant designations. After late interim, 56/60 patients had concordant designations (100%, 100%, 80%, and 50% and four patients had discordant designations. After end of treatment, 54/60 patients had concordant designations (100%, 100% and 71.4% and six patients has discordant designations. Conclusion: Response assessment according to the Deauville criteria classification showed good concordance with IHP classification. According to our findings, we recommend the use of Deauville criteria in reporting of PET/CT for staging and assessment of response to treatment. Keywords: PET/CT, Extranodal non-hodgkin lymphoma, Deauville criteria, IHP (International Harmonizing Project

Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria

NARCIS (Netherlands)

Price, Ric N.; Uhlemann, Anne-Catrin; van Vugt, Michele; Brockman, Al; Hutagalung, Robert; Nair, Shalini; Nash, Denae; Singhasivanon, Pratap; Anderson, Tim J. C.; Krishna, Sanjeev; White, Nicholas J.; Nosten, François

2006-01-01

Our study examined the relative contributions of host, pharmacokinetic, and parasitological factors in determining the therapeutic response to artemether-lumefantrine (AL). On the northwest border of Thailand, patients with uncomplicated Plasmodium falciparum malaria were enrolled in prospective

A theoretical and methodological proposal for the descriptive assessment of therapeutic interactions.

Science.gov (United States)

Froján-Parga, María Xesús; Ruiz-Sancho, Elena M; Calero-Elvira, Ana

2016-01-01

The goal of this study is to show the development of a strategy for a descriptive assessment of the therapeutic interaction. In this study, we develop an observational methodology to analyze the dialogues that took place during 92 sessions conducted in a psychological center in Madrid, Spain, in which 19 adults were treated for various psychological problems by 9 behavioral therapists. A system was developed to codify vocal behavior of both the therapists and the clients; the software The Observer XT was used for recording. Therapeutic interactions were analyzed using sequential analysis. There are three main sequences that synthesize the therapist-client interaction: first, an utterance by the client preceded by a therapist's verbalization, specifically a question (discriminative morphology) and followed by an expression of approval (reinforcement morphology); second, verbalizations of failure or discomfort uttered by the client, followed most often by verbalizations of disapproval (punishing morphology) uttered by the therapist; and third, verbalizations uttered by the client that are discriminated by the therapist after an in-depth explanation and followed by different therapist's utterances (expressions of approval, technical information, etc.). Depending on how the client responds the results in this study present a starting point for the study of the functional sequences that form the basis of therapeutic change.

Effect of therapeutic touch on brain activation of preterm infants in response to sensory punctate stimulus: a near-infrared spectroscopy-based study.

Science.gov (United States)

Honda, Noritsugu; Ohgi, Shohei; Wada, Norihisa; Loo, Kek Khee; Higashimoto, Yuji; Fukuda, Kanji

2013-05-01

The purpose of this study was to determine whether therapeutic touch in preterm infants can ameliorate their sensory punctate stimulus response in terms of brain activation measured by near-infrared spectroscopy. The study included 10 preterm infants at 34-40 weeks' corrected age. Oxyhaemoglobin (Oxy-Hb) concentration, heart rate (HR), arterial oxygen saturation (SaO2) and body movements were recorded during low-intensity sensory punctate stimulation for 1 s with and without therapeutic touch by a neonatal development specialist nurse. Each stimulation was followed by a resting phase of 30 s. All measurements were performed with the infants asleep in the prone position. sensory punctate stimulus exposure significantly increased the oxy-Hb concentration but did not affect HR, SaO2 and body movements. The infants receiving therapeutic touch had significantly decreased oxy-Hb concentrations over time. Therapeutic touch in preterm infants can ameliorate their sensory punctate stimulus response in terms of brain activation, indicated by increased cerebral oxygenation. Therefore, therapeutic touch may have a protective effect on the autoregulation of cerebral blood flow during sensory punctate stimulus in neonates.

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

Science.gov (United States)

Walsh, Joseph C.; Lebedev, Artem; Aten, Edward; Madsen, Kathleen; Marciano, Liane

2014-01-01

I. Introduction II. The Clinical Importance of Tumor Hypoxia A. Pathophysiology of hypoxia B. Hypoxia's negative impact on the effectiveness of curative treatment 1. Hypoxic tumors accumulate and propagate cancer stem cells 2. Hypoxia reduces the effectiveness of radiotherapy 3. Hypoxia increases metastasis risk and reduces the effectiveness of surgery 4. Hypoxic tumors are resistant to the effects of chemotherapy and chemoradiation C. Hypoxia is prognostic for poor patient outcomes III. Diagnosis of Tumor Hypoxia A. Direct methods 1. Oxygen electrode—direct pO2 measurement most used in cancer research 2. Phosphorescence quenching—alternative direct pO2 measurement 3. Electron paramagnetic resonance 4. 19F-magnetic resonance spectroscopy 5. Overhauser-enhanced MRI B. Endogenous markers of hypoxia 1. Hypoxia-inducible factor-1α 2. Carbonic anhydrase IX 3. Glucose transporter 1 4. Osteopontin 5. A combined IHC panel of protein markers for hypoxia 6. Comet assay C. Physiologic methods 1. Near-infrared spectroscopy/tomography—widely used for pulse oximetry 2. Photoacoustic tomography 3. Contrast-enhanced color duplex sonography 4. MRI-based measurements 5. Blood oxygen level-dependent MRI 6. Pimonidazole 7. EF5 (pentafluorinated etanidazole) 8. Hypoxia PET imaging—physiologic hypoxia measurement providing tomographic information a. 18F-fluoromisonidazole b. 18F-fluoroazomycinarabinofuranoside c. 18F-EF5 (pentafluorinated etanidazole) d. 18F-flortanidazole e. Copper (II) (diacetyl-bis (N4-methylthiosemicarbazone)) f. 18F-FDG imaging of hypoxia IV. Modifying Hypoxia to Improve Therapeutic Outcomes A. Use of hypoxia information in radiation therapy planning B. Use of hypoxia assessment for selection of patients responsive to nimorazole C. Use of hypoxia assessment for selection of patients responsive to tirapazamine D. Use of hypoxia assessment for selection of patients

Personality assessment of substance-dependent patients in a therapeutic community.

Science.gov (United States)

Moffett, L A; Steinberg, S L; Rohde, P

1996-01-01

The design and implementation of a personality assessment system for severely substance-dependent men in a therapeutic community (TC) are described. The system was designed from a treatment utility perspective (Hayes, Nelson, & Jarrett, 1987) and uses the Personality Research Form E (Jackson, 1984) to provide each patient with feedback (a) describing his normal personality traits, (b) predicting his probable pattern of adjustment to the treatment setting, and (c) prescribing specific actions he can take to address potentially problematic behaviors. Discussing the the results with the patient helps him cope with the TC. Reviewing the assessment results with the staff promotes their empathy for the patient as a person whose behavior can be understood as an interaction of his personality with the specific demands of the TC rather than seeing the patient in exclusively pathological terms. Specific suggestions for behavior change guide both the patient and the staff and are potentially useful in various treatment settings.

Facilitators and barriers to the provision of therapeutic interventions by school psychologists

Science.gov (United States)

Squires, Garry; Bragg, Joanna; Muscutt, Janet; Wasilewski, David

2014-01-01

There is growing concern internationally about the prevalence of mental health problems among school-aged children and their access to specialist services. School psychologists (SPs) may be one group of professionals well-positioned to support the well-being of children and young people, due to their position as applied psychologists working within educational settings and their capability to deliver therapeutic interventions. This research considers findings from a large scale, United Kingdom (UK)-wide survey of the views of SPs (N = 455) about facilitators and barriers to the provision of therapeutic interventions to children and young people. Principal Components Analyses of ranked questionnaire responses yielded three components: The role of the SP; training and practice; and support and psychology service context. Quantitative findings were then triangulated, using qualitative responses from the survey. Greater direction and clarification of the role of the SP as a provider of therapeutic interventions is recommended, particularly given the diverse roles undertaken by SPs and competing demands, particularly from assessment activities. PMID:26412911

PYTHIOSIS: A THERAPEUTIC APPROACH

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C. M. C. Falcão

2015-10-01

Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

The Assessment of the Colo-rectal Polyps in Order to the New Diagnostic and Therapeutic Strategies

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Raluca Diac Andreea

2015-09-01

Full Text Available Objective. Assessment of the histological and endoscopic features of the colo-rectal polyps is requered for the application of the new diagnostic and therapeutical strategies in the managment of the diminutive polyps.

The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region

NARCIS (Netherlands)

van Schie, K. A.; Hart, M. H.; de Groot, E. R.; Kruithof, S.; Aarden, L. A.; Wolbink, G. J.; Rispens, T.

2015-01-01

In a subset of patients, anti tumour necrosis factor (TNF) therapeutic antibodies are immunogenic, resulting in the formation of antidrug antibodies (ADAs). Neutralising ADAs compete with TNF for its binding site and reduces the effective serum concentration, causing clinical non-response. It is

Psychological Considerations in the Assessment and Treatment of Pain in Neurorehabilitation and Psychological Factors Predictive of Therapeutic Response: Evidence and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

Science.gov (United States)

Castelnuovo, Gianluca; Giusti, Emanuele M; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A M; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G; Wiederhold, Brenda; Tamburin, Stefano

2016-01-01

In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics. To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the psychological aspects that are involved. The

Therapeutic Assessment in Personality Disorders: Toward the Restoration of Epistemic Trust.

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Kamphuis, Jan H; Finn, Stephen E

2018-06-06

Research evidence suggests Therapeutic Assessment positively affects clients with problems in living, including clients with personality disorders, who are typically quite resistant to change. Importantly, this change takes place quickly, in relatively few sessions. This article draws on a relatively new evolutionary-based theory of epistemic trust (ET) and epistemic hypervigilance (EH) as a lens to plausibly explain the efficacy of TA, and especially its influence on PD clients' alliance and motivation for subsequent psychotherapy (Fonagy, Luyten, & Alison, 2015 ). ET is the willingness to take in relevant interpersonally transmited information and it is essential to the immediate success of psychotherapy and its long-term impact. The collaborative, intersubjective framework of TA and many of its specific techniques might be understood as highly relevant to restoring ET in clients, especially those with PD. We close by discussing implications for psychological assessment, psychotherapy, and research.

Lab-on-fiber optofluidic platform for in-situ study of therapeutic peptides and bacterial response (Rising Researcher Presentation) (Conference Presentation)

Science.gov (United States)

Tian, Fei; Yang, Fan; Liang, Junfeng

2017-05-01

Hospital acquired infections in indwelling device have become a life-threatening issue accompanied by the wide use of medical devices and implants. The infection process typically involves the attachment, growth and eventual assemblage of microbial cells into biofilms, with the latter exhibiting extremely higher antibiotic tolerance than planktonic bacteria. Surface constructed antimicrobial coatings offer a viable solution for bacteria responsive antibiotic strategy in medical devices such as catheter and stents. Therapeutic peptide has pioneered the field for their attractive pharmacological profile with broad antibacterial spectrum, great efficacy and long life-span. It has been a common practice to separately assess bacteria responses through commercially available activity assay kits after their exposure to antibiotic coatings, limiting the assessment of their activity in vitro with a discontinuous fashion. We developed and demonstrated an innovative all-optical lab-on-fiber optofluidic platform (LOFOP) to fill in this technical gap by allowing in situ measurement of the bacteria attachment in a continuous manner. This LOFOP allows for evaluation of drug release and resultant bacterial response by integrating glass capillary with lytic peptide-containing LbL-coated long period graing (LPG) as its core. S. aureus suspension is introduced through the assembled optofluidic platform with the capillary and the peptide-coated LPG. The efficacy of the peptide-containing coating is evaluated in situ by monitoring the attachment of bacteria and the ensuing development of biofilms using the LPG. LPG without antimicrobial coatings will be explored and compared as control.

A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response.

Directory of Open Access Journals (Sweden)

John R Bankston

2007-12-01

Full Text Available SCN5A encodes the alpha-subunit (Na(v1.5 of the principle Na(+ channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS variant 3 (LQT-3 in adults by disrupting inactivation of the Na(v1.5 channel. Pharmacological targeting of mutation-altered Na(+ channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+ channel blockers flecainide and mexiletine. Our goal was to determine the Na(+ channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+ channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C and a common variant in KCNH2 (K897T. Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+ channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.The results of our study provide further evidence of the grave vulnerability of newborns to Na(+ channel defects and suggest that both genetic background and age are

A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

Directory of Open Access Journals (Sweden)

Isabela Resende Pereira

2015-01-01

Full Text Available Chagas disease (CD, caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd carrying sequences of amastigote surface protein-2 (rAdASP2 and trans-sialidase (rAdTS T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi, when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFNγ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi and the boost (analysis at 180 and 230 dpi. Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28, CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells

Factors that influence therapeutic outcomes in symptomatic gastroesophageal reflux disease.

LENUS (Irish Health Repository)

Quigley, Eamonn M M

2012-02-03

The term "symptomatic gastroesophageal reflux disease" (GERD) refers to those patients who present with the typical GERD symptoms of heartburn and regurgitation, yet do not have endoscopic evidence of esophagitis. The primary goals of managing symptomatic GERD are to control symptoms and improve quality of life. A clinical assessment of the GERD patient can identify important clinical features, such as atypical and extraesophageal symptoms for which acid-suppressive agents tend to be less effective. Performing an endoscopy can further identify the patient as having nonerosive reflux disease, erosive esophagitis, or Barrett\\'s esophagus-diagnoses which can help determine treatment but may not prove predictive of therapeutic response. Determining acid exposure through pH testing can predict therapeutic response, with those revealing an abnormal acid exposure time being more responsive to acid-suppressive therapy. However, the performance of an endoscopy and pH testing on each patient is clearly not practical. Whereas the natural history of symptomatic GERD is still largely undefined, acid-suppressive therapy appears to be the best approach available for both the short-term and long-term management of this disease.

PARALLEL MODELS OF ASSESSMENT: INFANT MENTAL HEALTH AND THERAPEUTIC ASSESSMENT MODELS INTERSECT THROUGH EARLY CHILDHOOD CASE STUDIES.

Science.gov (United States)

Gart, Natalie; Zamora, Irina; Williams, Marian E

2016-07-01

Therapeutic Assessment (TA; S.E. Finn & M.E. Tonsager, 1997; J.D. Smith, 2010) is a collaborative, semistructured model that encourages self-discovery and meaning-making through the use of assessment as an intervention approach. This model shares core strategies with infant mental health assessment, including close collaboration with parents and caregivers, active participation of the family, a focus on developing new family stories and increasing parents' understanding of their child, and reducing isolation and increasing hope through the assessment process. The intersection of these two theoretical approaches is explored, using case studies of three infants/young children and their families to illustrate the application of TA to infant mental health. The case of an 18-month-old girl whose parents fear that she has bipolar disorder illustrates the core principles of the TA model, highlighting the use of assessment intervention sessions and the clinical approach to preparing assessment feedback. The second case follows an infant with a rare genetic syndrome from ages 2 to 24 months, focusing on the assessor-parent relationship and the importance of a developmental perspective. Finally, assessment of a 3-year-old boy illustrates the development and use of a fable as a tool to provide feedback to a young child about assessment findings and recommendations. © 2016 Michigan Association for Infant Mental Health.

Unresolved Questions Concerning the Effectiveness of Psychological Assessment as a Therapeutic Intervention: Comment on Poston and Hanson (2010)

Science.gov (United States)

Lilienfeld, Scott O.; Garb, Howard N.; Wood, James M.

2011-01-01

In a recent article in this journal, Poston and Hanson (2010) reported a meta-analysis of 17 studies on the use of psychological assessment as a therapeutic intervention (PATI) and concluded that "psychological assessment procedures--when combined with personalized, collaborative, and highly involving test feedback--have positive, clinically…

Assessment of Bridelia ferruginea benth for its therapeutic potential ...

African Journals Online (AJOL)

McRoy

onset or first recognition during pregnancy. ... ferruginea in gestational diabetes by assessing the anti-glycaemic effects of ... oral administration of aqueous extracts of B. ferruginea to pregnant albino rats. Key words: Gestational diabetes, pregnancy-induced diabetes, hypoglycaemic, glycaemic response, glucose tolerance.

Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

Science.gov (United States)

Guidry, Erin N; Farand, Julie; Soheili, Arash; Parish, Craig A; Kevin, Nancy J; Pipik, Brenda; Calati, Kathleen B; Ikemoto, Nori; Waldman, Jacob H; Latham, Andrew H; Howell, Bonnie J; Leone, Anthony; Garbaccio, Robert M; Barrett, Stephanie E; Parmar, Rubina Giare; Truong, Quang T; Mao, Bing; Davies, Ian W; Colletti, Steven L; Sepp-Lorenzino, Laura

2014-02-19

Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents in vitro and in vivo; however, most suffer from cytotoxicity due in part to a lack of selectivity for endosomal versus cell membrane lysis. For polymer based carriers to move beyond the laboratory and into the clinic, it is critical to find carriers that are not only efficacious, but also have margins that are clinically relevant. In this paper we report three distinct categories of polymer conjugates that improve the selectivity of endosomal membrane lysis by relying on the change in pH associated with endosomal trafficking, including incorporation of low pKa heterocycles, acid cleavable amino side chains, or carboxylic acid pH sensitive charge switches. Additionally, we determine the therapeutic index of our polymer conjugates in vivo and demonstrate that the incorporation of pH responsive elements dramatically expands the therapeutic index to 10-15, beyond that of the therapeutic index (less than 3), for polymer conjugates previously reported.

FDG PET/CT in initial staging and early response to chemotherapy assessment of paediatric rhabdomyosarcomas

International Nuclear Information System (INIS)

Eugene, T.; Ansquer, C.; Oudoux, A.; Carlier, T.; Kraeber-Bodere, T.; Bodet-Milin, C.; Corradini, N.; Thomas, C.; Dupas, B.

2010-01-01

Purpose: The objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma. Patients and methods: Prior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years). Results: PET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years). Conclusion: This study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment. (authors)

Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics.

Science.gov (United States)

Gupta, Shalini; Devanarayan, Viswanath; Finco, Deborah; Gunn, George R; Kirshner, Susan; Richards, Susan; Rup, Bonita; Song, An; Subramanyam, Meena

2011-07-15

The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors. Copyright © 2011 Elsevier B.V. All rights reserved.

QUANTITATIVE EVALUATION OF THERAPEUTIC RESPONSE BY FDG PET-CT IN METASTATIC BREAST CANCER

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Dorothée eGOULON

2016-05-01

Full Text Available Purpose To assess the therapeutic response for metastatic breast cancer with 18F-FDG PET, this retrospective study aims to compare the performance of 6 different metabolic metrics with PERCIST, PERCIST with optimal thresholds and an image-based parametric approach.MethodsThirty six metastatic breast cancer patients underwent 128 PET scans and 123 lesions were identified. In a per-lesion and per-patient analysis, the performance of 6 metrics: SUVmax (maximum Standardized Uptake Value, SUVpeak, SAM (Standardized Added Metabolic activity, SUVmean, metabolic volume (MV, TLG (total lesion glycolysis and a parametric approach (SULTAN were determined and compared to the gold standard (defined by clinical assessment and biological and conventional imaging according RECIST 1.1. The evaluation was performed using PERCIST thresholds (for per-patient analysis only and optimal thresholds (determined by the Youden criterion from the Receiver Operating Characteristic curves.ResultsIn the per-lesion analysis, 210 pairs of lesion evolutions were studied. Using the optimal thresholds, SUVmax, SUVpeak, SUVmean, SAM and TLG were significantly correlated with the gold standard. SUVmax, SUVpeak and SUVmean reached the best sensitivity (91 %, 88 % and 83% respectively, specificity (93%, 95% and 97% respectively and negative predictive value (NPV, 90%, 88% and 83% respectively. For the per-patient analysis, 79 pairs of PET were studied. The optimal thresholds compared to the PERCIST threshold did not improve performance for SUVmax, SUVpeak and SUVmean. Only SUVmax, SUVpeak, SUVmean and TLG were correlated with the gold standard. SULTAN also performed equally: 83% sensitivity, 88% specificity and NPV 86%.ConclusionsThis study showed that SUVmax and SUVpeak were the best parameters for PET evaluation of metastatic breast cancer lesions. Parametric imaging is helpful in evaluating serial studies.

Strategic characterization of anti-drug antibody responses for the assessment of clinical relevance and impact.

Science.gov (United States)

Tatarewicz, Suzanna M; Mytych, Daniel T; Manning, Marta Starcevic; Swanson, Steven J; Moxness, Michael S; Chirmule, Narendra

2014-06-01

All therapeutic proteins have the potential to induce anti-drug antibodies (ADA). Clinically relevant ADA can impact efficacy and/or safety of a biological therapeutic. Immunogenicity assessment strategy evaluates binding and neutralizing ADA, and the need for additional characterization (e.g., epitope, titer and so on) is determined using a risk-based approach. The choice of characterization assays depends on the type, application and immunogenicity of the therapeutic. ADA characterization can impact the interpretation of the risk profile of a given therapeutic, and offers insight into opportunities for risk mitigation and management. This article describes common ADA characterization methods. Strategic assessment and characterization of clinically relevant ADA are discussed, in order to support clinical options for safe and effective patient care and disease management.

A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice.

Science.gov (United States)

Buchmann, Pascale; Dembek, Claudia; Kuklick, Larissa; Jäger, Clemens; Tedjokusumo, Raindy; von Freyend, Miriam John; Drebber, Uta; Janowicz, Zbigniew; Melber, Karl; Protzer, Ulrike

2013-02-06

Therapeutic vaccines are currently being developed for chronic hepatitis B and C. As an alternative to long-term antiviral treatment or to support only partially effective therapy, they should activate the patient's immune system effectively to fight and finally control the virus. A paradigm of therapeutic vaccination is the potent induction of T-cell responses against key viral antigens - besides activation of a humoral immune response. We have evaluated the potential of a novel vaccine formulation comprising particulate hepatitis B surface (HBsAg) and core antigen (HBcAg), and the saponin-based ISCOMATRIX™ adjuvant for its ability to stimulate T and B cell responses in C57BL/6 mice and its ability to break tolerance in syngeneic HBV transgenic (HBVtg) mice. In C57BL/6 mice, the vaccine induced multifunctional HBsAg- and HBcAg-specific CD8+ T cells detected by staining for IFNγ, TNFα and IL-2, as well as high antibody titers against both antigens. Vaccination of HBVtg animals induced potent HBsAg- and HBcAg-specific CD8+ T-cell responses in spleens and HBcAg-specific CD8+ T-cell responses in livers as well as anti-HBs seroconversion two weeks post injection. Vaccination further reduced HBcAg expression in livers of HBVtg mice without causing liver damage. In summary, this study demonstrates therapeutic efficacy of a novel vaccine formulation in a mouse model of immunotolerant, chronic HBV infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Predictive and therapeutic markers in ovarian cancer

Science.gov (United States)

Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

2013-03-26

Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

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.

Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI

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Balducci Anthony

2012-06-01

Full Text Available Abstract Background Non-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA, and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by 19F MRI. With no 19F background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present. Methods Collagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using 19F MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and 19F MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of the PFC contrast agent and 19F MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28. Results Quantification of 19F signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in 19F signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in 19F signal was observed in animals receiving treatment which resulted in clinical resolution of disease. Conclusion These results indicate that 19F MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of 19F MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory

Therapeutic applications of histone deacetylase inhibitors in sarcoma.

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Tang, Fan; Choy, Edwin; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

2017-09-01

Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis. Importantly, preclinical studies have revealed that HDIs can not only sensitize sarcomas to chemotherapy and radiotherapy, but also increase treatment responses when combined with other chemotherapeutic drugs. Several phase I and II clinical trials have been conducted to assess the efficacy of HDIs either as monotherapy or in combination with standard chemotherapeutic agents or targeted therapeutic drugs for sarcomas. Combination regimen for sarcomas appear to be more promising than monotherapy when using HDIs. This review summarizes our current understanding and therapeutic applications of HDIs in sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disentangling the change-alliance relationship: Observational assessment of the therapeutic alliance during change and stuck episodes.

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Mellado, Augusto; Suárez, Nicolás; Altimir, Carolina; Martínez, Claudio; Pérez, Janet; Krause, Mariane; Horvath, Adam

2017-09-01

The therapeutic alliance is considered the most robust process variable associated with positive therapeutic outcome in a variety of psychotherapeutic models [Alexander, L. B., & Luborsky, L. (1986). The Penn Helping Alliance Scales. In L. S. Greenberg & W. M. Pinsoff (Eds.), The psychotherapeutic process: A research handbook (pp. 325-356). New York: Guilford Press; Horvath, A. O., Gaston, L., & Luborsky, L. (1993). The alliance as predictor of benefits of counseling and therapy. In N. Miller, L. Luborsky, J. Barber, & J. P. Docherty (Eds.), Psychodynamic treatment research: A handbook for clinical practice (pp. 247-274). New York, NY: Basic Books; Horvath, A. O., Del Re, A. C., Flückiger, C., & Symonds, D. (2011). Alliance in individual psychotherapy. Psychotherapy, 48, 9-16; Orlinky, D., Grawe, K., & Parks, B. (1994). Process and outcome in psychotherapy: Noch einmal. In A. Bergin & J. S. Garfield (Eds.), Handbook of psychotherapy and behaviour change (4th ed., pp. 270-378). New York, NY: Wiley and Sons]. The relationship between alliance and outcome has traditionally been studied based on measures that assess these therapy factors at a global level. However, the specific variations of the alliance process and their association with therapy segments that are relevant for change have not yet been fully examined. The present study examines the variations in the therapeutic alliance in 73 significant in-session events: 35 change and 38 stuck episodes identified through the observation of 14 short-term therapies of different theoretical orientations. Variations in the alliance were assessed using the VTAS-SF [Shelef, K., & Diamond, G. (2008). Short form of the revised Vanderbilt Therapeutic Alliance Scale: Development, reliability, and validity. Psychotherapy Research, 18, 433-443]. Nested analyses (HLM) indicate a statistically significant better quality of the alliance during change episodes.

Outcome of Gaucher Disease in India: Lessons from Prevalent Diagnostic and Therapeutic Practices.

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Muranjan, Mamta; Patil, Smita

2016-08-08

To study disease severity and response to enzyme replacement therapy in Gaucher disease. Updated data was captured from records of 37 patients (35 reported previously) with confirmed diagnosis of Gaucher disease from January 1995 through December 2011 (31, 83.8 %) and prospectively from January 2012 through June 2013 (6, 16.2 %). Severity of manifestations was determined by Gaucher disease Severity Score Index. Response to enzyme replacement therapy was assessed in terms of attainment of therapeutic goals. Moderate to severe manifestations (domain score of > 2) were observed in treated patients at baseline (83%, 58%, 66% and 25% for anemia, thrombocytopenia, hepatomegaly and leucopenia, respectively and 100% for splenomegaly and elevated plasma chitotriosidase). None of the 11 patients treated with synthetic enzyme (average annual dose 23 to 53 units/kg) attained all therapeutic goals in the recommended time frame, particularly the visceral, skeletal and growth domains. Early onset of moderate to severe disease in Indian patients mandates early therapy with optimum doses to ensure attainment of all recommended therapeutic goals.

Systematic Identification and Assessment of Therapeutic Targets for Breast Cancer Based on Genome-Wide RNA Interference Transcriptomes

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Yang Liu

2017-02-01

Full Text Available With accumulating public omics data, great efforts have been made to characterize the genetic heterogeneity of breast cancer. However, identifying novel targets and selecting the best from the sizeable lists of candidate targets is still a key challenge for targeted therapy, largely owing to the lack of economical, efficient and systematic discovery and assessment to prioritize potential therapeutic targets. Here, we describe an approach that combines the computational evaluation and objective, multifaceted assessment to systematically identify and prioritize targets for biological validation and therapeutic exploration. We first establish the reference gene expression profiles from breast cancer cell line MCF7 upon genome-wide RNA interference (RNAi of a total of 3689 genes, and the breast cancer query signatures using RNA-seq data generated from tissue samples of clinical breast cancer patients in the Cancer Genome Atlas (TCGA. Based on gene set enrichment analysis, we identified a set of 510 genes that when knocked down could significantly reverse the transcriptome of breast cancer state. We then perform multifaceted assessment to analyze the gene set to prioritize potential targets for gene therapy. We also propose drug repurposing opportunities and identify potentially druggable proteins that have been poorly explored with regard to the discovery of small-molecule modulators. Finally, we obtained a small list of candidate therapeutic targets for four major breast cancer subtypes, i.e., luminal A, luminal B, HER2+ and triple negative breast cancer. This RNAi transcriptome-based approach can be a helpful paradigm for relevant researches to identify and prioritize candidate targets for experimental validation.

The Role of Diffusion-Weighted Imaging (DWI in Locoregional Therapy Outcome Prediction and Response Assessment for Hepatocellular Carcinoma (HCC: The New Era of Functional Imaging Biomarkers

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Johannes M. Ludwig

2015-11-01

Full Text Available Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC. Current response assessment is mainly based on: (1 changes in size, which is at times unreliable and lag behind the result of therapy; and (2 contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI techniques, such as diffusion-weighted imaging (DWI have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement, which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies.

TU-G-BRA-06: PET-Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

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Dalah, E; Tai, A; Oshima, K; Hall, W; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2015-06-15

Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3) for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment

Diffusion-weighted magnetic resonance imaging: biomarker for treatment response in oncology

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Maria Luiza Testa

2013-06-01

Full Text Available The authors report a case where a quantitative assessment of the apparent diffusion coefficient (ADC of liver metastasis in a patient undergoing chemotherapy has shown to be an effective early marker for predicting therapeutic response, anticipating changes in tumor size. A lesion with lower initial ADC value and early increase in such value in the course of the treatment tends to present a better therapeutic response.

[End therapeutic nihilism towards COPD].

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Juergens, Uwe R

2007-03-15

Prevention of COPD requires appropriate patient education, especially of adolescents, as well as the establishment of an effective national health policy. The new GOLD guidelines represent the current standard of knowledge on the management of chronic, progressive, obstructive pulmonary diseases. It points out that COPD is avoidable and treatable,and hence, there is no reason for therapeutic nihilism. Chronic bronchitis preceding a progressive respiratory obstruction cannot be improved with the presently available respiratory therapeutics. For this reason, therapeutic measures concentrate on the avoidance of exacerbations, which are primarily responsible for the severity of the course of COPD.

Toxicological perspectives of inhaled therapeutics and nanoparticles.

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Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Therapeutic cloning in individual parkinsonian mice

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Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

2009-01-01

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

Coupled multiple-response versus free-response conceptual assessment: An example from upper-division physics

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Bethany R. Wilcox

2014-10-01

Full Text Available Free-response research-based assessments, like the Colorado Upper-division Electrostatics Diagnostic (CUE, provide rich, fine-grained information about students’ reasoning. However, because of the difficulties inherent in scoring these assessments, the majority of the large-scale conceptual assessments in physics are multiple choice. To increase the scalability and usability of the CUE, we set out to create a new version of the assessment that preserves the insights afforded by a free-response format while exploiting the logistical advantages of a multiple-choice assessment. We used our extensive database of responses to the free-response CUE to construct distractors for a new version where students can select multiple responses and receive partial credit based on the accuracy and consistency of their selections. Here, we describe the development of this modified CUE format, which we call coupled multiple response (CMR, and present data from direct comparisons of both versions. We find that the two formats have the same average score and perform similarly on multiple measures of validity and reliability, suggesting that the new version is a potentially viable alternative to the original CUE for the purpose of large-scale research-based assessment. We also compare the details of student responses on each of the two versions. While the CMR version does not capture the full scope of potential student responses, nearly three-quarters of our students’ responses to the free-response version contained one or more elements that matched options provided on the CMR version.

Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription.

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Hoffmann, Aswin L; Huizenga, Henk; Kaanders, Johannes H A M

2013-03-07

In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians' or patients' choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels.

Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

International Nuclear Information System (INIS)

Hoffmann, Aswin L; Huizenga, Henk; Kaanders, Johannes HAM

2013-01-01

In current practice, patients scheduled for radiotherapy are treated according to ‘rigid’ protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians’ or patients’ choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels

Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma

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Qin, Lei [Dana-Farber Cancer Institute, Department of Imaging, Boston, MA (United States); Harvard Medical School, Department of Radiology, Boston, MA (United States); Li, Xiang; Qu, Jinrong [Affiliated Cancer Hospital of Zhengzhou University, Department of Radiology, Zhengzhou, Henan (China); Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Stroiney, Amanda [Dana-Farber Cancer Institute, Department of Imaging, Boston, MA (United States); Northeastern University, Department of Behavioral Neuroscience, College of Sciences, Boston, MA (United States); Helgager, Jeffrey [Brigham and Women' s Hospital, Department of Pathology, Boston, MA (United States); Reardon, David A. [Dana-Farber Cancer Institute, CenterforNeuro-Oncology, Boston, MA (United States); Department of Medicine, Boston, MA (United States); Young, Geoffrey S. [Harvard Medical School, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States)

2017-02-15

We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not. A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps. Intermediate ADC (IADC) VOI represented voxels within the FLAIR VOI having ADC in the range of highly cellular tumor (0.7-1.1 x 10{sup -3} mm{sup 2}/s) (IADC VOI). Therapeutic benefit was determined by tissue pathology and survival on trial. IADC VOI, pGdT1 VOI, FLAIR VOI, and RANO assessment results were correlated with patient benefit. Five patients were deemed to have received therapeutic benefit and the other five patients did not. The average time on trial for the benefit group was 194 days, as compared to 81 days for the no benefit group. IADC VOI correlated well with the presence or absence of clinical benefit in 10 patients. Furthermore, pGd VOI, FLAIR VOI, and RANO assessment correlated less well with response. MRI reveals an initial increase in volumes of abnormal tissue with contrast enhancement, edema, and intermediate ADC suggesting hypercellularity within the first 0-6 months of immunotherapy. Subsequent stabilization and improvement in IADC VOI appear to better predict ultimate therapeutic benefit from these agents than conventional imaging. (orig.)

Emotional Responses to Suicidal Patients: Factor Structure, Construct, and Predictive Validity of the Therapist Response Questionnaire-Suicide Form

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Shira Barzilay

2018-04-01

Full Text Available BackgroundMental health professionals have a pivotal role in suicide prevention. However, they also often have intense emotional responses, or countertransference, during encounters with suicidal patients. Previous studies of the Therapist Response Questionnaire-Suicide Form (TRQ-SF, a brief novel measure aimed at probing a distinct set of suicide-related emotional responses to patients found it to be predictive of near-term suicidal behavior among high suicide-risk inpatients. The purpose of this study was to validate the TRQ-SF in a general outpatient clinic setting.MethodsAdult psychiatric outpatients (N = 346 and their treating mental health professionals (N = 48 completed self-report assessments following their first clinic meeting. Clinician measures included the TRQ-SF, general emotional states and traits, therapeutic alliance, and assessment of patient suicide risk. Patient suicidal outcomes and symptom severity were assessed at intake and one-month follow-up. Following confirmatory factor analysis of the TRQ-SF, factor scores were examined for relationships with clinician and patient measures and suicidal outcomes.ResultsFactor analysis of the TRQ-SF confirmed three dimensions: (1 affiliation, (2 distress, and (3 hope. The three factors also loaded onto a single general factor of negative emotional response toward the patient that demonstrated good internal reliability. The TRQ-SF scores were associated with measures of clinician state anger and anxiety and therapeutic alliance, independently of clinician personality traits after controlling for the state- and patient-specific measures. The total score and three subscales were associated in both concurrent and predictive ways with patient suicidal outcomes, depression severity, and clinicians’ judgment of patient suicide risk, but not with global symptom severity, thus indicating specifically suicide-related responses.ConclusionThe TRQ-SF is a brief and reliable measure with a

Emotional Responses to Suicidal Patients: Factor Structure, Construct, and Predictive Validity of the Therapist Response Questionnaire-Suicide Form.

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Barzilay, Shira; Yaseen, Zimri S; Hawes, Mariah; Gorman, Bernard; Altman, Rachel; Foster, Adriana; Apter, Alan; Rosenfield, Paul; Galynker, Igor

2018-01-01

Mental health professionals have a pivotal role in suicide prevention. However, they also often have intense emotional responses, or countertransference, during encounters with suicidal patients. Previous studies of the Therapist Response Questionnaire-Suicide Form (TRQ-SF), a brief novel measure aimed at probing a distinct set of suicide-related emotional responses to patients found it to be predictive of near-term suicidal behavior among high suicide-risk inpatients. The purpose of this study was to validate the TRQ-SF in a general outpatient clinic setting. Adult psychiatric outpatients ( N  = 346) and their treating mental health professionals ( N  = 48) completed self-report assessments following their first clinic meeting. Clinician measures included the TRQ-SF, general emotional states and traits, therapeutic alliance, and assessment of patient suicide risk. Patient suicidal outcomes and symptom severity were assessed at intake and one-month follow-up. Following confirmatory factor analysis of the TRQ-SF, factor scores were examined for relationships with clinician and patient measures and suicidal outcomes. Factor analysis of the TRQ-SF confirmed three dimensions: (1) affiliation, (2) distress, and (3) hope. The three factors also loaded onto a single general factor of negative emotional response toward the patient that demonstrated good internal reliability. The TRQ-SF scores were associated with measures of clinician state anger and anxiety and therapeutic alliance, independently of clinician personality traits after controlling for the state- and patient-specific measures. The total score and three subscales were associated in both concurrent and predictive ways with patient suicidal outcomes, depression severity, and clinicians' judgment of patient suicide risk, but not with global symptom severity, thus indicating specifically suicide-related responses. The TRQ-SF is a brief and reliable measure with a 3-factor structure. It demonstrates

Recommendations of the Oligonucleotide Safety Working Group's Formulated Oligonucleotide Subcommittee for the Safety Assessment of Formulated Oligonucleotide-Based Therapeutics.

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Marlowe, Jennifer L; Akopian, Violetta; Karmali, Priya; Kornbrust, Douglas; Lockridge, Jennifer; Semple, Sean

2017-08-01

The use of lipid formulations has greatly improved the ability to effectively deliver oligonucleotides and has been instrumental in the rapid expansion of therapeutic development programs using oligonucleotide drugs. However, the development of such complex multicomponent therapeutics requires the implementation of unique, scientifically sound approaches to the nonclinical development of these drugs, based upon a hybrid of knowledge and experiences drawn from small molecule, protein, and oligonucleotide therapeutic drug development. The relative paucity of directly applicable regulatory guidance documents for oligonucleotide therapeutics in general has resulted in the generation of multiple white papers from oligonucleotide drug development experts and members of the Oligonucleotide Safety Working Group (OSWG). The members of the Formulated Oligonucleotide Subcommittee of the OSWG have utilized their collective experience working with a variety of formulations and their associated oligonucleotide payloads, as well as their insights into regulatory considerations and expectations, to generate a series of consensus recommendations for the pharmacokinetic characterization and nonclinical safety assessment of this unique class of therapeutics. It should be noted that the focus of Subcommittee discussions was on lipid nanoparticle and other types of particulate formulations of therapeutic oligonucleotides and not on conjugates or other types of modifications of oligonucleotide structure intended to facilitate delivery.

Item Response Theory for Peer Assessment

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Uto, Masaki; Ueno, Maomi

2016-01-01

As an assessment method based on a constructivist approach, peer assessment has become popular in recent years. However, in peer assessment, a problem remains that reliability depends on the rater characteristics. For this reason, some item response models that incorporate rater parameters have been proposed. Those models are expected to improve…

MR imaging of metabolic white matter diseases: Therapeutic response

International Nuclear Information System (INIS)

Gebarski, S.S.; Allen, R.

1987-01-01

In metabolic diseases affecting the brain, MR imaging abnormalities include white-matter signal aberrations suggesting myelination delay, dysmyelination and demyelination, pathologic iron storage, and finally, loss of substance usually in a nonspecific pattern. The authors suggest that MR imaging may have therapeutic implications: (1) classic galactosemia - white-matter signal aberration became normal after dietary therapy; (2) phenylketonuria - age- and sex-matched treated and nontreated adolescents showed marked differences in brain volume, with the treated patient's volume nearly normal; (3) maple syrup urine disease - gross white-matter signal aberration became nearly normal after dietary therapy; and (4) hyperglycinemia - relentless progression of white-matter signal aberration and loss of brain substance despite therapy. These data suggest that brain MR imaging may provide a therapeutic index in certain metabolic diseases

Obsessive-compulsive disorder comorbidity: clinical assessment and therapeutic implications

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Stefano ePallanti

2011-12-01

Full Text Available Obsessive-compulsive disorder (OCD is a neuropsychiatric disorder affecting approximately 1-3% of the population. OCD is probably an etiologically heterogeneous condition. Individuals with OCD frequently have additional psychiatric disorders concomitantly or at some time during their lifetime. Recently, some authors proposed an OCD sub-classification based on co-morbidity. An important issue in assessing comorbidity is the fact that the non-response to treatment often involves the presence of comorbid conditions. Non-responsive patients are more likely to meet criteria for comorbid axis I or axis II disorders and the presence of a specific comorbid condition could be a distinguishing feature in OCD, with influence on the treatment adequacy and outcome.

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT

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Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe (Japan); Fujisawa, Yasuko [Toshiba Medical Systems Corporation, Otawara (Japan); Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Sugihara, Naoki [Toshiba Medical Systems Corporation, Otawara (Japan); Yoshikawa, Takeshi [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe (Japan)

2017-01-15

Purpose: To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Materials and methods: Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR + PR) and 2) stable or progressive disease (SD + PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV{sub max}, and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. Results: The step-wise regression test showed that therapeutic effect (r{sup 2} = 0.63, p = 0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV{sub max}. Mean overall survival showed a significant difference for total perfusion (p = 0.003) and systemic arterial perfusion (p = 0.04). Conclusion: Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Fujisawa, Yasuko; Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2017-01-01

Purpose: To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Materials and methods: Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR + PR) and 2) stable or progressive disease (SD + PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. Results: The step-wise regression test showed that therapeutic effect (r 2 = 0.63, p = 0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV max . Mean overall survival showed a significant difference for total perfusion (p = 0.003) and systemic arterial perfusion (p = 0.04). Conclusion: Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT.

Science.gov (United States)

Ohno, Yoshiharu; Fujisawa, Yasuko; Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2017-01-01

To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR+PR) and 2) stable or progressive disease (SD+PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. The step-wise regression test showed that therapeutic effect (r 2 =0.63, p=0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV max . Mean overall survival showed a significant difference for total perfusion (p=0.003) and systemic arterial perfusion (p=0.04). Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial.

Science.gov (United States)

Johnston, Celeste; Campbell-Yeo, Marsha; Rich, Bonnie; Whitley, Julie; Filion, Francoise; Cogan, Jennifer; Walker, Claire-Dominique

2013-09-01

Preterm neonates below 30 weeks' gestational age undergo numerous painful procedures. Many management approaches are not appropriate for this population. Therapeutic Touch, an alternative approach based on the theory of energy medicine, has been shown to promote physiological stability in preterm neonates and reduce pain in some adult studies. The objective was to determine whether Therapeutic Touch is efficacious in decreasing pain in preterm neonates. Infants Touch (n = 27) with infant behind curtains, leaving the curtained area for the heel lance, performed by another. In the sham condition (n = 28), the therapist stood by the incubator with hands by her side. The Premature Infant Pain Profile was used for pain response and time for heart rate to return to baseline for recovery. Heart rate variability and stress response were secondary outcomes. There were no group differences in any of the outcomes. Mean Premature Infant Pain Profile scores across 2 minutes of heel lance procedure in 30-second blocks ranged from 7.92 to 8.98 in the Therapeutic Touch group and 7.64 to 8.46 in the sham group. Therapeutic Touch given immediately before and after heel lance has no comforting effect in preterm neonates. Other effective strategies involving actual touch should be considered.

Physiological and Emotional Responses of Disabled Children to Therapeutic Clowns: A Pilot Study

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Shauna Kingsnorth

2011-01-01

Full Text Available This pilot study examined the effects of Therapeutic Clowning on inpatients in a pediatric rehabilitation hospital. Ten disabled children with varied physical and verbal expressive abilities participated in all or portions of the data collection protocol. Employing a mixed-method, single-subject ABAB study design, measures of physiological arousal, emotion and behavior were obtained from eight children under two conditions—television exposure and therapeutic clown interventions. Four peripheral autonomic nervous system (ANS signals were recorded as measures of physiological arousal; these signals were analyzed with respect to measures of emotion (verbal self reports of mood and behavior (facial expressions and vocalizations. Semistructured interviews were completed with verbally expressive children (n = 7 and nurses of participating children (n = 13. Significant differences among children were found in response to the clown intervention relative to television exposure. Physiologically, changes in ANS signals occurred either more frequently or in different patterns. Emotionally, children's (self and nurses' (observed reports of mood were elevated positively. Behaviorally, children exhibited more positive and fewer negative facial expressions and vocalizations of emotion during the clown intervention. Content and themes extracted from the interviews corroborated these findings. The results suggest that this popular psychosocial intervention has a direct and positive impact on hospitalized children. This pilot study contributes to the current understanding of the importance of alternative approaches in promoting well-being within healthcare settings.

Therapeutic monoclonal antibody N-glycosylation - Structure, function and therapeutic potential.

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Cymer, Florian; Beck, Hermann; Rohde, Adelheid; Reusch, Dietmar

2018-03-01

Therapeutic antibodies (IgG-type) contain several post-translational modifications (PTMs) whereby introducing a large heterogeneity, both structural and functional, into this class of therapeutics. Of these modifications, glycosylation in the fragment crystallizable (Fc) region is the most heterogeneous PTM, which can affect the stability of the molecule and interactions with Fc-receptors in vivo. Hence, the glycoform distribution can affect the mode of action and have implications for bioactivity, safety and efficacy of the drug. Main topics of the manuscript include: What factors influence the (Fc) glycan pattern in therapeutic antibodies and how can these glycans be characterized? How does structure of the Fc-glycan relate to function and what methods are available to characterize those functions? Although heterogeneous in their scope, the different sections are intended to combine current knowledge on structure-function correlations of IgG glycan structures with regard to Fc (effector) functions, as well as basic aspects and methodologies for their assessment. Copyright © 2017. Published by Elsevier Ltd.

[Therapeutic goals and indications: psychotherapy patient's self-reports during diagnostic assessment].

Science.gov (United States)

Faller, H

2000-07-01

Although individual therapeutic goals are considered to be important factors motivating patients to engage in therapeutic work, they have gained little attention in empirical research. In the present study, patients were given a questionnaire containing 24 therapeutic goals which could be rated according to their subjective relevance on a 5-point scale. N = 152 patients (mean age 34.5 years, 59.2% female) who presented at a university psychotherapy outpatient department to attend a diagnostic interview participated in the study. "To solve my problems" and "to get relief from my complaints" were the goals that were rated as most important. Goals pertaining to mental health such as more contentness and calmness, self-assertion and insight scored high, too. Three rational scales were constructed: 1. insight, 2. sociability, and 3. self-assertion. These scales were correlated with both patients' causal attributions and therapy expectations in plausible ways. However, the general strength of intercorrelations point of the conception patients goals were not very succinct at the time of the intake interview. Indication groups regarding specific therapeutic measures did not differ with respect to therapy goals. Only the general decision whether to recommend a psychotherapeutic intervention or not seemed to be influenced by patients' therapeutic aims.

Psychedelics and hypnosis: Commonalities and therapeutic implications.

Science.gov (United States)

Lemercier, Clément E; Terhune, Devin B

2018-06-01

Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention. Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy. We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes. Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.

Assessing therapeutic relevance of biologically interesting, ampholytic substances based on their physicochemical and spectral characteristics with chemometric tools

Science.gov (United States)

Judycka, U.; Jagiello, K.; Bober, L.; Błażejowski, J.; Puzyn, T.

2018-06-01

Chemometric tools were applied to investigate the biological behaviour of ampholytic substances in relation to their physicochemical and spectral properties. Results of the Principal Component Analysis suggest that size of molecules and their electronic and spectral characteristics are the key properties required to predict therapeutic relevance of the compounds examined. These properties were used for developing the structure-activity classification model. The classification model allows assessing the therapeutic behaviour of ampholytic substances on the basis of solely values of descriptors that can be obtained computationally. Thus, the prediction is possible without necessity of carrying out time-consuming and expensive laboratory tests, which is its main advantage.

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.

Plasma C-type natriuretic peptide as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome.

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Jing Lin

Full Text Available POTS is a global public-health disease, but predictor for therapeutic response to metoprolol in children with POTS is lacking. This study was designed to investigate predictive value of plasma C-type natriuretic peptide (CNP in the therapeutic efficacy of metoprolol on postural tachycardia syndrome (POTS in children. Totally 34 children with POTS and 27 healthy children were included in the study. The head-up test or head-up tilt test was used to check heart rate and blood pressure from supine to upright in subjects. A double antibody (competitive sandwich immunoluminometric assay was used to detect plasma CNP. Metoprolol was used to treat children with POTS. The difference in plasma concentrations of CNP between responders and non-responders was compared. An ROC curve was used to analyze plasma CNP to predict efficacy of metoprolol on POTS in children. Plasma CNP in children with POTS was significantly higher than that of healthy children [(51.9 ± 31.4 vs. (25.1 ± 19.1 pg/ml, P 32.55 pg/ml yielded a sensitivity of 95.8% and specificity of 70% in predicting therapeutic efficacy of metoprolol on POTS children. Plasma CNP might serve as a useful predictor for the therapeutic efficacy of metoprolol on POTS in children.

Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance

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Arnold Bakker

2015-01-01

detected by fMRI in individuals with aMCI and therapeutic intervention using fMRI to detect target engagement in response to treatment.

Use of informed consent with therapeutic paradox.

Science.gov (United States)

Farkas, M M

1992-01-01

Debate persists in the literature and among clinicians about the ethical appropriateness of paradoxical interventions. It has been suggested that informed consent with therapeutic paradox would alleviate ethical concerns of deception, manipulation, harm to the client, and withholding of information from the client in therapy. The purpose of this study was to explore health care consumer reactions to the benefits and risks of therapeutic paradox as stated in a consent for treatment form. The study explored the responses of 32 medical patients to a hypothetical consent for treatment form for therapeutic paradox. Data were collected in a brief semistructured interview after subjects read the hypothetical consent form. Utilizing a case study, the investigator then offered an example of a successful paradoxical intervention and additional subject comments were solicited. Content analysis of the responses was made. Health care consumers had mixed responses to the consent form. While the consent form served as an obstacle for some consumers, many were willing to sign the consent form and accept treatment even though they had internal reservations and questions. Appropriateness of the consent form format is discussed.

99mTc-sestamibi muscle scintigraphy to assess the response to neuromuscular electrical stimulation of normal quadriceps femoris muscle

International Nuclear Information System (INIS)

Pekindil, Y.; Sarikaya, A.; Birtane, M.; Pekindil, G.; Salan, A.

2001-01-01

Neuromuscular electrical stimulation (NMES) is widely used for improving muscle strength by simultaneous contraction in the prevention of muscle atrophy. Although there exist many clinical methods for evaluating the therapeutic response of muscles, 99m Tc-sestamibi which is a skeletal muscle perfusion and metabolism agent has not previously been used for this purpose. The aim of our work was to ascertain whether 99m Tc-sestamibi muscle scintigraphy is useful in the monitoring of therapeutic response to NMES in healthy women. The study included 16 women aged between 21 and 45, with a mean age of 32.7±6.4. Both quadriceps femoris muscles (QFM) of each patient were studied. After randomization to remove the effect of the dominant side, one QFM of each patient was subjected to the NMES procedure for a period of 20 days. NMES was performed with an alternating biphasic rectangular current, from a computed electrical stimulator daily for 23 minutes. After measurement of skinfold thickness over the thigh, pre- and post-NMES girth measurements were assessed in centimeters. Sixty minutes after injections of 555 MBq 99m Tc-sestamibi, static images of the thigh were obtained for 5 minutes. The thigh-to-knee uptake ratio was calculated by semiquantitative analysis and normalized to body surface area (NUR=normalized uptake ratio). The difference between the pre and post NMES NUR values was significant (1.76±0.31 versus 2.25±0.38, p=0.0000). The percentage (%) increase in NUR values also well correlated with the % increase in thigh girth measurements (r=0.89, p=0.0000). These results indicated that 99m Tc-sestamibi muscle scintigraphy as a new tool may be useful in evaluating therapeutic response to NMES. (author)

Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease

International Nuclear Information System (INIS)

Barton, N.W.; Furbish, F.S.; Murray, G.J.; Garfield, M.; Brady, R.O.

1990-01-01

Enzyme replacement has been under consideration as a therapeutic strategy for patients with Gaucher disease for more than two decades. Previous studies indicated that single injections of purified glucocerebrosidase reduced the amount of storage material in the liver. It was important to determine whether administration of exogenous enzyme on a regular basis would be of clinical benefit. The authors weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase in a child with type 1 Gaucher disease increased hemoglobin over a 20-week period. The platelet count also increased. Phagocytic activity in the spleen decreased during the period of enzyme administration, and there was radiographic evidence of skeletal improvement. These observations document objective clinical responses to enzyme supplementation in a patient with a sphingolipid storage disorder

Mechanisms of Plasma Therapeutics

Science.gov (United States)

Graves, David

2015-09-01

In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

Federal Radiological Monitoring and Assessment Center: Phase I Response

International Nuclear Information System (INIS)

Riland, C.; Bowman, D.R.; Lambert, R.; Tighe, R.

1999-01-01

A Federal Radiological Monitoring and Assessment Center (FRMAC) is established in response to a Lead Federal Agency (LFA) or State request when a radiological emergency is anticipated or has occurred. The FRMAC coordinates the off-site monitoring, assessment, and analysis activities during such an emergency. The FRMAC response is divided into three phases. FRMAC Phase 1 is a rapid, initial-response capability that can interface with Federal or State officials and is designed for a quick response time and rapid radiological data collection and assessment. FRMAC Phase 1 products provide an initial characterization of the radiological situation and information on early health effects to officials responsible for making and implementing protective action decisions

Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

LENUS (Irish Health Repository)

Rooney, Terence

2012-02-01

OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

Localized scleroderma: assessment of the therapeutic response to phototherapy Esclerodermia cutânea: avaliação da resposta terapêutica à fototerapia

Directory of Open Access Journals (Sweden)

Roberta Buense

2012-02-01

Full Text Available BACKGROUND: Scleroderma is a chronic autoimmune disease characterized by progressive connective tissue sclerosis and microcirculatory changes. Localized scleroderma is considered a limited disease. However, in some cases atrophic and deforming lesions may be observed that hinder the normal development. Literature reports indicate phototherapy as a therapeutic modality with favorable response in cutaneous forms of scleroderma. OBJECTIVES: This study had the purpose of assessing the phototherapy treatment for localized scleroderma. METHODS: Patients with localized scleroderma were selected for phototherapy treatment. They were classified according to the type of localized scleroderma and evolutive stage of the lesions. Clinical examination and skin ultrasound were used to demonstrate the results thus obtained. RESULTS: Some clinical improvement was observed after an average of 10 phototherapeutic sessions. All skin lesions were softer at clinical palpation with scores reduction upon pre and post treatment comparison. The ultrasound showed that most of the assessed lesions presented a decrease in dermal thickness, and only five maintained their previous measure. Treatment response was similar regardless of the type of phototherapeutic treatment employed. CONCLUSIONS: The proposed treatment was effective for all lesions, regardless of the phototherapeutic modality employed. The improvement was observed in all treated skin lesions and confirmed by clinical evaluation and skin ultrasound.FUNDAMENTOS: A esclerodermia é uma doença autoimune caracterizada pela esclerose progressiva do tecido conjuntivo e alterações da microcirculação. A forma cutânea é considerada uma doença autolimitada. No entanto, em alguns casos, ocorrem lesões atróficas, deformantes, que dificultam o desenvolvimento normal. Relatos da literatura apontam a fototerapia como uma modalidade terapêutica com resposta favorável nas formas cutâneas da esclerodermia. OBJETIVOS

Assessment of Mobile Accident Response Capability

International Nuclear Information System (INIS)

1983-03-01

This report presents the results of a DOE-sponsored assessment of nuclear accident response resources. It identifies the mobile resources that could be required to respond to different types of nuclear accidents including major ones like TMI-2, identifies the resources currently available and makes recommendations for the design and construction of additional mobile accident response resources to supplement those already in existence. This project is referred to as the Mobile Accident Response Capability (MARC) program

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.

Assessment of Bridelia ferruginea benth for its therapeutic potential ...

African Journals Online (AJOL)

McRoy

Therapeutic effect of Bridelia ferruginea on pregnancy-induced impaired glucose tolerance. Int J Med Biomed ... A proportion of women with pregnancy-induced impaired glucose ... The long-term implications for ... The leaves were removed ...

Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

Science.gov (United States)

Schepetkin, Igor A; Quinn, Mark T

2006-03-01

Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

Therapeutic risk management of the suicidal patient: safety planning.

Science.gov (United States)

Matarazzo, Bridget B; Homaifar, Beeta Y; Wortzel, Hal S

2014-05-01

This column is the fourth in a series describing a model for therapeutic risk management of the suicidal patient. Previous columns presented an overview of the therapeutic risk management model, provided recommendations for how to augment risk assessment using structured assessments, and discussed the importance of risk stratification in terms of both severity and temporality. This final column in the series discusses the safety planning intervention as a critical component of therapeutic risk management of suicide risk. We first present concerns related to the relatively common practice of using no-suicide contracts to manage risk. We then present the safety planning intervention as an alternative approach and provide recommendations for how to use this innovative strategy to therapeutically mitigate risk in the suicidal patient.

Therapeutic bond judgments: Congruence and incongruence.

Science.gov (United States)

Atzil-Slonim, Dana; Bar-Kalifa, Eran; Rafaeli, Eshkol; Lutz, Wolfgang; Rubel, Julian; Schiefele, Ann-Kathrin; Peri, Tuvia

2015-08-01

The present study had 2 aims: (a) to implement West and Kenny's (2011) Truth-and-Bias model to simultaneously assess the temporal congruence and directional discrepancy between clients' and therapists' ratings of the bond facet of the therapeutic alliance, as they cofluctuate from session to session; and (b) to examine whether symptom severity and a personality disorder (PD) diagnosis moderate congruence and/or discrepancy. Participants included 213 clients treated by 49 therapists. At pretreatment, clients were assessed for a PD diagnosis and completed symptom measures. Symptom severity was also assessed at the beginning of each session, using client self-reports. Both clients and therapists rated the therapeutic bond at the end of each session. Therapists and clients exhibited substantial temporal congruence in their session-by-session bond ratings, but therapists' ratings tended to be lower than their clients' across sessions. Additionally, therapeutic dyads whose session-by-session ratings were more congruent also tended to have a larger directional discrepancy (clients' ratings being higher). Pretreatment symptom severity and PD diagnosis did not moderate either temporal congruence or discrepancy at the dyad level; however, during sessions when clients were more symptomatic, therapist and client ratings were both farther apart and tracked each other less closely. Our findings are consistent with a "better safe than sorry" pattern, which suggests that therapists are motivated to take a vigilant approach that may lead both to underestimation and to attunement to fluctuations in the therapeutic bond. (c) 2015 APA, all rights reserved).

The social dimensions of therapeutic horticulture.

Science.gov (United States)

Harris, Holly

2017-07-01

Harnessing nature to promote mental health is increasingly seen as a sustainable solution to healthcare across the industrialised world. The benefits of these approaches to well-being include reduced symptoms of anxiety, depression and improved social functioning. Many studies assume that contact with nature is the main therapeutic component of these interventions yet 'green care' programmes typically include activities not based on 'nature' that may contribute to positive outcomes. This study explored the views of service users participating in a Therapeutic Horticultural programme on what factors promoted their engagement in the project, to identify variables other than 'nature' that may be responsible for successful engagement in these programmes. A secondary aim was to assess the significance 'nature' plays including, for example whether a prior interest in horticultural-related activities, such as gardening, is significant. Two focus groups were held with mental health service users (n = 15) attending a gardening project in south-east England. Findings revealed that the social element of the project was the key facilitator to engagement; the flexible structure of the gardening project was also significant and allowed service users to feel empowered. 'Nature' evoked a sense of calm and provided participants with a non-threatening space that was engaging. © 2017 John Wiley & Sons Ltd.

Percutaneous Radiofrequency Ablation for the Hepatocellular Carcinoma Abutting the Diaphragm: Assessment of Safety and Therapeutic Efficacy

International Nuclear Information System (INIS)

Kang, Tae Wook; Rhim, Hyun Chul; Kim, Eun Young; Kim, Young Sun; Choi, Dong Il; Lee, Won Jae; Lim, Hyo K.

2009-01-01

To assess the safety and therapeutic efficacy of a percutaneous radiofrequency (RF) ablation for the hepatocellular carcinoma (HCC) abutting the diaphragm. We retrospectively assessed 80 patients who underwent a percutaneous RF ablation for a single nodular (< 4 cm) HCC over the last four years. Each patient underwent an ultrasound-guided RF ablation using internally cooled electrodes for the first-line treatment. We divided patients into two subgroups based on whether the index tumor was abutting (less than 5 mm) the diaphragm or not: group A (abutting; n = 31) versus group B (non-abutting; n = 49). We compared the two subgroups for complications and therapeutic efficacy using image and the review of medical records. The statistical assessment included an independent t-test, Fisher's exact test, and chi-square test. The assessment of the diaphragmatic swelling at CT immediately following the procedure was more severe in group A than group B (mean thickness change:1.44 vs. 0.46 mm, p = 0.00). Further, right shoulder pain was more common in group A than B (p = 0.01). Although minor complications (hemothorax 1 case, pleural effusion 1 case) were noted only in group A, no major thoracic complication occurred in either group. The technical success rate was lower in group A than group B (84% vs. 98%, p = 0.03). As well, the primary and secondary technique effectiveness rates in group A and group B were 90% versus 98% (p = 0.29) and 79% versus 91% (p = 0.25), respectively. The local tumor progression rate was higher in group A than in group B (29% vs. 6%, p = 0.02). We found that the percutaneous RF ablation for the HCC abutting the diaphragm is a safe procedure without major complications. However, it is less effective with regard to technical success and local tumor control

{sup 99m}Tc-sestamibi muscle scintigraphy to assess the response to neuromuscular electrical stimulation of normal quadriceps femoris muscle

Energy Technology Data Exchange (ETDEWEB)

Pekindil, Y.; Sarikaya, A.; Birtane, M.; Pekindil, G.; Salan, A. [Trakya Univ., Edirne (Turkey). Hospital

2001-08-01

Neuromuscular electrical stimulation (NMES) is widely used for improving muscle strength by simultaneous contraction in the prevention of muscle atrophy. Although there exist many clinical methods for evaluating the therapeutic response of muscles, {sup 99m}Tc-sestamibi which is a skeletal muscle perfusion and metabolism agent has not previously been used for this purpose. The aim of our work was to ascertain whether {sup 99m}Tc-sestamibi muscle scintigraphy is useful in the monitoring of therapeutic response to NMES in healthy women. The study included 16 women aged between 21 and 45, with a mean age of 32.7{+-}6.4. Both quadriceps femoris muscles (QFM) of each patient were studied. After randomization to remove the effect of the dominant side, one QFM of each patient was subjected to the NMES procedure for a period of 20 days. NMES was performed with an alternating biphasic rectangular current, from a computed electrical stimulator daily for 23 minutes. After measurement of skinfold thickness over the thigh, pre- and post-NMES girth measurements were assessed in centimeters. Sixty minutes after injections of 555 MBq {sup 99m}Tc-sestamibi, static images of the thigh were obtained for 5 minutes. The thigh-to-knee uptake ratio was calculated by semiquantitative analysis and normalized to body surface area (NUR=normalized uptake ratio). The difference between the pre and post NMES NUR values was significant (1.76{+-}0.31 versus 2.25{+-}0.38, p=0.0000). The percentage (%) increase in NUR values also well correlated with the % increase in thigh girth measurements (r=0.89, p=0.0000). These results indicated that {sup 99m}Tc-sestamibi muscle scintigraphy as a new tool may be useful in evaluating therapeutic response to NMES. (author)

A Study of Ethics Education within Therapeutic Recreation Curriculum.

Science.gov (United States)

Nisbett, Nancy; Brown-Welty, Sharon; O'Keefe, Cathy

2002-01-01

Explored the status of ethics education within therapeutic recreation. Researchers surveyed all entry-level undergraduate and graduate therapeutic recreation training programs in one state, examining responses for differences in content and delivery. Programs appeared consistent with regard to ethics instruction, integrating similar content…

Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

Science.gov (United States)

Kumar, Anoop

2016-01-01

Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

The therapeutic collaboration in life design counselling: The case of ...

African Journals Online (AJOL)

The collaboration coding system enables the assessment of each therapeutic exchange within and outside of the client's therapeutic zone of proximal development, defined as the space between the client's actual therapeutic developmental level and his/her potential developmental level fomented by a collaborative ...

[A therapeutic education tool in paediatric dentistry].

Science.gov (United States)

Marquillier, Thomas; Trentesaux, Thomas; Catteau, Céline; Delfosse, Caroline

Therapeutic education for children is developing in the treatment of dental caries. The Elmy pathway, a pedagogical game aiming to improve children's oral health skills, has been designed. The qualitative assessment of this tool seems to confirm its benefit for use in therapeutic education sessions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Therapeutic response to plasmapheresis in four cases with obsessive-compulsive disorder and tic disorder triggered by streptococcal infections].

Science.gov (United States)

Beşiroğlu, Lütfullah; Ağargün, Mehmet Yücel; Ozbebit, Ozgür; Sözen, Mehmet; Dilek, Imdat; Güleç, Mustafa

2007-01-01

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been assigned to a subgroup of patients experiencing pediatric onset obsessive-compulsive symptoms and tics as a result of autoimmune response to group A beta-hemolytic streptococcal infection. It has been hypothesized that an immune process initiated by infection affects the basal ganglia and causes neuropsychiatric symptoms. In cases with severe neuropsychiatric symptoms, the use of treatment strategies that interrupt the autoimmune process responsible for the pathogenesis of PANDAS, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed. In this paper, we discuss the effect of plasmapheresis treatment in 4 adult cases of obsessive-compulsive disorder and tic disorder triggered by streptococcal infections.

An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

Directory of Open Access Journals (Sweden)

Jan B W J Cornelissen

Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

Psychological treatment and therapeutic change in incarcerated rapists

Directory of Open Access Journals (Sweden)

Ana Martínez-Catena

2017-01-01

Full Text Available Abstract Most Spanish prisons provide specialised treatment for incarcerated sex offenders, both rapists and child molesters. This treatment is a cognitive-behavioural intervention that has shown relative effectiveness in previous research. With regard to offenders’ rehabilitation, recidivism assessments are necessary as a final measure of treatment effectiveness. However, the evaluation of recidivism by itself does not provide sufficient information on the treatment process and the specific effects that treated subjects could undergo. This paper aims to analyse the therapeutic effectiveness of psychological treatment provided to rapists (in general, males sentenced for committing a sexual offence against women. To this aim, a group of treated rapists (N=153 serving a sentence in prison was analysed. Using a specially designed scale (PASSO, the global therapeutic change and ten specific variables (including assertiveness, readiness to change, cognitive distortions, impulsivity, etc. were assessed. The within-subjects comparison showed that treated sex offenders improved, in therapeutic terms, globally as well as in most of the specific variables assessed (improvements not experimented by the control group. Also, different therapeutic subscales showed relevant associations between them. The findings regarding treatment effectiveness are discussed.

Rapid and Quantitative Assessment of Cancer Treatment Response Using In Vivo Bioluminescence Imaging

Directory of Open Access Journals (Sweden)

Alnawaz Rehemtulla

2000-01-01

Full Text Available Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating antineoplastic therapies [1 ]. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal [2], subcutaneous, and intravascular [3] cancer models. However, use of this approach for evaluating orthotopic tumor models has not been demonstrated. In this report, the ability of BLI to noninvasively quantitate the growth and therapeuticinduced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luciferase (9LLuc was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryogenically cooled CCD camera and magnetic resonance imaging (MRI, respectively. There was excellent correlation (r=0.91 between detected photons and tumor volume. A quantitative comparison of tumor cell kill determined from serial MRI volume measurements and BLI photon counts following 1,3-bis(2-chloroethyl-1-nitrosourea (BCNU treatment revealed that both imaging modalities yielded statistically similar cell kill values (P=.951. These results provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.

The impact of therapeutic opioid agonists on driving-related psychomotor skills assessed by a driving simulator or an on-road driving task: A systematic review.

Science.gov (United States)

Ferreira, Diana H; Boland, Jason W; Phillips, Jane L; Lam, Lawrence; Currow, David C

2018-04-01

Driving cessation is associated with poor health-related outcomes. People with chronic diseases are often prescribed long-term opioid agonists that have the potential to impair driving. Studies evaluating the impact of opioids on driving-related psychomotor skills report contradictory results likely due to heterogeneous designs, assessment tools and study populations. A better understanding of the effects of regular therapeutic opioid agonists on driving can help to inform the balance between individual's independence and community safety. To identify the literature assessing the impact of regular therapeutic opioid agonists on driving-related psychomotor skills for people with chronic pain or chronic breathlessness. Systematic review reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement; PROSPERO Registration CRD42017055909. Six electronic databases and grey literature were systematically searched up to January, 2017. Inclusion criteria were as follows: (1) empirical studies reporting data on driving simulation, on-the-road driving tasks or driving outcomes; (2) people with chronic pain or chronic breathlessness; and (3) taking regular therapeutic opioid agonists. Critical appraisal used the National Institutes of Health's quality assessment tools. From 3809 records screened, three studies matched the inclusion criteria. All reported data on people with chronic non-malignant pain. No significant impact of regular therapeutic opioid agonists on people's driving-related psychomotor skills was reported. One study reported more intense pain significantly worsened driving performance. This systematic review does not identify impaired simulated driving performance when people take regular therapeutic opioid agonists for symptom control, although more prospective studies are needed.

Response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient's therapeutic CPAP requirement.

Science.gov (United States)

Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A

2017-08-01

Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility. Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (P crit ) and ventilation at CPAP level of 0 cmH 2 O (V passive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHICPAP requirement compared with non-responders (6.6 (5.4-8.1)  cmH 2 O vs 8.9 (8.4-10.4) cmH 2 O, P = 0.007), consistent with their reduced collapsibility (lower P crit , P = 0.017, higher V passive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both P crit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and V passive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH 2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies. Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and

A thermodynamic assessment of therapeutic hypothermia techniques

International Nuclear Information System (INIS)

Mady, Carlos Eduardo Keutenedjian; Henriques, Izabela Batista; Oliveira, Silvio de

2015-01-01

According to literature, therapeutic hypothermia has been applied for treating conditions that causes an interruption in the delivery of oxygen to the brain, giving the patient better chances of survival with a neurological recovery and without any irreversible damage to the brain. Hypothermia is also used during surgeries and circulatory arrest. In this article, the objective temperature of hypothermia is 32 °C, which is considered mild: 32–35 °C. Three techniques of hypothermia induction were considered: external blood cooling, endovascular cooling with a catheter insertion and water bath. Energy and exergy analyses were performed to determine the clinical effectiveness of these techniques and to evaluate the best test parameters, from which it was possible to calculate the body internal temperature, destroyed exergy and exergy efficiency. Moreover, it was proposed an exergy performance index, which takes into account the ability of a given technique to change the exergy of the body. Results indicate that therapeutic hypothermia takes the subject to a state of lower destroyed exergy and higher body exergy efficiency. The exergy performance index shows that lower rates of cooling lead to a better transformation of the exergy removed from the body into variation of the body exergy. - Highlights: • Thermodynamic study of the human body under mild hypothermia. • Energy and Exergy analysis were applied to the human thermal model. • Calculation of destroyed exergy, exergy efficiency. • Hypothermia led the body to a state of lower destroyed exergy. • EBC achieved higher values of destroyed exergy and exergy efficiency

Emergency Response Capability Baseline Needs Assessment Compliance Assessment

Energy Technology Data Exchange (ETDEWEB)

Sharry, John A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2013-09-16

This document is the second of a two-part analysis of Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2013 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2009 BNA, the 2012 BNA document, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures.

Ethical considerations when using video games as therapeutic tools

OpenAIRE

Colman, Jason; Gnanayutham, Paul

2010-01-01

Video games have been used in a variety of therapeutic and rehabilitative contexts. However, there are health risks associated with playing video games, including the risk of epileptic seizure. Additionally, video games have been criticised for reasons including their portrayal of women and minorities. For games to be accepted as an ethically valid therapeutic tool, these concerns must be addressed. The authors believe that video games can be used as therapeutic tools when used responsibly

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

Science.gov (United States)

McMahon-Pratt, Diane; Saravia, Nancy Gore

2015-01-01

Background Therapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses. Methodology To achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays. Principal Findings Anti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine

Intuition, subjectivity, and Le bricoleur: cancer patients' accounts of negotiating a plurality of therapeutic options.

Science.gov (United States)

Broom, Alex

2009-08-01

Cancer patients are now combining complementary and alternative medicine (CAM) with biomedical cancer treatments, reflecting an increasingly pluralistic health care environment. However, there has been little research done on the ways in which cancer patients juggle multiplicity in claims to expertise, models of disease, and therapeutic practice. Drawing on the accounts of cancer patients who use CAM, in this article I develop a conceptualization of therapeutic decision making, utilizing the notion of bricolage as a key point of departure. The patient accounts illustrate the "piecing together" (or bricolage) of therapeutic trajectories, drawing on intuitive, embodied knowledge, as well as formalized "objective" scientific expertise. Le bricoleur, as characterized here, actively mediates, rather than accepts or rejects CAM or biomedicine, and utilizes a combination of scientific expertise, embodied physicality, and social knowledge to make decisions and assess therapeutic effectiveness. Although these "border crossings" are potentially subversive of established biomedical expertise, the analysis also illustrates the structural constraints (and penalties) associated with bricolage, and furthermore, the interplay of a repositioning of responsibility with neoliberal forms of self-governance.

Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8+ T Cell Responses During Chronic Retroviral Infection

Science.gov (United States)

Knuschke, Torben; Rotan, Olga; Bayer, Wibke; Kollenda, Sebastian; Dickow, Julia; Sutter, Kathrin; Hansen, Wiebke; Dittmer, Ulf; Lang, Karl S.; Epple, Matthias; Buer, Jan; Westendorf, Astrid M.

2018-01-01

T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP) nanoparticle (NP)-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8+ T cell response and improve the eradication of virus infected cells. However, the mechanisms underlying this effect were largely unclear. While type I interferons (IFNs I) are considered to drive T cell exhaustion by persistent immune activation during chronic viral infection, we here describe an indispensable role of IFN I induced by therapeutic vaccination to efficiently reinforce cytotoxic CD8+ T cells (CTL) and improve control of chronic retroviral infection. The induction of IFN I is CpG dependent and leads to significant IFN signaling indicated by upregulation of IFN stimulated genes. By vaccinating chronically retrovirus-infected mice lacking the IFN I receptor (IFNAR−/−) or by blocking IFN I signaling in vivo during therapeutic vaccination, we demonstrate that IFN I signaling is necessary to drive full reactivation of CTLs. Surprisingly, we also identified an impaired suppressive capability of regulatory T cells in the presence of IFNα, which implicates an important role for vaccine-induced IFNα in the regulation of the T cell response during chronic retroviral infection. Our data suggest that inducing IFN I signaling in conjunction with the presentation of viral antigens can reactivate immune functions and reduce viral loads in chronic infections. Therefore, we propose CaP NPs as potential therapeutic tool to treat chronic infections. PMID:29740425

Neuroscience in forensic psychiatry: From responsibility to dangerousness. Ethical and legal implications of using neuroscience for dangerousness assessments.

Science.gov (United States)

Gkotsi, Georgia Martha; Gasser, Jacques

2016-01-01

Neuroscientific evidence is increasingly being used in criminal trials as part of psychiatric testimony. Up to now, "neurolaw" literature remained focused on the use of neuroscience for assessments of criminal responsibility. However, in the field of forensic psychiatry, responsibility assessments are progressively being weakened, whereas dangerousness and risk assessment gain increasing importance. In this paper, we argue that the introduction of neuroscientific data by forensic experts in criminal trials will be mostly be used in the future as a means to evaluate or as an indication of an offender's dangerousness, rather than their responsibility. Judges confronted with the pressure to ensure public security may tend to interpret neuroscientific knowledge and data as an objective and reliable way of evaluating one's risk of reoffending. First, we aim to show how the current socio-legal context has reshaped the task of the forensic psychiatrist, with dangerousness assessments prevailing. In the second part, we examine from a critical point of view the promise of neuroscience to serve a better criminal justice system by offering new tools for risk assessment. Then we aim to explain why neuroscientific evidence is likely to be used as evidence of dangerousness of the defendants. On a theoretical level, the current tendency in criminal policies to focus on prognostics of dangerousness seems to be "justified" by a utilitarian approach to punishment, supposedly revealed by new neuroscientific discoveries that challenge the notions of free will and responsibility. Although often promoted as progressive and humane, we believe that this approach could lead to an instrumentalization of neuroscience in the interest of public safety and give rise to interventions which could entail ethical caveats and run counter to the interests of the offenders. The last part of this paper deals with some of these issues-the danger of stigmatization for brain damaged offenders because of

Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products : overall perspective and role of the pharmacoepidemiologist

NARCIS (Netherlands)

Radawski, Christine; Morrato, Elaine; Hornbuckle, Kenneth; Bahri, Priya; Smith, Meredith; Juhaeri, Juhaeri; Mol, Peter; Levitan, Bennett; Huang, Han-Yao; Coplan, Paul; Li, Hu

2015-01-01

Purpose Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper

Tool to assess causality of direct and indirect adverse events associated with therapeutic interventions.

Science.gov (United States)

Zorzela, Liliane; Mior, Silvano; Boon, Heather; Gross, Anita; Yager, Jeromy; Carter, Rose; Vohra, Sunita

2018-03-01

To develop and test a tool to assess the causality of direct and indirect adverse events associated with therapeutic interventions. The intervention was one or more drugs and/or natural health products, a device, or practice (professional delivering the intervention). Through the assessment of causality of adverse events, we can learn about factors contributing to the harm and consider what modification may prevent its reoccurrence. Existing scales (WHO-UMC, Naranjo and Horn) were adapted to develop a tool (algorithm and table) to evaluate cases of serious harmful events reported through a national surveillance study. We also incorporated a novel approach that assesses indirect harm (caused by the delay in diagnosis/treatment) and the health provider delivering the intervention (practice). The tool was tested, revised and then implemented to assess all reported cases of serious events resulting from use of complementary therapies. The use of complementary therapies was the trigger to report the event. Each case was evaluated by two assessors, out of a panel of five, representing different health care professionals. The tool was used in assessment of eight serious adverse events. Each event was independently evaluated by two assessors. The algorithm facilitated assessment of a serious direct or indirect harm. Assessors agreed in the final score on seven of eight cases (weighted kappa coefficient of 0.75). A tool to support the assessment of causality of adverse events was developed and tested. We propose a novel method to assess direct and indirect harms related to product(s), device(s), practice or a combination of the previous. Further research will probably help evaluate this approach across different settings and interventions.

Preexisting Antibodies to an F(ab′2 Antibody Therapeutic and Novel Method for Immunogenicity Assessment

Directory of Open Access Journals (Sweden)

Jane Ruppel

2016-01-01

Full Text Available Anti-therapeutic antibodies (ATAs may impact drug exposure and activity and induce immune complex mediated toxicity; therefore the accurate measurement of ATA is important for the analysis of drug safety and efficacy. Preexisting ATAs to the hinge region of anti-Delta like ligand 4 (anti-DLL4 F(ab′2, a potential antitumor therapeutic, were detected in cynomolgus monkey serum, which presented a challenge in developing assays for detecting treatment induced ATA. A total ATA assay was developed using a bridging ELISA that detected both anti-CDR and anti-framework ATA including anti-hinge reactivity. A competition assay that could detect 500 ng/mL of anti-CDR ATA in the presence of preexisting ATA was also developed to determine ATA specific to the anti-DLL4 F(ab′2 CDR using anti-DLL4 F(ab′2 and a control F(ab′2. We used these assay methods in a cynomolgus monkey in vivo study to successfully evaluate total and anti-CDR ATA. The preexisting anti-hinge reactivity was also observed to a lesser extent in human serum, and a similar approach could be applied for specific immunogenicity assessment in clinical trials.

Assessing Emergency Preparedness and Response Capacity Using Community Assessment for Public Health Emergency Response Methodology: Portsmouth, Virginia, 2013.

Science.gov (United States)

Kurkjian, Katie M; Winz, Michelle; Yang, Jun; Corvese, Kate; Colón, Ana; Levine, Seth J; Mullen, Jessica; Ruth, Donna; Anson-Dwamena, Rexford; Bayleyegn, Tesfaye; Chang, David S

2016-04-01

For the past decade, emergency preparedness campaigns have encouraged households to meet preparedness metrics, such as having a household evacuation plan and emergency supplies of food, water, and medication. To estimate current household preparedness levels and to enhance disaster response planning, the Virginia Department of Health with remote technical assistance from the Centers for Disease Control and Prevention conducted a community health assessment in 2013 in Portsmouth, Virginia. Using the Community Assessment for Public Health Emergency Response (CASPER) methodology with 2-stage cluster sampling, we randomly selected 210 households for in-person interviews. Households were questioned about emergency planning and supplies, information sources during emergencies, and chronic health conditions. Interview teams completed 180 interviews (86%). Interviews revealed that 70% of households had an emergency evacuation plan, 67% had a 3-day supply of water for each member, and 77% had a first aid kit. Most households (65%) reported that the television was the primary source of information during an emergency. Heart disease (54%) and obesity (40%) were the most frequently reported chronic conditions. The Virginia Department of Health identified important gaps in local household preparedness. Data from the assessment have been used to inform community health partners, enhance disaster response planning, set community health priorities, and influence Portsmouth's Community Health Improvement Plan.

Risk evaluation and monitoring in multiple sclerosis therapeutics.

Science.gov (United States)

Clanet, Michel C; Wolinsky, Jerry S; Ashton, Raymond J; Hartung, Hans-Peter; Reingold, Stephen C

2014-09-01

Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks. The objective of this review is to discuss risk assessment in MS therapeutics based on an international workshop and comprehensive literature search and recommend strategies for risk assessment/monitoring. Assessment and perception of therapeutic risks vary between patients, doctors and regulators. Acceptability of risk depends on the magnitude of risk and the demonstrated clinical benefits of any agent. Safety signals must be distinguishable from chance occurrences in a clinical trial and in long-term use of medications. Post-marketing research is crucial for assessing longer-term safety in large patient cohorts. Reporting of adverse events is becoming more proactive, allowing more rapid identification of risks. Communication about therapeutic risks and their relationship to clinical benefit must involve patients in shared decision making. It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions. © The Author(s) 2013.

18F-FDG PET/CT in tuberculosis: an early non-invasive marker of therapeutic response

International Nuclear Information System (INIS)

Martinez, V.; Grenier, G.; Fior, R.; Boue, F.; Castilla-Lievre, M.A.; Guillet-Caruba, C.; Desarnaud, S.

2012-01-01

To evaluate the potential of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for early therapeutic intervention in patients with probable or confirmed tuberculosis (TB). Twenty-one consecutive human immunodeficiency virus negative patients were prospectively included. All patients underwent 18 F-FDG PET/CT before and after 1 month of anti-tuberculosis treatment. The maximum standardised uptake value (SUV max ) of the most 18 F-FDG avid lesions was recorded. The median age of patients was 36 years (range 18-84); 33.3% were male, 80.9% were born in endemic countries, and 23.8% had a past history of TB. TB was confirmed on culture in 8, on histology in 9 and on the basis of clinical symptoms in 4 patients. 18 F-FDG PET/CT detected active pulmonary TB (n = 1), extrapulmonary (n = 10) or both (n = 10). The second 18 F-FDG PET/CT showed reduced radiotracer uptake intensity in 19 of 21 patients, with a median percentage decrease of SUV max of 31% (range 2-84). Two patients showed no improvement. TB was ruled out in one patient during follow-up; the final diagnosis was a non-Hodgkin's lymphoma. The other patient was smear-positive for 3 months. 18 F-FDG PET/CT allows an easy evaluation of early therapeutic response in patients with TB, particularly extra-pulmonary TB. (authors)

Role of FDG-PET in the Diagnosis of Recurrence and Assessment of Therapeutic Response in Cervical Cancer and Ovarian Cancer Patients: Comparison of Diagnostic Report between PET, Abdominal CT and Tumor Marker

International Nuclear Information System (INIS)

Han, You Mie; Choe, Jae Gol; Kang, Bung Chul

2008-01-01

We aimed to assess the role of positron emission tomography using fluorodeoxyglucose (FDG-PET) in the diagnosis of recurrence or the assessment of therapeutic response in cervical and ovarian cancer patients through making a comparison between FDG-PET, abdominal computed tomography (CT) and serum tumor marker. We included 103 cases (67 patients) performed FDG-PET and abdominal CT. There were 42 cervical cancers and 61 ovarian cancers. We retrospectively reviewed the interpretations of PET and CT images as well as the level of tumor marker. We calculated their sensitivity, specificity, positive predictive value and negative predictive value for these three modalities. And then we analyzed the differences between these three modalities. Tumor recurrences were diagnosed in 37 cases (11 cervical cancers and 26 ovarian cancers). For PET, CT and tumor marker, in cervical cancer group, sensitivity was 100% (11/11), 54.5% (6/11) and 81.1% (9/11), respectively. And specificity was 93.6% (29/31), 93.6% (29/31) and 100% (31/31). In ovarian cancer group, sensitivity was 96.2% (25/26), 84.6% (22/26) and 80.8% (21/26), and specificity was 94.3% (33/35), 94.3% (33/35), 94.3% (33/35). PET was highly sensitive to detect the intraperitoneal and extraperitoneal metastasis with the help of the CT images to localize the lesions. However, CT had limitations in differentiation of the recurrent tumor from benign fibrotic tissue, identification of viable tumors at the interface of tissues, and detecting extraperitoneal lesions. FDG-PET can be an essential modality to detect the recurrent or residual tumors in gynecologic cancer patients because of its great field of the application and high sensitivity

Reactor-produced therapeutic radioisotopes

International Nuclear Information System (INIS)

Knapp, F.F. Jr.

2002-01-01

The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products: overall perspective and role of the pharmacoepidemiologist.

Science.gov (United States)

Radawski, Christine; Morrato, Elaine; Hornbuckle, Kenneth; Bahri, Priya; Smith, Meredith; Juhaeri, Juhaeri; Mol, Peter; Levitan, Bennett; Huang, Han-Yao; Coplan, Paul; Li, Hu

2015-12-01

Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life-cycle approach to integrated Benefit-Risk Assessment, Communication, and Evaluation (BRACE). A review of the medical and regulatory literature was performed for the following steps involved in therapeutic benefit-risk optimization: benefit-risk evidence generation; data integration and analysis; decision making; regulatory and policy decision making; benefit-risk communication and risk minimization; and evaluation. Feedback from International Society for Pharmacoepidemiology members was solicited on the role of the pharmacoepidemiologist. The case example of natalizumab is provided to illustrate the cyclic nature of the benefit-risk optimization process. No single, globally adopted benefit-risk assessment process exists. The BRACE heuristic offers a way to clarify research needs and to promote best practices in a cyclic and integrated manner and highlight the critical importance of cross-disciplinary input. Its approach focuses on the integration of BRACE activities for risk minimization and optimization of the benefit-risk profile. The activities defined in the BRACE heuristic contribute to the optimization of the benefit-risk profile of therapeutic products in the clinical world at both the patient and population health level. With interdisciplinary collaboration, pharmacoepidemiologists are well suited for bringing in methodology expertise, relevant research, and public health perspectives into the BRACE process. Copyright © 2015 John Wiley & Sons, Ltd.

The role of diffusion-weighted MRI: In assessment of response to radiotherapy for prostate cancer

Directory of Open Access Journals (Sweden)

Manal H. Wahba

2015-03-01

Conclusion: With the use of a 1.5-T MR scanner, our preliminary results suggest that ADC values may be useful as a non-invasive imaging biomarker for monitoring therapeutic response of prostate cancer to radiotherapy.

Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8+ T Cell Responses During Chronic Retroviral Infection

Directory of Open Access Journals (Sweden)

Torben Knuschke

2018-04-01

Full Text Available T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP nanoparticle (NP-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8+ T cell response and improve the eradication of virus infected cells. However, the mechanisms underlying this effect were largely unclear. While type I interferons (IFNs I are considered to drive T cell exhaustion by persistent immune activation during chronic viral infection, we here describe an indispensable role of IFN I induced by therapeutic vaccination to efficiently reinforce cytotoxic CD8+ T cells (CTL and improve control of chronic retroviral infection. The induction of IFN I is CpG dependent and leads to significant IFN signaling indicated by upregulation of IFN stimulated genes. By vaccinating chronically retrovirus-infected mice lacking the IFN I receptor (IFNAR−/− or by blocking IFN I signaling in vivo during therapeutic vaccination, we demonstrate that IFN I signaling is necessary to drive full reactivation of CTLs. Surprisingly, we also identified an impaired suppressive capability of regulatory T cells in the presence of IFNα, which implicates an important role for vaccine-induced IFNα in the regulation of the T cell response during chronic retroviral infection. Our data suggest that inducing IFN I signaling in conjunction with the presentation of viral antigens can reactivate immune functions and reduce viral loads in chronic infections. Therefore, we propose CaP NPs as potential therapeutic tool to treat chronic infections.

Evidence Based Digoxin Therapeutic Monitoring - A Lower and Narrower Therapeutic Range

Directory of Open Access Journals (Sweden)

Amine BENLMOUDEN

2016-06-01

Full Text Available Cardiac glycosides have been used for congestive heart failure and certain cardiac arrhythmias for more than 200 years. Despite the introduction of a variety of new classes of drugs for the management of heart failure, specifically angiotensin-converting enzyme (ACE inhibitors, b-adrenergic antagonists (bblockers, and the aldosterone antagonist spironolactone, digoxin continues to have an important role in long-term outpatient management. However, a narrow margin exists between therapeutic and toxic doses of digoxin, resulting in a high incidence of digoxin toxicity in clinical practice.A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. The clinical relevance of digoxin therapeutic monitoring is also proved but the SDC (Serum Digoxin Conentrations required for optimal clinical efficacy and acceptable toxicity remains controversial. In the last years, international guidelines recommend 1.2 ng/mL as acceptable high level.In this bibliographic synthesis, we aim to collect pertinent informations from MedLine database about exposure-effect relationship in order to assess the evidence level scientific of new digoxin therapeutic monitoring. 

The therapeutic evaluation and mechanism on treating bronchial ...

African Journals Online (AJOL)

... the level of bronchial responsiveness, which proved a better curative effect of Chinese medicine. The mechanism is probably due to relieving the airway inflammation by keeping the balance between Th1 and Th2 cells. Keywords: Ziyinqingre prescription; cough; bronchial hyper-responsiveness; therapeutic mechanism ...

Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies.

Science.gov (United States)

Ponce, Rafael; Abad, Leslie; Amaravadi, Lakshmi; Gelzleichter, Thomas; Gore, Elizabeth; Green, James; Gupta, Shalini; Herzyk, Danuta; Hurst, Christopher; Ivens, Inge A; Kawabata, Thomas; Maier, Curtis; Mounho, Barbara; Rup, Bonita; Shankar, Gopi; Smith, Holly; Thomas, Peter; Wierda, Dan

2009-07-01

An evaluation of potential antibody formation to biologic therapeutics during the course of nonclinical safety studies and its impact on the toxicity profile is expected under current regulatory guidance and is accepted standard practice. However, approaches for incorporating this information in the interpretation of nonclinical safety studies are not clearly established. Described here are the immunological basis of anti-drug antibody formation to biopharmaceuticals (immunogenicity) in laboratory animals, and approaches for generating and interpreting immunogenicity data from nonclinical safety studies of biotechnology-derived therapeutics to support their progression to clinical evaluation. We subscribe that immunogenicity testing strategies should be adapted to the specific needs of each therapeutic development program, and data generated from such analyses should be integrated with available clinical and anatomic pathology, pharmacokinetic, and pharmacodynamic data to properly interpret nonclinical studies.

Escitalopram plasma levels and antidepressant response.

Science.gov (United States)

Florio, Vincenzo; Porcelli, Stefano; Saria, Alois; Serretti, Alessandro; Conca, Andreas

2017-09-01

Major Depression Disorder (MDD) has a highly variable treatment response due to the large inter-individual variation in the pharmacokinetics and pharmacodynamics of drug treatments. In detail the correlation between plasma level and efficacy has been much debated. Among first-line drugs for MDD, one of the most used is escitalopram. In the present study we investigated the association between serum concentration of escitalopram (SCE) and antidepressant response (AR). 70 MDD patients treated with escitalopram monotherapy were recruited and followed for three months. Hamilton Depression Rating Scale - 21 (HAMD-21) was administrated at baseline, month 1, and month 3 to assess AR. SCE was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCE and AR. We found an association between SCE and AR both at month 1 (pescitalopram the association between SCE and AR likely follows a nearly-asymptotic function, with poor AR at sub-therapeutic SCE and stable AR response at therapeutic SCE. Thus, when a patient reaches the therapeutic SCE range, further increase of escitalopram dosage seems to be useless, although further studies are needed to confirm our findings. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Individualised cancer therapeutics: dream or reality? Therapeutics construction.

Science.gov (United States)

Shen, Yuqiao; Senzer, Neil; Nemunaitis, John

2005-11-01

The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi.

Assessing responsiveness of a volatile and seasonal supply chain

DEFF Research Database (Denmark)

Wong, Chee Yew; Arlbjørn, Jan Stentoft; Hvolby, Hans Henrik

2006-01-01

‘‘market responsive’’ and ‘‘physically efficient’’ supply chains constitutes the backbone of this assessment. Four risk-influencing determinants—forecast uncertainty, demand variability, contribution margin, and time window of delivery are found suitable to assess the responsiveness of the toy supply chain......This paper describes a structural approach to assess the responsiveness of a volatile and seasonal supply chain. It is based on a case study in an international toy company. Fisher’s (Harvard Bus. Rev. 75(2) (1997) 105–117) Model of ‘‘innovative’’ and ‘‘functional’’ products and the corresponding...... with volatility, and to design for a responsive supply chain. These findings have also enabled the extension of Fisher’s Model to volatile supply chains. This new product differentiation model adds a physically responsive supply chain for ‘‘intermediate’’ products into the Fisher’s Model....

Impacts of the Human Gut Microbiome on Therapeutics.

Science.gov (United States)

Vázquez-Baeza, Yoshiki; Callewaert, Chris; Debelius, Justine; Hyde, Embriette; Marotz, Clarisse; Morton, James T; Swafford, Austin; Vrbanac, Alison; Dorrestein, Pieter C; Knight, Rob

2018-01-06

The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.

Riverland expedited response action assessment

International Nuclear Information System (INIS)

1995-06-01

The US Environmental Protection Agency (EPA) and Washington Department of Ecology (Ecology) recommended that the US Department of Energy (DOE) prepare an expedited response action (ERA) for the Riverland Railroad Car Wash Pit (located in the Riverland Rail Yard) and the 600 Area Army Munitions Burial Site (Munitions Cache). This assessment report details the actions taken to complete the Riverland ERA

[Recurrent vulvovaginitis: diagnostic assessment and therapeutic management].

Science.gov (United States)

Ramírez-Santos, A; Pereiro, M; Toribio, J

2008-04-01

Recurrent vulvovaginitis is a common problem in clinical practice. Management is often complicated by a long history of inappropriate treatments based on tentative diagnoses after an incomplete diagnostic workup. We review the most common causes of recurrent vulvovaginitis; the appropriate steps with which to establish a diagnosis, from the medical history through to the additional tests needed; and, finally, the best therapeutic options. We will focus on infectious, irritant, allergic, and hormonal causes as the ones of most interest to the dermatologist. Given that infection is the most frequent cause of these processes and also a common reason for inopportune treatment, we will pay particular attention to infectious etiologies and their differential diagnosis.

RNAi Therapeutics in Autoimmune Disease

Directory of Open Access Journals (Sweden)

Seunghee Cha

2013-03-01

Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.

Acute herpes zoster neuralgia: retrospective analysis of clinical aspects and therapeutic responsiveness.

Science.gov (United States)

Haas, N; Holle, E; Hermes, B; Henz, B M

2001-01-01

Although the efficacy of modern antiviral agents for the treatment of herpes zoster is unquestioned, their ability to affect the associated pain remains controversial. We have therefore evaluated the inpatient hospital records of 550 patients with herpes zoster with regard to pain-related clinical aspects and therapeutic responsiveness. Intensity of pain was quantified by calculating a daily pain equivalence index (PEI) on the basis of different classes of pain medication and the number of tablets used in each category. The mean age of patients was 66.7 years, cranial segments were predominantly involved (55%), 64% of patients suffered from associated diseases and 77% experienced herpes-related pain. The PEI was 0.90 in the entire patient population, with significantly higher values in women and in patients with 3 or more associated diseases. It was lower in sacral and cranial nerve involvement, and it decreased rapidly in patients prior to discharge from hospital. Although there were significant differences in hospital stay between patients who received aciclovir and those who did not (mean 20.3 vs. 23.8 days), and for high- versus low-dose oral or intravenous administration, no significant differences were noted between the two groups for initial PEI values and during the course of observation, irrespective of the route of administration or the dose of aciclovir and the individual patient's PEI value. The groups were otherwise closely similar with regard to basic demographic and clinical data. 23.3% predominantly aged female patients with more associated diseases than the total patient population had a persistently elevated PEI and stayed in hospital beyond 21 days (mean 35.1 days), representing patients who went on to postherpetic neuralgia. These data further delineate clinical aspects of acute herpes zoster neuralgia, underline the unsolved therapeutic problems associated with this condition despite otherwise effective antiviral treatment, and characterise a

Therapeutic Response to Non-genotoxic Activation of p53 by Nutlin3a Is Driven by PUMA-Mediated Apoptosis in Lymphoma Cells

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Liz J. Valente

2016-03-01

Full Text Available Nutlin3a is a small-molecule antagonist of MDM2 that promotes non-genotoxic activation of p53 through p53 protein stabilization and transactivation of p53 target genes. Nutlin3a is the forerunner of a class of cancer therapeutics that have reached clinical trials. Using transgenic and gene-targeted mouse models lacking the critical p53 target genes, p21, Puma, and Noxa, we found that only loss of PUMA conferred profound protection against Nutlin3a-induced killing in both non-transformed lymphoid cells and Eμ-Myc lymphomas in vitro and in vivo. CRISPR/Cas9-mediated targeting of the PUMA gene rendered human hematopoietic cancer cell lines markedly resistant to Nutlin3a-induced cell death. These results demonstrate that PUMA-mediated apoptosis, but not p21-mediated cell-cycle arrest or senescence, is a critical determinant of the therapeutic response to non-genotoxic p53 activation by Nutlin3a. Importantly, in human cancer, PUMA expression may predict patient responses to treatment with MDM2 antagonists.

The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.

Science.gov (United States)

Pál, Ildikó; Illés, Árpád; Gergely, Lajos; Pál, Tibor; Radnay, Zita; Szekanecz, Zoltán; Zilahi, Erika; Váróczy, László

2018-04-01

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL. The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes. Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant. Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.

Coupled Multiple-Response versus Free-Response Conceptual Assessment: An Example from Upper-Division Physics

Science.gov (United States)

Wilcox, Bethany R.; Pollock, Steven J.

2014-01-01

Free-response research-based assessments, like the Colorado Upper-division Electrostatics Diagnostic (CUE), provide rich, fine-grained information about students' reasoning. However, because of the difficulties inherent in scoring these assessments, the majority of the large-scale conceptual assessments in physics are multiple choice. To increase…

Therapeutic inertia amongst general practitioners with interest in diabetes.

Science.gov (United States)

Seidu, Samuel; Than, Tun; Kar, Deb; Lamba, Amrit; Brown, Pam; Zafar, Azhar; Hussain, Rizwan; Amjad, Ahmed; Capehorn, Mathew; Martin, Elizabeth; Fernando, Kevin; McMoran, Jim; Millar-Jones, David; Kahn, Shahzada; Campbell, Nigel; Brice, Richard; Mohan, Rahul; Mistry, Mukesh; Kanumilli, Naresh; St John, Joan; Quigley, Richard; Kenny, Colin; Khunti, Kamlesh

2018-02-01

As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p=0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

Science.gov (United States)

Greenbaum, Carla J; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M; Kolb, Hubert

2008-10-01

Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

Federal Radiological Monitoring and Assessment Center Phased Response Operations

International Nuclear Information System (INIS)

Riland, C.A.; Bowman, D.R.

1999-01-01

A Federal Radiological Monitoring and Assessment Center (FRMAC) is established in response to the Lead Federal Agency (LFA) or state request when a major radiological emergency is anticipated of has occurred. The FRMAC becomes a coalition of federal off-site monitoring and assessment activities to assist the LFA, state(s), local, and tribal authorities. State, local, and tribal authorities are invited to co-locate and prioritize monitoring and assessment efforts in the FRMAC. The Department of Energy is tasked by the Federal Radiological Emergency Response Plan to coordinate the FRMAC

Prediction of the therapeutic response after FOLFOX and FOLFIRI treatment for patients with liver metastasis from colorectal cancer using computerized CT texture analysis

Energy Technology Data Exchange (ETDEWEB)

Ahn, Su Joa, E-mail: joa0827@gmail.com [Department of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Jung Hoon, E-mail: jhkim2008@gmail.com [Department of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Sang Joon, E-mail: lunao78@naver.com [Department of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of); Han, Joon Koo, E-mail: hanjk@snu.ac.kr [Department of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2016-10-15

Purpose: To determine whether baseline CT texture analysis of hepatic metastasis from colorectal cancer (CRC) is predictive of therapeutic response after cytotoxic chemotherapy. Materials and methods: 235 patients with liver metastasis from CRC who underwent CT and cytotoxic chemotherapy using FOLFOX and FOLFIRI were divided into derivation cohort (n = 145) and validation cohort (n = 90). The CT texture of the hepatic metastasis was quantified using baseline CT. We analyzed the independent predictor for the response from derivation cohort and validated it using validation cohort. We also compared texture features between included four CT scanners. Results: 89 responding and 146 non-responding patients were evaluated. In the derivation cohort, lower skewness (OR, 6.739) in 2D, higher mean attenuation (OR, 2.587), and narrower standard deviation (SD) (OR, 3.163) in 3D were independently associated with response to chemotherapy. However, only lower skewness (P=0.213) on 2D and narrower SD on 3D analysis (P=0.097) did not show a significant difference on either CT scanner. When applied to the validation set, the lower skewness on 2D (AUC = 0.797) and narrower SD on 3D (AUC = 0.785) showed good performance. Conclusion: CT texture analysis is useful for prediction of therapeutic response after cytotoxic chemotherapy in patients with liver metastasis from colorectal cancer.

Therapeutic action of ghrelin in a mouse model of colitis.

Science.gov (United States)

Gonzalez-Rey, Elena; Chorny, Alejo; Delgado, Mario

2006-05-01

Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

Therapeutic vaccines for cancer: an overview of clinical trials

NARCIS (Netherlands)

Melero, I.; Gaudernack, G.; Gerritsen, W.R.; Huber, C.; Parmiani, G.; Scholl, S.; Thatcher, N.; Wagstaff, J.; Zielinski, C.; Faulkner, I.; Mellstedt, H.

2014-01-01

The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the

STIR: Assessing and Training Response Inhibition Abilities

Science.gov (United States)

2014-07-30

Learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inhibition. Addiction ...requires an abstract application of the core learning principle1,2, and viable examples are often hard to find and/or assess. If exposure to non...inhibition training that expands upon previous successful “near transfer” response inhibition training efforts—such as treating alcohol addictions by

Short-term sensory and cutaneous vascular responses to therapeutic ultrasound in the forearms of healthy volunteers.

Science.gov (United States)

Shaik, Shaguftha Sultana; MacDermid, Joy C; Birmingham, Trevor; Grewal, Ruby; Farooq, Baseer

2014-01-01

Therapeutic ultrasound (US) is used for a variety of clinical pathologies and is thought to accelerate tissue repair and help with pain reduction via its thermal and nonthermal effects. The evidence on physiological effects of US on both sensory and vascular functions in humans is incomplete. Hence, the purpose of this study was to determine the short-term impact of two doses of US (3 MHz, 1:4, 0.25 W/cm(2), 5 min; 1 MHz, continuous, 0.8 W/cm(2), 3 min), on sensory and vascular responses in the healthy forearms. Twenty healthy subjects were recruited (mean age, 29.6 ± 8.8 years) for the study. Superficial blood flow (SBF) in the distal forearms was determined using the tissue viability imaging system. Sensory perception thresholds (SPT) were determined from ring finger (C7, C8) to assess A-beta (at 2,000 Hz) and C fiber function (at 5 Hz), using a Neurometer CPT/C device. Subject's two hands were randomly allocated to group order (AB/BA). Scores were obtained before and immediately after the application of US and control. Differences in these were analyzed using repeated measures. Both 3 MHz pulsed US and 1 MHz continuous US showed small to moderate (effect size = 0.12 to 0.68), statistically significant reductions in SBF (3 MHz, mean change = 2.8 AU and 1 MHz, mean change = 3.9 AU, p 0.05). Age and gender also had no effect on all outcome measures (p > 0.05). This study demonstrated minor reductions in skin blood flow, skin temperatures, and C fiber perception thresholds immediately after 3 MHz, and 1 MHz US. The responses observed may have been due to a thermo-cooling effect of the gel or due to the direct effect of US on C fibers of median and ulnar nerves. US had a negligible effect on A-beta fibres. This would suggest that future studies looking at physiological effects of US should move towards investigating larger dosages and study the effects in patient populations.

Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

Directory of Open Access Journals (Sweden)

Laura W. Engstrom

2010-01-01

Full Text Available The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/0.12% cholesterol (HF/CH or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM. Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF, stromal vascular fraction (SVF, and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6.

Hepatitis B core protein as a therapeutic target.

Science.gov (United States)

Mak, Lung-Yi; Wong, Danny Ka-Ho; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man Fung

2017-12-01

Chronic hepatitis B virus (HBV) infection is difficult to cure, due to the presence of covalently-closed-circular DNA and virus-mediated blunting of host immune response. Existing therapies with nucleos(t)ide analogue or pegylated-interferon are not sufficient to achieve a high rate of HBV surface antigen seroclearance, a more desirable treatment outcome. Novel therapeutic agents targeting alternative viral replication steps are being developed. In this review, we will discuss the hepatitis B core antigen (HBcAg) as a therapeutic target. Areas covered: The basic structure and fundamental functions of HBcAg including nucleocapsid assembly, pre-genomic RNA encapsidation, reverse transcription, virion formation, cccDNA amplification, immune response regulation, and HBx protein interaction will be reviewed. Most of these are identified as therapeutic targets and tested in in vitro and in vivo studies, although clinical trials are scanty. Among the different components, the core protein allosteric modulators (CpAM) have been most widely investigated and appear promising in clinical trials. Expert opinion: The multiple and essential functions of HBcAg for HBV life cycle are important and attractive targets for HBV therapeutic interventions. Controlled trials involving CpAM are awaited. Apart from CpAM, drugs directed against different functions of HBcAg may be further explored to maximize the chance of cure.

Assessing therapeutic change in patients with severe dissociative disorders: the progress in treatment questionnaire, therapist and patient measures.

Science.gov (United States)

Schielke, Hugo; Brand, Bethany; Marsic, Angelika

2017-01-01

Background : Treatment research for dissociative identity disorder (DID) and closely related severe dissociative disorders (DD) is rare, and has been made more difficult by the lack of a reliable, valid measure for assessing treatment progress in these populations. Objective : This paper presents psychometric data for therapist and patient report measures developed to evaluate therapeutic progress and outcomes for individuals with DID and other DD: the Progress in Treatment Questionnaire - Therapist (PITQ-t; a therapist report measure) and the Progress in Treatment Questionnaire - Patient (PITQ-p; a patient self-report measure). Method : We examined the data of 177 patient-therapist pairs (total N  = 354) participating in the TOP DD Network Study, an online psychoeducation programme aimed at helping patients with DD establish safety, regulate emotions, and manage dissociative and posttraumatic symptoms. Results : The PITQ-t and PITQ-p demonstrated good internal consistency and evidence of moderate convergent validity in relation to established measures of emotional dysregulation, dissociation, posttraumatic stress disorder, and psychological quality of life, which are characteristic difficulties for DD patients. The measures also demonstrated significant relationships in the hypothesized directions with positive emotions, social relations, and self-harm and dangerous behaviours. The patient-completed PITQ-p, which may be used as an ongoing assessment measure to guide treatment planning, demonstrated evidence of stronger relationships with established symptom measures than the PITQ-t. Conclusions : The PITQ-t and PITQ-p merit use, additional research, and refinement in relation to the assessment of therapeutic progress with patients with DD.

Immunogenicity of therapeutic proteins: the use of animal models.

Science.gov (United States)

Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

2011-10-01

Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of immunogenicity during drug development and have become vital in studying the mechanisms underlying immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for immunogenicity prediction and summarizes the insights in immunogenicity that they have given so far.

Vehicle response-based track geometry assessment using multi-body simulation

Science.gov (United States)

Kraft, Sönke; Causse, Julien; Coudert, Frédéric

2018-02-01

The assessment of the geometry of railway tracks is an indispensable requirement for safe rail traffic. Defects which represent a risk for the safety of the train have to be identified and the necessary measures taken. According to current standards, amplitude thresholds are applied to the track geometry parameters measured by recording cars. This geometry-based assessment has proved its value but suffers from the low correlation between the geometry parameters and the vehicle reactions. Experience shows that some defects leading to critical vehicle reactions are underestimated by this approach. The use of vehicle responses in the track geometry assessment process allows identifying critical defects and improving the maintenance operations. This work presents a vehicle response-based assessment method using multi-body simulation. The choice of the relevant operation conditions and the estimation of the simulation uncertainty are outlined. The defects are identified from exceedances of track geometry and vehicle response parameters. They are then classified using clustering methods and the correlation with vehicle response is analysed. The use of vehicle responses allows the detection of critical defects which are not identified from geometry parameters.

Therapeutic drug monitoring in epilepsy clinic: a multi-disciplinary approach

Directory of Open Access Journals (Sweden)

Sunee Lertsinudom

2014-12-01

Full Text Available Epilepsy is a common public health problem and needs multi-disciplinary treatment. Therapeutic drug monitoring (TDM is one of step of the multi-disciplinary treatment in epilepsy at Epilepsy clinic, Khon Kaen University (Thailand. The TDM service has been established since 2008. Here, we aimed to study the roles of TDM order and epilepsy control. This is a prospective descriptive study in which data collection was done from January 1 to December 31, 2010, the period when pharmacists took part in assessing the appropriateness in measurement and interpretation of TDM in order to provide suggestions for physicians. The 112 patients under study had an average age of 38.21±15.36 years; 254 samples were collected for therapeutic drug monitoring; phenytoin was submitted mostly for drug monitoring at 46.46%; 44.49% of sub-missions for drug level monitoring were made owing to a suspected sub-therapeutic level. Associations were found between reasons of sending samples for drug level monitoring and the measured drug levels, i.e., 66.67% of drug levels found was so low that they were undetectable in sample for patients’ compliance investigation and 38.94% of the drug levels were found to be sub-therapeutic as for the case where submission of samples was done because of suspected sub-therapeutic level, 40% of the cases were found to be in toxicity range in the cases with suspected over-therapeutic levels and monitoring levels, 58.25% were found to be within the therapeutic range. Pharmacists used the interpreted results in patients’ care by recommending physicians to monitor therapeutic drug closely, to adjust the dosage of drugs, and to recommend checking patients’ compliance in their use of drugs at 56.5, 38.9, and 4.3%, respectively. Physicians’ responses were found to be absolute follow, partial follow and not follow at 77.95, 11.03, and 7.48%, respectively. In conclusion, associations were found between reasons of TDM order and measured drug

iRECIST : Guidelines for response criteria for use in trials testing immunotherapeutics

NARCIS (Netherlands)

Seymour, Lesley; Bogaerts, Jan; Perrone, Andrea; Ford, Robert; Schwartz, Lawrence H.; Mandrekar, Sumithra; Lin, Nancy U.; Litiere, Saskia; Dancey, Janet; Chen, Alice; Hodi, F. Stephen; Therasse, Patrick; Hoekstra, Otto S.; Shankar, Lalitha K.; Wolchok, Jedd D.; Ballinger, Marcus; Caramella, Caroline; de Vries, Elisabeth G. E.

Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden-a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus

Proteomic approaches in cancer risk and response assessment.

Science.gov (United States)

Petricoin, Emanuel F; Liotta, Lance A

2004-02-01

Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy.

Clinical characteristics and therapeutic response in patients with Burning Mouth Syndrome: accompanying 2 years

Directory of Open Access Journals (Sweden)

Vanessa Juliana Gomes CARVALHO

Full Text Available Abstract Introduction Burning Mouth Syndrome (BMS is a condition characterized by burning symptom of the oral mucosa in the absence of clinical signs. Its etiology is still unknown and, and to date there is no effective treatment. Purpose The aim of this study was to evaluate patients with BMS profile and the therapies results in a retrospective study. Material and method Clinical and therapeutic data were collected from records of patients with BMS diagnosed between January 2013 to April 2015 at the Clinic of Stomatology Clinic, Faculdade de Odontologia of Universidade de São Paulo, according to the criteria established by the International Headache Society in 2013. The therapies used for BMS control were also evaluated. Result Twelve patients were diagnosed with BMS at this period. All of them were women with a mean age of 61.18 years and the apex of the tongue was the most common affected site and the duration of the burning sensation ranged from 6 months to 25 years. Many therapies were prescribed for BMS control, such as topical capsaicin, topical clonazepan, low level laser therapy and homeopathy. Among the established therapies, capsaicin has immediate effect in reducing symptoms. Conclusion The present study showed that the challenges towards an effective treatment for BMS are varied and are mainly related to the lack knowing of the pathogenesis of this disease. The demographic profile of patients studied here was similar to that described in the available literature, however, the variables represented by secondary symptoms (medical history, anxiety and depression levels may be modifying factors of therapeutic response and the pathogenesis of the disease itself.

Assessment and monitoring of treatment response in adult ADHD patients: current perspectives.

Science.gov (United States)

Ramsay, J Russell

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome that emerges in childhood or early adolescence and persists into adulthood for a majority of individuals. There are many other adults with ADHD who may not seek out evaluation and treatment until adulthood, having been able to "get by" before struggling with inattention, hyperactivity, and/or impulsivity in adulthood, in addition to facing the associated features of disorganization, poor time management, and procrastination among many others. A lifetime diagnosis of ADHD is associated with a wide range of life impairments, which makes a comprehensive and accurate diagnostic assessment essential in order to obtain appropriate treatment. Moreover, while there are effective medical and psychosocial treatments for ADHD, it is important to be able to track treatment response in order to evaluate whether adjustments in specific interventions are needed or referrals for adjunctive treatments and supports are indicated to facilitate optimal therapeutic outcomes. The goal of this article is to provide a clinically useful review of the various measures that practicing clinicians can use to aid in the diagnostic assessment and monitoring of psychosocial and medical treatment of ADHD in adult patients. This review includes various structured interviews, screening scales, adult ADHD symptom inventories, measures of associated features of ADHD, as well as ratings of impairment and functioning which can be adapted to clinicians' practice needs in order to track treatment progress and optimize treatments for adults with ADHD.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

Energy Technology Data Exchange (ETDEWEB)

Denecke, Timm; Misch, Daniel; Steffen, Ingo G.; Plotkin, Michail; Stoever, Brigitte [Charite - Universitaetsmedizin Berlin, Klinik fuer Strahlenheilkunde, Campus Virchow-Klinikum, Berlin (Germany); Hundsdoerfer, Patrick; Henze, Guenter [Charite - Universitaetsmedizin Berlin, Klinik fuer Paediatrie m.S. Onkologie und Haematologie, Otto-Heubner-Zentrum, Campus Virchow-Klinikum, Berlin (Germany); Schoenberger, Stefan [Universitaetsklinikum der Heinrich-Heine-Universitaet Duesseldorf, Klinik fuer Kinder-Onkologie, -Haematologie und -Immunologie, Duesseldorf (Germany); Furth, Christian; Ruf, Juri [Otto-von-Guericke-Universitaet Magdeburg, Klinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany); Hautzel, Hubertus [Universitaetsklinikum der Heinrich Heine Universitaet Duesseldorf, Nuklearmedizinische Klinik, Duesseldorf (Germany); Kluge, Regine [Universitaetsklinikum Leipzig A.oe.R., Klinik und Poliklinik fuer Nuklearmedizin, Leipzig (Germany); Bierbach, Uta [Universitaetsklinikum Leipzig A.oe.R., Abteilung fuer Kinder-Haematologie, -Onkologie und -Haemostaseologie, Leipzig (Germany); Otto, Sylke [Universitaetsklinikum Greifswald, Institut fuer Diagnostische Radiologie und Neuroradiologie, Greifswald (Germany); Beck, James F. [Universitaetsklinikum Greifswald, Abteilung fuer Paediatrische Haematologie und Onkologie, Greifswald (Germany); Franzius, Christiane [MR- und PET/CT-Zentrum, Bremen-Mitte (Germany); Universitaetsklinikum Muenster, Klinik und Poliklinik fuer Nuklearmedizin, Muenster (Germany); Amthauer, Holger [Charite - Universitaetsmedizin Berlin, Klinik fuer Strahlenheilkunde, Campus Virchow-Klinikum, Berlin (Germany); Otto-von-Guericke-Universitaet Magdeburg, Klinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany)

2010-10-15

The objective of this study was to evaluate positron emission tomography (PET) using {sup 18}F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients. FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik. FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population ({nabla}SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients ({nabla}SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS. FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment. (orig.)

[Therapeutic response of Plasmodium vivax to chloroquine in Bolivia].

Science.gov (United States)

Añez, Arletta; Navarro-Costa, Dennis; Yucra, Omar; Garnica, Cecilia; Melgar, Viviana; Moscoso, Manuel; Arteaga, Ricardo; Nakao, Gladys

2012-01-01

Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.

34 CFR 200.2 - State responsibilities for assessment.

Science.gov (United States)

2010-07-01

... responsibilities for assessment. (a)(1) Each State, in consultation with its LEAs, must implement a system of high... multiple up-to-date measures of student academic achievement, including measures that assess higher-order thinking skills and understanding of challenging content, as defined by the State. These measures may...

Tools for predicting the PK/PD of therapeutic proteins.

Science.gov (United States)

Diao, Lei; Meibohm, Bernd

2015-07-01

Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. In this review, the authors discuss tools that are utilized to describe and predict the PK/PD features of therapeutic proteins and that are valuable additions in the armamentarium of drug development approaches to facilitate and accelerate their successful preclinical and clinical development. A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.

Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss

Directory of Open Access Journals (Sweden)

Masato eFujioka

2014-12-01

Full Text Available The inner ear was previously assumed to be an immune-privileged organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of insults, including noise exposure, ischemia, mitochondrial damage and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms, in the stria vascularis. These dedicated antigen-presenting cells also control vascular contraction and permeability. This review discusses a series of reports regarding inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets.

Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

Science.gov (United States)

Bresani Salvi, Cristiane Campello; Braga, Maria Cynthia; Figueirôa, José Natal; Batista Filho, Malaquias

2016-08-12

Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40�

Methodological approaches to the assessment level of social responsibility

OpenAIRE

Vorona, E.

2010-01-01

A study of current approaches to assessing the level of social responsibility. Proposed methodological approach to evaluating the performance of the social responsibility of railway transport. Conceptual Basis of social reporting in rail transport.

Federal Radiological Monitoring and Assessment Center Analytical Response

International Nuclear Information System (INIS)

Nielsen, E.C.

2003-01-01

The Federal Radiological Monitoring and Assessment Center (FR-MAC) is authorized by the Federal Radiological Emergency Response Plan to coordinate all off-site radiological response assistance to state and local government s, in the event of a major radiological emergency in the United States. The FR-MAC is established by the U.S. Department of Energy, National Nuclear Security Administration, to coordinate all Federal assets involved in conducting a comprehensive program of radiological environmental monitoring, sampling, radioanalysis, quality assurance, and dose assessment. During an emergency response, the initial analytical data is provided by portable field instrumentation. As incident responders scale up their response based on the seriousness of the incident, local analytical assets and mobile laboratories add additional capability and capacity. During the intermediate phase of the response, data quality objectives and measurement quality objectives are more rigorous. These higher objectives will require the use of larger laboratories, with greater capacity and enhanced capabilities. These labs may be geographically distant FR-om the incident, which will increase sample management challenges. This paper addresses emergency radioanalytical capability and capacity and its utilization during FR-MAC operations

Avian Diagnostic and Therapeutic Antibodies

Energy Technology Data Exchange (ETDEWEB)

Bradley, David Sherman [UND SMHS

2012-12-31

A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

The assessment of bee venom responses in an experimental model of mono-arthritis using Tc-99m DPD bone scintigraphy

International Nuclear Information System (INIS)

Yang, Chung-Yong; Park, Soon-Ah; Oh, Kyung-Jae; Yang, Yun-Sik

2010-01-01

Several recent studies have shown that bee venom (BV) has an anti-nociceptive and anti-inflammatory effect on arthritis. However, objective methods for evaluation of the therapeutic effect of BV is insufficient in animal studies and clinical trials. Our purpose was to determine the usefulness of bone scintigraphy using Tc-99m DPD (3,3-diphosphono-1,2-propan-dicarbonacid) about effects of BV applied to carrageenan-induced mono-arthritis (CIA) model. Mono-arthritis was induced by an intra-articular injection of carrageenan in Sprague-Dawley rats. Administration of BV (0.8 mg/kg) was performed at 30 min before and at 4 h after the induction of mono-arthritis. We assigned rats to BV-before, BV-after, control-before and control-after groups and compared the results of each group by the weight-loading test and bone scintigraphy. The rats received an intravenous injection of 37 MBq of Tc-99m DPD by the tail vein and then scanning was performed at 4 and 24 h after the injection. Visual assessment and quantitative analysis were performed for both knees. The BV-before and BV-after groups were more improved than the control groups on the weight load test (p<0.05). Bone scintigraphy showed lower activity in the BV-before group than in the control-before group (p<0.05) on the 4 h imaging. However, a significant difference in the BV-before and BV-after groups was not observed on the 24 h imaging. BV had therapeutic effects by anti-nociceptive and anti-inflammatory activity in the CIA and bone scintigraphy performed on 4 h imaging provided visual and quantitative information for the assessment of the therapeutic response to BV as an objective method in mono arthritis model. (author)

Writing, Evaluating and Assessing Data Response Items in Economics.

Science.gov (United States)

Trotman-Dickenson, D. I.

1989-01-01

Describes some of the problems in writing data response items in economics for use by A Level and General Certificate of Secondary Education (GCSE) students. Examines the experience of two series of workshops on writing items, evaluating them and assessing responses from schools. Offers suggestions for producing packages of data response items as…

Immunological mechanism underlying the immune response to tecombinant human protein therapeutics

NARCIS (Netherlands)

Sauerborn, M.S.; Brinks, V.; Jiskoot, W.; Schellekens, H.

2010-01-01

Recombinant human (rhu) protein therapeutics are powerful tools to treat several severe diseases such as multiple sclerosis and diabetes mellitus, among others. A major drawback of these proteins is the production of anti-drug antibodies (ADAs). In some cases, these ADAs have neutralizing capacity

Therapeutic alliance in a randomized clinical trial for bulimia nervosa.

Science.gov (United States)

Accurso, Erin C; Fitzsimmons-Craft, Ellen E; Ciao, Anna; Cao, Li; Crosby, Ross D; Smith, Tracey L; Klein, Marjorie H; Mitchell, James E; Crow, Scott J; Wonderlich, Stephen A; Peterson, Carol B

2015-06-01

This study examined the temporal relation between therapeutic alliance and outcome in two treatments for bulimia nervosa (BN). Eighty adults with BN symptoms were randomized to 21 sessions of integrative cognitive-affective therapy (ICAT) or enhanced cognitive-behavioral therapy (CBT-E). Bulimic symptoms (i.e., frequency of binge eating and purging) were assessed at each session and posttreatment. Therapeutic alliance (Working Alliance Inventory) was assessed at Sessions 2, 8, 14, and posttreatment. Repeated-measures analyses using linear mixed models with random intercepts were conducted to determine differences in alliance growth by treatment and patient characteristics. Mixed-effects models examined the relation between alliance and symptom improvement. Overall, patients in both treatments reported strong therapeutic alliances. Regardless of treatment, greater therapeutic alliance between (but not within) subjects predicted greater reductions in bulimic behavior; reductions in bulimic behavior also predicted improved alliance. Patients with higher depression, anxiety, or emotion dysregulation had a stronger therapeutic alliance in CBT-E than ICAT, while those with more intimacy problems had greater improvement in therapeutic alliance in ICAT compared to CBT-E. Therapeutic alliance has a unique impact on outcome, independent of the impact of symptom improvement on alliance. Within- and between-subjects effects revealed that changes in alliance over time did not predict symptom improvement, but rather that individuals who had a stronger alliance overall had better bulimic symptom outcomes. These findings indicate that therapeutic alliance is an important predictor of outcome in the treatment of BN. (c) 2015 APA, all rights reserved).

Evaluation of Fluorophotometry to Assess the Vitreal Pharmacokinetics of Protein Therapeutics.

Science.gov (United States)

Dickmann, Leslie J; Yip, Victor; Li, Cuiwen; Abundes, Juan; Maia, Mauricio; Young, Cynthia; Stainton, Shannon; Hass, Philip E; Joseph, Sean B; Prabhu, Saileta; Boswell, C Andrew

2015-10-01

In this work, we assessed the ability of fluorophotometry to measure the vitreal pharmacokinetics (PK) of fluorescently-labeled ranibizumab in the rabbit after intravitreal injection. We compared these values to those obtained using enzyme-linked immunosorbent assays (ELISA). Data obtained in this study were also compared to historical ranibizumab ocular PK data, either measured in-house or previously published. Three individual in vivo studies were performed in New Zealand White rabbits to assess the feasibility of using fluorophotometry to measure rabbit ocular PK of ranibizumab; explore the dynamic range of dosing fluorescently-labeled ranibizumab; and directly compare ranibizumab concentrations and calculated PK parameters measured by vitreal fluorophotometry to those measured using ELISA. In direct comparisons between fluorophotometry and ELISA, the calculated clearance (CL) values were 0.26 and 0.21 mL/day, the volumes of distribution at steady state (Vss) were 0.80 and 0.94 mL, the half-lives (t₁/₂) were 3.1 and 2.9 days and the dose normalized areas under the curve (AUC/D) were 4.7 and 3.9 μg·day/mL/μg, respectively. These values fell within the ranges of 0.13 to 0.44 mL/day for CL, 0.5 to 1.8 mL for Vss, 2.8 to 3.5 days for t1/2, and 2.3 to 7.9 μg·day/mL/μg for AUC/D that have been either measured previously in-house or published elsewhere. Although not suitable for measuring retinal concentrations, fluorophotometry is a valuable, noninvasive method to measure vitreous concentrations of protein therapeutics after intravitreal injection.

Assessment of cognitive functions after prophylactic and therapeutic whole brain irradiation using neuropsychological testing

International Nuclear Information System (INIS)

Penitzka, S.; Wannenmacher, M.; Steinvorth, S.; MIT, Cambridge, MT; Sehlleier, S.; Universitaetsklinikum Wuerzburg; Fuss, M.; Texas Univ., San Antonio, TX; Wenz, F.; Universitaetsklinikum Mannheim

2002-01-01

Purpose: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. Patients and Method: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). Results: Patients with SCLC showed test results significantly below average before PCI (n=28, mean IQ=83, SD=17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). Conclusion: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible. (orig.) [de

Emergency Response Capability Baseline Needs Assessment - Compliance Assessment

Energy Technology Data Exchange (ETDEWEB)

Sharry, John A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-09-01

This document was prepared by John A. Sharry, LLNL Fire Marshal and Division Leader for Fire Protection and was reviewed by LLNL Emergency Management Department Head, James Colson. This document is the second of a two-part analysis on Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2016 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2016 BNA, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures. The 2013 BNA was approved by NNSA’s Livermore Field Office on January 22, 2014.

Assessing item fit for unidimensional item response theory models using residuals from estimated item response functions.

Science.gov (United States)

Haberman, Shelby J; Sinharay, Sandip; Chon, Kyong Hee

2013-07-01

Residual analysis (e.g. Hambleton & Swaminathan, Item response theory: principles and applications, Kluwer Academic, Boston, 1985; Hambleton, Swaminathan, & Rogers, Fundamentals of item response theory, Sage, Newbury Park, 1991) is a popular method to assess fit of item response theory (IRT) models. We suggest a form of residual analysis that may be applied to assess item fit for unidimensional IRT models. The residual analysis consists of a comparison of the maximum-likelihood estimate of the item characteristic curve with an alternative ratio estimate of the item characteristic curve. The large sample distribution of the residual is proved to be standardized normal when the IRT model fits the data. We compare the performance of our suggested residual to the standardized residual of Hambleton et al. (Fundamentals of item response theory, Sage, Newbury Park, 1991) in a detailed simulation study. We then calculate our suggested residuals using data from an operational test. The residuals appear to be useful in assessing the item fit for unidimensional IRT models.

Bacterial–viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects

Directory of Open Access Journals (Sweden)

D’Anna SE

2016-03-01

Full Text Available Silvestro Ennio D’Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefalù, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO and Cassano delle Murge (BA, 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung. Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways. Bacterial variety diminishes with increasing COPD severity. Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections. In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD. In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial–viral infections and related immune response in COPD phenotypes need to be better clarified. Our paper would address these points that we consider of great importance for the clinical management of COPD.Keywords: COPD phenotype, biomarkers, exacerbations, severity of COPD, microbiome

Regulatory T cell derived Exosomes: possible therapeutic and diagnostic tools in transplantation

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Akansha eAgarwal

2014-11-01

Full Text Available Exosomes are extracellular vesicles released by many cells of the body. These small vesicles play an important part in intercellular communication both in the local environment and systemically, facilitating in the transfer of proteins, cytokines as well as miRNA between cells. The observation that exosomes isolated from immune cells such as dendritic cells (DCs modulate the immune response has paved the way for these structures to be considered as potential immunotherapeutic reagents. Indeed clinical trials using DC derived exosomes to facilitate immune responses to specific cancer antigens are now underway. Exosomes can also have a negative effect on the immune response and exosomes isolated from regulatory T cells (Tregs and other subsets of T cells have been shown to have immune suppressive capacities. Here we review what is currently known about Treg derived exosomes and their contribution to immune regulation, as well as highlighting their possible therapeutic potential for preventing graft rejection, and their possible use as diagnostic tools to assess transplant outcome.

Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

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Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

2016-01-01

Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, poptimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (poptimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

Developing patient rapport, trust and therapeutic relationships.

Science.gov (United States)

Price, Bob

2017-08-09

Rapport is established at the first meeting between the patient and nurse, and is developed throughout the therapeutic relationship. However, challenges can arise during this process. Initially, nurses can establish trust with the patient through the questions they ask, however, as care progresses, the nurse will be required to demonstrate a commitment to maintaining the patient's psychological well-being. When the therapeutic relationship ends, the nurse should assist the patient to assess progress and plan the next stage of recovery. This article provides three reflective exercises using case study examples to demonstrate how rapport is developed and sustained. Evidence is provided to identify why challenges arise in the therapeutic relationship and how the nurse can ensure they provide care that the patient regards as genuine.

Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes

Science.gov (United States)

Greenbaum, Carla J.; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M.; Kolb, Hubert

2008-01-01

OBJECTIVE—β-Cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS—In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS—Among individuals with up to 4 years’ duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R2 = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS—The MMTT is preferred for the assessment of β-cell function in therapeutic trials in type 1 diabetes. PMID:18628574

Modulating the innate immune response to influenza A virus: potential therapeutic use of anti-inflammatory drugs

Directory of Open Access Journals (Sweden)

Irene eRamos

2015-07-01

Full Text Available Infection by influenza A viruses (IAV is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV is a consequence of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. Indeed, some anti-inflammatory agents have been shown to be effective in animal models at reducing IAV pathology as a proof of principle. The main challenge in developing such therapies is to selectively modulate signaling pathways that contribute to lung injury while maintaining the ability of the host cells to mount an antiviral response to control virus replication. However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e. NF kappa B transcription factors and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies.

Systematic Review of the Diagnostic Accuracy and Therapeutic Effectiveness of Sacroiliac Joint Interventions.

Science.gov (United States)

Simopoulos, Thomas T; Manchikanti, Laxmaiah; Gupta, Sanjeeva; Aydin, Steve M; Kim, Chong Hwan; Solanki, Daneshvari; Nampiaparampil, Devi E; Singh, Vijay; Staats, Peter S; Hirsch, Joshua A

2015-01-01

The sacroiliac joint is well known as a cause of low back and lower extremity pain. Prevalence estimates are 10% to 25% in patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis based on multiple diagnostic studies and systematic reviews. However, at present there are no definitive management options for treating sacroiliac joint pain. To evaluate the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. A systematic review of the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. The available literature on diagnostic and therapeutic sacroiliac joint interventions was reviewed. The quality assessment criteria utilized were the Quality Appraisal of Reliability Studies (QAREL) checklist for diagnostic accuracy studies, Cochrane review criteria to assess sources of risk of bias, and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) criteria for randomized therapeutic trials and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for observational therapeutic assessments. The level of evidence was based on a best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. Data sources included relevant literature published from 1966 through March 2015 that were identified through searches of PubMed and EMBASE, manual searches of the bibliographies of known primary and review articles, and all other sources. For the diagnostic accuracy assessment, and for the therapeutic modalities, the primary outcome measure of pain relief and improvement in functional status were utilized. A total of 11 diagnostic accuracy studies and 14 therapeutic studies were included. The evidence for diagnostic accuracy is Level II for dual diagnostic blocks with at least 70% pain relief as the criterion

Crossing the cultural divide: issues in translation, mistrust, and cocreation of meaning in cross-cultural therapeutic assessment.

Science.gov (United States)

Rosenberg, Audrey; Almeida, Angelica; Macdonald, Heather

2012-01-01

This article examines cross-cultural therapeutic assessment in a community mental health clinic. The first case describes the work between a Caucasian assessor and a Mexican American family. The authors explore the metaphorical and literal translation of the findings from English to Spanish and the parallel process of translation of the self, experienced by both assessor and client. The second case describes the work between a Caucasian assessor and an African American adolescent. We describe the inherent challenge between the Eurocentric "task" orientation of the evaluation and the Afrocentric "relationship" orientation. We suggest that bridging the gap between cultures and overcoming cultural mistrust lay in the building of the assessor-client relationship. Fischer's concepts of rapport and intimacy are emphasized and expanded on as we emphasize the importance of cocreated meaning in cross-cultural assessment work.

Interactions of silica nanoparticles with therapeutics for oxidative stress attenuation in neurons

Science.gov (United States)

White-Schenk, Desiree; Shi, Riyi; Leary, James F.

2015-03-01

Oxidative stress plays a major role in many disease pathologies, notably in the central nervous system (CNS). For instance, after initial spinal cord injury, the injury site tends to increase during a secondary chemical injury process based on oxidative stress from necrotic cells and the inflammatory response. Prevention of this secondary chemical injury would represent a major advance in the treatment of people with spinal cord injuries. Few therapeutics are useful in combating such stress in the CNS due to side effects, low efficacy, or half-life. Mesoporous silica nanoparticles show promise for delivering therapeutics based on the formation of a porous network during synthesis. Ideally, they increase the circulation time of loaded therapeutics to increase the half-life while reducing overall concentrations to avoid side effects. The current study explored the use of silica nanoparticles for therapeutic delivery of anti-oxidants, in particular, the neutralization of acrolein which can lead to extensive tissue damage due to its ability to generate more and more copies of itself when it interacts with normal tissue. Both an FDA-approved therapeutic, hydralazine, and natural product, epigallocatechin gallate, were explored as antioxidants for acrolein with nanoparticles for increased efficacy and stability in neuronal cell cultures. Not only were the nanoparticles explored in neuronal cells, but also in a co-cultured in vitro model with microglial cells to study potential immune responses to near-infrared (NIRF)-labeled nanoparticles and uptake. Studies included nanoparticle toxicity, uptake, and therapeutic response using fluorescence-based techniques with both dormant and activated immune microglia co-cultured with neuronal cells.

Rethinking the Response to Emerging Microbes: Vaccines and Therapeutics in the Ebola Era--a Conference at Harvard Medical School.

Science.gov (United States)

Knipe, David M; Whelan, Sean P

2015-08-01

Harvard Medical School convened a meeting of biomedical and clinical experts on 5 March 2015 on the topic of "Rethinking the Response to Emerging Microbes: Vaccines and Therapeutics in the Ebola Era," with the goals of discussing the lessons from the recent Ebola outbreak and using those lessons as a case study to aid preparations for future emerging infections. The speakers and audience discussed the special challenges in combatting an infectious agent that causes sporadic outbreaks in resource-poor countries. The meeting led to a call for improved basic medical care for all and continued support of basic discovery research to provide the foundation for preparedness for future outbreaks in addition to the targeted emergency response to outbreaks and targeted research programs against Ebola virus and other specific emerging pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

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Kristin Brekke

Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

Perspectives for Preventive and Therapeutic HPV Vaccines

Science.gov (United States)

Lin, Ken; Doolan, Kimberley; Hung, Chien-Fu; Wu, T-C

2010-01-01

Cervical cancer is the second most common cause of female cancer death worldwide. Persistent infection with `high risk' HPV genotypes is the major etiological factor in cervical cancer and thus effective vaccination against HPV provides an opportunity to reduce the morbidity and mortality associated with HPV. The FDA has approved two preventive vaccines to limit the spread of HPV. However, these are unlikely to impact upon HPV prevalence and cervical cancer rates for many years. Furthermore, preventive vaccines do not exert therapeutic effects on pre-existing HPV infections and HPV-associated lesions. In order to further impact upon the burden of HPV infections worldwide, therapeutic vaccines are being developed. These vaccines aim to generate a cell-mediated immune response to infected cells. This review discusses current preventive and therapeutic HPV vaccines and their future directions. PMID:20123582

Therapeutic Vaccination for HPV Induced Cervical Cancers

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Joeli A. Brinkman

2007-01-01

Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives

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Maria-Jesus Pinazo

2015-05-01

Full Text Available The definition of a biomarker provided by the World Health Organization is any substance, structure, or process that can be measured in the body, or its products and influence, or predict the incidence or outcome of disease. Currently, the lack of prognosis and progression markers for chronic Chagas disease has posed limitations for testing new drugs to treat this neglected disease. Several molecules and techniques to detect biomarkers in Trypanosoma cruzi-infected patients have been proposed to assess whether specific treatment with benznidazole or nifurtimox is effective. Isolated proteins or protein groups from different T. cruzi stages and parasite-derived glycoproteins and synthetic neoglycoconjugates have been demonstrated to be useful for this purpose, as have nucleic acid amplification techniques. The amplification of T. cruzi DNA using the real-time polymerase chain reaction method is the leading test for assessing responses to treatment in a short period of time. Biochemical biomarkers have been tested early after specific treatment. Cytokines and surface markers represent promising molecules for the characterisation of host cellular responses, but need to be further assessed.

Evaluation of therapeutic response with 18-FDG PET-CT for non-small cell lung cancer: case report and literature review

International Nuclear Information System (INIS)

Bitencourt, Almir G.V.; Lima, Eduardo N.P.; Chojniak, Rubens; Haddad, Fabio J.; Dettino, Aldo L.A.; Cavicchioli, Marcelo; Torres, Ivone C.G.

2010-01-01

Positron Emission Tomography / Computed Tomography (PET-CT) is increasingly being used as to complement conventional imaging methods and improve the management of patients with non-small cells lung cancer (NSCLC). The objective of this work is to report on a case in which PET-CT was used as a complementary method to evaluate the therapeutic response in a patient with NSCLC, and to carry out a literature review of the theme. Female patient, 65 years-old, with NSCLC, stage IIIA (T2N2M0), was submitted to exclusive neoadjuvant chemotherapy and presented good response to the treatment, classified by the morphological criteria of the RECIST (Response Evaluation Criteria in Solid Tumors) as a partial response (reduction equal to or greater than 30% in the sum of the widest diameter of all the target lesions in the computed tomography). The metabolic evaluation by PET-CT showed a complete response (reduction equal to or higher than 80% at maximum SUV of the lesions), which was confirmed in the histopathological analysis of the surgical samples. In the case presented, and through the literature review, we show that the evaluation of response with metabolic criteria, associated with morphological criteria, may be more accurate than the use of morphological criteria alone. (author)

Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest

DEFF Research Database (Denmark)

Bro-Jeppesen, John; Kjaergaard, Jesper; Søholm, Helle

2014-01-01

AIM: Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopres......AIM: Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level...

Federal Radiological Monitoring and Assessment Center. The analytical response

International Nuclear Information System (INIS)

Nielsen, E.C.

2005-01-01

The Federal Radiological Monitoring and Assessment Center (FRMAC) is authorized by the Federal Radiological Emergency Response Plan to coordinate all off-site radiological response assistance to state and local governments, in the event of a major radiological emergency in the United States. The FRMAC is established by the U.S. Department of Energy, National Nuclear Security Administration, to coordinate all Federal assets involved in conducting a comprehensive program of radiological environmental monitoring, sampling, radioanalysis, quality assurance, and dose assessment. During an emergency response, the initial analytical data is provided by portable field instrumentation. As incident responders scale up their response based on the seriousness of the incident, local analytical assets and mobile laboratories add additional capability and capacity. During the intermediate phase of the response, data quality objectives and measurement quality objectives are more rigorous. These higher objectives will require the use of larger laboratories, with greater capacity and enhanced capabilities. These labs may be geographically distant from the incident, which will increase sample management challenges. Emergency radioanalytical capability and capacity and its utilization during FRMAC operations are discussed. (author)

Study and evaluation of radiometry in photo therapeutic treatment of the neonatal hyperbilirubinaemia

International Nuclear Information System (INIS)

Caly, Jose Pucci

2009-01-01

Phototherapy is a procedure established more than 50 years ago in the treatment of the newborn jaundice. However there is no a standard method to quantify the photo therapeutic dose in published clinical studies, hindering the comparison of previous studies on photo therapeutic effectiveness, as well as the establishment of safe and predictable doses. The photo therapeutic dose depends, among other factors, on the effective mean irradiance produced by the photo therapeutic unit. There are no standard procedures, however, neither to quantify the effective irradiance, nor to estimate the mean effective irradiance. As a consequence, large measurement variations in a same photo therapeutic unit are observed using different commercially available radiometers, as a consequence of the vast diversity of spectral responsivities of the instruments. An objective of this work was to adapt and to apply the bases of the wideband ultraviolet radiometry to quantify the available irradiance from photo therapeutic units, establishing procedures that allow us to compare measured irradiances from different sources, using radiometers presenting different spectral responsivities. Another objective was to characterize samples of photo therapeutic units commonly used, focusing the problem of the estimation of the effective mean irradiance from photo therapeutic units, proposing a method to estimate of the effective irradiance from focused sources. The experimental results allow us to conclude that it is not only necessary to standardize the photo therapeutic radiometry, but also the method of estimation of the effective mean irradiance. (author)

Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent

International Nuclear Information System (INIS)

Altomare, Deborah A; Rybak, Susanna M; Pei, Jianming; Maizel, Jacob V; Cheung, Mitchell; Testa, Joseph R; Shogen, Kuslima

2010-01-01

Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action. In this study, microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 μg/ml Onconase for 24 h. A total of 155 genes were found to be regulated by Onconase that were common to both epithelial and biphasic MM cell lines. Some of these genes are known to significantly affect apoptosis (IL-24, TNFAIP3), transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1) or inflammation and the immune response (IL-6, COX-2). RT-PCR analysis of selected up- or down-regulated genes treated with varying doses and times of Onconase generally confirmed the expression array findings in four MM cell lines. Onconase treatment consistently resulted in up-regulation of IL-24, previously shown to have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive MM cell lines, as defined by DNA fragmentation analysis. In addition to apoptosis, gene ontology analysis indicated that pathways impacted by Onconase include MAPK signaling, cytokine-cytokine-receptor interactions, and Jak-STAT signaling. These results provide a broad picture of gene activity after treatment with a drug that targets small non-coding RNAs and contribute to our overall understanding of MM cell response to Onconase as a therapeutic strategy. The findings provide insights regarding mechanisms that may contribute to the efficacy of this novel drug in clinical trials of MM patients who have failed first line chemotherapy or radiation treatment

Reconceptualizing Pain through Patient-Centered Care in the Complementary and Alternative Medicine Therapeutic Relationship.

Science.gov (United States)

Agarwal, Vinita

2018-06-05

The study aim was to understand the patient description of the therapeutic relationship with their CAM provider in the context of pain self-management. Because pain is a subjective state, its assessment depends on patient perception of and response to pain. For nurses to provide empathetic and compassionate care, there is a need to explicate patient perceptions of the therapeutic relationship to (re)conceptualize models of patient-centered care. Inductive qualitative content analysis of patient interviews was conducted to identify how patients described therapeutic relationship themes and understand self-management of pain. Participants were individuals working with a CAM practitioner and solicited through purposive and snowball sampling in collaboration with the practitioners from the mid-Atlantic region of the United States in 2016 (N=13). Verbatim transcriptions of audio-recorded semi-structured in-depth interviews (430 single-spaced pages approximately) were content analyzed. Patients described the therapeutic relationship with the provider as a (a) giver, who was "in-tune" with their sense of self to support self-affirmation through empathetic listening and (b) guide, who connected the mind and body through their practice to support self-reflective learning. This description of the CAM therapeutic relationship advances understandings of readjustment of patient relationship with pain through the provider's empathetic listening and connecting the mind and the body to support patient self-affirmation of pain experiences and self-reflective learning. The findings illuminate how a feminist standpoint contributes to understandings of the therapeutic relationship that centers patient subjectivity and co-construction of meaning-making processes to support self-management of pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Therapeutic Cancer Vaccines in Prostate Cancer: The Quest for Intermediate Markers of Response

International Nuclear Information System (INIS)

Kim, Joseph W.; Bilusic, Marijo; Heery, Christopher J.; Madan, Ravi A.

2012-01-01

Despite recent advances in cancer immunotherapy, no prospectively validated intermediate biomarkers exist to predict response. These biomarkers are highly desirable given modern immunotherapy’s paradoxical pattern of clinical benefit; that is, improvement in overall survival without short-term change in progression. Immunotherapy clinical trials have evaluated biomarkers that may correlate with clinical outcomes. Many of them are performed on peripheral blood to evaluate the systemic response, such as tumor-targeted humoral and cellular immunity, and cytokine responses. Accumulating evidence suggests that immune infiltrates in tumors may suggest evidence for the therapy’s mechanism of action, and have greater potential for providing prognostic and predictive information. In addition, a non-immunologic biomarker, such as tumor growth kinetics, may explain this paradoxical pattern of clinical benefit, and predict survival in patients treated with an immunotherapy. Prospective assessment and validation of these and other intermediate markers would be required to better understand their potential clinical role

Therapeutic Cancer Vaccines in Prostate Cancer: The Quest for Intermediate Markers of Response

Energy Technology Data Exchange (ETDEWEB)

Kim, Joseph W.; Bilusic, Marijo; Heery, Christopher J.; Madan, Ravi A., E-mail: madanr@mail.nih.gov [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

2012-11-21

Despite recent advances in cancer immunotherapy, no prospectively validated intermediate biomarkers exist to predict response. These biomarkers are highly desirable given modern immunotherapy’s paradoxical pattern of clinical benefit; that is, improvement in overall survival without short-term change in progression. Immunotherapy clinical trials have evaluated biomarkers that may correlate with clinical outcomes. Many of them are performed on peripheral blood to evaluate the systemic response, such as tumor-targeted humoral and cellular immunity, and cytokine responses. Accumulating evidence suggests that immune infiltrates in tumors may suggest evidence for the therapy’s mechanism of action, and have greater potential for providing prognostic and predictive information. In addition, a non-immunologic biomarker, such as tumor growth kinetics, may explain this paradoxical pattern of clinical benefit, and predict survival in patients treated with an immunotherapy. Prospective assessment and validation of these and other intermediate markers would be required to better understand their potential clinical role.

Dispositional optimism and therapeutic expectations in early-phase oncology trials.

Science.gov (United States)

Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

2016-04-15

Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; Poptimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (Poptimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early-phase oncology research. © 2016 American Cancer Society.

Maximizing therapeutic gain with gemcitabine and fractionated radiation

International Nuclear Information System (INIS)

Mason, Kathy A.; Milas, Luka; Hunter, Nancy R.; Elshaikh, Mohamed; Buchmiller, Lara; Kishi, Kazushi; Hittelman, K. Walter; Ang, K. Kian

1999-01-01

Purpose/Objective: The nucleoside analogue gemcitabine inhibits cellular repair and repopulation, induces apoptosis, causes tumor growth delay, and enhances radiation-induced growth delay. After single doses of drug and radiation, maximum enhancement of tumor response was obtained when gemcitabine preceded radiation by at least 24 h. Conversely, the cellular radioresponse of the normal gastrointestinal epithelium was slightly protected when gemcitabine and radiation were separated by 24 h. This differential response created a time frame within which therapeutic gain could be maximized. In our present investigation, we sought to define the most therapeutically beneficial scheme of gemcitabine administration when combined with fractionated radiotherapy. Methods and Materials: C3Hf/Kam mice were given identical drug and radiation schedules of administration, and both normal tissue (jejunal mucosa) and tumor (Sa-NH) responses were measured. Irradiation was given once per day for 5 days in normal tissue and tumor growth delay studies and twice per day for the tumor cure endpoint. A total dose of 25 mg/kg gemcitabine was given i.p. in 1 of 3 schedules: a single dose of 25 mg/kg 24 h before the start of fractionated irradiation, 12.5 mg/kg 24 h before the first and third radiation doses, or 24 h before each of 5 radiation doses. Groups of mice bearing 7- or 8-mm diameter tumors were treated with gemcitabine alone or in combination with fractionated irradiation under ambient or hypoxic conditions. The survival response of the jejunal mucosa was quantified by the microcolony assay and histologically by quantifying apoptosis, mitosis, S-phase fraction, and crypt cellularity. Results: For tumor growth delay, dose-modifying factors (DMFs) were similar (1.34-1.46) for all 3 schedules of drug administration. In contrast, the response of the jejunum was strongly dependent on the schedule of gemcitabine administration. A single dose of gemcitabine before the start of fractionated

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.

Using enzyme folding to explore the mechanism of therapeutic touch: a feasibility study.

Science.gov (United States)

Strickland, Mallory L; Boylan, Helen M

2010-07-01

The goal of this research is to design a novel model using protein folding to study Therapeutic Touch, a noncontact form of energy manipulation healing. Presented is a feasibility study suggesting that the denaturation path of ribonuclease A may be a useful model to study the energy exchange underlying therapeutic touch. The folding of ribonuclease A serves as a controlled energy-requiring system in which energy manipulation can be measured by the degree of folding achieved. A kinetic assay and fluorescence spectroscopy are used to assess the enzyme-folding state. The data suggest that the kinetic assay is a useful means of assessing the degree of refolding, and specifically, the enzyme function. However, fluorescence spectroscopy was not shown to be an effective measurement of enzyme structure for the purposes of this work. More research is needed to assess the underlying mechanism of therapeutic touch to complement the existing studies. An enzyme-folding model may provide a useful means of studying the energy exchange in therapeutic touch.

Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with {sup 64}Cu-DOTA-trastuzumab

Energy Technology Data Exchange (ETDEWEB)

Niu, Gang; Cao, Qizhen; Chen, Xiaoyuan [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Li, Zibo [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Keck School of Medicine, USC Molecular Imaging Center, Department of Radiology, Los Angeles, CA (United States)

2009-09-15

17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat-shock protein 90 (Hsp90) inhibitor, has been intensively investigated for cancer therapy and is undergoing clinical trials. Human epidermal growth factor receptor 2 (HER-2) is one of the client proteins of Hsp90 and its expression is decreased upon 17-DMAG treatment. In this study, we aimed to noninvasively monitor the HER-2 response to 17-DMAG treatment in xenografted mice. The sensitivity of human ovarian cancer SKOV-3 cells to 17-DMAG in vitro was measured by MTT assay. HER-2 expression in SKOV-3 cells was determined by flow cytometry. Nude mice bearing SKOV-3 tumors were treated with 17-DMAG and the therapeutic efficacy was evaluated by tumor size measurement. Both treated and control mice were imaged with microPET using {sup 64}Cu-DOTA-trastuzumab and {sup 18}F-FDG. Biodistribution studies and immunofluorescence staining were performed to validate the microPET results. SKOV-3 cells are sensitive to 17-DMAG treatment, in a dose-dependent manner, with an IC{sub 50} value of 24.72 nM after 72 h incubation. The tumor growth curve supported the inhibition effect of 17-DMAG on SKOV-3 tumors. Quantitative microPET imaging showed that {sup 64}Cu-DOTA-trastuzumab had prominent tumor accumulation in untreated SKOV-3 tumors, which was significantly reduced in 17-DMAG-treated tumors. There was no uptake difference detected by FDG PET. Immunofluorescence staining confirmed the significant reduction in tumor HER-2 level upon 17-DMAG treatment. The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using {sup 64}Cu-DOTA-trastuzumab. This approach may be valuable in monitoring the therapeutic response in HER-2-positive cancer patients under 17-DMAG treatment. (orig.)

Patient-Reported Outcome Coordinator Did Not Improve Quality of Life Assessment Response Rates: A Report from the Children's Oncology Group.

Directory of Open Access Journals (Sweden)

Donna Johnston

Full Text Available Health related quality of life (HRQL assessments during therapy for pediatric cancer provide valuable information to better understand the patient experience. Our objective was to determine the impact of a patient-reported outcome (PRO coordinator on HRQL questionnaire completion rates during a pediatric acute myeloid leukemia (AML trial.AAML1031 is a multicenter Children's Oncology Group therapeutic trial for de novo AML with a secondary aim to assess HRQL of children and adolescents treated with chemotherapy and hematopoietic stem cell transplantation (HSCT. Parents/guardians are the primary respondents and four questionnaires are administered at eight time points. The questionnaires are the PedsQL 4.0 Generic Core Scales, PedsQL 3.0 Acute Cancer Module, PedsQL Multidimensional Fatigue Scale, and the Pediatric Inventory for Parents. To improve response rates, a central PRO coordinator was instituted and reminded sites about upcoming and delinquent questionnaires. The proportion of HRQL questionnaires completed were compared prior to, and following institution of the PRO coordinator. This analysis evaluated the first five assessment time points.There were231 families who consented to participate in the HRQL aim. Overall response rates for all questionnaires were 73-83%. At time point 1, within 14 days of chemotherapy initiation, post-PRO coordinator completion rates were significantly higher for three of four questionnaires. However, the effect was not sustained and at time point 4, one month following last chemotherapy or HSCT, completion rates were significantly lower post-PRO coordinator for all four questionnaires.Addition of a central PRO coordinator did not result in sustained improvement in HRQL questionnaire completion rates. Efforts to improve response rates must consider other strategies.

Monitoring T-Cell Responses in Translational Studies: Optimization of Dye-Based Proliferation Assay for Evaluation of Antigen-Specific Responses

Directory of Open Access Journals (Sweden)

Anja Ten Brinke

2017-12-01

Full Text Available Adoptive therapy with regulatory T cells or tolerance-inducing antigen (Ag-presenting cells is innovative and promising therapeutic approach to control undesired and harmful activation of the immune system, as observed in autoimmune diseases, solid organ and bone marrow transplantation. One of the critical issues to elucidate the mechanisms responsible for success or failure of these therapies and define the specificity of the therapy is the evaluation of the Ag-specific T-cell responses. Several efforts have been made to develop suitable and reproducible assays. Here, we focus on dye-based proliferation assays. We highlight with practical examples the fundamental issues to take into consideration for implementation of an effective and sensitive dye-based proliferation assay to monitor Ag-specific responses in patients. The most critical points were used to design a road map to set up and analyze the optimal assay to assess Ag-specific T-cell responses in patients undergoing different treatments. This is the first step to optimize monitoring of tolerance induction, allowing comparison of outcomes of different clinical studies. The road map can also be applied to other therapeutic interventions, not limited to tolerance induction therapies, in which Ag-specific T-cell responses are relevant such as vaccination approaches and cancer immunotherapy.

Therapeutic physical exercise in neural injury: friend or foe?

Science.gov (United States)

Park, Kanghui; Lee, Seunghoon; Hong, Yunkyung; Park, Sookyoung; Choi, Jeonghyun; Chang, Kyu-Tae; Kim, Joo-Heon; Hong, Yonggeun

2015-12-01

[Purpose] The intensity of therapeutic physical exercise is complex and sometimes controversial in patients with neural injuries. This review assessed whether therapeutic physical exercise is beneficial according to the intensity of the physical exercise. [Methods] The authors identified clinically or scientifically relevant articles from PubMed that met the inclusion criteria. [Results] Exercise training can improve body strength and lead to the physiological adaptation of skeletal muscles and the nervous system after neural injuries. Furthermore, neurophysiological and neuropathological studies show differences in the beneficial effects of forced therapeutic exercise in patients with severe or mild neural injuries. Forced exercise alters the distribution of muscle fiber types in patients with neural injuries. Based on several animal studies, forced exercise may promote functional recovery following cerebral ischemia via signaling molecules in ischemic brain regions. [Conclusions] This review describes several types of therapeutic forced exercise and the controversy regarding the therapeutic effects in experimental animals versus humans with neural injuries. This review also provides a therapeutic strategy for physical therapists that grades the intensity of forced exercise according to the level of neural injury.

Role of imaging in the staging and response assessment of lymphoma

DEFF Research Database (Denmark)

Barrington, Sally F; Mikhaeel, N George; Kostakoglu, Lale

2014-01-01

emission tomography (PET)–computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver....... CONCLUSION: This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials....

Annual in Therapeutic Recreation. Volume 2.

Science.gov (United States)

Crawford, Michael E., Ed.; Card, Jaclyn A., Ed.

This volume focuses on therapeutic recreation, as a subject of inquiry and as a treatment tool. The 11 articles include original field based research, program development initiatives, issue and theory of practice papers, and original tutorials in assessment and research. The article titles are: "The Role of Leisure Education with Family…

Review of Therapeutic Education: Working Alongside Troubled and Troublesome Children (Book Review)

OpenAIRE

Bigger, Stephen

2008-01-01

Therapeutic education requires a move from “a punitive, blame-based, unfairly competitive and deviant-defined culture” to “one that celebrates diversity and cultural differences” (p.11), from a deficit model of SEN and deviant model of challenging behaviour to “a more humane and therapeutic approach to education and learning generally (p.12). Therapeutic education is holistic and encourages agency and responsibility. How adults relate to learners is viewed as more important than what is taugh...

Psychological considerations in the assessment and treatment of pain in neurorehabilitation and psychological factors predictive of therapeutic response: evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

Directory of Open Access Journals (Sweden)

Gianluca eCastelnuovo

2016-04-01

Full Text Available BackgroundIn order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation aimed to collate the evidence available across these topics. ObjectivesTo determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. MethodsTwo reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation.ResultsThe first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy and conditions associated with complex disability with regards to the

Pharmacology and Therapeutics Education in the European Union Needs Harmonization and Modernization: A Cross-sectional Survey Among 185 Medical Schools in 27 Countries.

Science.gov (United States)

Brinkman, D J; Tichelaar, J; Okorie, M; Bissell, L; Christiaens, T; Likic, R; Mačìulaitis, R; Costa, J; Sanz, E J; Tamba, B I; Maxwell, S R; Richir, M C; van Agtmael, M A

2017-11-01

Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery, and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students' preparedness for prescribing. In all, 185 medical schools (64%) from 27 EU countries responded. Traditional learning methods were mainly used. The majority of respondents did not provide students with the opportunity to practice real-life prescribing and believed that their students were not well prepared for prescribing. There is a marked difference in the quality and quantity of CPT education within and between EU countries, suggesting that there is considerable scope for improvement. A collaborative approach should be adopted to harmonize and modernize the undergraduate CPT education across the EU. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Prevalence and likelihood ratio of symptoms in patients with good therapeutic response to Lycopodium clavatum. A retrospective study.

Science.gov (United States)

Eizayaga, José Enrique; Pozzi, María Isabel; Canan, María Clara; Saravia, Laura

2016-02-01

Assessment of the likelihood ratio (LR) of symptoms has been proposed as a rational means for detecting indicators to homeopathic medicines. To investigate the prevalence and LR of symptoms commonly attributed to the homeopathic medicine Lycopodium clavatum (Lyc). Secondarily, to answer the question if experienced homeopaths could intuitively infer which the main symptoms of this medicine are. The presence of 35 selected symptoms, prescribed medicines and therapeutic response were assessed retrospectively. The symptoms' prevalence in the Lyc responding population and the LR of the symptoms compared to their prevalence in the remainder of the population were calculated. Two hundred and two Lyc and 550 non Lyc cases (total 752) were included for analysis. Twenty-two symptoms were confirmed as pertaining to Lyc's semiology (prevalence %; LR): contemptuous (3.3; 6.7), urinary stones history (2.7; 5.4), egotism (5.6; 3.6), dictatorial (33.3; 3.4), haughty (8.7; 3.3), sleeps on abdomen (3.3; 3.3), intolerance to clothing in abdomen (12.0; 3.1), reproaches (4.0; 3.0), helplessness (24.0; 2.7), fear of failure (10.7; 2.6), irritability on waking in the morning (16.7; 2.5), constipation alternating with diarrhea (8.7; 2.5), intolerant to contradiction (59.3; 2.3), want of self confidence (30.0; 2.4), abdominal distension after eating (23.3; 2.1); ailments from anticipation (32.0; 1.9), irritability before menses (23.3; 1.8), conscientious (26.0; 1.6), desire of sweets (52.0; 1.6), desire of chocolate (16.7; 1.6), lack of vital heat (41.3; 1.3), and flatterer (1.3; ∞). Surveyed homeopaths' intuitive inferences correlated well with symptoms' prevalence but not with their LR. Lycopodium's main symptoms are well known by homeopaths, but their knowledge correlates well with the symptoms' prevalence and not with their LR. Retrospective assessment of prevalence and LR of symptoms in good responders might be a means for better selection of symptoms for prospective studies

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

Science.gov (United States)

Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

2013-11-11

The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

Science.gov (United States)

2013-01-01

Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

Assessment of surgical portosystemic shunts and associated complications: The diagnostic and therapeutic role of radiologists

Energy Technology Data Exchange (ETDEWEB)

Taslakian, Bedros, E-mail: btaslakian@gmail.com [Department of Radiology, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon); Faraj, Walid, E-mail: wf07@aub.edu.lb [Department of General Surgery, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon); Khalife, Mohammad, E-mail: mk12@aub.edu.lb [Department of General Surgery, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon); Al-Kutoubi, Aghiad, E-mail: mk00@aub.edu.lb [Department of Radiology, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon); El-Merhi, Fadi, E-mail: fe19@aub.edu.lb [Department of Radiology, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon); Saade, Charbel, E-mail: cs39@aub.edu.lb [Department of Radiology, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon); Hallal, Ali, E-mail: ah05@aub.edu.lb [Department of General Surgery, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon); Haydar, Ali, E-mail: ah24@aub.edu.lb [Department of Radiology, American University of Beirut Medical Center, Riad El-Solh 1107 2020—PO Box: 11-0236, Beirut (Lebanon)

2015-08-15

Highlights: • Portal hypertension is the pathological increase in portal venous pressure. • Surgical portosystemic shunting is an accepted methods to decrease portal venous pressure. • Surgical portosystemic shunts are divided into selective and nonselective. • Shunt thrombosis is a serious complication, resulting in shunt dysfunction. • Imaging is essential in the assessment of the shunt function and anatomy. - Abstract: Surgical portosystemic shunting, the formation of a vascular connection between the portal and systemic venous circulation, has been used as a treatment to reduce portal venous pressure. Although the use of portosystemic shunt surgery in the management of portal hypertension has declined during the past decade in favour of alternative therapies, and subsequently surgeons and radiologists became less familiar with the procedure, it remains a well-established treatment. Knowledge of different types of surgical portosystemic shunts, their pathophysiology and complications will help radiologists improve communication with surgeons and enhance their understanding of the diagnostic and therapeutic role of radiology in the assessment and management of these shunts. Optimal assessment of the shunt is essential to determine its patency and allow timely intervention. Both non-invasive and invasive imaging modalities complement each other in the evaluation of surgical portosystemic shunts. Interventional radiology plays an important role in the management of complications, such as shunt thrombosis and stenosis. This article describes the various types of surgical portosystemic shunts, explains the anatomy and pathophysiology of these shunts, illustrates the pearls and pitfalls of different imaging modalities in the assessment of these shunts and demonstrates the role of radiologists in the interventional management of complications.

Assessment of surgical portosystemic shunts and associated complications: The diagnostic and therapeutic role of radiologists

International Nuclear Information System (INIS)

Taslakian, Bedros; Faraj, Walid; Khalife, Mohammad; Al-Kutoubi, Aghiad; El-Merhi, Fadi; Saade, Charbel; Hallal, Ali; Haydar, Ali

2015-01-01

Highlights: • Portal hypertension is the pathological increase in portal venous pressure. • Surgical portosystemic shunting is an accepted methods to decrease portal venous pressure. • Surgical portosystemic shunts are divided into selective and nonselective. • Shunt thrombosis is a serious complication, resulting in shunt dysfunction. • Imaging is essential in the assessment of the shunt function and anatomy. - Abstract: Surgical portosystemic shunting, the formation of a vascular connection between the portal and systemic venous circulation, has been used as a treatment to reduce portal venous pressure. Although the use of portosystemic shunt surgery in the management of portal hypertension has declined during the past decade in favour of alternative therapies, and subsequently surgeons and radiologists became less familiar with the procedure, it remains a well-established treatment. Knowledge of different types of surgical portosystemic shunts, their pathophysiology and complications will help radiologists improve communication with surgeons and enhance their understanding of the diagnostic and therapeutic role of radiology in the assessment and management of these shunts. Optimal assessment of the shunt is essential to determine its patency and allow timely intervention. Both non-invasive and invasive imaging modalities complement each other in the evaluation of surgical portosystemic shunts. Interventional radiology plays an important role in the management of complications, such as shunt thrombosis and stenosis. This article describes the various types of surgical portosystemic shunts, explains the anatomy and pathophysiology of these shunts, illustrates the pearls and pitfalls of different imaging modalities in the assessment of these shunts and demonstrates the role of radiologists in the interventional management of complications

Assessment of Extracorporeal Shock Wave Lithotripsy (ESWL) Therapeutic Efficiency in Urolithiasis.

Science.gov (United States)

Tomescu, P; Pănuş, A; Mitroi, G; Drăgoescu, O; Stoica, L; Dena, S; Enache, E

2009-01-01

Extracorporeal shock wave lithotripsy (ESWL) revolutionized the treatment of urolithiasis and gradually became the favorite treatment option so that today it is considered to be the first line of treatment for more than 75% of the patients with urolithiasis. The purpose of this study was the assessment of the therapeutic efficiency, complications and limitations of ESWL in urolithiasis in the initial experience using a third generation electromagnetic lithotripter.  Between 2007 and 2008 we performed ESWL for 167 patients with urolithiasis. We recorded 92 patients with single stone (55.1%) and 72 with multiple lithiasis (44.9%). Stone size varied between 7 and 24 mm with an average of 12.3±7.1 mm. Radioopac stones were found in 104 patients (62.3%) while radiolucent stones in 63 only (37.6%).    Complete stone disintegration and clearance was achieved in most cases (86.2%). Complications were mostly minor and rare (transitory haematuria, renal colic). Severe complications (renal hematoma, steinstrasse) were diagnosed for a limited number of patients (3.6%) and their management was mostly nonsurgical or minimally invasive (retrograde ureteroscopy). ESWL is therefore the first line of treatment for urolithiasis with stone size smaller than 2.5 cm. It has an efficiency rate above 85%, low procedure time, high safety and good tolerability (new generation lithotripters do not require anesthesia) and minimal complications.

[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.

Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe.

Science.gov (United States)

Geelen, Inge G P; Thielen, Noortje; Janssen, Jeroen J W M; Hoogendoorn, Mels; Roosma, Tanja J A; Valk, Peter J M; Visser, Otto; Cornelissen, Jan J; Westerweel, Peter E

2018-04-01

The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available. In a population-based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated. The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular "warning." The development of additional cytogenetic abnormalities was always accompanied with molecular failure. We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re-assessment should still be performed when molecular response is suboptimal. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities

Directory of Open Access Journals (Sweden)

Lozano D

2015-01-01

Full Text Available Diego Lozano,* Gabriel S Gonzales-Portillo,* Sandra Acosta, Ike de la Pena, Naoki Tajiri, Yuji Kaneko, Cesar V Borlongan Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA *These authors contributed equally to this work Abstract: Traumatic brain injury (TBI is a serious public health problem accounting for 1.4 million emergency room visits by US citizens each year. Although TBI has been traditionally considered an acute injury, chronic symptoms reminiscent of neurodegenerative disorders have now been recognized. These progressive neurodegenerative-like symptoms manifest as impaired motor and cognitive skills, as well as stress, anxiety, and mood affective behavioral alterations. TBI, characterized by external bumps or blows to the head exceeding the brain’s protective capacity, causes physical damage to the central nervous system with accompanying neurological dysfunctions. The primary impact results in direct neural cell loss predominantly exhibiting necrotic death, which is then followed by a wave of secondary injury cascades including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood–brain barrier disruption, and inflammation. All these processes exacerbate the damage, worsen the clinical outcomes, and persist as an evolving pathological hallmark of what we now describe as chronic TBI. Neuroinflammation in the acute stage of TBI mobilizes immune cells, astrocytes, cytokines, and chemokines toward the site of injury to mount an antiinflammatory response against brain damage; however, in the chronic stage, excess activation of these inflammatory elements contributes to an “inflamed” brain microenvironment that principally contributes to secondary cell death in TBI. Modulating these inflammatory cells by changing their phenotype from proinflammatory to antiinflammatory would likely promote therapeutic effects on TBI. Because neuroinflammation occurs at

Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.

Science.gov (United States)

Novikova, Natalia; Hofmeyr, G Justus; Essilfie-Appiah, George

2012-09-12

Amnioinfusion aims to relieve umbilical cord compression during labour by infusing a liquid into the uterine cavity. The objective of this review was to assess the effects of prophylactic amnioinfusion for women in labour with oligohydramnios, but not fetal heart deceleration, compared with therapeutic amnioinfusion only if fetal heart rate decelerations or thick meconium-staining of the liquor occur. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2012). Randomised trials comparing prophylactic amnioinfusion in women in labour with oligohydramnios but not fetal heart rate deceleration in labour with therapeutic amnioinfusion. The authors assessed trial quality and extracted data. One randomized trial of 116 women was included. No differences were found in the rate of caesarean section (risk ratio 1.29, 95% confidence interval 0.60 to 2.74). There were no differences in cord arterial pH, oxytocin augmentation, neonatal pneumonia or postpartum endometritis. Prophylactic amnioinfusion was associated with increased intrapartum fever (risk ratio 3.48, 95% confidence interval 1.21 to 10.05). There appears to be no advantage of prophylactic amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart rate decelerations or thick meconium-staining of the liquor occur.

[Pharmacokinetic alterations in pregnancy and use of therapeutic drug monitoring].

Science.gov (United States)

Panchaud, Alice; Weisskopf, Etienne; Winterfeld, Ursula; Baud, David; Guidi, Monia; Eap, Chin B; Csajka, Chantal; Widmer, Nicolas

2014-01-01

Following the thalidomide tragedy, pharmacological research in pregnant women focused primarily on drug safety for the unborn child and remains only limited regarding the efficacy and safety of treatment for the mother. Significant physiological changes during pregnancy may yet affect the pharmacokinetics of drugs and thus compromise its efficacy and/or safety. Therapeutic drug monitoring (TDM) would maximize the potential effectiveness of treatments, while minimizing the potential risk of toxicity for the mother and the fetus. At present, because of the lack of concentration-response relationship studies in pregnant women, TDM can rely only on individual assessment (based on an effective concentration before pregnancy) and remains reserved only to unexpected situations such as signs of toxicity or unexplained inefficiency. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers.

Science.gov (United States)

de Oliveira, Carolina C; Abud, Ana Paula R; de Oliveira, Simone M; Guimarães, Fernando de S F; de Andrade, Lucas F; Di Bernardi, Raffaello P; Coletto, Ediely L de O; Kuczera, Diogo; Da Lozzo, Eneida J; Gonçalves, Jenifer P; Trindade, Edvaldo da S; Buchi, Dorly de F

2011-10-26

In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.

In Vivo Visualizing the IFN-β Response Required for Tumor Growth Control in a Therapeutic Model of Polyadenylic-Polyuridylic Acid Administration.

Science.gov (United States)

Nocera, David Andrés; Roselli, Emiliano; Araya, Paula; Nuñez, Nicolás Gonzalo; Lienenklaus, Stefan; Jablonska, Jadwiga; Weiss, Siegfried; Gatti, Gerardo; Brinkmann, Melanie M; Kröger, Andrea; Morón, Gabriel; Maccioni, Mariana

2016-03-15

The crucial role that endogenously produced IFN-β plays in eliciting an immune response against cancer has recently started to be elucidated. Endogenous IFN-β has an important role in immune surveillance and control of tumor development. Accordingly, the role of TLR agonists as cancer therapeutic agents is being revisited via the strategy of intra/peritumoral injection with the idea of stimulating the production of endogenous type I IFN inside the tumor. Polyadenylic-polyuridylic acid (poly A:U) is a dsRNA mimetic explored empirically in cancer immunotherapy a long time ago with little knowledge regarding its mechanisms of action. In this work, we have in vivo visualized the IFN-β required for the antitumor immune response elicited in a therapeutic model of poly A:U administration. In this study, we have identified the role of host type I IFNs, cell populations that are sources of IFN-β in the tumor microenvironment, and other host requirements for tumor control in this model. One single peritumoral dose of poly A:U was sufficient to induce IFN-β, readily visualized in vivo. IFN-β production relied mainly on the activation of the transcription factor IFN regulatory factor 3 and the molecule UNC93B1, indicating that TLR3 is required for recognizing poly A:U. CD11c(+) cells were an important, but not the only source of IFN-β. Host type I IFN signaling was absolutely required for the reduced tumor growth, prolonged mice survival, and the strong antitumor-specific immune response elicited upon poly A:U administration. These findings add new perspectives to the use of IFN-β-inducing compounds in tumor therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

Assessment and monitoring of treatment response in adult ADHD patients: current perspectives

Directory of Open Access Journals (Sweden)

Ramsay JR

2017-01-01

Full Text Available J Russell Ramsay Adult ADHD Treatment & Research Program, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a neurodevelopmental syndrome that emerges in childhood or early adolescence and persists into adulthood for a majority of individuals. There are many other adults with ADHD who may not seek out evaluation and treatment until adulthood, having been able to “get by” before struggling with inattention, hyperactivity, and/or impulsivity in adulthood, in addition to facing the associated features of disorganization, poor time management, and procrastination among many others. A lifetime diagnosis of ADHD is associated with a wide range of life impairments, which makes a comprehensive and accurate diagnostic assessment essential in order to obtain appropriate treatment. Moreover, while there are effective medical and psychosocial treatments for ADHD, it is important to be able to track treatment response in order to evaluate whether adjustments in specific interventions are needed or referrals for adjunctive treatments and supports are indicated to facilitate optimal therapeutic outcomes. The goal of this article is to provide a clinically useful review of the various measures that practicing clinicians can use to aid in the diagnostic assessment and monitoring of psychosocial and medical treatment of ADHD in adult patients. This review includes various structured interviews, screening scales, adult ADHD symptom inventories, measures of associated features of ADHD, as well as ratings of impairment and functioning which can be adapted to clinicians’ practice needs in order to track treatment progress and optimize treatments for adults with ADHD. Keywords: adult attention-deficit/hyperactivity disorder, adult ADHD, pharmacotherapy, psychosocial treatment, symptoms, functional impairments, executive functions

Genome Engineering for Personalized Arthritis Therapeutics.

Science.gov (United States)

Adkar, Shaunak S; Brunger, Jonathan M; Willard, Vincent P; Wu, Chia-Lung; Gersbach, Charles A; Guilak, Farshid

2017-10-01

Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

Directory of Open Access Journals (Sweden)

Danielle Maria Camelo Cid

2013-01-01

Full Text Available Background: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This retrospective study was based on information obtained from patients'records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC. All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. Results: The study population consisted of 100 patients who were mostly male (51% with ages rangingbetween 21 and 40 years (42%, from the countryside (59%, in the chronic phase (95%, with high-riskprognostic factors (40%; the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

MicroRNAs in cancer therapeutics: "from the bench to the bedside".

Science.gov (United States)

Monroig-Bosque, Paloma del C; Rivera, Carlos A; Calin, George A

2015-01-01

MicroRNAs (miRNAs) are non-coding RNA transcripts that regulate physiological processes by targeting proteins directly. Their involvement in research has been robust, and evidence of their regulative functions has granted them the title: master regulators of the human genome. In cancer, they are considered important therapeutic agents, due to the fact that their aberrant expression contributes to disease development, progression, metastasis, therapeutic response and patient overall survival. This has endeavored fields of biomedical sciences to invest in developing and exploiting miRNA-based therapeutics thoroughly. Herein we highlight relevant ongoing/open clinical trials involving miRNAs and cancer.

Generic procedures for assessment and response during a radiological emergency

International Nuclear Information System (INIS)

2000-08-01

One of the most important aspects of managing a radiological emergency is the ability to promptly and adequately determine and take actions to protect members of the public and emergency workers. Radiological accident assessment must take account of all critical information available at any time and must be an iterative and dynamic process aimed at reviewing the response as more detailed and complete information becomes available. This manual provides the tools, generic procedures and data needed for an initial response to a non-reactor radiological accident. This manual is one out of a set of IAEA publications on emergency preparedness and response, including Method for the Development of Emergency Response Preparedness for Nuclear or Radiological Accidents (IAEA-TECDOC-953), Generic Assessment Procedures for Determining Protective Actions During a Reactor Accident (IAEA-TECDOC-955) and Intervention Criteria in a Nuclear or Radiation Emergency (Safety Series No. 109)

Therapeutic management of radiation-induced oral mucositis

International Nuclear Information System (INIS)

Doerr, W.; Doelling-Jochem, I.; Baumann, M.; Herrmann, T.

1997-01-01

Background: Acute reactions of oral mucosa are a frequent side effect of radiotherapy, which often necessitates interruption of the treatment. Marked proliferation of tumor stem cells during treatment interruptions may occur in squamous cell carcinomata, which represent the majority of tumors in the head and neck area. Hence a fatal consequence of treatment breaks may be a significant decrease in tumor cure rates. Furthermore, marked acute responses frequently result in increased late sequelae ('consequential damage'). Therefore, amelioration of the mucosal response aiming at avoiding treatment breaks and at reduction of late reactions coul definitely increase the therapeutic success of radiation treatment. Results: A variety of prophylactic and therapeutic methods have been proposed for the management of acute radiation reactions of the oral mucosa. Frequently, their efficiacy has been established for chemotherapy or in combination with other immunosuppressive treatments. Hence, systemical rather than local effects have to be considered. Conclusions: In general, prophylaxis of oral mucositis is mainly based on dental restoration or edentation, in combination with frequent oral hygienic measures after the meals and with antiseptic mouthwashes. Intensive personal care is recommended. The necessity of a percutaneous endoscopic gastrostoma is dependent on the status of the patient and on size and localization of the treatment area, i.e. the impairment of food uptake which is to be expected. Therapeutic intervention is restricted to local or systemic treatment of pain and local application of antimycotics and antibiotics. (orig./VHE) [de

The use of PET in assessing tumor response after neoadjuvant chemoradiation for rectal cancer

International Nuclear Information System (INIS)

Mak, Daisy; Joon, Daryl Lim; Chao, Michael; Wada, Morikatsu; Joon, Michael Lim; See, Andrew; Feigen, Malcolm; Jenkins, Patricia; Mercuri, Angelina; McNamara, Joanne; Poon, Aurora; Khoo, Vincent

2010-01-01

Purpose: To assess the correlation of 18F-FDG-PET (PET) response to pathological response after neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer. Methods and materials: Twenty patients with locally advanced rectal cancer were identified between 2001 and 2005. The median age was 57 years (range 37-72) with 14 males and 6 females. All patients were staged with endorectal ultrasound and/or MRI, CT, and PET. The clinical staging was T3N0M0 (16), T3N1M0 (2), and T3N0M1 (2). Restaging PET was performed after CRT, and prior to definitive surgery. The response on PET and pathology was assessed and correlated. Patient outcome according to PET response was also assessed. Results: Following CRT, a complete PET response occurred in 7 patients, incomplete response in 10, and no response in 3 patients. At surgery, complete pathological response was recorded in 7 patients, incomplete response in 10 and no response in 3. There was a good correlation of PET and pathological responses in complete responders (5/7 cases) and non-responders (3/3 cases). After a median follow-up of 62 months (range 7-73), twelve patients were alive with no evidence of disease. All patients achieving complete metabolic response were alive with no evidence of disease, while as those who had no metabolic response, all died as a result of metastatic disease. Conclusions: PET is a promising complementary assessment tool for assessing tumor response after CRT if there is a complete or no response. PET response may also predict for outcome.

Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody.

Science.gov (United States)

Xue, L; Hickling, T; Song, R; Nowak, J; Rup, B

2016-01-01

Reliable risk assessment for biotherapeutics requires accurate evaluation of risk factors associated with immunogenicity. Immunogenicity risk assessment tools were developed and applied to investigate the immunogenicity of a fully human therapeutic monoclonal antibody, ATR-107 [anti-interleukin (IL)-21 receptor] that elicited anti-drug antibodies (ADA) in 76% of healthy subjects in a Phase 1 study. Because the ATR-107 target is expressed on dendritic cells (DCs), the immunogenicity risk related to engagement with DC and antigen presentation pathways was studied. Despite the presence of IL-21R on DCs, ATR-107 did not bind to the DCs more extensively than the control therapeutic antibody (PF-1) that had elicited low clinical ADA incidence. However, ATR-107, but not the control therapeutic antibody, was translocated to the DC late endosomes, co-localized with intracellular antigen-D related (HLA-DR) molecules and presented a dominant T cell epitope overlapping the complementarity determining region 2 (CDR2) of the light chain. ATR-107 induced increased DC activation exemplified by up-regulation of DC surface expression of CD86, CD274 (PD-L1) and CD40, increased expansion of activated DC populations expressing CD86(hi), CD40(hi), CD83(hi), programmed death ligand 1 (PD-L1)(hi), HLA-DR(hi) or CCR7(hi), as well as elevated secretion of tumour necrosis factor (TNF)-α by DCs. DCs exposed to ATR-107 stimulated an autologous T cell proliferative response in human donor cells, in concert with the detection of immunoglobulin (Ig)G-type anti-ATR-107 antibody response in clinical samples. Collectively, the enhanced engagement of antigen presentation machinery by ATR-107 was suggested. The approaches and findings described in this study may be relevant to identifying lower immunogenicity risk targets and therapeutic molecules. © 2015 British Society for Immunology.

Therapeutics of Ebola hemorrhagic fever: whole-genome transcriptional analysis of successful disease mitigation.

Science.gov (United States)

Yen, Judy Y; Garamszegi, Sara; Geisbert, Joan B; Rubins, Kathleen H; Geisbert, Thomas W; Honko, Anna; Xia, Yu; Connor, John H; Hensley, Lisa E

2011-11-01

The mechanisms of Ebola (EBOV) pathogenesis are only partially understood, but the dysregulation of normal host immune responses (including destruction of lymphocytes, increases in circulating cytokine levels, and development of coagulation abnormalities) is thought to play a major role. Accumulating evidence suggests that much of the observed pathology is not the direct result of virus-induced structural damage but rather is due to the release of soluble immune mediators from EBOV-infected cells. It is therefore essential to understand how the candidate therapeutic may be interrupting the disease process and/or targeting the infectious agent. To identify genetic signatures that are correlates of protection, we used a DNA microarray-based approach to compare the host genome-wide responses of EBOV-infected nonhuman primates (NHPs) responding to candidate therapeutics. We observed that, although the overall circulating immune response was similar in the presence and absence of coagulation inhibitors, surviving NHPs clustered together. Noticeable differences in coagulation-associated genes appeared to correlate with survival, which revealed a subset of distinctly differentially expressed genes, including chemokine ligand 8 (CCL8/MCP-2), that may provide possible targets for early-stage diagnostics or future therapeutics. These analyses will assist us in understanding the pathogenic mechanisms of EBOV infection and in identifying improved therapeutic strategies.

Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics

DEFF Research Database (Denmark)

Olsen, Christina Kurre; Brennum, Lise Tøttrup; Kreilgaard, Mads

2008-01-01

response behaviour correlates well with the relationship between human dopamine D2 receptor occupancy and clinical effect. The aim of the present study was to evaluate how pharmacokinetic/pharmacodynamic (PK/PD) predictions of therapeutic effective steady-state plasma levels by means of conditioned...... the rat dopamine D2 receptor occupancy levels providing 50% response in the conditioned avoidance response test and the dopamine D2 receptor occupancy levels reported from responding schizophrenic patients treated with antipsychotics. Predictions of therapeutically effective steady-state levels...... for sertindole (+dehydrosertindole) and olanzapine were 3-4-fold too high whereas for haloperidol, clozapine and risperidone the predicted steady-state EC50 in conditioned avoidance responding rats correlated well with the therapeutically effective plasma levels observed in patients. Accordingly, the proposed PK...

Mechanism of oral tolerance induction to therapeutic proteins.

Science.gov (United States)

Wang, Xiaomei; Sherman, Alexandra; Liao, Gongxian; Leong, Kam W; Daniell, Henry; Terhorst, Cox; Herzog, Roland W

2013-06-15

Oral tolerance is defined as the specific suppression of humoral and/or cellular immune responses to an antigen by administration of the same antigen through the oral route. Due to its absence of toxicity, easy administration, and antigen specificity, oral tolerance is a very attractive approach to prevent unwanted immune responses that cause a variety of diseases or that complicate treatment of a disease. Many researchers have induced oral tolerance to efficiently treat autoimmune and inflammatory diseases in different animal models. However, clinical trials yielded limited success. Thus, understanding the mechanisms of oral tolerance induction to therapeutic proteins is critical for paving the way for clinical development of oral tolerance protocols. This review will summarize progress on understanding the major underlying tolerance mechanisms and contributors, including antigen presenting cells, regulatory T cells, cytokines, and signaling pathways. Potential applications, examples for therapeutic proteins and disease targets, and recent developments in delivery methods are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

Science.gov (United States)

Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

2017-12-01

Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects

Science.gov (United States)

Slob, Wout

2015-01-01

Background When chemical health hazards have been identified, probabilistic dose–response assessment (“hazard characterization”) quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. Objectives We developed a unified framework for probabilistic dose–response assessment. Methods We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose–response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, “effect metrics” can be specified to define “toxicologically equivalent” sizes for this underlying individual response; and d) dose–response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose–response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Results Probabilistically derived exposure limits are based on estimating a “target human dose” (HDMI), which requires risk management–informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%–10% effect sizes. Conclusions Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk

Assessment of Wind Turbine Structural Integrity using Response Surface Methodology

DEFF Research Database (Denmark)

Toft, Henrik Stensgaard; Svenningsen, Lasse; Moser, Wolfgang

2016-01-01

Highlights •A new approach to assessment of site specific wind turbine loads is proposed. •The approach can be applied in both fatigue and ultimate limit state. •Two different response surface methodologies have been investigated. •The model uncertainty introduced by the response surfaces...

Metastatic nasopharyngeal carcinoma: clinical study and therapeutic results of 95 cases

International Nuclear Information System (INIS)

Khanfir, A.; Frikha, M.; Ghorbel, A.; Drira, M.M.; Karray, H.; Daoud, J.

2006-01-01

Purpose. -- The objective of this retrospective study was to discuss the epidemio-clinical criteria and the therapeutic results of metastatic nasopharyngeal carcinoma. Patients and methods. - The current study concerned 95 patients with histologically proven nasopharyngeal carcinoma who were metastatic at diagnosis or who had developed late metastasis. We reviewed the epidemio-clinical records of all the patients. Patients were treated with chemotherapy (BEC regimen: bleomycin, epirubicin and cisplatin or PBF regimen: bleomycin, 5-fluorouracil and cisplatin) and radiotherapy of pauci metastatic localizations (single or double) or bone metastasis with high risk of compression or fracture ±associated with locoregional radiotherapy for patients who were metastatic at diagnosis. Response was assessed according to the WHO criteria. Overall survival was calculated according to the Kaplan-Meier method. A long-term disease-free survival was defined from 36 months. Results. - There were 34 patients who were metastatic at diagnosis and 61 patients who had developed late metastasis. The mean age was 41.5 years (sex-ratio: 3.1). Bone metastases were the most frequent (83%). Objective and complete response rates were respectively 75% and 70%, and 32% and 16% for BEC and PBF regimens. Twenty-five patients received radiotherapy for pauci metastatic localizations, among whom 19 patients who were metastatic at diagnosis received locoregional irradiation. The overall survival probability was of 15% for three years. Eleven patients were long survivors (extremes: 36 and 134 months). Conclusion. - Therapeutic results were comparable to those reported in other series using platin combination chemotherapy. Radiotherapy of metastasis yielded to long-term survival. (authors)

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

Science.gov (United States)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

Motivation for change as a predictor of treatment response for dysthymia.

Science.gov (United States)

Frías Ibáñez, Álvaro; González Vallespí, Laura; Palma Sevillano, Carol; Farriols Hernando, Núria

2016-05-01

Dysthymia constitutes a chronic, mild affective disorder characterized by heterogeneous treatment effects. Several predictors of clinical response and attendance have been postulated, although research on the role of the psychological variables involved in this mental disorder is still scarce. Fifty-four adult patients, who met criteria for dysthymia completed an ongoing naturalistic treatment based on the brief interpersonal psychotherapy (IPT-B), which was delivered bimonthly over 16 months. As potential predictor variables, the therapeutic alliance, coping strategies, perceived self-efficacy, and motivation for change were measured at baseline. Outcome variables were response to treatment (Clinical Global Impression and Beck’s Depression Inventory) and treatment attendance. Stepwise multiple linear regression analyses revealed that higher motivation for change predicted better response to treatment. Moreover, higher motivation for change also predicted treatment attendance. Therapeutic alliance was not a predictor variable of neither clinical response nor treatment attendance. These preliminary findings support the adjunctive use of motivational interviewing (MI) techniques in the treatment of dysthymia. Further research with larger sample size and follow-up assessment is warranted.

"Why won't my parents help me?": Therapeutic assessment of a child and her family.

Science.gov (United States)

Hamilton, Amy M; Fowler, Johnathan L; Hersh, Brooke; Austin, Cynthia A; Finn, Stephen E; Tharinger, Deborah J; Parton, Victoria; Stahl, Katharine; Arora, Prerna

2009-03-01

We present a case study of a child's psychological assessment using the methods of Therapeutic Assessment (TA). The case illustrates how TA can help assessors understand the process and structure of a family by highlighting how maladaptive family processes and interactions impact a child's development. It also illustrates how TA with a child can serve as a family intervention. In this case, it became apparent that the child's social difficulties were significant, not minor as initially reported by the parents, and were rooted in an insecure attachment, underlying depression, an idiosyncratic view of the world, and longing for attention, all of which were hidden or expressed in grandiose, expansive, and off-putting behaviors. In addition, the familial hierarchy was inverted; the parents felt ineffective and the child felt too powerful, leading to enhanced anxiety for the child. Intervention throughout, punctuated by the family session and feedback sessions, allowed the parents to develop a new "story" about their child and for the child to experience a new sense of safety. Following the TA, the parents and child indicated high satisfaction, enhanced family functioning, and decreased child symptomatology. Subsequent family therapy sessions allowed the family to further implement the interventions introduced in the TA.

A Systemic Approach to Culturally Responsive Assessment Practices and Evaluation

Science.gov (United States)

Slee, June

2010-01-01

In an earlier paper, Slee and Keenan demonstrated that it was possible for tertiary education institutions to design culturally responsive assessment procedures that complied with standardised assessment policy. The authors' paper described "Growing Our Own," an initiative between Charles Darwin University and Northern Territory Catholic…

Experimental Myocardial Infarction: The quest for novel therapeutics

NARCIS (Netherlands)

Hout, G.P.J. van

2015-01-01

Myocardial infarction (MI) and its consequences are associated with high mortality rates and considerable health care costs. Novel therapeutics that protect the heart after MI are therefore required. To assess safety and efficacy before exposing patients to experimental compounds, thorough

Epigenetics and Therapeutic Targets Mediating Neuroprotection

Science.gov (United States)

Qureshi, Irfan A.; Mehler, Mark F.

2015-01-01

The rapidly evolving science of epigenetics is transforming our understanding of the nervous system in health and disease and holds great promise for the development of novel diagnostic and therapeutic approaches targeting neurological diseases. Increasing evidence suggests that epigenetic factors and mechanisms serve as important mediators of the pathogenic processes that lead to irrevocable neural injury and of countervailing homeostatic and regenerative responses. Epigenetics is, therefore, of considerable translational significance to the field of neuroprotection. In this brief review, we provide an overview of epigenetic mechanisms and highlight the emerging roles played by epigenetic processes in neural cell dysfunction and death and in resultant neuroprotective responses. PMID:26236020

Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy?

Science.gov (United States)

Nickl-Jockschat, Thomas; Palomero Gallagher, Nicola; Kumar, Vinod; Hoffstaedter, Felix; Brügmann, Elisabeth; Habel, Ute; Eickhoff, Simon B; Grözinger, Michael

2016-04-01

The neurotrophic hypothesis has become the favorite model to explain the antidepressant properties of electroconvulsive therapy (ECT). It is based on the assumption that a restoration of previously defective neural networks drives therapeutic effects. Recent data in rather young patients suggest that neurotrophic effects of ECT might be detectable by diffusion tensor imaging. We here aimed to investigate whether the therapeutic response to ECT necessarily goes along with mesoscopic effects in gray matter (GM) or white matter (WM) in our patients in advanced age. Patients (n = 21, 15 males and 7 females) suffering from major depressive disorder were treated with ECT. Before the start of treatment and after the completion of the index series, they underwent magnetic resonance imaging, including a diffusion-weighed sequence. We used voxel-based morphometry to assess GM changes and tract-based spatial statistics and an SPM-based whole-brain analysis to detect WM changes in the course of treatment. Patients significantly improved clinically during the course of ECT. This was, however, not accompanied by GM or WM changes. This result challenges the notion that mesoscopic brain structure changes are an obligatory prerequisite for the antidepressant effects of ECT.

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

A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

Science.gov (United States)

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis.

Science.gov (United States)

Johns, Lennart D

2002-07-01

To present the frequency resonance hypothesis, a possible mechanical mechanism by which treatment with non-thermal levels of ultrasound stimulates therapeutic effects. The review encompasses a 4-decade history but focuses on recent reports describing the effects of nonthermal therapeutic levels of ultrasound at the cellular and molecular levels. A search of MEDLINE from 1965 through 2000 using the terms ultrasound and therapeutic ultrasound. The literature provides a number of examples in which exposure of cells to therapeutic ultrasound under nonthermal conditions modified cellular functions. Nonthermal levels of ultrasound are reported to modulate membrane properties, alter cellular proliferation, and produce increases in proteins associated with inflammation and injury repair. Combined, these data suggest that nonthermal effects of therapeutic ultrasound can modify the inflammatory response. The concept of the absorption of ultrasonic energy by enzymatic proteins leading to changes in the enzymes activity is not novel. However, recent reports demonstrating that ultrasound affects enzyme activity and possibly gene regulation provide sufficient data to present a probable molecular mechanism of ultrasound's nonthermal therapeutic action. The frequency resonance hypothesis describes 2 possible biological mechanisms that may alter protein function as a result of the absorption of ultrasonic energy. First, absorption of mechanical energy by a protein may produce a transient conformational shift (modifying the 3-dimensional structure) and alter the protein's functional activity. Second, the resonance or shearing properties of the wave (or both) may dissociate a multimolecular complex, thereby disrupting the complex's function. This review focuses on recent studies that have reported cellular and molecular effects of therapeutic ultrasound and presents a mechanical mechanism that may lead to a better understanding of how the nonthermal effects of ultrasound may be

Potential prospects of nanomedicine for targeted therapeutics in inflammatory bowel diseases

OpenAIRE

Pichai, Madharasi VA; Ferguson, Lynnette R

2012-01-01

Inflammatory bowel diseases (IBDs) such as Crohn’s disease are highly debilitating. There are inconsistencies in response to and side effects in the current conventional medications, failures in adequate drug delivery, and the lack of therapeutics to offer complete remission in the presently available treatments of IBD. This suggests the need to explore beyond the horizons of conventional approaches in IBD therapeutics. This review examines the arena of the evolving IBD nanomedicine, studied ...

Achievement of Therapeutic Goals with Low-Dose Imiglucerase in Gaucher Disease: A Single-Center Experience

Directory of Open Access Journals (Sweden)

Irina Tukan

2013-01-01

Full Text Available Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity. Disease-specific enzyme replacement therapy (ERT has been shown to reverse or ameliorate disease-specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts bone manifestations, including bone crises, bone pain, and appearance of new osteonecrosis, and improves bone mineral density to varying degrees. The objective of this study was to assess achievement of predefined therapeutic goals based on international registry outcomes for Israeli patients with Gaucher disease receiving imiglucerase for four consecutive years on a low-dose regimen followed in a single center. All data were taken from patient files. The therapeutic goals were taken from standards published in the literature for disease-specific clinical parameters. Among 164 patients at baseline, values for spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar spine and femoral were significantly different from the goal. After four years ERT, there was a significant improvement ( in each of the therapeutic goal parameters from baseline. 15.2% of these patients achieved all hematology-visceral goals. In children, there was achievement of linear growth and puberty. This survey highlights the good overall response in symptomatic patients receiving low-dose ERT with imiglucerase in Israel.

Structural and functional assessment of intense therapeutic ultrasound effects on partial Achilles tendon transection

Science.gov (United States)

Barton, Jennifer K.; Rice, Photini S.; Howard, Caitlin C.; Koevary, Jen W.; Danford, Forest; Gonzales, David A.; Vande Geest, Jon; Latt, L. Daniel; Szivek, John A.; Amodei, Richard; Slayton, Michael

2018-02-01

Tendinopathies and tendon tears heal slowly because tendons have a limited blood supply. Intense therapeutic ultrasound (ITU) is a treatment modality that creates very small, focal coagula in tissue, which can stimulate a healing response. This pilot study investigated the effects of ITU on rabbit and rat models of partial Achilles tendon rupture. The right Achilles tendons of 20 New Zealand White rabbits and 118 rats were partially transected. Twenty-four hours after surgery, ITU coagula were placed in the tendon and surrounding tissue, alternating right and left legs. At various time points, the following data were collected: ultrasound imaging, optical coherence tomography (OCT) imaging, mechanical testing, gene expression analysis, histology, and multiphoton microscopy (MPM) of sectioned tissue. Ultrasound visualized cuts and treatment lesions. OCT showed the effect of the interventions on birefringence banding caused by collagen organization. MPM showed inflammatory infiltrate, collagen synthesis and organization. By day 14- 28, all tendons had a smooth appearance and histology, MPM and OCT still could still visualize residual healing processes. Few significant results in gene expression were seen, but trends were that ITU treatment caused an initial decrease in growth and collagen gene expression followed by an increase. No difference in failure loads was found between control, cut, and ITU treatment groups, suggesting that sufficient healing had occurred by 14 days to restore all test tissue to control mechanical properties. These results suggest that ITU does not cause harm to tendon tissue. Upregulation of some genes suggests that ITU may increase healing response.

Assessment of the long-term response to rehabilitation of two ...

African Journals Online (AJOL)

Assessing the ecological outcomes of wetland rehabilitation activities is an important need recognised by the 'Working for Wetlands' programme in South Africa. An assessment of ecological response was conducted in the Killarney and Kruisfontein wetlands, KwaZulu-Natal, in 2005 prior to rehabilitation in 2006, and again ...

Field assessment of a model tuberculosis outbreak response plan for low-incidence areas

Directory of Open Access Journals (Sweden)

Pascopella Lisa

2007-10-01

Full Text Available Abstract Background For a regional project in four low-incidence states, we designed a customizable tuberculosis outbreak response plan. Prior to dissemination of the plan, a tuberculosis outbreak occurred, presenting an opportunity to perform a field assessment of the plan. The purpose of the assessment was to ensure that the plan included essential elements to help public health professionals recognize and respond to outbreaks. Methods We designed a semi-structured questionnaire and interviewed all key stakeholders involved in the response. We used common themes to assess validity of and identify gaps in the plan. A subset of participants provided structured feedback on the plan. Results We interviewed 11 public health and six community stakeholders. The assessment demonstrated that (1 almost all of the main response activities were reflected in the plan; (2 the plan added value by providing a definition of a tuberculosis outbreak and guidelines for communication and evaluation. These were areas that lacked written protocols during the actual outbreak response; and (3 basic education about tuberculosis and the interpretation and use of genotyping data were important needs. Stakeholders also suggested adding to the plan questions for evaluation and a section for specific steps to take when an outbreak is suspected. Conclusion An interactive field assessment of a programmatic tool revealed the value of a systematic outbreak response plan with a standard definition of a tuberculosis outbreak, guidelines for communication and evaluation, and response steps. The assessment highlighted the importance of education and training for tuberculosis in low-incidence areas.

CT perfusion imaging in response assessment of pulmonary metastases undergoing stereotactic ablative radiotherapy

International Nuclear Information System (INIS)

Sawyer, Brooke; Pun, Emma; Tay, Huilee; Kron, Tomas; Bressel, Mathias; Ball, David; Siva, Shankar; Samuel, Michael

2015-01-01

Stereotactic ablative body radiotherapy (SABR) is an emerging treatment technique for pulmonary metastases in which conventional Response Evaluation Criteria in Solid Tumours (RECIST) may be inadequate. This study aims to assess the utility of CT perfusion imaging in response assessment of pulmonary metastases after SABR. In this ethics board-approved prospective study, 11 patients underwent a 26-Gy single fraction of SABR to pulmonary metastases. CT perfusion imaging occurred prior to and at 14 and 70 days post-SABR. Blood flow (mL/100 mL/min), blood volume (mL/100 mL), time to peak (seconds) and surface permeability (mL/100 mL/min), perfusion parameters of pulmonary metastases undergoing SABR, were independently assessed by two radiologists. Inter-observer variability was analysed. CT perfusion results were analysed for early response assessment comparing day 14 with baseline scans and for late response by comparing day 70 with baseline scans. The largest diameter of the pulmonary metastases undergoing SABR was recorded. Ten patients completed all three scans and one patient had baseline and early response assessment CT perfusion scans only. There was strong level of inter-observer agreement of CT perfusion interpretation with a median intraclass coefficient of 0.87 (range 0.20–0.98). Changes in all four perfusion parameters and tumour sizes were not statistically significant. CT perfusion imaging of pulmonary metastases is a highly reproducible imaging technique that may provide additional response assessment information above that of conventional RECIST, and it warrants further study in a larger cohort of patients undergoing SABR.

Computer Security Incident Response Team Effectiveness: A Needs Assessment.

Science.gov (United States)

Van der Kleij, Rick; Kleinhuis, Geert; Young, Heather

2017-01-01

Computer security incident response teams (CSIRTs) respond to a computer security incident when the need arises. Failure of these teams can have far-reaching effects for the economy and national security. CSIRTs often have to work on an ad hoc basis, in close cooperation with other teams, and in time constrained environments. It could be argued that under these working conditions CSIRTs would be likely to encounter problems. A needs assessment was done to see to which extent this argument holds true. We constructed an incident response needs model to assist in identifying areas that require improvement. We envisioned a model consisting of four assessment categories: Organization, Team, Individual and Instrumental. Central to this is the idea that both problems and needs can have an organizational, team, individual, or technical origin or a combination of these levels. To gather data we conducted a literature review. This resulted in a comprehensive list of challenges and needs that could hinder or improve, respectively, the performance of CSIRTs. Then, semi-structured in depth interviews were held with team coordinators and team members of five public and private sector Dutch CSIRTs to ground these findings in practice and to identify gaps between current and desired incident handling practices. This paper presents the findings of our needs assessment and ends with a discussion of potential solutions to problems with performance in incident response.

Computer Security Incident Response Team Effectiveness: A Needs Assessment

Directory of Open Access Journals (Sweden)

Rick Van der Kleij

2017-12-01

Full Text Available Computer security incident response teams (CSIRTs respond to a computer security incident when the need arises. Failure of these teams can have far-reaching effects for the economy and national security. CSIRTs often have to work on an ad hoc basis, in close cooperation with other teams, and in time constrained environments. It could be argued that under these working conditions CSIRTs would be likely to encounter problems. A needs assessment was done to see to which extent this argument holds true. We constructed an incident response needs model to assist in identifying areas that require improvement. We envisioned a model consisting of four assessment categories: Organization, Team, Individual and Instrumental. Central to this is the idea that both problems and needs can have an organizational, team, individual, or technical origin or a combination of these levels. To gather data we conducted a literature review. This resulted in a comprehensive list of challenges and needs that could hinder or improve, respectively, the performance of CSIRTs. Then, semi-structured in depth interviews were held with team coordinators and team members of five public and private sector Dutch CSIRTs to ground these findings in practice and to identify gaps between current and desired incident handling practices. This paper presents the findings of our needs assessment and ends with a discussion of potential solutions to problems with performance in incident response.

Assessing response to therapy in idiopathic pulmonary arterial hypertension: a consensus survey of Canadian pulmonary hypertension physicians.

Science.gov (United States)

Borrie, Adrienne E; Ostrow, David N; Levy, Robert D; Swiston, John R

2011-01-01

Many treatment options are now available for patients with idiopathic pulmonary arterial hypertension (IPAH). Data regarding the optimal combination of therapies are lacking, as is consensus on how to assess response to therapy and when to change therapeutic regimens. To gather the opinions of Canadian pulmonary hypertension (PH) experts regarding standard practice in the care of IPAH patients after therapy is initiated. Canadian PH physicians were surveyed using short questionnaires to assess their opinions and practices in the care of IPAH patients. A Delphi forecasting approach was used to gain consensus among Canadian physicians on the most important clinical parameters to consider when assessing patients after the initiation of therapy. Twenty-six of 37 Canadian PH experts who were invited to participate completed the study. All endorsed the use of combination therapy for IPAH patients despite the lack of universal provincial coverage for this approach. By consensus, WHO functional class, 6 min walk distance and hospitalization for right heart failure were the most important clinical parameters. The most highly rated physical examination parameters were jugular venous pressure, peripheral edema, the presence of ascites and body weight. The overall approach to care of IPAH patients is similar across PH centres in Canada. A limited number of clinical and physical examination parameters were considered to be most important to reassess patients after therapy is initiated. These parameters, along with definition of threshold values, will facilitate the development of standard practice guidelines for IPAH patients in Canada.

Effect of radioimmunoassay procedures on therapeutic drug monitoring

International Nuclear Information System (INIS)

Kampa, I.S.

1985-01-01

Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

Assessment of exposure-response functions for rocket-emission toxicants

National Research Council Canada - National Science Library

Subcommittee on Rocket-Emission Toxicants, National Research Council

... aborted launch that results in a rocket being destroyed near the ground. Assessment of Exposure-Response Functions for Rocket-Emmission Toxicants evaluates the model and the data used for three rocket emission toxicants...

Comment Response on the Final Report: Peer Review of the Total System Performance Assessment-Viability Assessment (TSPA-VA)

International Nuclear Information System (INIS)

Pendleton, M. W.

1999-01-01

), updated where appropriate, as well as new findings that the Panel developed during its review of the Total System Performance Assessment-Viability Assessment (DOE 1998a). In the Final Report (Whipple et al. 1999), the Panel notes that the objective of the Total System Performance Assessment-Viability Assessment (DOE 1998a) was to describe the probable behavior of the potential repository. This report documents the comments provided in the Final Report (Whipple et al. 1999) and the Management and Operating Contractor responses to these comments. The responses were based on input from a number of scientists from the Management and Operating Contractor, several national laboratories, and the U.S. Geological Survey. The comments and responses are organized to be consistent with the major headings in the Final Report (Whipple et al. 1999). Excerpts from the Final Report (Whipple et al. 1999) are in italics; the Management and Operating Contractor responses to the comments are in straight text

Assessing Underreporting Response Bias on the MMPI-2

Science.gov (United States)

Bagby, R. Michael; Marshall, Margarita B.

2004-01-01

The authors assess the replicability of the two-factor model of underreporting response style. They then examine the relative performance of scales measuring these styles in analog (ARD) and differential prevalence group (DPG) designs. Principal components analysis produced a two-factor structure corresponding to self-deceptive (SD) and impression…

Adapted Physical Education and Therapeutic Recreation in Schools

Science.gov (United States)

Etzel-Wise, D; Mears, B

2004-01-01

Adapted physical education is a mandated service, whereas therapeutic recreation and traditional recreation are considered related services under the Individuals with Disabilities Education Act. In this article, the authors describe the distinctions between the services, recognition of need for referral, methods of assessment, sample…

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

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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.

Comparison of cell-based and non-cell-based assay platforms for the detection of clinically relevant anti-drug neutralizing antibodies for immunogenicity assessment of therapeutic proteins.

Science.gov (United States)

Hu, Jenny; Wala, Iwona; Han, Hong; Nagatani, Janice; Barger, Troy; Civoli, Francesca; Kaliyaperumal, Arunan; Zhuang, Yao; Gupta, Shalini

2015-04-01

Anti-drug neutralizing antibodies (NAbs) formed due to unwanted immunogenicity of a therapeutic protein point towards a mature immune response. NAb detection is important in interpreting the therapeutic's efficacy and safety in vivo. In vitro cell-based NAb assays provide a physiological system for NAb detection, however are complex assays. Non-cell-based competitive ligand binding (CLB) approaches are also employed for NAb detection. Instead of cells, CLB assays use soluble receptor and conjugated reagents and are easier to perform, however have reduced physiological relevance. The aim of this study was to compare the performance of CLB assays to established cell-based assays to determine the former's ability to detect clinically relevant NAbs towards therapeutics that (i) acted as an agonist or (ii) acted as antagonists by binding to a target receptor. We performed a head-to-head comparison of the performance of cell-based and CLB NAb assays for erythropoietin (EPO) and two anti-receptor monoclonal antibodies (AMG-X and AMG 317). Clinically relevant NAb-positive samples identified previously by a cell-based assay were assessed in the corresponding CLB format(s). A panel of 12 engineered fully human anti-EPO monoclonal antibodies (MAbs) was tested in both EPO NAb assay formats. Our results showed that the CLB format was (i) capable of detecting human anti-EPO MAbs of differing neutralizing capabilities and affinities and (ii) provided similar results as the cell-based assay for detecting NAbs in patient samples. The cell-based and CLB assays also behaved comparably in detecting NAbs in clinical samples for AMG-X. In the case of anti-AMG 317 NAbs, the CLB format failed to detect NAbs in more than 50% of the tested samples. We conclude that assay sensitivity, drug tolerance and the selected assay matrix played an important role in the inability of AMG 317 CLB assays to detect clinically relevant NAbs. Copyright © 2015 Elsevier B.V. All rights reserved.

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

Science.gov (United States)

Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

2010-09-01

Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and

Clinical usefulness of therapeutic drug monitoring of voriconazole in a university hospital.

Science.gov (United States)

Cabral-Galeano, Evelyn; Ruiz-Camps, Isabel; Len-Abad, Oscar; Pou-Clavé, Leonor; Sordé-Masip, Roger; Meije-Castillo, Yolanda; Blanco-Grau, Albert; Barba-Suñol, Pere; Monforte-Torres, Victor; Román-Broto, Antonio; Pahissa-Berga, Albert; Gavaldà-Santapau, Joan

2015-05-01

The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital. A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5μg/mL. The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: 5.5μg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p=.005) and cystic fibrosis as the underlying disease (p=.04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1μg/mL at the first TDM had a successful outcome (96%). Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Somatostatin receptor scintigraphy to predict the clinical evolution and therapeutic response of thyroid-associated ophthalmopathy

International Nuclear Information System (INIS)

Nocaudie, M.; Bailliez, A.; Itti, E.; Marchandise, X.

1999-01-01

Management of thyroid-associated ophthalmopathy remains a topic of controversy. Immunosuppressive treatments have to be applied at peak disease activity and before criteria of severity develop. Expression of somatostatin receptors on activated lymphocytes allows scintigraphic imaging with indium-111 pentetreotide. We conducted a prospective study with 17 patients who presented severe ophthalmopathy (11 Graves' disease, four Hashimoto's thyroiditis, two isolated in appearance: Means' syndrome). Each patient underwent hormonal (free T 3 and TSH) and immunological (TBII) assessment, an orbital computed tomography scan or magnetic resonance imaging, a visual functional examination and 111 In-pentetreotide orbital scintigraphy before undergoing treatment by steroids and/or radiotherapy, independently of scintigraphic results. At 4 and 24 h after the intravenous injection of 111 MBq of 111 In-pentetreotide, planar imaging centred on the head and neck (anterior and both lateral views) was carried out. Retrobulbar uptake was assessed by visual semi-quantitative analysis (score given by two independent trained observers) and by quantitative analyses (regions of interest, orbit/brain uptake indices). Patients were ophthalmologically followed up for 6 months and then classified as improved or not. Visual semi-quantitative analysis of 4-h/24-h planar images was correlated with the ophthalmological evolution (χ 2 test, P 111 In-pentetreotide scintigraphy requires further developments, including quantitative single-photon emission tomographic acquisition, if its role as a guide to therapeutic strategy in thyroid-associated ophthalmopathy is to be confirmed. (orig.)

Novel diagnostic and therapeutic radionuclides for the development of innovative radiopharmaceuticals

CERN Multimedia

We propose the exploration of novel radionuclides with diagnostic or therapeutic properties from ISOLDE. Access to such unique isotopes will enable the fundamental research in radiopharmaceutical science towards superior treatment, e.g. in nuclear oncology. The systematic investigation of the biological response to the different characteristics of the decay radiation will be performed for a better understanding of therapeutic effects. The development of alternative diagnostic tools will be applied for the management and optimization of radionuclide therapy.

Penicillin: the medicine with the greatest impact on therapeutic outcomes.

Science.gov (United States)

Kardos, Nelson; Demain, Arnold L

2011-11-01

The principal point of this paper is that the discovery of penicillin and the development of the supporting technologies in microbiology and chemical engineering leading to its commercial scale production represent it as the medicine with the greatest impact on therapeutic outcomes. Our nomination of penicillin for the top therapeutic molecule rests on two lines of evidence concerning the impact of this event: (1) the magnitude of the therapeutic outcomes resulting from the clinical application of penicillin and the subsequent widespread use of antibiotics and (2) the technologies developed for production of penicillin, including both microbial strain selection and improvement plus chemical engineering methods responsible for successful submerged fermentation production. These became the basis for production of all subsequent antibiotics in use today. These same technologies became the model for the development and production of new types of bioproducts (i.e., anticancer agents, monoclonal antibodies, and industrial enzymes). The clinical impact of penicillin was large and immediate. By ushering in the widespread clinical use of antibiotics, penicillin was responsible for enabling the control of many infectious diseases that had previously burdened mankind, with subsequent impact on global population demographics. Moreover, the large cumulative public effect of the many new antibiotics and new bioproducts that were developed and commercialized on the basis of the science and technology after penicillin demonstrates that penicillin had the greatest therapeutic impact event of all times. © Springer-Verlag 2011

Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

Directory of Open Access Journals (Sweden)

de Oliveira Carolina C

2011-10-01

Full Text Available Abstract Background In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. Methods We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. Results None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS, nitric oxide (NO production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Conclusions Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.

Validity and Responsiveness of Concept Map Assessment Scores in Physical Education

Science.gov (United States)

Lee, Yun Soo; Jang, Yongkyu; Kang, Minsoo

2015-01-01

Concept map assessment has been applied to many education areas to measure students' knowledge structure. However, the proper and valid use of concept map assessment has not been examined in physical education. The purpose of this study was to evaluate the evidence of validity and responsiveness of the concept map assessment scores in physical…

Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.

Science.gov (United States)

Cone, Katherine; Lanpher, Janell; Kinens, Abigail; Richard, Philomena; Couture, Sarah; Brackin, Rebecca; Payne, Emily; Harrington, Kylee; Rice, Kenner C; Stevenson, Glenn W

2018-05-01

Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior. A mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation. SNC80 and methadone were used as selective/high efficacy delta and mu agonists, respectively. Both SNC80 and methadone alone produced a dose-dependent restoration of pain-depressed responding and dose-dependent response rate suppression. Three fixed ratio mixtures, based on the relative potencies of the drugs in the nociception assay, also produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that all three mixtures produced supra-additive antinociceptive effects and simply additive sedation effects. The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.

Therapeutic validity and effectiveness of preoperative exercise on functional recovery after joint replacement: a systematic review and meta-analysis.

NARCIS (Netherlands)

Hoogeboom, T.J.; Oosting, E.; Vriezekolk, J.E.; Veenhof, C.; Siemonsma, P.C.; Bie, R.A. de; Ende, C.H.M. van den; Meeteren, N.L.U. van

2012-01-01

Background: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the

Clinical Manifestations of an Anti-Drug Antibody Response: Autoimmune Reactions.

Science.gov (United States)

Swanson, Steven J

2014-12-01

Antibodies can be generated against a therapeutic protein upon administration to human subjects. When the therapeutic protein closely mimics one of the subject's endogenous proteins, those antibodies might bind to the endogenous protein in addition to the therapeutic protein. This scenario results when tolerance to the endogenous protein is broken. The consequences of breaking tolerance include an autoimmune response where antibodies are generated against the endogenous protein. These autoantibodies could have significant clinical relevance depending on several factors, including the redundancy of action of the endogenous protein as well as the concentration, binding affinity, and neutralizing potential of the antibodies. The consequences of a therapeutic-protein-induced autoimmune reaction can be challenging to manage as the stimulus for further perpetuation of the immune response can shift from the therapeutic protein to the endogenous protein. The potential for inducing an autoimmune response is one of the reasons that the immune response to a therapeutic protein should be monitored if it persists through the end of the study.

[The development of therapeutic vaccine for hepatitis C virus].

Science.gov (United States)

Kimura, Kiminori; Kohara, Michinori

2012-10-01

Chronic hepatitis C caused by infection with the hepatitis C virus(HCV)is a global health problem. HCV causes persistent infection that can lead to chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The therapeutic efficacy of antiviral drugs is not optimal in patients with chronic infection; furthermore, an effective vaccine has not yet been developed. To design an effective HCV vaccine, generation of a convenient animal model of HCV infection is necessary. Recently, we used the Cre/loxP switching system to generate an immunocompetent mouse model of HCV expression, thereby enabling the study of host immune responses against HCV proteins. At present vaccine has not yet been shown to be therapeutically effective against chronic HCV infection. We examined the therapeutic effects of a recombinant vaccinia virus(rVV)encoding HCV protein in a mouse model. we generated rVVs for 3 different HCV proteins and found that one of the recombinant viruses encoding a nonstructural protein(rVV-N25)resolved pathological chronic hepatitis C symptoms in the liver. We propose the possibility that rVV-N25 immunization has the potential for development of an effective therapeutic vaccine for HCV induced chronic hepatitis. The utilization of the therapeutic vaccine can protect progress to chronic hepatitis, and as a consequence, leads to eradication of hepatocellular carcinoma. In this paper, we summarized our current study for HCV therapeutic vaccine and review the vaccine development to date.

Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

Science.gov (United States)

Alsharif, Naser Z.; And Others

1997-01-01

Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

Plasmodium vivax dhfr and dhps mutations in isolates from Madagascar and therapeutic response to sulphadoxine-pyrimethamine

Directory of Open Access Journals (Sweden)

Jahevitra Martial

2008-02-01

Full Text Available Abstract Background Four of five Plasmodium species infecting humans are present in Madagascar. Plasmodium vivax remains the second most prevalent species, but is understudied. No data is available on its susceptibility to sulphadoxine-pyrimethamine, the drug recommended for intermittent preventive treatment during pregnancy. In this study, the prevalence of P. vivax infection and the polymorphisms in the pvdhfr and pvdhps genes were investigated. The correlation between these polymorphisms and clinical and parasitological responses was also investigated in P. vivax-infected patients. Methods Plasmodium vivax clinical isolates were collected in eight sentinel sites from the four major epidemiological areas for malaria across Madagascar in 2006/2007. Pvdhfr and pvdhps genes were sequenced for polymorphism analysis. The therapeutic efficacy of SP in P. vivax infections was assessed in Tsiroanomandidy, in the foothill of the central highlands. An intention-to-treat analysis of treatment outcome was carried out. Results A total of 159 P. vivax samples were sequenced in the pvdhfr/pvdhps genes. Mutant-types in pvdhfr gene were found in 71% of samples, and in pvdhps gene in 16% of samples. Six non-synonymous mutations were identified in pvdhfr, including two novel mutations at codons 21 and 130. For pvdhps, beside the known mutation at codon 383, a new one was found at codon 422. For the two genes, different combinations were ranged from wild-type to quadruple mutant-type. Among the 16 patients enrolled in the sulphadoxine-pyrimethamine clinical trial (28 days of follow-up and after adjustment by genotyping, 3 (19%, 95% CI: 5%–43% of them were classified as treatment failure and were pvdhfr 58R/117N double mutant carriers with or without the pvdhps 383G mutation. Conclusion This study highlights (i that genotyping in the pvdhfr and pvdhps genes remains a useful tool to monitor the emergence and the spread of P. vivax sulphadoxine

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

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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.

Myocardial scintigraphy using iodine-123 15-(p-Iodophenyl)-3-R, S-methylpentadecanoic acid predicts the response to beta-blocker therapy in patients with dilated cardiomyopathy but does not reflect therapeutic effect

Energy Technology Data Exchange (ETDEWEB)

Yoshinaga, Keiichiro; Tahara, Minoru; Torii, Hiroyuki; Akimoto, Masaki [Kagoshima City Medical Association Hopital (Japan); Kihara, Koichi; Tei, Chuwa

2000-05-01

Myocardial fatty acid metabolism is disturbed in patients with idiopathic dilated cardiomyopathy. Myocardial scintigraphy using iodine-123 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) was used to assess the response to {beta}-blocker therapy in 19 patients with dilated cardiomyopathy. BMIPP myocardial scintigraphy was performed before and 6 months after initiating {beta}-blocker therapy with metoprolol. Cardiac BMIPP uptake was assessed as the total defect score (TDS) and heart-to-mediastinum activity (H/M) ratio. Patients were classified retrospectively as responders with an improvement of at least one functional class (New York Heart Association) or an increase in ejection fraction of {>=}0.10 at 6 months, or as nonresponders meeting neither criterion. Responders had a significantly better pretreatment TDS (p<0.005) and H/M ratio (p<0.0001) than nonresponders. TDS exhibited no significant changes over 6 months in either group (responders: 13.2{+-}3.7 vs 12.5{+-}3.3; nonresponders: 20.8{+-}6.5 vs 20.5{+-}3.0). Responders showed no significant changes in H/M ratio (2.47{+-}0.28 vs 2.43{+-}0.42); paradoxically, nonresponders showed a significant increase from 1.82{+-}0.11 to 2.10{+-}0.19 (p<0.05), suggesting that {beta}-blocker therapy protected the myocardial fatty acid metabolism even in the absence of clinical improvement. BMIPP myocardial scintigraphy provides a prediction of response to {beta}-blocker treatment, but does not reflect the therapeutic effect in responders at 6 months. (author)

Assessment of health surveys: fitting a multidimensional graded response model.

Science.gov (United States)

Depaoli, Sarah; Tiemensma, Jitske; Felt, John M

The multidimensional graded response model, an item response theory (IRT) model, can be used to improve the assessment of surveys, even when sample sizes are restricted. Typically, health-based survey development utilizes classical statistical techniques (e.g. reliability and factor analysis). In a review of four prominent journals within the field of Health Psychology, we found that IRT-based models were used in less than 10% of the studies examining scale development or assessment. However, implementing IRT-based methods can provide more details about individual survey items, which is useful when determining the final item content of surveys. An example using a quality of life survey for Cushing's syndrome (CushingQoL) highlights the main components for implementing the multidimensional graded response model. Patients with Cushing's syndrome (n = 397) completed the CushingQoL. Results from the multidimensional graded response model supported a 2-subscale scoring process for the survey. All items were deemed as worthy contributors to the survey. The graded response model can accommodate unidimensional or multidimensional scales, be used with relatively lower sample sizes, and is implemented in free software (example code provided in online Appendix). Use of this model can help to improve the quality of health-based scales being developed within the Health Sciences.

Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

Science.gov (United States)

Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

2015-04-01

Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Preexisting Antibodies to an F(ab′)2 Antibody Therapeutic and Novel Method for Immunogenicity Assessment

OpenAIRE

Ruppel, Jane; Brady, Ann; Elliott, Rebecca; Leddy, Cecilia; Palencia, Marco; Coleman, Daniel; Couch, Jessica A.; Wakshull, Eric

2016-01-01

Anti-therapeutic antibodies (ATAs) may impact drug exposure and activity and induce immune complex mediated toxicity; therefore the accurate measurement of ATA is important for the analysis of drug safety and efficacy. Preexisting ATAs to the hinge region of anti-Delta like ligand 4 (anti-DLL4) F(ab′)2, a potential antitumor therapeutic, were detected in cynomolgus monkey serum, which presented a challenge in developing assays for detecting treatment induced ATA. A total ATA assay was develop...

Therapeutic Vaccination Using Cationic Liposome-Adjuvanted HIV Type 1 Peptides Representing HLA-Supertype-Restricted Subdominant T Cell Epitopes

DEFF Research Database (Denmark)

Román, Victor Raúl Gómez; Jensen, Kristoffer Jarlov; Jensen, Sanne Skov

2013-01-01

We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity...... were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts......, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization...

Evaluation of various therapeutic measures in striae rubra

Directory of Open Access Journals (Sweden)

Umesh Karsandas Karia

2016-01-01

Full Text Available Background: Striae are linear atrophic depressions that form in areas of dermal damage in the skin. As on date, no consensus or protocol exists for the treatment of stria rubra. Topical retinoids, chemical peels, microdermabrasion, radiofrequency, photothermolysis, intense pulsed light and lasers are some of the modalities used. Aims and Objective: To compare the efficacy of various therapeutic modalities in striae rubra. Methods: This prospective cohort study comprised of a total of fifty patients from August-2012 to October-2013 in a tertiary care center in Western India, Gujarat having striae rubra. They were randomly divided into five groups of ten patients each. Patients were evaluated on the basis of visual assessment, both by doctor as well as the patient. Group I was given topical tretinoin (0.1% w/w gel applied once at night, Group II-microdermabrasion (MDA combined with trichloroacetic acid (TCA (30% peel, Group III-mesotherapy, Group IV-Q-switched Nd: YAG laser, and Group V-combination treatment of microdermabrasion, salicylic acid peel and retinol (yellow peel. Patients were treated at an interval of 15 days for 2 months and then at monthly intervals. Objective assessment was done at 2nd month, 6th month, and at the end of 1st year. Results: Patients in Group I treated with topical tretinoin showed the least response with 80% (8 of them showing minimal clinical improvement (0–25% as compared to patients in Group V in which 60% (6 patients showed moderate clinical improvement (50–75%. While majority of the patients in Group II, III, and IV showed mild clinical improvement (25–50%. Conclusions: Striae rubra is a common cause of concern for adolescent population. Combination treatment with microdermabrasion, salicylic acid and retinol yellow peel gave superior results as compared to other therapeutic options. Mild to moderate improvement was seen with Nd: YAG laser, mesotherapy and MDA + TCA whereas minimal improvement were seen

Evaluation of Various Therapeutic Measures in Striae Rubra

Science.gov (United States)

Karia, Umesh Karsandas; Padhiar, Bela Bhemabhai; Shah, Bela Jaswantbhai

2016-01-01

Background: Striae are linear atrophic depressions that form in areas of dermal damage in the skin. As on date, no consensus or protocol exists for the treatment of stria rubra. Topical retinoids, chemical peels, microdermabrasion, radiofrequency, photothermolysis, intense pulsed light and lasers are some of the modalities used. Aims and Objective: To compare the efficacy of various therapeutic modalities in striae rubra. Methods: This prospective cohort study comprised of a total of fifty patients from August-2012 to October-2013 in a tertiary care center in Western India, Gujarat having striae rubra. They were randomly divided into five groups of ten patients each. Patients were evaluated on the basis of visual assessment, both by doctor as well as the patient. Group I was given topical tretinoin (0.1% w/w) gel applied once at night, Group II-microdermabrasion (MDA) combined with trichloroacetic acid (TCA) (30%) peel, Group III-mesotherapy, Group IV-Q-switched Nd: YAG laser, and Group V-combination treatment of microdermabrasion, salicylic acid peel and retinol (yellow) peel. Patients were treated at an interval of 15 days for 2 months and then at monthly intervals. Objective assessment was done at 2nd month, 6th month, and at the end of 1st year. Results: Patients in Group I treated with topical tretinoin showed the least response with 80% (8) of them showing minimal clinical improvement (0–25%) as compared to patients in Group V in which 60% (6) patients showed moderate clinical improvement (50–75%). While majority of the patients in Group II, III, and IV showed mild clinical improvement (25–50%). Conclusions: Striae rubra is a common cause of concern for adolescent population. Combination treatment with microdermabrasion, salicylic acid and retinol yellow peel gave superior results as compared to other therapeutic options. Mild to moderate improvement was seen with Nd: YAG laser, mesotherapy and MDA + TCA whereas minimal improvement were seen with

Assessing the hydrologic response to wildfires in mountainous regions

Science.gov (United States)

Havel, Aaron; Tasdighi, Ali; Arabi, Mazdak

2018-04-01

This study aims to understand the hydrologic responses to wildfires in mountainous regions at various spatial scales. The Soil and Water Assessment Tool (SWAT) was used to evaluate the hydrologic responses of the upper Cache la Poudre Watershed in Colorado to the 2012 High Park and Hewlett wildfire events. A baseline SWAT model was established to simulate the hydrology of the study area between the years 2000 and 2014. A procedure involving land use and curve number updating was implemented to assess the effects of wildfires. Application of the proposed procedure provides the ability to simulate the hydrologic response to wildfires seamlessly through mimicking the dynamic of the changes due to wildfires. The wildfire effects on curve numbers were determined comparing the probability distribution of curve numbers after calibrating the model for pre- and post-wildfire conditions. Daily calibration and testing of the model produced very good results. No-wildfire and wildfire scenarios were created and compared to quantify changes in average annual total runoff volume, water budgets, and full streamflow statistics at different spatial scales. At the watershed scale, wildfire conditions showed little impact on the hydrologic responses. However, a runoff increase up to 75 % was observed between the scenarios in sub-watersheds with high burn intensity. Generally, higher surface runoff and decreased subsurface flow were observed under post-wildfire conditions. Flow duration curves developed for burned sub-watersheds using full streamflow statistics showed that less frequent streamflows become greater in magnitude. A linear regression model was developed to assess the relationship between percent burned area and runoff increase in Cache la Poudre Watershed. A strong (R2 > 0.8) and significant (p statistics through application of flow duration curves revealed that the wildfires had a higher effect on peak flows, which may increase the risk of flash floods in post

Dose-response relationship in the treatment of gastrointestinal disorders.

Science.gov (United States)

Weihrauch, T R; Demol, P

1989-08-01

Numerous clinical studies have been performed to establish efficacy and safety of drugs in gastroenterological disorders. Only in a few if any of these studies, however, the rationale for the optimal dose and the dose regimens, respectively, have been addressed. Adequate and well-controlled dose finding studies play a key role in the clinical assessment of new drugs and in the evaluation of new indications. Hereby the range from the minimal effective dose to the maximal effective and well tolerated dose can be assessed and thus the optimal dose-range and dosage regimen be determined. Meaningful pharmacodynamic studies can be performed in the gastrointestinal tract also in healthy volunteers provided that a method with a high predictability for the desired therapeutic effect is available such as measurement of gastric acid secretion and its inhibition by a drug. Dose finding studies in gastroenterology can be carried out under two main aspects: First, to assess the pharmacodynamic and therapeutic effect of a compound on the gastrointestinal tract (e.g. anti-ulcer drug). Second, to evaluate the side effects of a drug on the gastrointestinal tract (e.g. gastric mucosal damage by non-steroidal anti-inflammatory drugs). For the evaluation of new drugs in gastrointestinal therapy a number of methods are available which yield accurate and reproducible data. While careful clinical-pharmacological dose-response studies using these methods have been carried out already more than a decade ago, it is surprising that therapeutic dose finding studies have become available only during the past few years. For scientific as well as for ethical reasons more trials which determine the optimal therapeutic dose are warranted.

Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

Science.gov (United States)

Mocellin, Simone; Nitti, Donato

2008-05-01

Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

MAY GLYPICAN-3 BE A NOVEL BIOMARKER AND POTENTIAL THERAPEUTIC TARGET IN HEPATOCELLULAR CANCER?

Directory of Open Access Journals (Sweden)

Irina I. Ivanova

2018-03-01

Full Text Available The burden of advanced chronic liver disease is increasing worldwide, despite the recent advances in the management of chronic hepatitis viral infections. The abdominal ultrasound is the only approved method for surveillance of patients with cirrhosis, a premalignant condition for hepatocellular cancer (HCC. Although alpha fetoprotein has been known as a tumour marker for HCC, it is not commonly used for screening due to suboptimal sensitivity and specificity. There is a need to introduce a novel biomarker for definition of HCC in early stage and for prognostic and therapeutic response assessment. A review of the current evidences, encouraging the use of glypican-3 in management of patients with cirrhosis and HCC is presented.

Three-dimensional volumetric assessment of response to treatment

International Nuclear Information System (INIS)

Willett, C.G.; Stracher, M.A.; Linggood, R.M.; Leong, J.C.; Skates, S.J.; Miketic, L.M.; Kushner, D.C.; Jacobson, J.O.

1988-01-01

From 1981 to 1986, 12 patients with Stage I and II diffuse large cell lymphoma of the mediastinum were treated with 4 or more cycles of multiagent chemotherapy and for nine patients this was followed by mediastinal irradiation. The response to treatment was assessed by three-dimensional volumetric analysis utilizing thoracic CT scans. The initial mean tumor volume of the five patients relapsing was 540 ml in contrast to an initial mean tumor volume of 360 ml for the seven patients remaining in remission. Of the eight patients in whom mediastinal lymphoma volumes could be assessed 1-2 months after chemotherapy prior to mediastinal irradiation, the three patients who have relapsed had volumes of 292, 92 and 50 ml (mean volume 145 ml) in contrast to five patients who have remained in remission with residual volume abnormalities of 4-87 ml (mean volume 32 ml). Four patients in prolonged remission with CT scans taken one year after treatment have been noted to have mediastinal tumor volumes of 0-28 ml with a mean value of 10 ml. This volumetric technique to assess the extent of mediastinal large cell lymphoma from thoracic CT scans appears to be a useful method to quantitate the amount of disease at presentation as well as objectively monitor response to treatment. 13 refs.; 2 figs.; 1 table

Therapeutic Effects of Horseback Riding Interventions: A Systematic Review and Meta-analysis.

Science.gov (United States)

Stergiou, Alexandra; Tzoufi, Meropi; Ntzani, Evangelia; Varvarousis, Dimitrios; Beris, Alexandros; Ploumis, Avraam

2017-10-01

Equine-assisted therapies, such as therapeutic riding and hippotherapy, are believed to have positive physical and emotional effects in individuals with neuromotor, developmental, and physical disabilities. The purpose of this review was to determine whether therapeutic riding and hippotherapy improve balance, motor function, gait, muscle symmetry, pelvic movement, psychosocial parameters, and the patients' overall quality of life. In this study, a literature search was conducted on MEDLINE, CINAHL, MBASE, SportDiscus, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, PEDro, DARE, Google Scholar, and Dissertation Abstracts. Only studies with a control/comparison group or self-controlled studies performing preintervention and postintervention assessment were included. Excluded were (1) studies not providing data on baseline score or end-point outcome, (2) single-subject studies, (3) studies providing only qualitative data, and (4) studies that used a mechanical horse. Sixteen trials were included. The methodologic quality of each study was evaluated using Downs and Black quality assessment tool. Most of the studies showed a trend toward a beneficial effect of therapeutic riding and hippotherapy on balance and gross motor function. The meta-analysis showed improvement in both the Berg Balance Scale and the Gross Motor Function Measure in therapeutic riding and hippotherapy programs. Programs such as therapeutic riding and hippotherapy are a viable intervention option for patients with balance, gait, and psychomotor disorders.

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

OpenAIRE

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Na?ra; Rau, Fr?d?rique; Jollet, Arnaud; Edom-Vovard, Fr?d?rique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois

2017-01-01

International audience; Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded rep...

Identifying a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients.

Science.gov (United States)

Gupta, Meenal; Moily, Nagaraj S; Kaur, Harpreet; Jajodia, Ajay; Jain, Sanjeev; Kukreti, Ritushree

2013-08-01

Atypical antipsychotic (AAP) drugs are the preferred choice of treatment for schizophrenia patients. Patients who do not show favorable response to AAP monotherapy are subjected to random prolonged therapeutic treatment with AAP multitherapy, typical antipsychotics or a combination of both. Therefore, prior identification of patients' response to drugs can be an important step in providing efficacious and safe therapeutic treatment. We thus attempted to elucidate a genetic signature which could predict patients' response to AAP monotherapy. Our logistic regression analyses indicated the probability that 76% patients carrying combination of four SNPs will not show favorable response to AAP therapy. The robustness of this prediction model was assessed using repeated 10-fold cross validation method, and the results across n-fold cross-validations (mean accuracy=71.91%; 95%CI=71.47-72.35) suggest high accuracy and reliability of the prediction model. Further validations of these results in large sample sets are likely to establish their clinical applicability. Copyright © 2013 Elsevier Inc. All rights reserved.

Bridge Condition Assessment based on Vibration Responses of Passenger Vehicle

International Nuclear Information System (INIS)

Miyamoto, Ayaho; Yabe, Akito

2011-01-01

In this paper, we propose a new method of assessing the condition of existing short- and medium-span reinforced/prestressed concrete bridges based on vibration monitoring data obtained from a public bus. This paper not only describes details of a prototype monitoring system that uses information technology and sensors capable of providing more accurate knowledge of bridge performance than conventional ways but also shows a few specific examples of bridge condition assessment based on vehicle vibrations measured by using an in-service public bus equipped with vibration measurement instrumentation. This paper also describes a sensitivity analysis of deteriorating bridges based on simulation of the acceleration response of buses conducted by the 'substructure method' employing a finite element model to verify the above bridge performance results. The main conclusions obtained in this study can be summarized as follows: (1) Because the vibration responses of passenger vehicles, such as buses, have a good linear relationship with the vibration responses of the target bridges, the proposed system can be used as a practical monitoring system for bridge condition assessment. (2) The results of sensitivity analysis performed by the substructure method show that bus vibration responses are useful for evaluating target bridge performance. (3) The proposed method was applied to a network of real bridges in a local area to evaluate its effectiveness. The results indicate that the proposed method can be used to prioritize the repair/strengthening works of existing bridges based on various vibration information in order to help bridge administrators establish rational maintenance strategies.

HIV-1 Gag-specific exosome-targeted T cell-based vaccine stimulates effector CTL responses leading to therapeutic and long-term immunity against Gag/HLA-A2-expressing B16 melanoma in transgenic HLA-A2 mice

Directory of Open Access Journals (Sweden)

Rong Wang

2014-01-01

Full Text Available Human immunodeficiency virus type-1 (HIV-1-specific dendritic cell (DC vaccines have been applied to clinical trials that show only induction of some degree of immune responses, warranting the search of other more efficient vaccine strategies. Since HIV-1-specific CD8+ cytotoxic T lymphocytes (CTLs have been found to recognize some HIV-1 structural protein Gag conserved and cross-strain epitopes, Gag has become one of the most attractive target candidates for HIV-1 vaccine development. In this study, we generated HIV-1 Gag-specific Gag-Texo vaccine by using ConA-stimulated polyclonal CD8+ T-cells with uptake of Gag-expressing adenoviral vector AdVGag-transfected DC (DCGag-released exosomes (EXOs, and assessed its stimulation of Gag-specific CD8+ CTL responses and antitumor immunity. We demonstrate that Gag-Texo and DCGag vaccines comparably stimulate Gag-specific effector CD8+ CTL responses. Gag-Texo-stimulated CTL responses result in protective immunity against Gag-expressing BL6-10Gag melanoma in 8/8 wild-type C57BL/6 mice. In addition, we show that Gag-Texo vaccine also induces CTL responses leading to protective and long-term immunity against Gag/HLA-A2-expressing BL6-10Gag/A2 melanoma in 8/8 and 2/8 transgenic HLA-A2 mice, respectively. The average number of lung tumor colonies in mice with 30-days post-immunization is only 23, which is significantly less than that (>300 in control ConA-T-immunized HLA-A2 mice. Furthermore, Gag-Texo vaccine also induces some degree of therapeutic immunity. The average number (50 and size (0.23 mm in diameter of lung tumor colonies in Gag-Texo-immunized HLA-A2 mice bearing 6-day-established lung BL6-10Gag/A2 melanoma metastasis are significantly less than the average number (>300 and size (1.02 mm in diameter in control ConA-T-immunized HLA-A2 mice. Taken together, HIV-1 Gag-Texo vaccine capable of stimulating Gag-specific CTL responses and therapeutic immunity may be useful as a new immunotherapeutic

Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay.

Science.gov (United States)

Hodgson, Derek J; Aubin, Yves

2017-05-10

A number of recombinant protein therapeutic products, such as filgrastim (methionyl granulocyte colony stimulating factor [Met-GCSF] used to boost the immune system in chemotherapy treated cancer patients), and interferon alpha-2 (used for the treatment of various viral infections), have been chemically modified with the addition of a polyethylene glycol (PEG) chain. This modification prolongs residency of the drug in the body and reduces metabolic degradation, which allows less frequent administration of the products. Here we show how NMR spectroscopy methods can assess the higher order structure (HOS) of pegylated-filgrastim (Neulasta®), pegylated interferon-α2a (Pegasys®) pegylated interferon-α2b (PEG-Intron®) purchased from the marketplace. The addition of the PEG moiety effectively doubles the molecular weight of the three products. This presents a significant challenge for the application of NMR techniques. Nevertheless, the results showed that high-resolution spectra could be recorded for two of the three products. Comparison of the spectra of the pegylated protein and the non-pegylated protein shows that the chemical modification did not alter the HOS of these proteins. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Epidemiological methods for assessing dose-response and dose-effect relationships

DEFF Research Database (Denmark)

Kjellström, Tord; Grandjean, Philippe

2007-01-01

Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity General Considerations of Dose-Effect and Dose-Response Relationships Interactions in Metal Toxicology Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships Essential Metals: Assessing Risks from Deficiency......Description Handbook of the Toxicology of Metals is the standard reference work for physicians, toxicologists and engineers in the field of environmental and occupational health. This new edition is a comprehensive review of the effects on biological systems from metallic elements...... access to a broad range of basic toxicological data and also gives a general introduction to the toxicology of metallic compounds. Audience Toxicologists, physicians, and engineers in the fields of environmental and occupational health as well as libraries in these disciplines. Will also be a useful...

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.

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.

Lawrence Livermore National Laboratory Emergency Response Capability Baseline Needs Assessment Requirement Document

Energy Technology Data Exchange (ETDEWEB)

Sharry, J A

2009-12-30

This revision of the LLNL Fire Protection Baseline Needs Assessment (BNA) was prepared by John A. Sharry, LLNL Fire Marshal and LLNL Division Leader for Fire Protection and reviewed by Martin Gresho, Sandia/CA Fire Marshal. The document follows and expands upon the format and contents of the DOE Model Fire Protection Baseline Capabilities Assessment document contained on the DOE Fire Protection Web Site, but only address emergency response. The original LLNL BNA was created on April 23, 1997 as a means of collecting all requirements concerning emergency response capabilities at LLNL (including response to emergencies at Sandia/CA) into one BNA document. The original BNA documented the basis for emergency response, emergency personnel staffing, and emergency response equipment over the years. The BNA has been updated and reissued five times since in 1998, 1999, 2000, 2002, and 2004. A significant format change was performed in the 2004 update of the BNA in that it was 'zero based.' Starting with the requirement documents, the 2004 BNA evaluated the requirements, and determined minimum needs without regard to previous evaluations. This 2010 update maintains the same basic format and requirements as the 2004 BNA. In this 2010 BNA, as in the previous BNA, the document has been intentionally divided into two separate documents - the needs assessment (1) and the compliance assessment (2). The needs assessment will be referred to as the BNA and the compliance assessment will be referred to as the BNA Compliance Assessment. The primary driver for separation is that the needs assessment identifies the detailed applicable regulations (primarily NFPA Standards) for emergency response capabilities based on the hazards present at LLNL and Sandia/CA and the geographical location of the facilities. The needs assessment also identifies areas where the modification of the requirements in the applicable NFPA standards is appropriate, due to the improved fire protection

Emergency Response Capability Baseline Needs Assessment - Requirements Document

Energy Technology Data Exchange (ETDEWEB)

Sharry, J A

2016-10-04

This document was prepared by John A. Sharry, LLNL Fire Marshal and LLNL Division Leader for Fire Protection and reviewed by LLNL Emergency Management Department Head James Colson. The document follows and expands upon the format and contents of the DOE Model Fire Protection Baseline Capabilities Assessment document contained on the DOE Fire Protection Web Site, but only addresses emergency response.

Fenetylline: therapeutic use, misuse and/or abuse.

Science.gov (United States)

Kristen, G; Schaefer, A; von Schlichtegroll, A

1986-06-01

Fenetylline (CAPTAGON) is included in a list of compounds to be considered by a World Health Organization (WHO) Expert Committee in April 1985 for possible international scheduling under the Convention on Psychotropic Substances, 1971. For over 23 years, this central stimulant has been used therapeutically in hyperkinetic children and other indications in place of amphetamines and other central stimulants with higher risk levels. In good correspondence with recent animal data fenetylline also shows significant qualitative and quantitative differences compared to amphetamine in man. It has few adverse side effects, a lower abuse potential and little actual abuse compared to amphetamine. Thus its benefit/risk assessment is substantially more favourable than that of other central stimulants. For proper therapeutic use of the substance, prescription status is or should be required by national authorities.

Indicators for Assessing the Socio-Economic Responsibility of Entrepreneurship in Ukraine

Directory of Open Access Journals (Sweden)

Dielini Maryna M.

2017-12-01

Full Text Available The aim of the article is to determine the main indicators that can be used for assessing the socio-economic responsibility of Ukrainian enterprises, and group these indicators by categories of stakeholders. There presented main recipients towards which the socio-economic responsibility of entrepreneurship is directed, namely, enterprise employees; owners (shareholders; consumers of products; suppliers and competitors; society and state. Forms and instruments for realizing the socio-economic responsibility of enterprises (SERE are presented, and on this basis a system of indicators is developed that can be used in the assessment of the SERE. The indicators have both quantitative and qualitative representation and also provide an opportunity to cover the full scale of the manifestation of the SERE regarding the interest groups. Much attention is paid to the ensuring of profitability of an enterprise (as the main objective of corporate social responsibility, according to A. Carroll, as well as deductions for the development of personnel, both professional and recreational, and for the development of society, welfare of the population in the form of spending on social investment, socially responsible marketing, monetary grants for research, charitable activities, and other tools of the SEPE manifestation.

Targeting the Immune System’s Natural Response to Cell Death to Improve Therapeutic Response in Breast Cancers

Science.gov (United States)

2016-09-01

pharmacological MerTK inhibition, measuring intra-tumoral leukocytes and tumor epithelial cell signaling in the post-therapeutic setting using flow...7Department of Pediatrics, National Jewish Health, Denver, Colorado, USA. 8Departments of Pharmacology and Medicine and UNC Lineberger Comprehensive...tail vein injection into lethally irradiated 6-week-old female MMTV-PyVmT recipients. (B) Average tumor volume ± SEM measured in live mice by MRI at

Relationship of HIV Reservoir Characteristics with Immune Status and Viral Rebound Kinetics in an HIV Therapeutic Vaccine Study

Science.gov (United States)

Li, Jonathan Z.; Heisey, Andrea; Ahmed, Hayat; Wang, Hongying; Zheng, Lu; Carrington, Mary; Wrin, Terri; Schooley, Robert T.; Lederman, Michael M.; Kuritzkes, Daniel R.

2014-01-01

Objectives To evaluate the impact of therapeutic HIV vaccination on the HIV reservoir, and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics. Design Retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine. Methods Participants received vaccine/placebo at weeks 0, 4, and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia (RV) were quantified at weeks 0, 8, and 38. HIV-specific CD4+/CD8+ activity were assessed by an intracellular cytokine staining assay. Results At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4+ interferon-γ-producing cells (CA-RNA: r = −0.23, P=0.03 and CA-DNA: r = −0.28, P<0.01, N=93). Therapeutic HIV vaccination induced HIV-specific CD4+ activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable RV at week 8 had higher frequencies of HIV-specific CD4+ and CD8+ interferon-γ-producing cells (undetectable versus detectable RV: 277 versus 161 CD4+ cells/106 lymphocytes, P=0.03 and 1326 versus 669 CD8+ cells/106 lymphocytes, P=0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P<0.01 and CA-DNA: r = 0.47, P<0.01). Conclusions Vaccine-induced T-cell responses were associated with a modest transient effect on RV, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics. PMID:25254301

Mucociliary and cough clearance as a biomarker for therapeutic development

DEFF Research Database (Denmark)

Bennett, William D; Daviskas, Evangelia; Hasani, Amir

2010-01-01

or therapeutic evaluation presented details of their methodologies. Attendees participating in the workshop discussions included those interested in the physiology of MCC/CC, some of who use in vitro or animal methods for its study, pharmaceutical companies developing muco-active therapies, and many who were......A workshop/symposium on “Mucociliary and Cough Clearance (MCC/CC) as a Biomarker for Therapeutic Development” was held on October 21–22, 2008, in Research Triangle Park, NC, to discuss the methods for measurement of MCC/CC and how they may be optimized for assessing new therapies designed...

Evaluation of the possibility of estimating therapeutic response to Donepezil in patients with dat using ezis

International Nuclear Information System (INIS)

Joji Kawabe; Shigeaki Higashiyama; Terue Okamura; Hiroshi Hashimoto; Hisanori Akiyama; Kouki Inoue; Nobuo Kiriike; Kenji Torii; Hirotaka Ishizu; Etsushi Kawamura; Jin Kotani; Ai Oe; Takehiro Hayashi

2004-01-01

high sensitivity and specificity in detection, but it is difficult to obtain three-dimensional spatial information of abnormalities from surface projection images. eZIS is a new statistical imaging analysis system permitting brain standardization using SPM and statistical analysis of the entire brain using Z-values. In this study, we examined the possibility of estimating therapeutic response to Donepezil in patients with DAT using eZIS. Methods: Eighteen patients (5 men, 13 women, age range, 66-83 years old; mean age, 73.6 years old) who complained of memory impairment were recruited from an outpatient dementia clinic of the Department of Neuro psychiatry of Osaka City University Hospital, between 2001 and 2003. The clinical diagnosis of DAT was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The patients received daily oral doses of Donepezil (5 mg/d). Each patient underwent the Alzheimer's Disease Assessment Scale Japanese edition (ADAS-Jcog) test, a recognition function test, and baseline SPECT examination at the time of initial evaluation and was clinically followed by a second ADAS-Jcog test and SPECT examination 12 weeks later. Informed consent of each patient was obtained after a detailed explanation concerning this study before beginning treatment. Before SPECT scanning was performed, an intravenous line was established in the right cubital vein of all patients while they were supine with their eyes closed. Each patient received a 740-MBq intravenous injection of Tc- 99m -ethyl cysteinate dimer (ECD). Dynamic data were collected (70 x 1-s frame images) simultaneously with the injection using a large field of view encompassing the cranial and thoracic regions. Thirty minutes after injection of Tc- 99m -ECD, brain SPECT imaging was performed with a 128 x 128 pixel matrix in step and shoot mode and with a triple-head SPECT system (GCA 9300 A/HG, Toshiba Medical Systems, Inc., Tokyo, Japan). All subsequent image

Using Item Response Theory to Describe the Nonverbal Literacy Assessment (NVLA)

Science.gov (United States)

Fleming, Danielle; Wilson, Mark; Ahlgrim-Delzell, Lynn

2018-01-01

The Nonverbal Literacy Assessment (NVLA) is a literacy assessment designed for students with significant intellectual disabilities. The 218-item test was initially examined using confirmatory factor analysis. This method showed that the test worked as expected, but the items loaded onto a single factor. This article uses item response theory to…

Therapeutic effect of norisoboldine, an alkaloid isolated from Radix Linderae, on collagen-induced arthritis in mice.

Science.gov (United States)

Luo, Y; Liu, M; Xia, Y; Dai, Y; Chou, G; Wang, Z

2010-08-01

The alkaloid fraction of Radix Linderae, the main active component of this herb drug, has been proven to exhibit anti-inflammatory, analgesic and antimicrobial activities. The present study was undertaken to investigate the therapeutic potential of norisoboldine, the major isoquinoline alkaloid present in Radix Linderae, in collagen II -induced arthritis (CIA) of mice as well as the possible mechanisms. CIA was induced in mice by immunization with chicken type II collagen (II). After boosted on day 21, mice were treated with norisoboldine (10, 20, 40 mg/kg) for twenty consecutive days. The clinical scores, body weight changes and joint histopathology were evaluated. Norisoboldine treatment significantly alleviated the severity of the disease, based on the reduced clinical scores and elevated the lowered body weights of model mice. Meanwhile, this alkaloid dose-dependently reduced the infiltration of inflammatory cells, synovial hyperplasia and protected joint from destruction. Additionally, the serum level of anti-CII IgG and the CII-stimulated lymphocyte proliferation were remarkably decreased in the groups administered with norisoboldine. An assessment of Th1 function using the delayed-type hypersensitivity model confirmed that norisoboldine also significantly suppressed the enhanced T cell responses in vivo. These findings suggest that norisoboldine might be a potential therapeutic agent for rheumatoid arthritis, and it functions through protecting joint destruction as well as regulating the abnormal immune responses. 2010 Elsevier GmbH. All rights reserved.

Utility of immunodeficient mouse models for characterizing the preclinical pharmacokinetics of immunogenic antibody therapeutics.

Science.gov (United States)

Myzithras, Maria; Bigwarfe, Tammy; Li, Hua; Waltz, Erica; Ahlberg, Jennifer; Giragossian, Craig; Roberts, Simon

Prior to clinical studies, the pharmacokinetics (PK) of antibody-based therapeutics are characterized in preclinical species; however, those species can elicit immunogenic responses that can lead to an inaccurate estimation of PK parameters. Immunodeficient (SCID) transgenic hFcRn and C57BL/6 mice were used to characterize the PK of three antibodies that were previously shown to be immunogenic in mice and cynomolgus monkeys. Four mouse strains, Tg32 hFcRn SCID, Tg32 hFcRn, SCID and C57BL/6, were administered adalimumab (Humira®), mAbX and mAbX-YTE at 1 mg/kg, and in SCID strains there was no incidence of immunogenicity. In non-SCID strains, drug-clearing ADAs appeared after 4-7 days, which affected the ability to accurately calculate PK parameters. Single species allometric scaling of PK data for Humira® in SCID and hFcRn SCID mice resulted in improved human PK predictions compared to C57BL/6 mice. Thus, the SCID mouse model was demonstrated to be a useful tool for assessing the preclinical PK of immunogenic therapeutics.

Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

OpenAIRE

Lagarde, Fabien; Beausoleil, Claire; Belcher, Scott M; Belzunces, Luc P; Emond, Claude; Guerbet, Michel; Rousselle, Christophe

2015-01-01

International audience; Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that repor...

Undergraduate nursing students writing therapeutic letters to families: an educational strategy.

Science.gov (United States)

Erlingsson, Christen

2009-02-01

Writing therapeutic letters to families is discussed in this article as an educational strategy encouraging students to think reflectively about family nursing. At the University of Kalmar, Sweden, undergraduate nursing students in a primary care module interviewed families using the Calgary Family Assessment Model and wrote therapeutic letters to these families. This article describes (a) the examination process, which was the context for writing therapeutic letters, (b) results of analyses of the letters, and (c) student's post-examination evaluation comments. Results indicate that most students needed encouragement to focus on the family's strengths and resources instead of focusing on own feelings or problems they perceived the family as having. Students also needed support in relinquishing their hierarchical role of "expert nurse." Students' evaluation comments showed that writing therapeutic letters provided students with opportunities to reflect about the connections between family nursing theory and the family itself.

Pain and endometriosis: Etiology, impact, and therapeutics

Directory of Open Access Journals (Sweden)

Robert N. Taylor

2012-12-01

Full Text Available The association of pain and endometriosis was recognized with the first definitive published reports of this disorder. Unfortunately, the precise etiologies and pathways leading to nociception and pain symptoms in endometriosis remain poorly understood, and as a result, effective therapeutic interventions are lacking with consequent profound effects on affected women’s quality of life. In this opinion paper we summarize selected proceedings presented at the 28th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE in Istanbul, Turkey, and review the clinical and translational evidence of chronic pain, neurogenesis, and the pernicious impact of dyspareunia on women with symptomatic endometriosis. The effectiveness of medical treatments is critically assessed and the findings indicate that good therapeutic options are available with extant medications effective in some sub-groups of women with endometriosis, many of which are affordable globally. Nevertheless, new management strategies and drugs need to be developed to increase the options of all afflicted women to minimize and ideally eradicate painful symptoms of endometriosis. However, only by elucidating distinctions among sub-groups with specific symptoms, suggesting different mechanisms, are we likely to derive truly successful therapeutic strategies.

Cone-beam computed tomography imaging: therapeutic staff dose during chemoembolisation procedure

International Nuclear Information System (INIS)

Paul, Jijo; Vogl, Thomas J; Chacko, Annamma; Mbalisike, Emmanuel C

2014-01-01

Cone-beam computed tomography (CBCT) imaging is an important requirement to perform real-time therapeutic image-guided procedures on patients. The purpose of this study is to estimate the personal-dose-equivalent and annual-personal-dose from CBCT imaging during transarterial chemoembolisation (TACE). Therapeutic staff doses (therapeutic and assistant physician) were collected during 200 patient (65  ±  15 years, range: 40–86) CBCT examinations over six months. Absorbed doses were assessed using thermo-luminescent dosimeters during patient hepatic TACE therapy. We estimated personal-dose-equivalent (PDE) and annual-personal-dose (APD) from absorbed dose based on international atomic energy agency protocol. APD for therapeutic procedure was calculated (therapeutic physician: 5.6 mSv; assistant physician: 5.08 mSv) based on institutional work load. Regarding PDE, the hands of the staff members received a greater dose compared to other anatomical locations (therapeutic physician: 56 mSv, 72 mSv; assistant physician: 12 mSv, 14 mSv). Annual radiation doses to the eyes and hands of the staff members were lower compared to the prescribed limits by the International Commission on Radiological Protection (ICRP). PDE and APD of both therapeutic staff members were within the recommended ICRP-103 annual limit. Dose to the assistant physician was lower than the dose to the therapeutic physician during imaging. Annual radiation doses to eye-lenses and hands of both staff members were lower than prescribed limits. (paper)

Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

Science.gov (United States)

Sheikhbahaei, Sara; Mena, Esther; Pattanayak, Puskar; Taghipour, Mehdi; Solnes, Lilja B; Subramaniam, Rathan M

2017-01-01

A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiotherapy in conjunction with 7-hydroxystaurosporine: a multimodal approach with tumor pO2 as a potential marker of therapeutic response.

Science.gov (United States)

Khan, Nadeem; Mupparaju, Sriram P; Hou, Huagang; Lariviere, Jean P; Demidenko, Eugene; Swartz, Harold M; Eastman, Alan

2009-11-01

Checkpoint inhibitors potentially could be used to enhance cell killing by DNA-targeted therapeutic modalities such as radiotherapy. UCN-01 (7-hydroxystaurosporine) inhibits S and G2 checkpoint arrest in the cells of various malignant cell lines and has been investigated in combination with chemotherapy. However, little is known about its potential use in combination with radiotherapy. We report the effect of 20 Gy radiation given in conjunction with UCN-01 on the pO2 and growth of subcutaneous RIF-1 tumors. Multisite EPR oximetry was used for repeated, non-invasive tumor pO2 measurements. The effect of UCN-01 and/or 20 Gy on tumor pO2 and tumor volume was investigated to determine therapeutic outcomes. Untreated RIF-1 tumors were hypoxic with a tissue pO2 of 5-7 mmHg. Treatment with 20 Gy or UCN-01 significantly reduced tumor growth, and a modest increase in tumor pO2 was observed in tumors treated with 20 Gy. However, irradiation with 20 Gy 12 h after UCN-01 treatment resulted in a significant inhibition of tumor growth and a significant increase in tumor pO2 to 16-28 mmHg from day 1 onward compared to the control, UCN-01 or 20-Gy groups. Treatment with UCN-01 12 h after 20 Gy also led to a similar growth inhibition of the tumors and a similar increase in tumor pO2. The changes in tumor pO2 observed after the treatment correlated inversely with the tumor volume in the groups receiving UCN-01 with 20 Gy. This multimodal approach could be used to enhance the outcome of radiotherapy. Furthermore, tumor pO2 could be a potential marker of therapeutic response.

New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses.

Science.gov (United States)

Ahluwalia, Neil; Shea, Barry S; Tager, Andrew M

2014-10-15

Idiopathic pulmonary fibrosis (IPF) is a devastating disease, with a median survival as short as 3 years from the time of diagnosis and no pharmacological therapies yet approved by the U.S. Food and Drug Administration. To address the great unmet need for effective IPF therapy, a number of new drugs have recently been, or are now being, evaluated in clinical trials. The rationales for most of these therapeutic candidates are based on the current paradigm of IPF pathogenesis, in which recurrent injury to the alveolar epithelium is believed to drive aberrant wound healing responses, resulting in fibrosis rather than repair. Here we discuss drugs in recently completed or currently ongoing phase II and III IPF clinical trials in the context of their putative mechanisms of action and the aberrant repair processes they are believed to target: innate immune activation and polarization, fibroblast accumulation and myofibroblast differentiation, or extracellular matrix deposition and stiffening. Placed in this context, the positive results of recently completed trials of pirfenidone and nintedanib, and results that will come from ongoing trials of other agents, should provide valuable insights into the still-enigmatic pathogenesis of this disease, in addition to providing benefits to patients with IPF.

New Therapeutic Targets in Idiopathic Pulmonary Fibrosis. Aiming to Rein in Runaway Wound-Healing Responses

Science.gov (United States)

Ahluwalia, Neil; Shea, Barry S.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease, with a median survival as short as 3 years from the time of diagnosis and no pharmacological therapies yet approved by the U.S. Food and Drug Administration. To address the great unmet need for effective IPF therapy, a number of new drugs have recently been, or are now being, evaluated in clinical trials. The rationales for most of these therapeutic candidates are based on the current paradigm of IPF pathogenesis, in which recurrent injury to the alveolar epithelium is believed to drive aberrant wound healing responses, resulting in fibrosis rather than repair. Here we discuss drugs in recently completed or currently ongoing phase II and III IPF clinical trials in the context of their putative mechanisms of action and the aberrant repair processes they are believed to target: innate immune activation and polarization, fibroblast accumulation and myofibroblast differentiation, or extracellular matrix deposition and stiffening. Placed in this context, the positive results of recently completed trials of pirfenidone and nintedanib, and results that will come from ongoing trials of other agents, should provide valuable insights into the still-enigmatic pathogenesis of this disease, in addition to providing benefits to patients with IPF. PMID:25090037

Comparison of manual and automated size measurements of lung metastases on MDCT images: Potential influence on therapeutic decisions

International Nuclear Information System (INIS)

Pauls, Sandra; Kuerschner, Christian; Dharaiya, Ekta; Muche, Rainer; Schmidt, Stefan A.; Krueger, Stefan; Brambs, Hans-Juergen; Aschoff, Andrik J.

2008-01-01

Purpose: The goal of this study was to evaluate the influence of automated measurement of diameter, area, and volume from chest CT scans on therapeutic decisions of lung nodules as compared to manual 2-D measurements. Patients and method: The retrospective study involved 25 patients with 75 lung metastases. Contrast enhanced CT scans (16 row) of the lung were performed three times during chemotherapy with a mean time interval of 67.9 days between scans. In each patient, three metastases were evaluated (n = 225). Automatic measurements were compared to manual assessment for the following parameters: diameter, area, and density. The influence on the therapeutic decisions was evaluated using the RECIST criteria. Results: The maximum diameter measured by the automatic application was on an average 27% (S.D. 39; CI: 0.22-0.32; p < 0.0001) higher than the maximum diameter with manual assessment, and the differences depended on metastases size. Based on diameter calculation, manual and automated assessment disagreed in up to 32% of therapeutic decisions. Volumetric assessment tended towards more changes in therapy as compared to diameter calculation. The calculation of mean transversal area of metastases was 36% (S.D. 0.305; CI: -0.40 to -0.32; p < 0.0001) less with automated measurement. Therapeutic strategy would be changed in up to 25.7% of nodules using automated area calculation. Automated assessment of nodules' area and volume could influence the therapeutic decisions in up to 51.4% of all nodules. Density of the nodules was not validated to determine the influence on therapeutic decisions. Conclusion: There is a discrepancy between the manual and automated size measurement of lung metastases which could be significant

Comparison of manual and automated size measurements of lung metastases on MDCT images: Potential influence on therapeutic decisions

Energy Technology Data Exchange (ETDEWEB)

Pauls, Sandra [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: sandra.pauls@uni-ulm.de; Kuerschner, Christian [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: chris.kuerschner@web.de; Dharaiya, Ekta [CT-Clinical Science, Philips Medical Systems, Highland Heights, OH 44143 (United States)], E-mail: ekta.shah@philips.com; Muche, Rainer [Institute of Biometrics, University of Ulm, Schwabstrasse 13, 89075 Ulm (Germany)], E-mail: rainer.muche@uni-ulm.de; Schmidt, Stefan A. [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: stefan-a.schmidt@gmx.de; Krueger, Stefan [Department of Internal Medicine II, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: s.krueger@uniklinik-ulm.de; Brambs, Hans-Juergen [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: hans-juergen.brambs@uniklinik-ulm.de; Aschoff, Andrik J. [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: andrik.aschoff@uni-ulm.de

2008-04-15

Purpose: The goal of this study was to evaluate the influence of automated measurement of diameter, area, and volume from chest CT scans on therapeutic decisions of lung nodules as compared to manual 2-D measurements. Patients and method: The retrospective study involved 25 patients with 75 lung metastases. Contrast enhanced CT scans (16 row) of the lung were performed three times during chemotherapy with a mean time interval of 67.9 days between scans. In each patient, three metastases were evaluated (n = 225). Automatic measurements were compared to manual assessment for the following parameters: diameter, area, and density. The influence on the therapeutic decisions was evaluated using the RECIST criteria. Results: The maximum diameter measured by the automatic application was on an average 27% (S.D. 39; CI: 0.22-0.32; p < 0.0001) higher than the maximum diameter with manual assessment, and the differences depended on metastases size. Based on diameter calculation, manual and automated assessment disagreed in up to 32% of therapeutic decisions. Volumetric assessment tended towards more changes in therapy as compared to diameter calculation. The calculation of mean transversal area of metastases was 36% (S.D. 0.305; CI: -0.40 to -0.32; p < 0.0001) less with automated measurement. Therapeutic strategy would be changed in up to 25.7% of nodules using automated area calculation. Automated assessment of nodules' area and volume could influence the therapeutic decisions in up to 51.4% of all nodules. Density of the nodules was not validated to determine the influence on therapeutic decisions. Conclusion: There is a discrepancy between the manual and automated size measurement of lung metastases which could be significant.

The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

DEFF Research Database (Denmark)

Hudson, Brian D; Ulven, Trond; Milligan, Graeme

2013-01-01

G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery

Science.gov (United States)

Badeau, Barry A.; Comerford, Michael P.; Arakawa, Christopher K.; Shadish, Jared A.; Deforest, Cole A.

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Therapeutic potential of gel-based injectables for vocal fold regeneration

Science.gov (United States)

Bartlett, Rebecca S.; Thibeault, Susan L.; Prestwich, Glenn D.

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. PMID:22456756

Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.

Science.gov (United States)

Roybal, Kole T; Lim, Wendell A

2017-04-26

The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

Therapeutic potential of gel-based injectables for vocal fold regeneration

International Nuclear Information System (INIS)

Bartlett, Rebecca S; Thibeault, Susan L; Prestwich, Glenn D

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. (paper)

Methodology for Assessment of Inertial Response from Wind Power Plants

DEFF Research Database (Denmark)

Altin, Müfit; Teodorescu, Remus; Bak-Jensen, Birgitte

2012-01-01

High wind power penetration levels result in additional requirements from wind power in order to improve frequency stability. Replacement of conventional power plants with wind power plants reduces the power system inertia due to the wind turbine technology. Consequently, the rate of change...... of frequency and the maximum frequency deviation increase after a disturbance such as generation loss, load increase, etc. Having no inherent inertial response, wind power plants need additional control concepts in order to provide an additional active power following a disturbance. Several control concepts...... have been implemented in the literature, but the assessment of these control concepts with respect to power system requirements has not been specified. In this paper, a methodology to assess the inertial response from wind power plants is proposed. Accordingly, the proposed methodology is applied...

Effect of therapeutic class on counseling in community pharmacies.

Science.gov (United States)

Vainio, Kirsti K; Airaksinen, Marja S A; Hyykky, Tarja T; Enlund, K Hannes

2002-05-01

To assess the effect and importance of the therapeutic class of a drug as a determinant for verbal counseling by community pharmacists. Direct external observations (n = 1431) of pharmacist-customer interactions at the point of delivery of prescription medicines were conducted in 7 community pharmacies in Finland. Trained observers noted whether the pharmacist provided information on directions for use, mode of action, and adverse effects. To examine factors associated with counseling, a multiple logistic regression analysis was constructed, with the dependent variable being counseling of any of the 3 observed topics. In addition to therapeutic class, other independent variables were the pharmacy; pharmacist's age, gender, and degree; and the customer's age, gender, previous use of medicine, and question asking. Provision of counseling differed significantly according to therapeutic classes. Counseling on any of the 3 observed topics was most likely to be provided for customers with antibiotics (80%) and least likely for customers with gynecologic preparations (18%). Differences between therapeutic classes remained statistically significant when the effects of the other variables were controlled for. Other significant predictors for any verbal counseling were the pharmacy, customer's previous use of the medicine, and question asking. Therapeutic class is an important variable that should be included in further studies and considered when comparing studies on patient counseling in community pharmacies.

Comparison of Classical Test Theory and Item Response Theory in Individual Change Assessment

NARCIS (Netherlands)

Jabrayilov, Ruslan; Emons, Wilco H. M.; Sijtsma, Klaas

2016-01-01

Clinical psychologists are advised to assess clinical and statistical significance when assessing change in individual patients. Individual change assessment can be conducted using either the methodologies of classical test theory (CTT) or item response theory (IRT). Researchers have been optimistic

QUANTITATION OF MOLECULAR ENDPOINTS FOR THE DOSE-RESPONSE COMPONENT OF CANCER RISK ASSESSMENT

Science.gov (United States)

Cancer risk assessment involves the steps of hazard identification, dose-response assessment, exposure assessment and risk characterization. The rapid advances in the use of molecular biology approaches has had an impact on all four components, but the greatest overall current...

Therapeutic Value of the Periodic Health Examination

Energy Technology Data Exchange (ETDEWEB)

Lincoln, T. A.; Hurt, H. B.

1965-09-01

The Oak Ridge National Laboratory has been conducting periodic health examinations on all of its employees for over 10 years. The original purpose of this program was the early detection of disease to be followed by referral or appropriate counseling. Because of the relatively young age of this group, we expected that this service would be of greatest benefit to only the small percentage who had significant findings. However, over this 10 year period we have been increasingly impressed that those who had no significant findings have expressed almost as much enthusiasm and gratitude as those in whom we found early but potentially serious disease. This response caused us to look more critically at the reasons for this favorable reaction. As a result, we have become convinced that these examinations have an important therapeutic value to the healthy, as well as the sick, and that this fact should be considered in their justification. A health examination can quite properly be considered therapeutic, even though no disease is found or treated, providing it "serves" or meets some of the needs of the person being examined. After all, the literal definition of the word therapeutic is service, since it is derived from the Greek word therapeutikos, which means an attendant or servant.

Oak Ridge National Laboratory Corrective Action Plan in response to Tiger Team assessment

International Nuclear Information System (INIS)

1991-01-01

This report presents a complete response to the Tiger Team assessment that was conducted to Oak Ridge National Laboratory (ORNL) and at the US Department of Energy (DOE) Oak Ridge Operations Office (ORO) from October 2, 1990, through November 30, 1990. The action plans have undergone both a discipline review and a cross-cutting review with respect to root cause. In addition, the action plans have been integrated with initiatives being pursued across Martin Marietta Energy Systems, Inc., in response to Tiger Team findings at other DOE facilities operated by Energy Systems. The root cause section is complete and describes how ORNL intends to address the root cause of the findings identified during the assessment. This report is concerned with reactors safety and health findings, responses, and planned actions. Specific areas include: organization and administration; quality verification; operations; maintenance; training and certification; auxiliary systems; emergency preparedness; technical support; nuclear criticality safety; security/safety interface; experimental activities; site/facility safety review; radiological protection; personnel protection; fire protection; management findings, responses, and planned actions; self-assessment findings, responses, and planned actions; and summary of planned actions, schedules, and costs

Assessment of the response to cholera outbreaks in two districts in Ghana.

Science.gov (United States)

Ohene, Sally-Ann; Klenyuie, Wisdom; Sarpeh, Mark

2016-11-02

Despite recurring outbreaks of cholera in Ghana, very little has been reported on assessments of outbreak response activities undertaken in affected areas. This study assessed the response activities undertaken in two districts, Akatsi District in Volta Region and Komenda-Edina-Eguafo-Abirem (KEEA) Municipal in Central Region during the 2012 cholera epidemic in Ghana. We conducted a retrospective assessment of the events, strengths and weaknesses of the cholera outbreak response activities in the two districts making use of the WHO cholera evaluation tool. Information sources included surveillance and facility records, reports and interviews with relevant health personnel involved in the outbreak response from both district health directorates and health facilities. We collected data on age, sex, area of residence, date of reporting to health facility of cholera cases, district population data and information on the outbreak response activities and performed descriptive analyses of the outbreak data by person, time and place. The cholera outbreak in Akatsi was explosive with a high attack rate (AR) of 374/100,000 and case fatality rate (CFR) of 1.2 % while that in KEEA was on a relatively smaller scale AR of 23/100,000 but with a high case fatality rate of 18.8 %. For both districts, we identified multiple strengths in the response to the outbreak including timely notification of the district health officials which triggered prompt investigation of the suspected outbreak facilitating confirmation of cholera and initiation of public health response activities. Others were coordination of the activities by multi-sectoral committees, instituting water, sanitation and hygiene measures and appropriate case management at health facilities. We also found areas that needed improvement in both districts including incomplete surveillance data, sub-optimal community based surveillance considering the late reporting and the deaths in the community and the inadequate

Therapeutic management of acute pulmonary embolism.

Science.gov (United States)

Tromeur, Cécile; Van Der Pol, Liselotte M; Couturaud, Francis; Klok, Frederikus A; Huisman, Menno V

2017-08-01

Acute pulmonary embolism (PE) is a potentially fatal manifestation of venous thromboembolism. Prompt anticoagulant treatment is crucial for PE patients, which can decrease morbidity and mortality. Risk assessment is the cornerstone of the therapeutic management of PE. It guides physicians to the most appropriate treatment and selects patients for early discharge or home treatment. Areas covered: Here, we review the current treatments of acute PE according to contemporary risk stratification strategies, highlighting each step of PE therapeutic management. Expert commentary: Currently, direct oral anticoagulants (DOACs) represent the first-line therapy of patients presenting with non-high risk PE with a better risk-benefit ratios than vitamin K antagonists (VKAs) due to lower risk of major bleeding. Only high-risk patients with PE who present in shock should be treated with systematic thrombolysis, while surgical thrombectomy or catheter direct thrombolysis (CDT) should only be considered when thrombolysis is contraindicated because of too high bleeding risk.

Momentary assessment of contextual influences on affective response during physical activity.

Science.gov (United States)

Dunton, Genevieve Fridlund; Liao, Yue; Intille, Stephen; Huh, Jimi; Leventhal, Adam

2015-12-01

Higher positive and lower negative affective response during physical activity may reinforce motivation to engage in future activity. However, affective response during physical activity is typically examined under controlled laboratory conditions. This research used ecological momentary assessment (EMA) to examine social and physical contextual influences on momentary affective response during physical activity in naturalistic settings. Participants included 116 adults (mean age = 40.3 years, 73% female) who completed 8 randomly prompted EMA surveys per day for 4 days across 3 semiannual waves. EMA surveys measured current activity level, social context, and physical context. Participants also rated their current positive and negative affect. Multilevel models assessed whether momentary physical activity level moderated differences in affective response across contexts controlling for day of the week, time of day, and activity intensity (measured by accelerometer). The Activity Level × Alone interaction was significant for predicting positive affect (β = -0.302, SE = 0.133, p = .024). Greater positive affect during physical activity was reported when with other people (vs. alone). The Activity Level × Outdoors interaction was significant for predicting negative affect (β = -0.206, SE = 0.097, p = .034). Lower negative affect during physical activity was reported outdoors (vs. indoors). Being with other people may enhance positive affective response during physical activity, and being outdoors may dampen negative affective response during physical activity. (c) 2015 APA, all rights reserved).

A therapeutic gain model for brachytherapy

International Nuclear Information System (INIS)

Wigg, D.R.

2003-01-01

When treating with continuous irradiation the potential therapeutic gain or loss depends on several treatment, normal tissue and tumour variables. There are similarities between equations defining tissue effects with fractionated treatment and brachytherapy. The former is sensitive to dose per fraction (and incomplete repair for short intervals between treatments) and the later is sensitive to dose rate and continuous repair factors. Because of these similarities, for typical tumours and normal tissues, dose per fraction and dose rates generally work in similar directions. As the dose per fraction or dose rate increases the therapeutic gain falls. With continuous irradiation the dose rates effects are determined by Beta cell kill and hence the absolute value of Beta . Minimal sensitivity occurs at very low and very high dose rates. The magnitude of cell kill also depends on the Continuous Repair Factor (g) which is a function of the treatment time and the Repair Half Time (in hours) of the tissues (Repair Half Time T 1/2Ln(2)/h, when h the Repair Constant). An interactive optimising model has been written to predict the therapeutic gain or loss as the parameter values are varied. This model includes the tumour and normal tissue parameters alpha and beta Gy (or individual values), their Repair Half Times, dose rates and overall treatment time. The model is based on the Linear-Quadratic equation and the Total Effect (TE) method of Thames and Hendry although the Extrapolated Response Dose (ERD) method of Barendsen produces the same results. The model is written so that the gain or loss may be seen when treatment is always to normal tissue tolerance doses. The magnitude of the therapeutic loss as the dose rate increases and its sensitivity to changes in normal tissue and tumour parameter values is clearly demonstrated

Screening of traditional Chinese medicines with therapeutic potential on chronic obstructive pulmonary disease through inhibiting oxidative stress and inflammatory response.

Science.gov (United States)

Zhou, Ming-Xing; Wei, Xuan; Li, Ai-Ling; Wang, Ai-Min; Lu, Ling-Zi; Yang, Yue; Ren, Dong-Mei; Wang, Xiao-Ning; Wen, Xue-Sen; Lou, Hong-Xiang; Shen, Tao

2016-09-13

Chronic obstructive pulmonary disease (COPD) is a major public health problem and gives arise to severe chronic morbidity and mortality in the world. Inflammatory response and oxidative stress play dominant roles in the pathological mechanism of COPD, and have been regarded to be two important targets for the COPD therapy. Traditional Chinese medicines (TCMs) possess satisfying curative effects on COPD under guidance of the TCM theory in China, and merit in-depth investigations as a resource of lead compounds. One hundred ninety-six of TCMs were collected, and extracted to establish a TCM extract library, and then further evaluated for their potency on inhibitions of oxidative stress and inflammatory response using NADP(H):quinone oxidoreductase (QR) assay and nitric oxide (NO) production assay, respectively. Our investigation observed that 38 of the tested TCM extracts induced QR activity in hepa 1c1c7 murine hepatoma cells, and 55 of them inhibited NO production in RAW 264.7 murine macrophages at the tested concentrations. Noteworthily, 20 of TCM extracts simultaneously inhibited oxidative stress and inflammatory responses. The observed bioactive TCMs, particularly these 20 TCMs with dual inhibitory effects, might be useful for the treatment of COPD. More importantly, the results of the present research afford us an opportunity to discover new lead molecules as COPD therapeutic agents from these active TCMs.

Development of an analytical method to assess the occupational health risk of therapeutic monoclonal antibodies using LC-HRMS.

Science.gov (United States)

Reinders, Lars M H; Klassen, Martin D; Jaeger, Martin; Teutenberg, Thorsten; Tuerk, Jochen

2018-04-01

Monoclonal antibodies are a group of commonly used therapeutics, whose occupational health risk is still discussed controversially. The long-term low-dose exposure side effects are insufficiently evaluated; hence, discussions are often based on a theoretical level or extrapolating side effects from therapeutic dosages. While some research groups recommend applying the precautionary principle for monoclonal antibodies, others consider the exposure risk too low for measures taken towards occupational health and safety. However, both groups agree that airborne monoclonal antibodies have the biggest risk potential. Therefore, we developed a peptide-based analytical method for occupational exposure monitoring of airborne monoclonal antibodies. The method will allow collecting data about the occupational exposure to monoclonal antibodies. Thus, the mean daily intake for personnel in pharmacies and the pharmaceutical industry can be determined for the first time and will help to substantiate the risk assessment by relevant data. The introduced monitoring method includes air sampling, sample preparation and detection by liquid chromatography coupled with high-resolution mass spectrometry of individual monoclonal antibodies as well as sum parameter. For method development and validation, a chimeric (rituximab), humanised (trastuzumab) and a fully humanised (daratumumab) monoclonal antibody are used. A limit of detection between 1 μg per sample for daratumumab and 25 μg per sample for the collective peptide is achieved. Graphical abstract Demonstration of the analytical workflow, from the release of monoclonal antibodies to the detection as single substances as well as sum parameter.

Assessment of Pathological Response of Breast Carcinoma in Modified Radical Mastectomy Specimens after Neoadjuvant Chemotherapy

Directory of Open Access Journals (Sweden)

Dhanya Vasudevan

2015-01-01

Full Text Available Aim. Paclitaxel based neoadjuvant chemotherapy regimen (NAT in the setting of locally advanced breast cancer (LABC can render inoperable tumor (T4, N2/N3 resectable. The aim of this study was to assess the status of carcinoma in the breast and lymph nodes after paclitaxel based NAT in order to find out the patient and the tumor characteristics that correspond to the pathological responses which could be used as a surrogate biomarker to assess the treatment response. Materials and Methods. Clinical and tumor characteristics of patients with breast carcinoma (n=48 were assessed preoperatively. These patients were subjected to modified radical mastectomy after 3 courses of paclitaxel based NAT regimen. The pathological responses of the tumor in the breast and the lymph nodes were studied by using Chevallier’s system which graded the responses into pathological complete response (pCR, pathological partial response (pPR, and pathological no response (pNR. Results. Our studies showed a pCR of 27.1% and a pPR of 70.9% . Clinically small sized tumors (2–5 cms and Bloom Richardson’s grade 1 tumors showed a pCR. Mean age at presentation was 50.58 yrs. 79.2% of cases were invasive ductal carcinoma NOS; only 2.1% were invasive lobular carcinoma, their response to NAT being the same. There was no downgrading of the tumor grades after NAT. Ductal carcinoma in situ and lymphovascular invasion were found to be resistant to chemotherapy. The histopathological changes noted in the lymph nodes were similar to that found in the tumor bed. Discussion and Conclusion. From our study we conclude that histopathological examination of the tumor bed is the gold standard for assessing the chemotherapeutic tumor response. As previous studies have shown pCR can be used as a surrogate biomarker to assess the tumor response.

Aligning Objectives and Assessment in Responsible Conduct of Research Instruction

Science.gov (United States)

Antes, Alison L.; DuBois, James M.

2014-01-01

Efforts to advance research integrity in light of concerns about misbehavior in research rely heavily on education in the responsible conduct of research (RCR). However, there is limited evidence for the effectiveness of RCR instruction as a remedy. Assessment is essential in RCR education if the research community wishes to expend the effort of instructors, students, and trainees wisely. This article presents key considerations that instructors and course directors must consider in aligning learning objectives with instructional methods and assessment measures, and it provides illustrative examples. Above all, in order for RCR educators to assess outcomes more effectively, they must align assessment to their learning objectives and attend to the validity of the measures used. PMID:25574258

Assessing Stress Responses in Beaked and Sperm Whales in the Bahamas

Science.gov (United States)

2016-05-23

sex and reproductive status (i.e. other physiologic influences) when interpreting levels of GCs as indicators of stress responses. 2.2 2.2 0 Adult... Stress Responses in Beaked and Sperm Whales in the Bahamas" Please find attached final reports for the above referenced ONR award for the period ending...Assessing Stress Responses in Beaked and Sperm Whales in the Bahamas Rosalind M. Rolland D.V.M., Kathleen E. Hunt Ph.D., Elizabeth A. Burgess M.Sc. Ph.D

Making assessments while taking repeated risks: a pattern of multiple response pathways.

Science.gov (United States)

Pleskac, Timothy J; Wershbale, Avishai

2014-02-01

Beyond simply a decision process, repeated risky decisions also require a number of cognitive processes including learning, search and exploration, and attention. In this article, we examine how multiple response pathways develop over repeated risky decisions. Using the Balloon Analogue Risk Task (BART) as a case study, we show that 2 different response pathways emerge over the course of the task. The assessment pathway is a slower, more controlled pathway where participants deliberate over taking a risk. The 2nd pathway is a faster, more automatic process where no deliberation occurs. Results imply the slower assessment pathway is taken as choice conflict increases and that the faster automatic response is a learned response. Based on these results, we modify an existing formal cognitive model of decision making during the BART to account for these dual response pathways. The slower more deliberative response process is modeled with a sequential sampling process where evidence is accumulated to a threshold, while the other response is given automatically. We show that adolescents with conduct disorder and substance use disorder symptoms not only evaluate risks differently during the BART but also differ in the rate at which they develop the more automatic response. More broadly, our results suggest cognitive models of judgment decision making need to transition from treating observed decisions as the result of a single response pathway to the result of multiple response pathways that change and develop over time.

Patient personality and therapist response: an empirical investigation.

Science.gov (United States)

Colli, Antonello; Tanzilli, Annalisa; Dimaggio, Giancarlo; Lingiardi, Vittorio

2014-01-01

The aim of this study was to examine the relationship between therapists' emotional responses and patients' personality disorders and level of psychological functioning. A random national sample of psychiatrists and clinical psychologists (N=203) completed the Therapist Response Questionnaire to identify patterns of therapists' emotional response, and the Shedler-Westen Assessment Procedure-200 to assess personality disorders and level of psychological functioning in a randomly selected patient currently in their care and with whom they had worked for a minimum of eight sessions and a maximum of 6 months (one session per week). There were several significant relationships between therapists' responses and patients' personality pathology. Paranoid and antisocial personality disorders were associated with criticized/mistreated countertransference, and borderline personality disorder was related to helpless/inadequate, overwhelmed/disorganized, and special/overinvolved countertransference. Disengaged countertransference was associated with schizotypal and narcissistic personality disorders and negatively associated with dependent and histrionic personality disorders. Schizoid personality disorder was associated with helpless/inadequate responses. Positive countertransference was associated with avoidant personality disorder, which was also related to both parental/protective and special/overinvolved therapist responses. Obsessive-compulsive personality disorder was negatively associated with special/overinvolved therapist responses. In general, therapists' responses were characterized by stronger negative feelings when working with lower-functioning patients. Patients' specific personality pathologies are associated with consistent emotional responses, which suggests that clinicians can make diagnostic and therapeutic use of their responses to patients.

Asparagus racemosus: a review on its phytochemical and therapeutic potential.

Science.gov (United States)

Singh, Ram

2016-09-01

Asparagus racemosus (Willd.) is a widely found medicinal plant in tropical and subtropical parts of India. The therapeutic applications of this plant have been reported in Indian and British Pharmacopoeias and in traditional system of medicine, such as Ayurveda, Unani and Siddha. The crude, semi-purified and purified extracts obtained from different parts of this plant have been useful in therapeutic applications. Numerous bioactive phytochemicals mostly saponins and flavonoids have been isolated and identified from this plant which are responsible alone or in combination for various pharmacological activities. This review aims to give a comprehensive overview of traditional applications, current knowledge on the phytochemistry, pharmacology and overuse of A. racemosus.

Therapeutic self-disclosure with borderline patients.

Science.gov (United States)

Wilkinson, S M; Gabbard, G O

1993-01-01

The therapeutic use of countertransference disclosure as a means of highlighting the borderline patient's intrapsychic and interpersonal use of the therapist is discussed.Countertransference disclosure is narrowly defined as a form of clinical honesty that focuses on the therapist's experience of the patient in the here-and-now moment of the session. The effects of disclosure on transference exploration, neutrality, and patient revelations are explored through examination of detailed process notes of therapy sessions.Technical issues such as indirect versus direct disclosure and responses to direct questions are also addressed.

Avaliação prognóstica individual na UTI: é possível diferenciar insistência terapêutica de obstinação terapêutica? Individual prognostic assessment in the intensive care unit: can therapeutic persistence be distinguished from therapeutic obstinacy?

Directory of Open Access Journals (Sweden)

Cristiano Corrêa Batista

2009-08-01

Full Text Available OBJETIVOS: A disponibilidade de alta tecnologia na unidade de terapia intensiva tem-se transformado, muitas vezes, em instrumento potencializador de sofrimento ao aumentar o tempo do processo de morrer. Diferenciar insistência terapêutica de obstinação terapêutica tem sido um grande desafio da medicina atual. O objetivo deste estudo foi avaliar a relação benefício versus malefício do uso de terapias que sustentam as funções vitais por meio de um sistema evolutivo de avaliação prognóstica individual. MÉTODOS: Estudo de coorte, prospectivo, observacional, desenvolvido na unidade de tratamento intensivo do Hospital Universitário São Francisco de Paula da UCPel, Pelotas, RS no período de 1° de março de 2006 a 31 de agosto de 2007. Foram registradas: a avaliação prognóstica individual por meio de um sistema evolutivo, utilizando o índice UNICAMP II associado aos níveis séricos de albumina, transferrina e linfócitos; as terapias mantenedoras das funções vitais; o desfecho. A análise estatística foi realizada utilizando o teste t de Student, a ANOVA, o teste do Qui-quadrado, o teste exato de Fisher, o teste de correlação de Spearman e a curva ROC. Foi considerado estatisticamente significativo um valor p OBJECTIVES: Availability of state-of-the-art technology at intensive care units has often turned into a tool aggravating suffering by prolonging the end-of-life process. Distinguishing therapeutic persistence from therapeutic obstinacy has become a great challenge for present-day medicine. The aim of this study was to assess the benefit-harm relation in the use of life-sustaining therapies by means of an evolutionary system of individual prognostic assessment. METHODS: A cohort, prospective, observational study at the intensive care unit of the São Francisco De Paula University Hospital of UCPel, Pelotas RS from March 2006 to August 31, 2007. Individual prognostic assessments were recorded by using an evolutionary

Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges.

Science.gov (United States)

Gulati, Karan; Ivanovski, Sašo

2017-08-01

The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO 2 nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization. Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity. Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.

Therapeutic hypothermia for neonatal encephalopathy: a UK survey of opinion, practice and neuro-investigation at the end of 2007.

Science.gov (United States)

Kapetanakis, Andrew; Azzopardi, Denis; Wyatt, John; Robertson, Nicola J

2009-04-01

The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited. To benchmark current opinion and practice to inform future strategies for optimal knowledge transfer for therapeutic hypothermia. A web based questionnaire (30 sections related to opinion and practice of management of NE) sent to the clinical leads of Level I, II and III neonatal units throughout the UK in November/December 2007. One hundred and twenty-five (out of 195) UK neonatal units responded (response rate 66%). Ten percent, 37.5% and 51.5% responses were from level I, II and III units respectively. Twenty eight percent of all units provided therapeutic hypothermia locally (52% of level III units), however 80% of responders would offer therapeutic hypothermia if there was the facility. Overall, 57% of responders considered therapeutic hypothermia effective or very effective - similar for all unit levels; 43% considered more data are required. Regional availability of therapeutic hypothermia exists in 55% of units and 41% of units offer transfer to a regional centre for therapeutic hypothermia. In the UK in 2007, access to therapeutic hypothermia was widespread although not universal. More than half of responders considered therapeutic hypothermia effective. Fifty-five percent of perinatal networks have the facility to offer therapeutic hypothermia. The involvement of national bodies may be necessary to ensure the adoption of therapeutic hypothermia according to defined protocols and standards; registration is important and will help ensure universal neurodevelopmental follow up.

Therapeutic radiation and hyperparathyroidism. A case-control study in Rochester, Minn

International Nuclear Information System (INIS)

Beard, C.M.; Heath, H. III; O'Fallon, W.M.; Anderson, J.A.; Earle, J.D.; Melton, L.J. III

1989-01-01

A case-control study was conducted among residents of Rochester, Minn, to assess the influence of prior therapeutic radiation on the risk of primary hyperparathyroidism. Fifty-one cases of surgically proven primary hyperparathyroidism diagnosed from 1975 through 1983 were each matched by age and gender to two control subjects, with radiation exposure documented through preexisting medical records. The overall odds ratio for any prior therapeutic radiation therapy was 1.9 (95% confidence interval, 0.9 to 4.4) and it was 2.3 (95% confidence interval, 0.9 to 5.7) when limited to those with prior head and neck radiation. Among women, the figures were 2.9 (95% confidence interval, 1.1 to 7.5) for any prior therapeutic radiation and 3.4 (95% confidence interval, 1.2 to 10.2) for head and neck exposure. This study confirms the association between primary hyperparathyroidism and prior therapeutic radiation exposure, at least for women in this population

Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma.

Science.gov (United States)

Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K; Sims, Peter A; Sarkaria, Jann N; Canoll, Peter; White, Forest M

2016-06-01

Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. ©2016 AACR. ©2016 American Association for Cancer Research.

Assessing the Heterogeneity of the Fc-Glycan of a Therapeutic Antibody Using an engineered FcγReceptor IIIa-Immobilized Column.

Science.gov (United States)

Kiyoshi, Masato; Caaveiro, Jose M M; Tada, Minoru; Tamura, Hiroko; Tanaka, Toru; Terao, Yosuke; Morante, Koldo; Harazono, Akira; Hashii, Noritaka; Shibata, Hiroko; Kuroda, Daisuke; Nagatoishi, Satoru; Oe, Seigo; Ide, Teruhiko; Tsumoto, Kouhei; Ishii-Watabe, Akiko

2018-03-02

The N-glycan moiety of IgG-Fc has a significant impact on multifaceted properties of antibodies such as in their effector function, structure, and stability. Numerous studies have been devoted to understanding its biological effect since the exact composition of the Fc N-glycan modulates the magnitude of effector functions such as the antibody-dependent cell mediated cytotoxicity (ADCC), and the complement-dependent cytotoxicity (CDC). To date, systematic analyses of the properties and influence of glycan variants have been of great interest. Understanding the principles on how N-glycosylation modulates those properties is important for the molecular design, manufacturing, process optimization, and quality control of therapeutic antibodies. In this study, we have separated a model therapeutic antibody into three fractions according to the composition of the N-glycan by using a novel FcγRIIIa chromatography column. Notably, Fc galactosylation was a major factor influencing the affinity of IgG-Fc to the FcγRIIIa immobilized on the column. Each antibody fraction was employed for structural, biological, and physicochemical analysis, illustrating the mechanism by which galactose modulates the affinity to FcγRIIIa. In addition, we discuss the benefits of the FcγRIIIa chromatography column to assess the heterogeneity of the N-glycan.

Characterization of the therapeutic properties of Chinese herbal materials by measuring delayed luminescence and dendritic cell-based immunomodulatory response

NARCIS (Netherlands)

Sun, M.; Chang, W.T.; Wijk, E. van; He, M.; Koval, S.; Lin, M.K.; Van Wijk, R.; Hankemeier, T.; Greef, J. van der; Wang, M.

2017-01-01

Based on the traditional Chinese medicine theory, the Chinese pharmacopeia assigns a therapeutic description of “taste” to all herbs; thus, an herb's “taste” is valued in traditional Chinese medicine as a major ethnopharmacological category and reflects the herb's therapeutic properties. These

"Therapeutic" bed rest in pregnancy: unethical and unsupported by data.

Science.gov (United States)

McCall, Christina A; Grimes, David A; Lyerly, Anne Drapkin

2013-06-01

"Therapeutic" bed rest continues to be used widely, despite evidence of no benefit and known harms. In this commentary, we summarize the Cochrane reviews of bed rest and propose an ethical argument for discontinuing this practice. Cochrane systematic reviews do not support "therapeutic" bed rest for threatened abortion, hypertension, preeclampsia, preterm birth, multiple gestations, or impaired fetal growth. This assessment has been echoed in other comprehensive reviews. Prescribing bed rest is inconsistent with the ethical principles of autonomy, beneficence, and justice. Hence, if bed rest is to be used, it should be only within a formal clinical trial.

Impact of response shift on the assessment of treatment effects using the Oral Health Impact Profile.

Science.gov (United States)

Reissmann, Daniel R; Remmler, Antje; John, Mike T; Schierz, Oliver; Hirsch, Christian

2012-12-01

The assessment of changes in oral health-related quality of life (OHRQoL) is challenging because individuals' concepts and internal standards of OHRQoL may change over time. The aim of this study was to detect response shifts in OHRQoL assessments made using the Oral Health Impact Profile (OHIP). Oral health-related quality of life was assessed in a consecutive sample of 126 patients seeking prosthodontic care. Patients were asked to rate their OHRQoL before treatment started and 1 month after treatment was finished, using the German 49-item version of the OHIP. When rating their OHRQoL after treatment, patients were also asked to rate their pre-treatment OHRQoL without having access to their baseline data. The response shift was calculated as the difference in OHIP summary scores between the initial assessment and the retrospective baseline assessment. The OHIP mean scores decreased from 31.8 at the initial baseline assessment to 24.4 after treatment. The retrospective baseline assessment resulted in an OHIP mean score of 38.1, corresponding to a response shift of 6.3 OHIP points. The effect size (Cohen's d = 0.21) of the response shift was considered small. The response shift phenomenon and its magnitude have important implications for dental practice, where patients and dentists often assess perceived treatment effects retrospectively. © 2012 Eur J Oral Sci.

Psychological Assessment of Patients With Biotin-Thiamine-Responsive Basal Ganglia Disease.

Science.gov (United States)

Alfadhel, Majid; Al-Bluwi, Amal

2017-01-01

Biotin-thiamine-responsive basal ganglia disease is a devastating autosomal recessive inherited neurological disorder. We conducted a retrospective chart review of all patients with biotin-thiamine-responsive basal ganglia disease who underwent a formal psychological assessment. Six females and 3 males were included. Five patients (56%) had an average IQ, two patients (22%) had mild delay, and two (22%) had severe delay. A normal outcome was directly related to the time of diagnosis and initiation of treatment. Early diagnosis and immediate commencement of treatment were associated with a favorable outcome and vice versa. The most affected domain was visual motor integration, while understanding and mathematical problem-solving were the least affected. In summary, this is the first study discussing the psychological assessment of patients with biotin-thiamine-responsive basal ganglia disease. The results of this study alert clinicians to consider prompt initiation of biotin and thiamine in any patient presenting with neuroregression and a basal ganglia lesion on a brain magnetic resonance imaging.

Cost Utility Analysis of Cervical Therapeutic Medial Branch Blocks in Managing Chronic Neck Pain.

Science.gov (United States)

Manchikanti, Laxmaiah; Pampati, Vidyasagar; Kaye, Alan D; Hirsch, Joshua A

2017-01-01

Background: Controlled diagnostic studies have established the prevalence of cervical facet joint pain to range from 36% to 67% based on the criterion standard of ≥ 80% pain relief. Treatment of cervical facet joint pain has been described with Level II evidence of effectiveness for therapeutic facet joint nerve blocks and radiofrequency neurotomy and with no significant evidence for intraarticular injections. However, there have not been any cost effectiveness or cost utility analysis studies performed in managing chronic neck pain with or without headaches with cervical facet joint interventions. Study Design: Cost utility analysis based on the results of a double-blind, randomized, controlled trial of cervical therapeutic medial branch blocks in managing chronic neck pain. Objectives: To assess cost utility of therapeutic cervical medial branch blocks in managing chronic neck pain. Methods: A randomized trial was conducted in a specialty referral private practice interventional pain management center in the United States. This trial assessed the clinical effectiveness of therapeutic cervical medial branch blocks with or without steroids for an established diagnosis of cervical facet joint pain by means of controlled diagnostic blocks. Cost utility analysis was performed with direct payment data for the procedures for a total of 120 patients over a period of 2 years from this trial based on reimbursement rates of 2016. The payment data provided direct procedural costs without inclusion of drug treatments. An additional 40% was added to procedural costs with multiplication of a factor of 1.67 to provide estimated total costs including direct and indirect costs, based on highly regarded surgical literature. Outcome measures included significant improvement defined as at least a 50% improvement with reduction in pain and disability status with a combined 50% or more reduction in pain in Neck Disability Index (NDI) scores. Results: The results showed direct

Toll-like receptors as therapeutic targets in cystic fibrosis.

LENUS (Irish Health Repository)

Greene, Catherine M

2008-12-01

Background: Toll-like receptors (TLRs) are pattern recognition receptors that act as a first-line of defence in the innate immune response by recognising and responding to conserved molecular patterns in microbial factors and endogenous danger signals. Cystic fibrosis (CF)-affected airways represent a milieu potentially rich in TLR agonists and the chronic inflammatory phenotype evident in CF airway epithelial cells is probably due in large part to activation of TLRs. Objective\\/methods: To examine the prospects of developing novel therapies for CF by targeting TLRs. We outline the expression and function of TLRs and explore the therapeutic potential of naturally-occurring and synthetic TLR inhibitors for CF. Results\\/conclusion: Modulation of TLRs has therapeutic potential for the inflammatory lung manifestations of CF.

PIRATE: pediatric imaging response assessment and targeting environment

Science.gov (United States)

Glenn, Russell; Zhang, Yong; Krasin, Matthew; Hua, Chiaho

2010-02-01

By combining the strengths of various imaging modalities, the multimodality imaging approach has potential to improve tumor staging, delineation of tumor boundaries, chemo-radiotherapy regime design, and treatment response assessment in cancer management. To address the urgent needs for efficient tools to analyze large-scale clinical trial data, we have developed an integrated multimodality, functional and anatomical imaging analysis software package for target definition and therapy response assessment in pediatric radiotherapy (RT) patients. Our software provides quantitative tools for automated image segmentation, region-of-interest (ROI) histogram analysis, spatial volume-of-interest (VOI) analysis, and voxel-wise correlation across modalities. To demonstrate the clinical applicability of this software, histogram analyses were performed on baseline and follow-up 18F-fluorodeoxyglucose (18F-FDG) PET images of nine patients with rhabdomyosarcoma enrolled in an institutional clinical trial at St. Jude Children's Research Hospital. In addition, we combined 18F-FDG PET, dynamic-contrast-enhanced (DCE) MR, and anatomical MR data to visualize the heterogeneity in tumor pathophysiology with the ultimate goal of adaptive targeting of regions with high tumor burden. Our software is able to simultaneously analyze multimodality images across multiple time points, which could greatly speed up the analysis of large-scale clinical trial data and validation of potential imaging biomarkers.

Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt

Science.gov (United States)

Abdel-Moneim, Adel; Morsy, Basant M.; Mahmoud, Ayman M.; Abo-Seif, Mohamed A.; Zanaty, Mohamed I.

2013-01-01

Hepatitis C is a major global health burden and Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. The current study was designed to evaluate the beneficial therapeutic effects of ethanolic extracts of Nigella sativa, Zingiber officinale and their mixture in Egyptian HCV patients. Sixty volunteer patients with proven HCV and fifteen age matched healthy subjects were included in this study. Exclusion criteria included patients on interferon alpha (IFN-α) therapy, infection with hepatitis B virus, drug-induced liver diseases, advanced cirrhosis, hepatocellular carcinoma (HCC) or other malignancies, blood picture abnormalities and major severe illness. Liver function enzymes, albumin, total bilirubin, prothrombin time and concentration, international normalized ratio, alpha fetoprotein and viral load were all assessed at baseline and at the end of the study. Ethanolic extracts of Nigella sativa and Zingiber officinale were prepared and formulated into gelatinous capsules, each containing 500 mg of Nigella sativa and/or Zingiber officinale. Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. Both extracts as well as their mixture significantly ameliorated the altered viral load, alpha fetoprotein, liver function parameters; with more potent effect for the combined therapy. In conclusion, administration of Nigella sativa and/or Zingiber officinale ethanolic extracts to HCV patients exhibited potential therapeutic benefits via decreasing viral load and alleviating the altered liver function, with more potent effect offered by the mixture. PMID:27298610

Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt.

Science.gov (United States)

Abdel-Moneim, Adel; Morsy, Basant M; Mahmoud, Ayman M; Abo-Seif, Mohamed A; Zanaty, Mohamed I

2013-01-01

Hepatitis C is a major global health burden and Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. The current study was designed to evaluate the beneficial therapeutic effects of ethanolic extracts of Nigella sativa, Zingiber officinale and their mixture in Egyptian HCV patients. Sixty volunteer patients with proven HCV and fifteen age matched healthy subjects were included in this study. Exclusion criteria included patients on interferon alpha (IFN-α) therapy, infection with hepatitis B virus, drug-induced liver diseases, advanced cirrhosis, hepatocellular carcinoma (HCC) or other malignancies, blood picture abnormalities and major severe illness. Liver function enzymes, albumin, total bilirubin, prothrombin time and concentration, international normalized ratio, alpha fetoprotein and viral load were all assessed at baseline and at the end of the study. Ethanolic extracts of Nigella sativa and Zingiber officinale were prepared and formulated into gelatinous capsules, each containing 500 mg of Nigella sativa and/or Zingiber officinale. Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. Both extracts as well as their mixture significantly ameliorated the altered viral load, alpha fetoprotein, liver function parameters; with more potent effect for the combined therapy. In conclusion, administration of Nigella sativa and/or Zingiber officinale ethanolic extracts to HCV patients exhibited potential therapeutic benefits via decreasing viral load and alleviating the altered liver function, with more potent effect offered by the mixture.

Energy distribution of projectile fragment particles in heavy ion therapeutic beam

Energy Technology Data Exchange (ETDEWEB)

Matsufuji, Naruhiro; Tomura, Hiromi; Futami, Yasuyuki [National Inst. of Radiological Sciences, Chiba (Japan)] [and others

1998-03-01

Production of fragment particles in a patient`s body is one of important problems for heavy charged particle therapy. It is required to know the yield and the energy spectrum for each fragment element - so called `beam quality` to understand the effect of therapeutic beam precisely. In this study, fragment particles produced by practical therapeutic beam of HIMAC were investigated with using tissue-equivalent material and a detector complex. From the results, fragment particles were well identified by difference of their atomic numbers and the beam quality was derived. Responses of the detectors in this energy region were also researched. (author)

Healing bodies: Contemporary spirituality, practice and therapeutic landscapes

DEFF Research Database (Denmark)

Matejskova, Tatiana

In response to the reductionist accounts of contemporary non-religious spiritual practices as simply a by-product of post-modern consumerism, geographers have recently stressed the need to take such practices seriously. This paper heeds this call by focusing on a particular aspect of modern spiri...... therapeutic and spiritual landscapes - traditionally relying on impoverished conceptions of body – as dynamic and relational emergences effectuated quite literally in and through the bodily...

Goodness-of-Fit Assessment of Item Response Theory Models

Science.gov (United States)

Maydeu-Olivares, Alberto

2013-01-01

The article provides an overview of goodness-of-fit assessment methods for item response theory (IRT) models. It is now possible to obtain accurate "p"-values of the overall fit of the model if bivariate information statistics are used. Several alternative approaches are described. As the validity of inferences drawn on the fitted model…

Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

Science.gov (United States)

Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

2016-01-01

This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

International Nuclear Information System (INIS)

Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; Hart, Marieke van der; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

2012-01-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

Energy Technology Data Exchange (ETDEWEB)

Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Wisialowski, Todd A. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Cremers, Thomas; Hart, Marieke van der [Brains On-Line B.V., University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (Netherlands); Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States)

2012-11-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

Federal Radiological Monitoring and Assessment Center advanced part phase response actions

International Nuclear Information System (INIS)

Hurley, B.

1997-01-01

Federal Radiological Monitoring and Assessment Center (FRMAC) response actions are carried out in Advance Party and Main Party phases of deployment. Response activities are initiated by a FRMAC Home Team prior to and during Advance Party deployment, with Home Team support continuing until the FRMAC Main Party is fully deployed. Upon arrival at the incident scene, the Advance Party establishes communications with other federal, state, and local response organizations, Following an Advance Party Meeting with these response organizations, FRMAC begins formulation of an initial monitoring and sampling plan, in coordination with the jurisdictional state and the Lead Federal Agency, and initiates detailed logistical arrangements for Main Party deployment and operations

Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

Science.gov (United States)

Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

2017-07-01

Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.