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Sample records for interferons open prospective

  1. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    Directory of Open Access Journals (Sweden)

    Lopez-Saura Pedro

    2009-07-01

    Full Text Available Abstract Background Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC or squamous cell skin carcinomas (SCSC. Methods Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Results Sixteen elder (median 70 years-old patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination, 40% PR (>30% tumor reduction, and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. Conclusion The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Trial registration Current Controlled Trials RPCEC00000052.

  2. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    International Nuclear Information System (INIS)

    Anasagasti-Angulo, Lorenzo; Garcia-Vega, Yanelda; Barcelona-Perez, Silvia; Lopez-Saura, Pedro; Bello-Rivero, Iraldo

    2009-01-01

    Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC). Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Current Controlled Trials RPCEC00000052

  3. Interferon

    CERN Multimedia

    De Somer,P

    1975-01-01

    Le Prof.Pierre de Somer est né en Belgique et a fait ses études de médecine à l'Université de Louvin où il a obtenu en 1942 son diplôme. En 1961 il a été nommé professeur ordinaire d'hygiène et de microbiologie à cette même Université et depuis 1967 il est recteur de l'Université catholique flamande de Louvin, président de la société belge de microbiologie et expert de l'O.M.S. Il nous parle de l'interferon et de ses perspectives dans le traitement de maladies virales avec présentation des clichées.

  4. From public open access to common property: the prospects and ...

    African Journals Online (AJOL)

    From public open access to common property: the prospects and challenges of institutionalizing boundaries for self-governance and management of community irrigation dams in the Upper East Region, Ghana.

  5. The Dutch Open Telescope: History, Status, Prospects

    NARCIS (Netherlands)

    Rutten, R.J.

    1999-01-01

    After many years of persistent telescope design and telescope construction, R.H. Hammerschlag has installed his Dutch Open Telescope (DOT) on La Palma. I brie y review its history and design. The future of optical solar physics at Utrecht hinges on a recently-funded three- year DOT science

  6. DADOS-Prospective: an open source application for Web-based prospective data collection

    Directory of Open Access Journals (Sweden)

    Nguyen Lam

    2006-11-01

    Full Text Available Abstract Background Randomized, prospective trials involving multi-institutional collaboration have become a central part of clinical and translational research. However, data management and coordination of multi-center studies is a complex process that involves developing systems for data collection and quality control, tracking data queries and resolutions, as well as developing communication procedures. We describe DADOS-Prospective, an open-source Web-based application for collecting and managing prospective data on human subjects for clinical and translational trials. DADOS-Prospective not only permits users to create new clinical research forms (CRF and supports electronic signatures, but also offers the advantage of containing, in a single environment, raw research data in downloadable spreadsheet format, source documentation and regulatory files stored in PDF format, and audit trails. Results Feedback from formal and field usability tests was used to guide the design and development of DADOS-Prospective. To date, DADOS-Prospective has been implemented in five prospective clinical studies at our institution. Four of these studies are still in the CRF creation phase and one study has been entirely launched. Conclusion DADOS-Prospective has significant advantages over existing Web-based data collecting programs. At our institution, it has been demonstrated to be an efficient tool for prospective clinical studies.

  7. Problems and Prospects of Open and Distance Education in Nigeria

    Directory of Open Access Journals (Sweden)

    Mudasiru Olalere YUSUF

    2006-01-01

    Full Text Available Problems and Prospects of Open and Distance Education in Nigeria Mudasiru Olalere YUSUF (Ph.D Senior lecturer (Educational Technology Department of Curriculum Studies and Educational Technology, Faculty of Education University of Ilorin, Ilorin NIGERIA ABSTRACT Distance education as a mean of providing access to education, particularly tertiary level education, has gained great prominence in the world. Nigeria has taken giant steps of recent to introduce open and distance education programme. This paper explores the major terms inherent in open and distance education, its potentials, possible factors that may inhibit successful implementation of the programme, and the use of low and high technological tools for its implementation. The paper recommended the use of Organisation Element Model (OEM as suggested by (Kaufman, Watkins & Guerra, 2001 for its planning and implementation, and also stressed the need for improvement in electricity and communication services.

  8. Psychomotor retardation and vulnerability to interferon alpha induced major depressive disorder: Prospective study of a chronic hepatitis C cohort.

    Science.gov (United States)

    Whale, Richard; Fialho, Renata; Rolt, Michael; Eccles, Jessica; Pereira, Marco; Keller, Majella; File, Alexandra; Haq, Inam; Tibble, Jeremy

    2015-12-01

    Major depressive disorder (MDD) is a common consequence of interferon alpha (IFNα) treatment and important supporting evidence of a role of inflammation in the aetiology of depression. This study aimed to expand the knowledge of baseline clinical vulnerability characteristics to IFNα induced MDD, particularly exploring sub-threshold depressive symptoms. A prospective cohort of chronic HCV patients undergoing treatment with pegylated-IFNα and ribavirin was studied. MDD was assessed using the Structured Clinical Interview for DSM-IV (SCID-I). Depressive symptoms and severity were assessed at baseline and monthly with the Hamilton Depression Rating Scale (HAMD). Subjects with MDD or taking antidepressant treatment at baseline were excluded. 278 patients were assessed for this cohort with a final study sample of 190. 94.2% had contracted HCV through intravenous drug use. During six months IFNα treatment, 53.2% of patients transitioned to DSM-IV threshold MDD. In the multivariate logistic analysis, independent factors significantly associated with development of MDD were younger age (OR 0.96, 95% CI 0.93-1.00, p=0.028), past history of MDD (OR 3.82, 95% CI 1.63-8.92, p=0.002), baseline HAMD items psychomotor retardation (OR 15.21, 95% CI 1.33-173.41, p=0.032) and somatic symptoms (general) (OR 2.96, 95% CI 1.44-6.08, p=0.003), and HCV genotype 2 (OR 2.27, 95% CI 1.07-4.78, p=0.032). During IFNα treatment, the rate of transition to MDD was high in this cohort. Psychomotor retardation and somatic symptoms may represent a greater inflamed state pre-treatment. This iatrogenic model of MDD may offer important insights into wider depression aetiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Development of an open metadata schema for prospective clinical research (openPCR) in China.

    Science.gov (United States)

    Xu, W; Guan, Z; Sun, J; Wang, Z; Geng, Y

    2014-01-01

    In China, deployment of electronic data capture (EDC) and clinical data management system (CDMS) for clinical research (CR) is in its very early stage, and about 90% of clinical studies collected and submitted clinical data manually. This work aims to build an open metadata schema for Prospective Clinical Research (openPCR) in China based on openEHR archetypes, in order to help Chinese researchers easily create specific data entry templates for registration, study design and clinical data collection. Singapore Framework for Dublin Core Application Profiles (DCAP) is used to develop openPCR and four steps such as defining the core functional requirements and deducing the core metadata items, developing archetype models, defining metadata terms and creating archetype records, and finally developing implementation syntax are followed. The core functional requirements are divided into three categories: requirements for research registration, requirements for trial design, and requirements for case report form (CRF). 74 metadata items are identified and their Chinese authority names are created. The minimum metadata set of openPCR includes 3 documents, 6 sections, 26 top level data groups, 32 lower data groups and 74 data elements. The top level container in openPCR is composed of public document, internal document and clinical document archetypes. A hierarchical structure of openPCR is established according to Data Structure of Electronic Health Record Architecture and Data Standard of China (Chinese EHR Standard). Metadata attributes are grouped into six parts: identification, definition, representation, relation, usage guides, and administration. OpenPCR is an open metadata schema based on research registration standards, standards of the Clinical Data Interchange Standards Consortium (CDISC) and Chinese healthcare related standards, and is to be publicly available throughout China. It considers future integration of EHR and CR by adopting data structure and data

  10. Prospect for Development of Open Access in Argentina

    Science.gov (United States)

    Miguel, Sandra; Bongiovani, Paola C.; Gomez, Nancy D.; Bueno-de-la-Fuente, Gema

    2013-01-01

    This perspective article presents an overview of the Open Access movement in Argentina, from a global and regional (Latin American) context. The article describes the evolution and current state of initiatives by examining two principal approaches to Open Access in Argentina: "golden" and "green roads". The article will then…

  11. Vitamin D, d-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study

    Directory of Open Access Journals (Sweden)

    Laura W. Musselwhite

    2016-02-01

    Full Text Available To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS patients initiating antiretroviral therapy (ART. Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ, and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP, sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1 response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.

  12. The Openness of the University of the Philippines Open University: Issues and Prospects

    Directory of Open Access Journals (Sweden)

    Maria Fe Villamejor-Mendoza

    2013-05-01

    Full Text Available This paper is a self-reflection on the state of openness of the University of the Philippines Open University (UPOU. An exploratory and descriptive study, it aims not only to define the elements of openness of UPOU, but also to unravel the causes and solutions to the issues and concerns that limit its options to becoming a truly open university. It is based on four parameters of openness, which are widely universal in the literature, e.g., open admissions, open curricula, distance education at scale, and the co-creation, sharing and use of open educational resources (OER. It draws from the perception survey among peers, which the author conducted in UPOU in July and August 2012. It also relies on relevant secondary materials on the subject.

  13. ExtaviJect® 30G device for subcutaneous self-injection of interferon beta-1b for multiple sclerosis: a prospective European study

    Directory of Open Access Journals (Sweden)

    Boeru G

    2013-11-01

    Full Text Available Gabriel Boeru,1 Ivan Milanov,2 Francesca De Robertis,3 Wojciech Kozubski,4 Michael Lang,5 Sònia Rojas-Farreras,6 Mark Tomlinson7 1Military Hospital, Bucharest, Romania; 2University Hospital Saint Naum, Sofia, Bulgaria; 3Department of Neurology, Vito Fazzi Hospital of Lecce, Lecce, Italy; 4Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland; 5NeuroPoint Patient Academy and Neurological Practice, Ulm, Germany; 6IMS Health, Barcelona, Spain; 7Novartis Pharma AG, Basel, Switzerland Background: The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®, a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9 and EuroQol-5 Dimension (EQ-5D instruments, respectively. Results: Of 582 patients enrolled, 568 (98% received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93% attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97% patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%–98% of patients and 59%–98% of nurses were in agreement. There were nine serious adverse events (four disease-related reported among the 227 (39

  14. Ukraine Open University: Its prospects in distance education development

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    Bohdan Shunevych

    2002-01-01

    Full Text Available The genesis, initiation, and expansion of distance education at the Ukraine Open International University for Human Development, located in Kyiv, will be examined in this case study, starting with a brief look at the positive changes taking place in Ukraine's traditional educational system, as well as recent developments in the country's distance education (DE system. To help readers understand the University's development from an insider's perspective, societal factors that currently influence its inter- and extra-institutional environment will also be examined. Next, the history, organizational structure, institutional activities, and background of the Ukraine Open International University for Human Development, along with the reasons driving the University's dual mode activities - both traditional and distance education - will be briefly analyzed. Included in this analysis is a summary of the challenges surrounding the application of both traditional and distance education models.The author concludes his case study by reflecting upon Ukraine Open International University for Human Development's experiences within the context of its being both a traditional education provider and new dual-mode distance education provider. Also discussed are some key indicators and predictions about what the future may hold for the University.

  15. Open problems and future prospects for hypernuclear physics

    International Nuclear Information System (INIS)

    Dover, C.B.

    1992-01-01

    We appraise the current status of our knowledge of hypernuclear structure physics, and emphasize the unsolved problems. The prospects for significant advances in high resolution hypernuclear spectroscopy with CW electron beams at CEBAF or intense pion beams at the proposed PILAC facility at LPF are discussed. These facilities could greatly extend our understanding of strangeness S = -1 hypernuclear systems. For S = -2 systems, new events have been seen in a (K - ,K + ) hybrid counter-emulsion experiment at KEK in Japan. We give a theoretical interpretation of one of these events, as well as some further possibilities for the exploration of ΛΛ hypernuclear spectroscopy via Ξ - -atoms. We mention some possible enhancements of (K - ,K + ) or (K - ,K 0 ) cross sections to discrete states, due to ΞN-ΛΛ configuration mixing in a shell model description of S = -2 hypernuclei. Finally, we explore the possibilities for producing multi-strange nuclei or droplets of strange quark matter (''strangelets'') in relativistic heavy ion collisions

  16. A Prospective Study Comparing Ligasure and Open Hemorrhoidectomy

    Directory of Open Access Journals (Sweden)

    Rahimi M

    2011-11-01

    Full Text Available Background: Hemorrhoid is among the most common anorectal diseases and patients with high-grade disease conditions need surgical treatment. Many surgical procedures are available to treat the disease. The aim of this study was to compare the operative time and outcomes, (post-operative pain and complications of LigaSure hemorrhoidectomy with those of the open conventional method.Methods : This randomized single-blind clinical trial included 57 patients (28 in LigaSure and 29 in the open group. The primary variable was the operative time for the excision of a single hemorrhoidal packet. The other variables were post-operative pain measured by morphine doses administered to control pain, scores of visual analogue scale (VAS used to measure pain severity, pain during home stay measured by doses of oral ibuprofen and the mean daily VAS scores, early complications including bleeding and urinary retention, longer-term complications and time to return to work.Results : The demographic data were comparatively the same between the two groups. The average time to excise a single packet of hemorrhoid was significantly shorter in the LigaSure group (8.91 min vs. 17.35 min, P<0.001. Post-operative pain measurements (morphine doses and VAS scores were lower in the LigaSure group, but the differences were not statistically significant (P=0.055 and 0.077, respectively. Complications of the two procedures were also comparable. Neither of the groups returned to work in a shorter time.Conclusion: LigaSure hemorrhoidectomy seems to be a safe method and it can reduce the operative time significantly. It may also have a modest effect on post-operative pain.

  17. Prospects of open charm production at GSI-FAIR and J-PARC

    International Nuclear Information System (INIS)

    Riedl, J.; Schaefer, A.; Stratmann, M.

    2007-01-01

    We present a detailed phenomenological study of the prospects of open charm physics at the future pp and pp facilities GSI-FAIR and J-PARC, respectively. In particular, we concentrate on the differential cross sections and the charge and longitudinal double-spin asymmetries at next-to-leading order accuracy. Theoretical uncertainties for the proposed observables are estimated by varying the charm quark mass and the renormalization and factorization scales. (orig.)

  18. Interferons, properties and applications

    NARCIS (Netherlands)

    H. Schellekens (Huub); W. Weimar (Willem)

    1980-01-01

    textabstractThe main theme of this thesis is the clinical evaluation of interferon. From the biology of the interferon system and animal experiments it can be expected that exogenous interferon will exert its optimum effect when used to prevent acute infections or to modulate chronic

  19. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial.

    Science.gov (United States)

    de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B; Kuiken, Sjoerd D; Weijer, Sebastiaan; van Nieuwkerk, Carin M J; Zaaijer, Hans L; Molenkamp, Richard; Takkenberg, R Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W

    2017-08-01

    Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen [anti-HBs]). We assessed HBsAg loss during peg-interferon-alfa-2a (peg-IFN) and nucleotide analogue combination therapy in patients with chronic hepatitis B with a low viral load. In this randomised controlled, open-label trial, patients were enrolled from the Academic Medical Center (AMC), Amsterdam, Netherlands. Eligible patients were HBsAg positive and hepatitis B e antigen (HBeAg) negative for more than 6 months, could be treatment naive or treatment experienced, and had alanine aminotransferase (ALT) concentrations less than 5 × upper limit of normal (ULN). Participants were randomly assigned (1:1:1) by a computerised randomisation programme (ALEA Randomisation Service) to receive peg-IFN 180 μg/week plus adefovir 10 mg/day, peg-IFN 180 μg/week plus tenofovir disoproxil fumarate 245 mg/day, or no treatment for 48 weeks. The primary endpoint was the proportion of patients with serum HBsAg loss among those who received at least one dose of study drug or had at least one study visit (modified intention-to-treat population [mITT]). All patients have finished the initial study of 72 weeks and will be observed for up to 5 years of follow-up. This study is registered with ClinicalTrials.gov, number NCT00973219. Between Aug 4, 2009, and Oct 17, 2013, 167 patients were screened for enrolment, of whom 151 were randomly assigned (52 to peg-IFN plus adefovir, 51 to peg-IFN plus tenofovir, and 48 to no treatment). 46 participants in the peg-IFN plus adefovir group, 45 in the peg-IFN plus tenofovir group, and 43 in the no treatment group began treatment or observation and were included in the mITT population. At week 72, two (4%) patients in the peg-IFN plus adefovir group and two (4

  20. A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

    Science.gov (United States)

    Giles, F J; Shan, J; Advani, S H; Akan, H; Aydogdu, I; Aziz, Z; Azim, H A; Bapsy, P P; Buyukkececi, F; Chaimongkol, B; Chen, P M; Cheong, S K; Ferhanoglu, B; Hamza, R; Khalid, H M; Intragumtornchai, T; Kim, S W; Kim, S Y; Koc, H; Kumar, L; Kumar, R; Lei, K I; Lekhakula, A; Muthalib, A; Patel, M; Poovalingam, V P; Prayoonwiwat, W; Rana, F; Reksodiputro, A H; Ruff, P; Sagar, T G; Schwarer, A P; Song, H S; Suh, C W; Suharti, C; Supindiman, I; Tee, G Y; Thamprasit, T; Villalon, A H; Wickham, N R; Wong, J E; Yalcin, A; Jootar, S

    2000-12-01

    The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

  1. No difference in outcome for open versus arthroscopic rotator cuff repair: a prospective comparative trial.

    Science.gov (United States)

    Bayle, Xavier; Pham, Thuy-Trang; Faruch, Marie; Gobet, Aurelie; Mansat, Pierre; Bonnevialle, Nicolas

    2017-12-01

    Arthroscopic techniques tend to become the gold standard in rotator cuff repair. However, little data are reported in the literature regarding the improvement of postoperative outcomes and re-tear rate relative to conventional open surgery. The aim of this study was to compare clinical outcomes and cuff integrity after arthroscopic versus open cuff repair. We prospectively assessed clinical outcomes and cuff integrity after an arthroscopic or open rotator cuff repair with a minimum follow-up of 12 months. Clinical evaluation was based on Constant score, Simple Shoulder Value (SSV) and American Shoulder and Elbow Score (ASES). Rotator cuff healing was explored with ultrasound. 44 patients in arthroscopic group A (mean age 56-year-old) and 43 in open group O (mean age 61-year-old) fulfilled the inclusion criteria. Tendons were repaired with a single row technique associated with biceps tenodesis and subacromial decompression. All objective clinical scores significantly improved postoperatively in both groups. No statistical difference was identified between group A and O regarding, respectively, Constant score (72 vs 75 points; p = 0.3), ASES score (88 vs 91 points; p = 0.3), and SSV (81 vs 85%). The overall rate of re-tear (Sugaya type IV or V) reached 7 and 9%, respectively, in group A and O (p = 0.8). This study did not prove any difference of arthroscopic over open surgery in case of rotator cuff repair regarding clinical outcome and cuff integrity at 1-year follow-up. Prospective comparative study.

  2. Multicentre, open, noncomparative Phase II trial to evaluate the efficacy and tolerability of fotemustine, cisplatin, alpha-interferon and interleukin-2 in advanced melanoma patients.

    Science.gov (United States)

    Ridolfi, Laura; Fiorentini, Giammaria; Guida, Michele; Michiara, Maria; Freschi, Andrea; Aitini, Enrico; Ballardini, Michela; Bichisao, Ettore; Ridolfi, Ruggero

    2009-04-01

    The efficacy and tolerability of fotemustine, cisplatin, alpha-interferon and interleukin-2 biochemotherapy were evaluated in advanced melanoma patients. The schedule consisted of fotemustine (100 mg/m) and cisplatin (75 mg/m) intravenous on day 1, followed by subcutaneous interleukin-2 at a dose of 4.5 MIU on days 3-5 and 8-12 and alpha-interferon at a dose of 3 MU three times/week, every 3 weeks for six cycles. Sixty patients were evaluated for tumour response, 12 of whom had brain metastases (BM). One patient (1.7%) with BM achieved a complete response and partial responses were observed in 10 patients (16.7%), including one BM patient. Overall response rate was 18.4 and 16.6% in BM patients (median response duration 8.2 months). Disease control, defined as overall response and stable disease, was 58.4% in all patients and 75% in patients with BM. Median time to progression was 3.2 months (4.2 months in BM patients). Median overall survival was 8.9 months (7.6 months in BM patients). Toxic events were mild to moderate. This combination was well tolerated and showed acceptable clinical activity, especially in BM patients.

  3. Interferon induction by adenoviruses

    Energy Technology Data Exchange (ETDEWEB)

    Beladi, I; Bakay, M; Pusztai, R; Mucsi, I; Tarodi, B [University Medical School, Szeged (Hungary). Inst. of Microbiology

    1979-02-01

    All human, simian, bovine and avian adenovirus types tested so far and the canine hepatitis virus induce interferon production in chick cells. This finding indicated this property to be characteristic for viruses belonging to the adenovirus group. Trypsin treatment, which had no effect upon the infectivity, diminished or eliminated the interferon-inducing abilities of crude adenoviruses, and thus the need for a trypsin-sensitive protein in interferon induction was suggested. T antigen and interferon were formed simultaneously in chick embryo fibroblast cells infected with human adenovirus type 12, and there-fore the adenovirus-specific T antigen was resitant to the action of endogenous interferon synthetized by the same cells. In chicks inoculated with human types, the appearance of interferon was biphasic: an 'early' and a 'late' interferon could be demonstrated with maximum titre 4 and 10 hr, respectively, after virus infection. In chicks infected with adenoviruses, first interferon production and then a decreased primary immune response to sheep red blood cells was observed. It was assumed that in adenovirus-infected chicks the interferon produced by viral stimulus resulted in a transient immunosuppression.

  4. Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518.

    Science.gov (United States)

    Yao, James C; Guthrie, Katherine A; Moran, Cesar; Strosberg, Jonathan R; Kulke, Matthew H; Chan, Jennifer A; LoConte, Noelle; McWilliams, Robert R; Wolin, Edward M; Mattar, Bassam; McDonough, Shannon; Chen, Helen; Blanke, Charles D; Hochster, Howard S

    2017-05-20

    Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.

  5. Comparative prospective randomized trial: laparoscopic versus open common bile duct exploration

    Directory of Open Access Journals (Sweden)

    Vladimir Grubnik

    2011-06-01

    Full Text Available Introduction: Single-stage laparoscopic procedures for common bile duct (CBD stones are an alternative treatmentoption to two-stage endo-laparoscopic treatment and to open choledocholithotomy. Several reports have demonstratedthe feasibility, safety, efficiency and cost-effectiveness of laparoscopic techniques.Aim: To analyse the safety and benefits of laparoscopic compared to open common bile duct (CBD exploration.Material and methods: The prospective randomized trial included a total of 256 patients with CBD stones operated from2005 to 2009 in a single centre. The male/female ratio was 82/174, with a median age 62.3 ±5.8 years (range 27 to 87years. There were two groups of patients. Group I: laparoscopic CBD exploration (138 patients. Group II: open CBD exploration(118 patients. Patient comorbidity was assessed by means of the American Society of Anesthesiologists (ASA classification;ASA II – 109 patients, ASA III – 59 patients. Bile duct stones were visualized preoperatively by means of US examinationin 129 patients, by means of ERCP in 26 patients, and by magnetic resonance cholangiopancreatography (MRCPin 72 patients. Preoperative evaluation was done through medical history, biochemical tests and ultrasonography.Results: The mean duration of laparoscopic procedures was 82 min (range 40-160 min. The mean duration of openprocedures was 90 min (range 60-150 min. Mean blood loss was much lower in the laparoscopic group than in theopen group (20 ±2 v.s 285 ±27, p < 0.01. Postoperative complications were observed in 7 patients of the laparoscopicgroup and in 15 patients in the open group (p < 0.01. Laparoscopic common bile duct exploration was performedthrough a trans-cystic approach in 76 patients and via choledochotomy in 62 patients. The transcystic approach wassuccessful in 76 patients (74.5%. External drainage was used in 25 (32.8% patients with the transcystic approach.Conclusions: Laparoscopic CBD exploration can be performed with

  6. The Ex-PRESS glaucoma shunt versus trabeculectomy in open-angle glaucoma: a prospective randomized study

    NARCIS (Netherlands)

    de Jong, Leo A. M. S.

    2009-01-01

    The purpose of this study was to establish the efficacy and safety of the Ex-PRESS (Optonol Ltd., Neve Ilan, Israel) mini glaucoma shunt in open-angle glaucoma. This was a prospective, randomized trial. Eyes from enrolled patients were randomly assigned to either Ex-PRESS implantation under a

  7. Laparoscopic versus open cholecystectomy in cirrhotic patients: a prospective randomized study.

    Science.gov (United States)

    El-Awadi, Saleh; El-Nakeeb, Ayman; Youssef, Tamer; Fikry, Amir; Abd El-Hamed, Tito M; Ghazy, Hosam; Foda, Elyamany; Farid, Mohamed

    2009-02-01

    Improved laparoscopic experience and techniques have made laparoscopic cholecystectomy (LC) feasible options in cirrhotic patients. This study was designed to compare the risk and benefits of open cholecystectomy (OC) versus LC in compensated cirrhosis. A randomized prospective study, in the period from October 2002 till December 2006, where 110 cirrhotic patients with symptomatic gallstone were randomly divided into OC group (55 patients) and LC group (55 patients). There was no operative mortality. In LC group 4 (7.33%) patients were converted to OC. Mean surgical time was significantly longer in OC group than LC group (96.13+17.35 min versus 76.13+15.12) P<0.05, associated with significantly higher intraoperative bleeding in OC group (P<0.01), necessitating blood transfusions to 7 (12.72%) patients in OC group. The time to resume diet was 18.36+8.18 h in LC group which is significantly earlier than in OC group 47.84+14.6h P<0.005. Hospital stay was significantly longer in OC group than LC group (6+1.74 days versus 1.87+1.11 days) P<0.01 with low postoperative morbidity. LC in cirrhotics is still complicated and highly difficult which associates with significant morbidity compared with that of patients without cirrhosis. However, it offers lower morbidity, shorter operative time; early resume dieting with less need for blood transfusion and reducing hospital stay than OC.

  8. Homoeopathic management of Schizophrenia: A prospective, non-comparative, open-label observational study

    Directory of Open Access Journals (Sweden)

    Praveen Oberai

    2016-01-01

    Full Text Available Objectives: To evaluate the usefulness of homoeopathic intervention in Schizophrenia, in untreated cases and antipsychotic treatment resistant cases, to verify indications of medicines, and to assess relapse, if any. Materials and Methods: A prospective, non-comparative, open-label observational study was carried out from October 2005-September 2010 by CCRH at Central Research Institute (H, Kottayam, Kerala, India. Patients between 20 and 60 years of age, presenting with symptoms of Schizophrenia were screened for inclusion and exclusion criteria. The patients who were on antipsychotic drugs were allowed to continue the same along with homoeopathic medicine, the dose of antipsychotics was monitored by the Psychiatrist. The symptoms of each patient were repertorized, and medicine was initially prescribed in 30C potency after consulting Materia Medica. Patients were followed up for 12 months. Outcome of treatment was assessed with Brief Psychiatric Rating Scales (BPRS. Analysis was done using Statistical Package for the Social Sciences  SPSS Version 20.0. Results: Out of 188 enrolled patients, 17 cases did not complete the baseline information. Total 171 patients were analysed as per modified Intention to Treat Principle. Significant difference (P = 0.0001, P < 0.05 in the mean scores of BPRS, using paired t test was observed at end of the study. Sulphur, Lycopodium, Natrum muriaticum, Pulsatilla and Phosphorus were found to be the most useful medicines in treating schizophrenic patients. Conclusion: The study reflects the positive role of homoeopathic medicines in the management of patients suffering from schizophrenia as measured by BPRS.

  9. Prospective study comparing laparoscopic and open adenomectomy: Surgical and functional results.

    Science.gov (United States)

    Garcia-Segui, A; Angulo, J C

    Open adenomectomy (OA) is the surgery of choice for large volume benign prostatic hyperplasia, and laparoscopic adenomectomy (LA) represents a minimally invasive alternative. We present a long-term, prospective study comparing both techniques. The study consecutively included 199 patients with benign prostatic hyperplasia and prostate volumes>80g who were followed for more than 12 months. The patients underwent OA (n=97) or LA (n=102). We recorded and compared demographic and perioperative data, functional results and complications using a descriptive statistical analysis. The mean age was 69.2±7.7 years (range 42-87), and the mean prostate volume (measured by TRUS) was 112.1±32.7mL (range 78-260). There were no baseline differences among the groups in terms of age, ASA scale, prostate volume, PSA levels, Qmax, IPSS, QoL or treatments prior to the surgery. The surgical time (P<.0001) and catheter time (P<.0002) were longer in the LA group. Operative bleeding (P<.0001), transfusion rate (P=.0015) and mean stay (P<.0001) were significantly lower in the LA group. The LA group had a lower rate of complications (P=.04), but there were no significant differences between the groups in terms of major complications (Clavien score≥3) (P=.13) or in the rate of late complications (at one year) (P=.66). There were also no differences between the groups in the functional postoperative results: IPSS (P=.17), QoL (P=.3) and Qmax (P=.17). LA is a reasonable, safe and effective alternative that results in less bleeding, fewer transfusions, shorter hospital stays and lower morbidity than OA. LA has similar functional results to OA, at the expense of longer surgical times and longer catheter times. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Open release versus radiofrequency microtenotomy in the treatment of lateral epicondylitis: a prospective randomized controlled trial.

    Science.gov (United States)

    Hamlin, Katharine; Munro, Christopher; Barker, Scott L; McKenna, Sean; Kumar, Kapil

    2018-01-01

    Optimal surgical treatment of lateral epicondylitis remains uncertain. Recently, radiofrequency microtenotomy (RFMT) has been proposed as a suitable treatment. We compared RFMT with standard open release (OR) in this prospective randomized controlled trial. In total, 41 patients with symptoms for at least 6 months were randomized into two groups: 23 patients had RFMT and 18 had OR. Two patients from RFMT withdrew. Each patient underwent Numerical Rating Scale (NRS) pain score, grip strength and Disabilities of the Arm, Shoulder and Hand (DASH) scores pre-operatively and at 6 weeks. Pain and DASH scores were repeated at 6 months and 12 months. NRS pain scores improved by 4.8 points for RFMT and by 3.9 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Grip strength improved by 31% in the RFMT group compared to 38% in OR. There was no significant difference between the initial and 6 weeks scores or between treatments. At 1 year, DASH was 39.8 points for RFMT and 24.4 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Both groups showed significant improvements and similar benefit to the patient. The results of the present study do not show any benefit of RFMT over the standard OR. As a result of the extra expense of RFMT, we therefore recommend that OR is offered as the standard surgical management.

  11. Prospective study comparing laparoscopic and open radical cystectomy: Surgical and oncological results.

    Science.gov (United States)

    Esquinas, C; Alonso, J M; Mateo, E; Dotor, A; Martín, A M; Dorado, J F; Arance, I; Angulo, J C

    2018-03-01

    Laparoscopic radical cystectomy with lymphadenectomy and urinary diversion is an increasingly widespread operation. Studies are needed to support the oncological effectiveness and safety of this minimally invasive approach. A nonrandomised, comparative prospective study between open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) was conducted in a university hospital. The main objective was to compare cancer-specific survival. The secondary objective was to compare the surgical results and complications according to the Clavien-Dindo scale. We treated 156 patients with high-grade invasive bladder cancer with either ORC (n=70) or LRC (n=86). The mean follow-up was 33.5±23.8 (range 12-96) months. The mean age was 66.9+9.4 years, and the male to female ratio was 19:1. Both groups were equivalent in age, stage, positive lymph nodes, in situ carcinoma, preoperative obstructive uropathy, adjuvant chemotherapy and type of urinary diversion. There were no differences between the groups in terms of cancer-specific survival (log-rank; P=.71). The histopathology stage was the only independent variable that predicted the prognosis. The hospital stay (P=.01) and operative transfusion rates (P=.002) were less for LRC. The duration of the surgery was greater for LRC (P<.001). There were no differences in the total complications rate (p=.62) or major complications (P=.69). The risk of evisceration (P=.02), surgical wound infection (P=.005) and pneumonia (P=.017) was greater for ORC. The risk of rectal lesion (P=.017) and urethrorectal fistulae (P=.065) was greater for LRC. LRC is an equivalent treatment to ORC in terms of oncological efficacy and is advantageous in terms of transfusion rates and hospital stays but not in terms of operating room time and overall safety. Studies are needed to better define the specific safety profile for each approach. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. The Efficacy of Neurofeedback in Patients with Major Depressive Disorder: An Open Labeled Prospective Study.

    Science.gov (United States)

    Cheon, Eun-Jin; Koo, Bon-Hoon; Choi, Joong-Hyun

    2016-03-01

    The purpose of this study was to evaluate the effect of neurofeedback on depressive symptoms and electrophysiological disturbances in patients with major depressive disorder. We recruited participants suffering from depression to evaluate efficacy of left prefrontal beta with alpha/theta training. An 8-week, prospective, open-label study was undertaken. Twenty participants were recruited. The treatment protocol was twice or three times a week training of beta at F3 with alpha/theta at Pz for 8 weeks. When every visit, patients were received beta training for 30 min, and then alpha/theta training for 30 min. Baseline, 4 and 8 week scores of; the Hamilton rating scale for Depression (HAM-D), the Hamilton rating scale for Anxiety (HAM-A), the Beck Depression Inventory (BDI)-II, the Beck Anxiety Inventory (BAI), Clinical global impression-severity (CGI-S), and pre- and post-treatment resting state EEGs were compared. Interhemispheric alpha power asymmetry (A score) was computed for homologous sites F3-F4. Pre- and post-training clinical assessments revealed significant improvements in HAM-D, HAM-A, BDI, and CGI-S scores. Cumulative response rates by HAM-D were 35.0 and 75.0 % at 4 and 8 weeks, respectively, corresponding cumulative remission rates by HAM-D were 15.0 and 55.0 %, respectively. No significant differences were found between pre- and post-treatment A score. Neurofeedback treatment could improve depressive symptoms significantly. In addition, anxiety symptoms and clinical illness severity decreased significantly after neurofeedback treatment. Despite its several limitations, such as, small sample size and lack of a control group, this study suggested neurofeedback has significant effects in patients with major depressive disorder.

  13. Prognosis of Open Type 3-B Tibia Fractures By Ilizarov Technique: A Prospective Study

    OpenAIRE

    Janak Rathod, Taral Shah

    2012-01-01

    Background: Open fractures of the tibial shaft are both common and may be fraught with complications. Open fractures of the tibia, with associated vascular injuries, have historically had a very poor outcome. Malunion, delayed union, nonunion, and infection are all seen regularly after open tibia fractures. Objectives: Objective of the study is to explore advantage of primary or early ilizarov surgery in Open type 3- B fracture tibia. Methodology: A follow up study of 10 cases of open type 3-...

  14. Radioprotective effect of interferon

    Energy Technology Data Exchange (ETDEWEB)

    Zasukhina, G.

    1984-12-18

    A cycle of experiments performed jointly with associations of the Moscow Engineering Physics Institute reportedly demonstrated that interferons protect human cells cultivated in a test tube against the action of fast neutrons and gamma radiation. Cells treated in advance with interferon not only survived irradiation but were almost totally protected against harmful effects of fast neutrons on the structure of chromosomes, according to the author. She mentions that the laboratory has also been studying effects produced on cells by compounds of heavy metals and other chemical compounds, including ones which cause breaks in the DNA molecule. Interferon's ability to protect cells against effects of chemical compounds has been studied in this connection. Another direction of the laboratory's work is research on interferon's effects on blood cells of persons suffering from certain hereditary diseases in which restorative processes of cells are impaired. The purpose of this is to develop courses of treatment which will not cause irreversible damages to chromosomes, the author explains. Interferon has been found to stimulate the reparation systems of cells in cases of Marfan's syndrome, for example.

  15. Interferon Gamma-1b Injection

    Science.gov (United States)

    Interferon gamma-1b injection is used to reduce the frequency and severity of serious infections in people with chronic ... severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications called ...

  16. SU-E-T-65: A Prospective Trial of Open Face Masks for Head and Neck Radiotherapy

    International Nuclear Information System (INIS)

    Wiant, D; Squire, S; Maurer, J; Liu, H; Hayes, L; Sintay, B

    2015-01-01

    Purpose: Open face head and neck masks allow for active patient monitoring during treatment and may reduced claustrophobia and anxiety compared to closed masks. The ability of open masks to limit intrafraction motion and to preserve the patient shape/position from simulation over protracted treatments should be considered. Methods: Thirty-two head and neck patients were prospectively randomized to treatment in a closed mask or a novel open face mask. All patients received daily volumetric imaging. The daily images were automatically rigidly registered to the planning CT’s offline using a commercial image processing tool. The shifts needed to optimize the registration, the mutual information coefficient (MI), and the Pearson correlation (PC) coefficients were recorded to evaluate shape preservation. The open group was set-up and monitored with surface imaging at treatment. The real time surface imaging information was recorded to evaluate intrafraction motion. Results: Sixteen patients were included in each group. Evaluations were made over a total of 984 fractions. The mean MI and PC showed significantly higher shape preservation for the open group than for the closed group (p = 0). The mean rotations for the open group were smaller or < 0.15° larger versus the closed group. The mean intrafraction motion for the open group was 0.93 +/−0.99 mm (2 SD). The maximum single fraction displacement was 3.2 mm. Fourteen of 16 patients showed no significant correlation of motion with fraction number (p > 0.05). Conclusion: The open masks preserved shape as well as the closed masks, and they limited motion to < 2 mm for 95% of the treated fractions. These results are consistent over treatment courses of up to 35 fractions. The open mask is suitable for treatment with or without active monitoring. This work was partially supported by Qfix

  17. SU-E-T-65: A Prospective Trial of Open Face Masks for Head and Neck Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiant, D; Squire, S; Maurer, J; Liu, H; Hayes, L; Sintay, B [Cone Health Cancer Center, Greensboro, NC (United States)

    2015-06-15

    Purpose: Open face head and neck masks allow for active patient monitoring during treatment and may reduced claustrophobia and anxiety compared to closed masks. The ability of open masks to limit intrafraction motion and to preserve the patient shape/position from simulation over protracted treatments should be considered. Methods: Thirty-two head and neck patients were prospectively randomized to treatment in a closed mask or a novel open face mask. All patients received daily volumetric imaging. The daily images were automatically rigidly registered to the planning CT’s offline using a commercial image processing tool. The shifts needed to optimize the registration, the mutual information coefficient (MI), and the Pearson correlation (PC) coefficients were recorded to evaluate shape preservation. The open group was set-up and monitored with surface imaging at treatment. The real time surface imaging information was recorded to evaluate intrafraction motion. Results: Sixteen patients were included in each group. Evaluations were made over a total of 984 fractions. The mean MI and PC showed significantly higher shape preservation for the open group than for the closed group (p = 0). The mean rotations for the open group were smaller or < 0.15° larger versus the closed group. The mean intrafraction motion for the open group was 0.93 +/−0.99 mm (2 SD). The maximum single fraction displacement was 3.2 mm. Fourteen of 16 patients showed no significant correlation of motion with fraction number (p > 0.05). Conclusion: The open masks preserved shape as well as the closed masks, and they limited motion to < 2 mm for 95% of the treated fractions. These results are consistent over treatment courses of up to 35 fractions. The open mask is suitable for treatment with or without active monitoring. This work was partially supported by Qfix.

  18. A prospective clinical study evaluating the development of bowel wall edema during laparoscopic and open visceral surgery.

    Science.gov (United States)

    Marjanovic, Goran; Kuvendziska, Jasmina; Holzner, Philipp Anton; Glatz, Torben; Sick, Olivia; Seifert, Gabriel; Kulemann, Birte; Küsters, Simon; Fink, Jodok; Timme, Sylvia; Hopt, Ulrich Theodor; Wellner, Ulrich; Keck, Tobias; Karcz, Wojciech Konrad

    2014-12-01

    To examine bowel wall edema development in laparoscopic and open major visceral surgery. In a prospective study, 47 consecutively operated patients with gastric and pancreatic resections were included. Twenty-seven patients were operated in a conventional open procedure (open group) and 20 in a laparoscopic fashion (lap group). In all procedures, a small jejunal segment was resected during standard preparation, of which we measured the dry-wet ratio. Furthermore, HE staining was performed for measuring of bowel wall thickness and edema assessment. Mean value (±std) of dry-wet ratio was significantly lower in the open than in the lap group (0.169 ± 0.017 versus 0.179 ± 0.015; p = 0.03) with the same amount of fluid administration in both groups and a longer infusion interval during laparoscopic surgery. Subgroup analyses (only pancreatic resections) still showed similar results. Histologic examination depicted a significantly larger bowel wall thickness in the open group. Laparoscopic surgery does not seem to lead to the bowel wall edema observed to occur in open surgery regardless of the degree of intravenous fluid administration, thus supporting its use even in major visceral surgery.

  19. Awareness of "predatory" open-access journals among prospective veterinary and medical authors attending scientific writing workshops

    Directory of Open Access Journals (Sweden)

    Mary M Christopher

    2015-08-01

    Full Text Available Authors face many choices when selecting a journal for publication. Prospective authors, especially trainees, may be unaware of predatory online journals or how to differentiate them from legitimate journals. In this study we assessed awareness of open-access and predatory journals among prospective authors attending scientific writing workshops; our long-term goal was to inform educational goals for the workshops. We surveyed participants of writing workshops at veterinary and medical schools and an international conference over a 1-year period. The survey included 14 statements for respondents to indicate agreement level on a Likert-like scale and four questions on awareness of resources about predatory journals; respondents also defined predatory journal. A total of 145 participants completed the survey: 106 (73.1% from veterinary schools and 86 (59.3% graduate students or residents. Fewer faculty (vs trainees agreed that open access was an important factor in deciding where to publish; faculty and postdoctoral researchers were more likely to expect to pay more to publish in an open-access journal. Most respondents (120/145, 82.7% agreed/strongly agreed that the decision to accept a manuscript should not be influenced by publication charges, but 50% (56/112 indicated they didn’t know how publishing costs were supported. Of the 142 respondents who answered, 33 (23.0% indicated awareness of the term predatory journal; 34 (23.9% were aware of the Directory of Open Access Journals; 24 (16.9% were aware of the Science sting article about predatory journals; and 7 (4.8% were aware of Beall’s list. Most (93/144, 64.5% definitions of predatory journals described poor but not predatory journal practices, and some respondents misunderstood the term completely. Mentors should help novice authors to be aware of predatory journals and to distinguish between legitimate and illegitimate open-access journals, thus selecting the best journal for their

  20. Awareness of "Predatory" Open-Access Journals among Prospective Veterinary and Medical Authors Attending Scientific Writing Workshops.

    Science.gov (United States)

    Christopher, Mary M; Young, Karen M

    2015-01-01

    Authors face many choices when selecting a journal for publication. Prospective authors, especially trainees, may be unaware of "predatory" online journals or how to differentiate them from legitimate journals. In this study, we assessed awareness of open-access and predatory journals among prospective authors attending scientific writing workshops; our long-term goal was to inform educational goals for the workshops. We surveyed participants of writing workshops at veterinary and medical schools and an international conference over a 1-year period. The survey included 14 statements for respondents to indicate agreement level on a Likert-like scale and four questions on awareness of resources about predatory journals; respondents also defined "predatory journal." A total of 145 participants completed the survey: 106 (73.1%) from veterinary schools and 86 (59.3%) graduate students or residents. Fewer faculty (vs trainees) agreed that open access was an important factor in deciding where to publish; faculty and postdoctoral researchers were more likely to expect to pay more to publish in an open-access journal. Most respondents (120/145, 82.7%) agreed/strongly agreed that the decision to accept a manuscript should not be influenced by publication charges, but 50% (56/112) indicated that they "didn't know" how publishing costs were supported. Of the 142 respondents who answered, 33 (23.0%) indicated awareness of the term "predatory journal"; 34 (23.9%) were aware of the Directory of Open Access Journals; 24 (16.9%) were aware of the Science "sting" article about predatory journals; and 7 (4.8%) were aware of Beall's list. Most (93/144, 64.5%) definitions of predatory journals described poor but not predatory journal practices, and some respondents misunderstood the term completely. Mentors should help novice authors to be aware of predatory journals and to distinguish between legitimate and illegitimate open-access journals, thus selecting the best journal for their

  1. A prospective study of the impact of opening a casino on gambling behaviours: 2- and 4-year follow-ups.

    Science.gov (United States)

    Jacques, Christian; Ladouceur, Robert

    2006-10-01

    It is widely believed that the rate of pathological gambling is related to the accessibility and availability of gambling activities. Few empirical studies have yet been conducted to evaluate this hypothesis. Using a longitudinal prospective design, the current study evaluates the impact of a casino in Canada's Hull, Quebec region. A random sample of respondents from Hull (experimental group) and from Quebec City (comparison group) completed the South Oaks Gambling Screen (SOGS) and gambling- related questions before the opening of the Hull Casino (pretest), 1 year after the opening (posttest), and on follow-up at Years 2 and 4. Although, 1 year after the opening of the casino, we did observe an increase in playing casino games and in the maximum amount of money lost in 1 day's gambling, this trend was not maintained over time (2- and 4-year follow-ups). In the Hull cohort, the rate of at-risk and probable pathological gamblers and the number of criteria on the SOGS did not increase at the 2- and 4-year follow-ups. The residents' reluctance to open a local casino was generally stable over time following the casino's opening. The discussion raises different explanatory factors and focuses on the context of the Regional Exposure Model as a potentially more applicable measure of studying the expansion of gambling.

  2. Interferon in lyssavirus infection.

    Science.gov (United States)

    Rieder, Martina; Finke, Stefan; Conzelmann, Karl-Klaus

    2012-01-01

    Rabies is a zoonosis still claiming more than 50 000 human deaths per year. Typically, human cases are due to infection with rabies virus, the prototype of the Lyssavirus genus, but sporadic cases of rabies-like encephalitis caused by other lyssaviruses have been reported. In contrast to rabies virus, which has an extremely broad host range including many terrestrial warm-blooded animals, rabies-related viruses are associated predominantly with bats and rarely infect terrestrial species. In spite of a very close genetic relationship of rabies and rabies-related viruses, the factors determining the limited host range of rabies-related viruses are not clear. In the past years the importance of viral countermeasures against the host type I interferon system for establishment of an infection became evident. The rabies virus phosphoprotein (P) has emerged as a critical factor required for paralysing the signalling cascades leading to transcriptional activation of interferon genes as well as interferon signalling pathways, thereby limiting expression of antiviral and immune stimulatory genes. Comparative studies would be of interest in order to determine whether differential abilities of the lyssavirus P proteins contribute to the restricted host range of lyssaviruses.

  3. Nutritional Recovery after Open and Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Comparative Trial (CCOG1204).

    Science.gov (United States)

    Matsushita, Hidenobu; Tanaka, Chie; Murotani, Kenta; Misawa, Kazunari; Ito, Seiji; Ito, Yuichi; Kanda, Mitsuro; Mochizuki, Yoshinari; Ishigure, Kiyoshi; Yaguchi, Toyohisa; Teramoto, Jin; Nakayama, Hiroshi; Kawase, Yoshihisa; Fujiwara, Michitaka; Kodera, Yasuhiro

    2018-01-01

    Little information from prospective clinical trials is available on the influences of surgical approaches on postoperative body compositions and nutritional status. We designed a prospective non-randomized trial to compare postoperative chronological changes in body composition and nutritional status between laparoscopic and open distal gastrectomy for stage I gastric cancer (GC). Body compositions and nutritional indicators in blood tests were measured at the baseline and at the 1st, 3rd, 6th, and 12th postoperative months (POM). The primary end point was the decrease relative to the baseline in the body muscle mass at POM 6. Ninety-six patients for the laparoscopic group and 52 for the open group were eligible for data analysis. No significant differences were found in any baseline demographics, body compositions, and nutritional indicators between the groups. The changes of body muscle mass at POM 6 were similar in both groups. Overall, no significant differences between the groups were observed in any of the body composition and nutritional indicators during the first year after surgery. Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC. © 2017 S. Karger AG, Basel.

  4. On the Prospects and Concerns of Integrating Open Source Software Environment in Software Engineering Education

    Science.gov (United States)

    Kamthan, Pankaj

    2007-01-01

    Open Source Software (OSS) has introduced a new dimension in software community. As the development and use of OSS becomes prominent, the question of its integration in education arises. In this paper, the following practices fundamental to projects and processes in software engineering are examined from an OSS perspective: project management;…

  5. An Opening to Society: Chances and Prospects of Science, Research and Services.

    Science.gov (United States)

    Heckelmann, Dieter

    1989-01-01

    Describes how the Free University of Berlin (West Germany) has become more open to the public. The Free University has strengthened its cooperation with private companies in research and funding, promoted internal research, and increased its accelerated and continuing education programs in order to improve its image. (LS)

  6. Median mandibular flexure at different mouth opening and its relation to different facial types: A prospective clinical study

    Science.gov (United States)

    Prasad, Mandava; Hussain, Mohammed Z.; Shetty, Sharath K.; Kumar, T. Ashok; Khaur, Mohit; George, Suja A.; Dalwai, Sameen

    2013-01-01

    Objective: To measure the arch width and Median mandibular flexure (MMF) values at relative rest and maximum jaw opening in young adults with Dolichofacial, Mesofacial, and Brachyfacial types and tested whether the variation in the facial pattern is related to the MMF values in South Indian population. Materials and Methods: This Prospective clinical study consisted of sample of 60 young adults. The subjects were grouped into 3 groups: Group 1: Brachyfacial, Group 2: Mesofacial and types, Group 3: Dolichofacial. Impressions were taken for all the 60 subjects and the casts were scanned and digitized. The intermolar width was measured for Dolichofacial, Mesofacial, and Brachyfacial subjects at relative rest (R) and maximum opening (O). Results: The statistical analysis of the observations included Descriptive and Inferential statistics. The statistical analysis was executed by means of Sigma graph pad prism software, USA Version-4. Kruskal wallis (ANOVA) followed by Dunns post hoc test was performed. Mann Whitney U-test was performed to assess the difference in MMF values between Males and Females of the three groups. The Mean (SD) Mandibular flexure in individuals with Brachyfacial type was 1.12 (0.09), Mesofacial type was 0.69 (0.21), and Dolichofacial type was 0.39 (0.08). Conclusions: The Mean intermolar width was maximum in Brachyfacial type and minimum in Dolichofacial type. MMF was maximum at the maximum mouth opening position and was maximum in individuals with Brachyfacial type. PMID:24082745

  7. Improvement of lower urinary tract symptoms and sexual activity after open simple prostatectomy: Prospective analysis of 50 cases

    Directory of Open Access Journals (Sweden)

    Lorenzo Montesi

    2014-12-01

    Full Text Available Objectives: To evaluate the improvement of Lower Urinary Tract Symptoms (LUTS and Erectile Function (EF evaluated before and after Open Simple Prostatectomy, focusing on which patients this procedure allows better outcomes in term of sexual activity. Material and methods: 50 men with large size benign prostatic hyperplasia (BHP greater than 80 gr were prospectively evaluated before and 6 months after Open Simple Prostatectomy (Freyer procedure between October 2012 to September 2013. Patients had a pre-operative transrectal ultrasound (TRUS for volume evaluation and filled pre and post operative questionnaires for International Prostate Symptom Score (IPSS and International Index of Erectile Function (IIEF-5 score. Results: Mean patients age was 71 years (D.S. 3,5, mean prostate volume results 103 ml (D.S. 23,7; regarding LUTS and EF, mean improvement of IPSS score was 15,3 (D.S. 4 and mean increase of IIEF-5 score was 3,4 (D.S.3. This study highlights a correlation between patients’ age and increase of IIEF-5 score; no correlation with prostate size was found. Conclusion: According to the EAU Guidelines 2014, large size BPH (over 80-100 mL with LUTS refractory to medical management continue to have open prostatectomy as the treatment of choice. In our experience we found not only an reduction of LUTS after the procedure but also an improvement of erectile function; this improvement was related with patient’s age.

  8. Digitization and the open management of data: New prospects for electricity distributors

    International Nuclear Information System (INIS)

    Derdevet, Michel

    2017-01-01

    At the core of both the energy transition and the digital revolution are the grids for distributing electricity during this era of big data. The electricity grid is becoming smarter and smarter, as it is equipped with sensors capable of providing information and data - the leading example being the 35 million smart electricity meters to be installed in French households by 2021. Backed by recent legislation, the trend toward open data is, for distributors, both a requirement and a lever: an economic, social and environmental requirement for enabling localities to prove their sense of responsibility and for developing innovative services for citizens; but also a lever for distributors to become operators who, processing dynamic data, are open to their ecosystem - a lever for making new business models emerge for the local management of energy

  9. Gaia Data Release 1 Open cluster astrometry: performance, limitations, and future prospects

    Czech Academy of Sciences Publication Activity Database

    van Leeuwen, F.; Vallenari, A.; Jordi, C.; Lindegren, L.; Bastian, U.; Prusti, T.; de Bruijne, J.H.J.; Brown, A.G.A.; Babusiaux, C.; Bailer-Jones, C.A.L.; Fuchs, Jan; Koubský, Pavel; Votruba, Viktor

    2017-01-01

    Roč. 601, May (2017), A19/1-A19/65 E-ISSN 1432-0746 R&D Projects: GA MŠk(CZ) LG15010 Grant - others:ESA(XE) ESA-PECS project No. 98058 Institutional support: RVO:67985815 Keywords : astrometry * open clusters and associations * proper motion and parallax Subject RIV: BN - Astronomy , Celestial Mechanics, Astrophysics OBOR OECD: Astronomy (including astrophysics,space science) Impact factor: 5.014, year: 2016

  10. Delimiting the Prospect of Openness: An Examination of Initial Student Approaches to E-Learning

    Directory of Open Access Journals (Sweden)

    Christopher Naughton

    2011-02-01

    Full Text Available When converting from a paper-based distance mode to an online mode of teaching, certain expectations arise that students may engage not only in the development of extended research activity but that the quality of discussion and thinking will change. With access to open-ended discussion within the online forum the opportunity is afforded to students to share ideas and in turn develop their shared knowledge, a facility denied to them when in the paper distance mode. However, in a recent study conducted in New Zealand, it was shown that despite having access to online forums students moving to an online platform refrained from participation in this social exchange. A possible explanation for this indifference was thought to be the students realising that the online exchange made no impact on their assessment. Hence, the collaborative rhetoric of Web 2.0 made little impact when the summative evaluation remained unchanged from previous paper-based assessment. This paper reports on the introduction of online learning at a private tertiary college in New Zealand and describes the response of students who found difficulty in reconciling a community of learners and openness within what was perceived as an evaluation that remained individualistic and competitive in nature.

  11. Comparative health technology assessment of robotic-assisted, direct manual laparoscopic and open surgery: a prospective study.

    Science.gov (United States)

    Turchetti, Giuseppe; Pierotti, Francesca; Palla, Ilaria; Manetti, Stefania; Freschi, Cinzia; Ferrari, Vincenzo; Cuschieri, Alfred

    2017-02-01

    Despite many publications reporting on the increased hospital cost of robotic-assisted surgery (RAS) compared to direct manual laparoscopic surgery (DMLS) and open surgery (OS), the reported health economic studies lack details on clinical outcome, precluding valid health technology assessment (HTA). The present prospective study reports total cost analysis on 699 patients undergoing general surgical, gynecological and thoracic operations between 2011 and 2014 in the Italian Public Health Service, during which period eight major teaching hospitals treated the patients. The study compared total healthcare costs of RAS, DMLS and OS based on prospectively collected data on patient outcome in addition to healthcare costs incurred by the three approaches. The cost of RAS operations was significantly higher than that of OS and DMLS for both gynecological and thoracic operations (p DMLS. Total costs of general surgery RAS were significantly higher than those of OS (p DMLS general surgery. Indirect costs were significantly lower in RAS compared to both DMLS general surgery and OS gynecological surgery due to the shorter length of hospital stay of RAS approach (p < 0.001). Additionally, in all specialties compared to OS, patients treated by RAS experienced a quicker recovery and significantly less pain during the hospitalization and after discharge. The present HTA while confirming higher total healthcare costs for RAS operations identified significant clinical benefits which may justify the increased expenditure incurred by this approach.

  12. Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial.

    Science.gov (United States)

    Wozniak, Janet; Biederman, Joseph; Mick, Eric; Waxmonsky, James; Hantsoo, Liisa; Best, Catherine; Cluette-Brown, Joanne E; Laposata, Michael

    2007-01-01

    To test the effectiveness and safety of omega-3 fatty acids (Omegabrite(R) brand) in the treatment of pediatric bipolar disorder (BPD). Subjects (N=20) were outpatients of both sexes, 6 to 17 years of age, with a DSM-IV diagnosis of BPD and Young Mania Rating Scale (YMRS) score of >15 treated over an 8-week period in open-label trial with omega-3 fatty acids 1290 mg-4300 mg combined EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Subjects experienced a statistically significant but modest 8.9+/-2.9 point reduction in the YMRS scores (baseline YMRS=28.9+/-10.1; endpoint YMRS=19.1+/-2.6, pDHA increased in treated subjects. As only 35% of these subjects had a response by the usual accepted criteria of >50% decrease on the YMRS, omega-3 fatty acids treatment was associated with a very modest improvement in manic symptoms in children with BPD.

  13. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Berlant Jeffrey L

    2004-08-01

    Full Text Available Abstract Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5 or augmentation (n = 28. The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30, total symptoms declined by 49% at week 4 (paired t-test, P Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

  14. A prospective multi-centric open clinical trial of homeopathy in diabetic distal symmetric polyneuropathy.

    Science.gov (United States)

    Nayak, Chaturbhuja; Oberai, Praveen; Varanasi, Roja; Baig, Hafeezullah; Ch, Raveender; Reddy, G R C; Devi, Pratima; S, Bhubaneshwari; Singh, Vikram; Singh, V P; Singh, Hari; Shitanshu, Shashi Shekhar

    2013-04-01

    To evaluate homeopathic treatment in the management of diabetic distal symmetric polyneuropathy. A prospective multi-centric clinical observational study was carried out from October 2005 to September 2009 by Central Council for Research in Homeopathy (CCRH) (India) at its five institutes/units. Patients suffering from diabetes mellitus (DM) and presenting with symptoms of diabetic polyneuropathy (DPN) were screened, investigated and were enrolled in the study after fulfilling the inclusion and exclusion criteria. Patients were evaluated by the diabetic distal symmetric polyneuropathy symptom score (DDSPSS) developed by the Council. A total of 15 homeopathic medicines were identified after repertorizing the nosological symptoms and signs of the disease. The appropriate constitutional medicine was selected and prescribed in 30, 200 and 1 M potency on an individualized basis. Patients were followed up regularly for 12 months. Out of 336 patients (167 males and 169 females) enrolled in the study, 247 patients (123 males and 124 females) were analyzed. All patients who attended at least three follow-up appointments and baseline curve conduction studies were included in the analysis.). A statistically significant improvement in DDSPSS total score (p = 0.0001) was found at 12 months from baseline. Most objective measures did not show significant improvement. Lycopodium clavatum (n = 132), Phosphorus (n = 27) and Sulphur (n = 26) were the medicines most frequently prescribed. Adverse event of hypoglycaemia was observed in one patient only. This study suggests homeopathic medicines may be effective in managing the symptoms of DPN patients. Further studies should be controlled and include the quality of life (QOL) assessment. Copyright © 2013 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  15. Open wedge metatarsal osteotomy versus crescentic osteotomy to correct severe hallux valgus deformity - A prospective comparative study.

    Science.gov (United States)

    Wester, Jens Ulrik; Hamborg-Petersen, Ellen; Herold, Niels; Hansen, Palle Bo; Froekjaer, Johnny

    2016-03-01

    Different techniques of proximal osteotomies have been introduced to correct severe hallux valgus. The open wedge osteotomy is a newly introduced method for proximal osteotomy. The aim of this prospective randomized study was to compare the radiological and clinical results after operation for severe hallux valgus, comparing the open wedge osteotomy to the crescentic osteotomy which is our traditional treatment. Forty-five patients with severe hallux valgus (hallux valgus angle >35̊, and intermetatarsal angle >15̊) were included in this study. The treatment was proximal open wedge osteotomy and fixation with plate (Hemax), group 1, or operation with proximal crescentic osteotomy and fixation with a 3mm cannulated screw, group 2. The mean age was 52 years (19-71). Forty-one females and four males were included. Clinical and radiological follow-ups were performed 4 and 12 months after the operation. In group 1 the hallux valgus angle decreased from 39.0̊ to 24.1̊ after 4 months and 27.9̊ after 12 months. In group 2 the angle decreased from 38.3̊ to 21.4̊ after 4 months and 27.0̊ after 12 months. The intermetatarsal angle in group 1 was 19.0̊ preoperatively, 11.6̊ after 4 months and 12.6̊ after 12 months. In group 2 the mean intermetatarsal angle was 18.9̊ preoperatively, 12.0̊ after 4 months and 12.6̊ after 12 months. The AOFAS score improved from 59.3 to 81.5 in group 1 and from 61.8 to 84.8 in group 2 respectively measured 12 months postoperatively. The relative length of the 1 metatarsal compared to 2 metatarsal bone was 0.88 and 0.87 preoperatively and 0.88 and 0.86 for group 1 and 2 respectively measured after 12 months. Crescentic osteotomy and open wedge osteotomy improve AOFAS score and VAS scores on patients operated with severe hallux valgus. No significant difference was found in the two groups looking at the postoperative improvement of HVA and IMA measured 4 and 12 months postoperatively. The postoperative VAS score and AOFAS score were

  16. Opening the Internal Hematoma Membrane Does Not Alter the Recurrence Rate of Chronic Subdural Hematomas: A Prospective Randomized Trial.

    Science.gov (United States)

    Unterhofer, Claudia; Freyschlag, Christian F; Thomé, Claudius; Ortler, Martin

    2016-08-01

    Factors determining the recurrence of chronic subdural hematomas (CSDHs) are not clear. Whether opening the so-called internal hematoma membrane is useful has not been investigated. To investigate whether splitting the inner hematoma membrane influences the recurrence rate in patients undergoing burr-hole craniotomy for CSDH. Fifty-two awake patients undergoing surgery for 57 CSDHs were prospectively randomized to either partial opening of the inner hematoma membrane (group A) or not (group B) after enlarged burr-hole craniotomy and hematoma evacuation. Drainage was left in situ for several days postoperatively. Groups were comparable with regard to demographic, clinical, and imaging variables. Outcome was assessed after 3-6 weeks for the combined outcome variable of reoperation or residual hematoma of one third or more of the original hematoma thickness. Fourteen patients underwent reoperation for clinical deterioration or residual hematoma during follow-up (n = 6 in group A, 21%; n = 8 in group B, 28 %) (P = 0.537). Residual hematoma of ≥ one third not requiring surgery was present in 7 patients in group A (25%) and 10 patients in group B (36%) (P = 0.383). The overall cumulative failure rate (reoperation or hematoma thickness ≥ one third) was 13/28 (46%) in group A and 18/28 in group B (P = 0.178; relative risk, 0.722 [95% confidence interval, 0.445-1.172]; absolute risk reduction -16% [95% confidence interval, -38% to 8%]). Opening the internal hematoma membrane does not alter the rate of patients requiring revision surgery and the number of patients showing a marked residual hematoma 6 weeks after evacuation of a CSDH. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Dextrose and morrhuate sodium injections (prolotherapy) for knee osteoarthritis: a prospective open-label trial.

    Science.gov (United States)

    Rabago, David; Patterson, Jeffrey J; Mundt, Marlon; Zgierska, Aleksandra; Fortney, Luke; Grettie, Jessica; Kijowski, Richard

    2014-05-01

    This study determined whether injection with hypertonic dextrose and morrhuate sodium (prolotherapy) using a pragmatic, clinically determined injection schedule for knee osteoarthritis (KOA) results in improved knee pain, function, and stiffness compared to baseline status. This was a prospective three-arm uncontrolled study with 1-year follow-up. The setting was outpatient. The participants were 38 adults who had at least 3 months of symptomatic KOA and who were in the control groups of a prior prolotherapy randomized controlled trial (RCT) (Prior-Control), were ineligible for the RCT (Prior-Ineligible), or were eligible but declined the RCT (Prior-Declined). The injection sessions at occurred at 1, 5, and 9 weeks with as-needed treatment at weeks 13 and 17. Extra-articular injections of 15% dextrose and 5% morrhuate sodium were done at peri-articular tendon and ligament insertions. A single intra-articular injection of 6 mL 25% dextrose was performed through an inferomedial approach. The primary outcome measure was the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC). The secondary outcome measure was the Knee Pain Scale and postprocedure opioid medication use and participant satisfaction. The Prior-Declined group reported the most severe baseline WOMAC score (p=0.02). Compared to baseline status, participants in the Prior-Control group reported a score change of 12.4±3.5 points (19.5%, p=0.002). Prior-Decline and Prior-Ineligible groups improved by 19.4±7.0 (42.9%, p=0.05) and 17.8±3.9 (28.4%, p=0.008) points, respectively; 55.6% of Prior-Control, 75% of Prior-Decline, and 50% of Prior-Ineligible participants reported score improvement in excess of the 12-point minimal clinical important difference on the WOMAC measure. Postprocedure opioid medication resulted in rapid diminution of prolotherapy injection pain. Satisfaction was high and there were no adverse events. Prolotherapy using dextrose and morrhuate sodium injections for

  18. Interferon Induced Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Yusuf Kayar

    2016-01-01

    Full Text Available Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

  19. Ribavirin plus interferon versus interferon for chronic hepatitis C

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise Lotte; Gluud, Christian

    2010-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality. Standard therapy is ribavirin plus pegylated interferon to achieve undetectable level of virus in the blood, but the effect on clinical outcomes is controversial.......Hepatitis C is a major cause of liver-related morbidity and mortality. Standard therapy is ribavirin plus pegylated interferon to achieve undetectable level of virus in the blood, but the effect on clinical outcomes is controversial....

  20. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    Science.gov (United States)

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

  1. Interferons: between structure and function

    Directory of Open Access Journals (Sweden)

    Katarzyna Bandurska

    2014-05-01

    Full Text Available Interferons are a family of proteins that are released by a variety of cells in response to infections caused by viruses. Currently, we distinguish three types of interferons. They are classified based on the nucleotide sequence, interaction with specific receptors, chromosomal location, structure and physicochemical properties. The following interferons are classified as type I: α, β, ω, κ, ε, ζ, τ, δ, ν. They are recognized and bound by a receptor formed by two peptides, IFN-αR1 and IFN-αR2. Representative of type II interferons is interferon-γ. It binds to a receptor composed of chains IFNGR-1 and IFNGR-2. The recently classified type III interferons comprise IFN-λ1, IFN-λ2, and IFN-λ3. They act on receptors formed by λR1 IFN-and IL-10R2 subunits. A high level of antiviral protection is achieved by IFN-α, IFN-β and IFN-λ. Antiviral activity of interferons is based on the induction and regulation of innate and acquired immune mechanisms. By binding to transmembrane receptors, IFN interacts with target cells mainly by activating the JAK/STAT, but also other signaling pathways. This leads to induction and activation of many antiviral agents, such as protein kinase RNA-activated (PKR, ribonuclease 2-5A pathway, and Mx proteins, as well as numerous apoptotic pathways. As a result of the protective effect of interferons, the virus binding to cells and viral particles penetration into cells is stopped, and the release of the nucleocapsid from an envelope is suppressed. Disruption of transcription and translation processes of the structural proteins prevents the formation of virions or budding of viruses, and as a result degradation of the viral mRNA; the started processes inhibit the chain synthesis of viral proteins and therefore further stimulate the immune system cells.

  2. A prospective randomized study of operative treatment for noncomminuted humeral shaft fractures: conventional open plating versus minimal invasive plate osteosynthesis.

    Science.gov (United States)

    Kim, Ji Wan; Oh, Chang-Wug; Byun, Young-Soo; Kim, Jung Jae; Park, Ki Chul

    2015-04-01

    To compare the clinical and radiologic results of conventional open plating (COP) and minimally invasive plate osteosynthesis (MIPO) in the treatment of noncomminuted humeral shaft fractures. Randomized prospective study. Five level 1 trauma centers. Sixty-eight consecutive patients were randomized into 2 study groups: those treated by COP (COP group; n = 32) and those treated by MIPO (MIPO group; n = 36). Simple humeral shaft fractures (AO/OTA classification types A and B) were reduced by open reduction or closed reduction and fixed with a narrow 4.5/5.0 locking compression plate, metaphyseal locking compression plate, or proximal humeral internal locking system plate to the anterior lateral aspect of the humerus. Fracture healing time, operative time, radiation exposure time, and intraoperative nerve injury. To assess shoulder and elbow function, we used the University of California, Los Angeles (UCLA) scoring system and the Mayo elbow performance index, including the range of motion and pain. Radiographic measurements included fracture alignment, delayed union, and nonunion. Thirty-one fractures (97%) healed in the COP group within 16 weeks, whereas 36 fractures (100%) were healed in the MIPO group by 15 weeks. No significant difference was observed in the operative time or complication rates. In both groups, all fractures achieved union without malunion and with excellent functional outcomes by definition of the Mayo elbow performance index and UCLA scoring system. This study confirmed a high overall rate of union and excellent functional outcomes in both MIPO and COP groups. MIPO is equivalent to COP as a safe and effective method for simple types of humeral shaft fractures when surgery is indicated, and the surgeon is experienced in the technique. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

  3. Hypobaric Unilateral Spinal Anaesthesia versus General Anaesthesia in Elderly Patients Undergoing Hip Fracture Surgical Repair: A Prospective Randomised Open Trial.

    Science.gov (United States)

    Meuret, Pascal; Bouvet, Lionel; Villet, Benoit; Hafez, Mohamed; Allaouchiche, Bernard; Boselli, Emmanuel

    2018-04-01

    Intraoperative hypotension during hip fracture surgery is frequent in the elderly. No study has compared the haemodynamic effect of hypobaric unilateral spinal anaesthesia (HUSA) and standardised general anaesthesia (GA) in elderly patients undergoing hip fracture surgical repair. We performed a prospective, randomised open study, including 40 patients aged over 75 years, comparing the haemodynamic effects of HUSA (5 mg isobaric bupivacaine with 5 μg sufentanil and 1 mL sterile water) and GA (induction with etomidate/remifentanil and maintenance with desflurane/remifentanil). An incidence of severe hypotension, defined by a decrease in systolic blood pressure of >40% from baseline, was the primary endpoint. The incidence of severe hypotension was lower in the HUSA group compared with that in the GA group (32% vs. 71%, respectively, p=0.03). The median [IQR] ephedrine consumption was lower (p=0.001) in the HUSA group (6 mg, 0-17 mg) compared with that in the GA group (36 mg, 21-57 mg). Intraoperative muscle relaxation and patients' and surgeons' satisfaction were similar between groups. No difference was observed in 5-day complications or 30-day mortality. This study shows that HUSA provides better haemodynamic stability than GA, with lower consumption of ephedrine and similar operating conditions. This new approach of spinal anaesthesia seems to be safe and effective in elderly patients undergoing hip fracture surgery.

  4. The role of long-term doxycycline in patients of idiopathic pulmonaryfibrosis: The results of an open prospective trial

    Directory of Open Access Journals (Sweden)

    Bhattacharyya Parthasarathi

    2009-01-01

    Full Text Available Objective: To evaluate the effect of long term use of doxycycline in IPF patients. Materials and Methods: Patients of IPF, selected randomly from out patient services and diagnosed on the basis of HRCT chest, were put on doxycycline in an open prospective trial. They were followed up with monitoring of subjective well being along with measurement of pulse rate and arterial oxygen saturation at rest and after a fixed and certain exercise, forced vital capacity, six minutes walk test, St Georges Respiratory questionnaire, and serial chest X-rays. Results: Out of seven patients put on doxycycline, six of them continued the drug for a mean period of 531.43 (± 328.88 days. All the patients tolerated the drug well and had shown uniform subjective and overall objective improvement in all the parameters concerned; the change in the radiological parameter being statistically significant. Conclusion: Doxycycline merits an appropriate clinical trial in the management of idiopathic pulmonary fibrosis. This widely used and relatively safe drug can add a new dimension to the therapeutic regimen. However, further in-depth studies will be required to evaluate its role in the management of IPF.

  5. Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study

    DEFF Research Database (Denmark)

    Møller, Eigild; Pedersen, Søren Anker; Vinicoff, Pablo Gustavo

    2015-01-01

    The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean...... age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect...... in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response....

  6. A prospective, open, comparative study of 5% potassium hydroxide solution versus cryotherapy in the treatment of genital warts in men.

    Science.gov (United States)

    Camargo, Caio Lamunier de Abreu; Belda Junior, Walter; Fagundes, Luiz Jorge; Romiti, Ricardo

    2014-01-01

    Genital warts are caused by human papillomavirus infection and represent one of the most common sexually transmitted diseases. Many infections are transient but the virus may recur, persist, or become latent. To date, there is no effective antiviral treatment to eliminate HPV infection and most therapies are aimed at the destruction of visible lesions. Potassium hydroxide is a strong alkali that has been shown to be safe and effective for the treatment of genital warts and molluscum contagiosum. Cryotherapy is considered one of the most established treatments for genital warts. No comparative trials have been reported to date on the use of potassium hydroxide for genital warts. A prospective, open-label, randomized clinical trial was conducted to compare topical potassium hydroxide versus cryotherapy in the treatment of genital warts affecting immunocompetent, sexually active men. Over a period of 10 months, 48 patients were enrolled. They were randomly divided into two groups and selected on an alternative basis for either potassium hydroxide therapy or cryotherapy. While response to therapy did not differ substantially between both treatment modalities, side effects such as local pain and post-treatment hypopigmentation were considerably more prevalent in the groups treated using cryotherapy. In our study, potassium hydroxide therapy proved to be at least as effective as cryotherapy and offered the benefit of a better safety profile. Topical 5% potassium hydroxide presents an effective, safe, and low-cost treatment modality for genital warts in men and should be included in the spectrum of therapies for genital warts.

  7. Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

    Science.gov (United States)

    Rosenberg, Evan C; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel

    2017-08-01

    Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  8. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Specht, Lena; Skovgaard, Gunhild L

    2008-01-01

    causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration......PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years......]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4...

  9. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.

    Science.gov (United States)

    Bourlière, Marc; Rabiega, Pascaline; Ganne-Carrie, Nathalie; Serfaty, Lawrence; Marcellin, Patrick; Barthe, Yoann; Thabut, Dominique; Guyader, Dominique; Hezode, Christophe; Picon, Magali; Causse, Xavier; Leroy, Vincent; Bronowicki, Jean Pierre; Carrieri, Patrizia; Riachi, Ghassan; Rosa, Isabelle; Attali, Pierre; Molina, Jean Michel; Bacq, Yannick; Tran, Albert; Grangé, Jean Didier; Zoulim, Fabien; Fontaine, Hélène; Alric, Laurent; Bertucci, Inga; Bouvier-Alias, Magali; Carrat, Fabrice

    2017-03-01

    Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (sida et les hépatites virales (France Recherche Nord&sud Sida-vih Hepatites). Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study).

    Science.gov (United States)

    Starling, Amaal J; Tepper, Stewart J; Marmura, Michael J; Shamim, Ejaz A; Robbins, Matthew S; Hindiyeh, Nada; Charles, Andrew C; Goadsby, Peter J; Lipton, Richard B; Silberstein, Stephen D; Gelfand, Amy A; Chiacchierini, Richard P; Dodick, David W

    2018-05-01

    Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a -2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (-0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of -2

  11. A prospective comparison of patient body image after robotic thyroidectomy and conventional open thyroidectomy in patients with papillary thyroid carcinoma.

    Science.gov (United States)

    Lee, Sohee; Kim, Ha Yan; Lee, Cho Rok; Park, Seulkee; Son, Haiyoung; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

    2014-07-01

    Body image is associated with self-esteem and identity and has a close relationship with quality of life (QoL). We compared the impact of surgical scars on the patient's perception of body image between conventional open thyroidectomy (OT) and robotic thyroidectomy (RT) in female papillary thyroid carcinoma patients. From October 2009 to December 2010, we enrolled prospectively 116 papillary thyroid carcinoma patients who underwent total thyroidectomy at the Yonsei University Health System (Seoul, Korea). Of these 116 patients, 56 had OT and 60 RT. Their scars were assessed using the Vancouver Scar Scale (VSS), and psychometric properties were evaluated using the Body Image Scale (BIS) questionnaire postoperatively. Both groups were compared using cross-sectional and time-series methods. Mean age was significantly younger in the RT group. Regarding scar quality, the OT group showed superiority in scar pigmentation and the total VSS score during the early postoperative period, but the VSS score improved over time and was similar between both groups at 9 months. The RT group had better scores regarding most of the BIS items, a trend that remained relatively constant over time. In patients with noticeable scars (VSS ≥ 2) at 9 months, the RT group had better BIS scores regarding almost all items, including "self-conscious," "physical attractiveness," "feeling of less feminine," "sexual attractiveness," "dissatisfaction with body, scar and appearance when dressed," and "avoidance of people due to appearance." RT provides a better self-body image and improves QoL compared with conventional OT by avoiding a noticeable cervical scar. Copyright © 2014 Mosby, Inc. All rights reserved.

  12. Effect of thread embedding acupuncture for facial wrinkles and laxity: a single-arm, prospective, open-label study

    Directory of Open Access Journals (Sweden)

    Younghee Yun

    2017-12-01

    Full Text Available Background: There is a growing trend for patients to seek the least invasive treatments with less risk of complications and downtime for facial rejuvenation. Thread embedding acupuncture has become popular as a minimally invasive treatment. However, there is little clinical evidence in the literature regarding its effects. Methods: This single-arm, prospective, open-label study recruited participants who were women aged 40–59 years, with Glogau photoaging scale III–IV. Fourteen participants received thread embedding acupuncture one time and were measured before and after 1 week from the procedure. The primary outcome was a jowl to subnasale vertical distance. The secondary outcomes were facial wrinkle distances, global esthetic improvement scale, Alexiades–Armenakas laxity scale, and patient-oriented self-assessment scale. Results: Fourteen participants underwent thread embedding acupuncture alone, and 12 participants revisited for follow-up outcome measures. For the primary outcome measure, both jowls were elevated in vertical height by 1.87 mm (left and 1.43 mm (right. Distances of both melolabial and nasolabial folds showed significant improvement. In the Alexiades–Armenakas laxity scale, each evaluator evaluated for four and nine participants by 0.5 grades improved. In the global aesthetic improvement scale, improvement was graded as 1 and 2 in nine and five cases, respectively. The most common adverse events were mild bruising, swelling, and pain. However, adverse events occurred, although mostly minor and of short duration. Conclusion: In this study, thread embedding acupuncture showed clinical potential for facial wrinkles and laxity. However, further large-scale trials with a controlled design and objective measurements are needed. Keywords: polydioxanone, rejuvenation, rhytidoplasty, skin aging, thread embedding acupuncture

  13. A prospective, open, comparative study of 5% potassium hydroxide solution versus cryotherapy in the treatment of genital warts in men*

    Science.gov (United States)

    Camargo, Caio Lamunier de Abreu; Belda, Walter; Fagundes, Luiz Jorge; Romiti, Ricardo

    2014-01-01

    BACKGROUND Genital warts are caused by human papillomavirus infection and represent one of the most common sexually transmitted diseases. Many infections are transient but the virus may recur, persist, or become latent. To date, there is no effective antiviral treatment to eliminate HPV infection and most therapies are aimed at the destruction of visible lesions. Potassium hydroxide is a strong alkali that has been shown to be safe and effective for the treatment of genital warts and molluscum contagiosum. Cryotherapy is considered one of the most established treatments for genital warts. No comparative trials have been reported to date on the use of potassium hydroxide for genital warts. OBJECTIVE A prospective, open-label, randomized clinical trial was conducted to compare topical potassium hydroxide versus cryotherapy in the treatment of genital warts affecting immunocompetent, sexually active men. METHODS Over a period of 10 months, 48 patients were enrolled. They were randomly divided into two groups and selected on an alternative basis for either potassium hydroxide therapy or cryotherapy. While response to therapy did not differ substantially between both treatment modalities, side effects such as local pain and post-treatment hypopigmentation were considerably more prevalent in the groups treated using cryotherapy. RESULT In our study, potassium hydroxide therapy proved to be at least as effective as cryotherapy and offered the benefit of a better safety profile. CONCLUSION Topical 5% potassium hydroxide presents an effective, safe, and low-cost treatment modality for genital warts in men and should be included in the spectrum of therapies for genital warts. PMID:24770498

  14. Men's sexual response to female partner's intranasal oxytocin administration for hypoactive sexual desire disorder: an open prospective cohort study.

    Science.gov (United States)

    Muin, Dana A; Sheikh Rezaei, Safoura; Tremmel-Scheinost, Max; Salama, Mohamed; Luger, Anton; Wolzt, Michael; Husslein, Peter W; Bayerle-Eder, Michaela

    2017-03-01

    To study sexual function, quality of life, and depression in men, whose female partners are undergoing double-blind placebo-controlled randomized treatment for hypoactive sexual desire disorder (HSDD). Open prospective cohort study of 22 weeks. Academic medical center. Male partners of 30 premenopausal and postmenopausal women with HSDD. Baseline, 3-month, and 5-month assessment (for 8 weeks each) of male response to female partner's use of oxytocin nasal spray (32 IE) and placebo within 50 minutes before sexual intercourse. Primary outcome parameters were Sexual Life Quality Questionnaire-Male, Sexual Activity Record, Partner Performance Questionnaire, and Hamilton Depression Scale. Male Sexual Life Quality questionnaire improved significantly from -7.4 ± 9.9 at baseline to 8.2 ± 12 with female partners' treatment with oxytocin nasal spray and to 10.8 ± 13.8 with placebo. Frequency of intercourse improved slightly but not significantly from 6.3 ± 3.9 at baseline to 7.3 ± 4 with female oxytocin therapy, but not with placebo. Male desire and arousal remained stable throughout the study period. Evaluation of female partners' performance by men improved significantly from 8.9 ± 2.8 at baseline to 10.6 ± 2.2 with oxytocin and to 11.2 ± 2.6 with placebo. Female treatment with either oxytocin or placebo for HSDD significantly improves male sexual quality of life and evaluation of female partner's sexual performance with no difference between oxytocin and placebo on any outcome parameters. A nonsignificant improvement was seen in the frequency of intercourse, male arousal, desire, satisfaction, and Hamilton depression scale. NCT02229721. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. High-dose nifuratel for simple and mixed aerobic vaginitis: A single-center prospective open-label cohort study.

    Science.gov (United States)

    Liang, Qian; Li, Nan; Song, Shurong; Zhang, Aihua; Li, Ni; Duan, Ying

    2016-10-01

    The efficacy and safety of two nifuratel dosages for the treatment of aerobic vaginitis (AV) were compared. This was a prospective open-label cohort study of patients diagnosed and treated at the Tianjin Third Central Hospital between January 2012 and December 2013. The co-presence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or/and trichomonal vaginitis (TV; mixed AV) was determined. Patients were randomized to nifuratel-500 (500 mg nifuratel, intravaginal, 10 days) or nifuratel-250 (250 mg nifuratel, intravaginal, 10 days), and followed-up for three to seven days after treatment completion. Primary and secondary outcomes were recovery rate and adverse events, respectively. The study included 142 patients with AV. Age was not significantly different between the groups (n = 71 each), and disease distribution was identical: 29 (40.85%) simple AV and 42 (59.15%) mixed AV (AV + BV, 42.86 %; AV + VVC, 30.95%; AV + TV, 26.19%). In patients with simple AV, the recovery rate did not differ significantly between the nifuratel-500 (26/29, 89.66%) and nifuratel-250 (22/29, 75.86%) groups. In patients with mixed AV, recovery rates were significantly higher in the nifuratel-500 than in the nifuratel-250 group (AV + BV, 88.89% vs 50.00 %; AV + VVC, 76.92 % vs 30.77 %; AV + TV, 90.91 % vs 36.36%; all P < 0.05). Only one patient (nifuratel-500) reported an adverse event (mild anaphylactic reaction). Nifuratel 500 mg showed good clinical efficacy for the treatment of AV, particularly mixed AV, and is superior to the 250 mg dosage in the treatment of mixed AV. © 2016 Japan Society of Obstetrics and Gynecology.

  16. Prospective, unmasked evaluation of the iStent® inject system for open-angle glaucoma: synergy trial.

    Science.gov (United States)

    Voskanyan, Lilit; García-Feijoó, Julián; Belda, Jose I; Fea, Antonio; Jünemann, Anselm; Baudouin, Christophe

    2014-02-01

    Micro-invasive glaucoma surgical implantation of trabecular micro-bypass stents, previously shown to be safe and effective for open-angle glaucoma (OAG) subjects during cataract surgery, was considered for evaluation as a sole procedure. The aim of this study was to evaluate the safety and intraocular pressure (IOP)-lowering efficacy after ab interno implantation of two Glaukos Trabecular Micro-Bypass iStent inject second generation devices in subjects with OAG. This study was performed at sites in France, Germany, Italy, Republic of Armenia, and Spain. In this pan-European, multi-center prospective, post-market, unmasked study, 99 patients with OAG on at least two topical ocular hypotensive medications who required additional IOP lowering to control glaucoma disease underwent implantation of two GTS400 stents in a stand-alone procedure. Patients were qualified if they presented with preoperative mean IOP between 22 and 38 mmHg after medication washout. Postoperatively, subjects were assessed at Day 1, Months 1, 3, 6, 7, 9, and 12. IOP, medication use and safety were assessed at each visit. Sixty-six percent of subjects achieved IOP ≤18 mmHg at 12 months without medication, and 81% of subjects achieved Month 12 IOP ≤ 18 mmHg with either a single medication or no medication. Mean baseline washout IOP values decreased by 10.2 mmHg or 39.7% from 26.3 (SD 3.5) mmHg to 15.7 (SD 3.7) mmHg at Month 12. Mean IOP at 12 months was 14.7 (SD 3.1) mmHg in subjects not using ocular hypotensive medications. Reduction from preoperative medication burden was achieved in 86.9% of patients, including 15.2% with reduction of one medication and 71.7% with reduction of two or more medications. Postoperative complications occurred at a low rate and resolved without persistent effects. In this series, implantation of two trabecular micro-bypass second generation stents in subjects with OAG resulted in IOP and medication reduction and favorable safety outcomes.

  17. THE RATIONALE FOR ALPHA-INTERFERON IMMUNOTHERAPY IN INFANTS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS AND ACUTE INVASIVE INTESTINAL INFECTION

    Directory of Open Access Journals (Sweden)

    E. R. Meskina

    2015-01-01

    Full Text Available Background: Acute intestinal  infections  in children are a considerable  medical and social problem  worldwide. Immune therapy  could  help  to reduce the frequency of post-infectious functional intestinal dysfunction  in patients  with comorbidities. Aim: To evaluate  the  efficacy of human  recombinant interferon  alpha-2b, administered at acute  phase  of an acute  invasive intestinal  infection to infants in the first months  of age, suffering from functional  bowel  disorders. Materials and methods: This  was  an  open-label,  randomized (envelope method, prospective  study in two parallel groups. The study included  59 infants of the  first months  of life, who were breastfed, had a history of intestinal  dysfunction  and were hospitalized  to  an  infectious  department. We studied  efficacy of recombinant interferon  alpha-2b administered in rectal suppositories  at a dose  of   chromatography with measurement of short-chain fatty acids. Results: Standard treatment was ineffective in 63.3% (95% CI 43.9–80.0% of patients. Administration   of  interferon   alpha-2b   reduced the rate of treatment failure by day 14 to 32% (95% CI 9–56% and  the  risk of persistent  diarrhea  for more than  one month  to 29% (95% CI 5–53%. In those patients  who were administered interferon, inflammation at days 25 to 55 was less severe and the levels of i-forms of short-chain fatty acids were lower. Conclusion: Immunotherapy with recombinant interferon alpha-2b seems to be a promising way to improve  combination treatment of acute invasive intestinal infections in infants with a history of intestinal dysfunction, as it reduces the risk of post-infectious intestinal disorders.

  18. Laparoscopic Complete Mesocolic Excision versus Open Complete Mesocolic Excision for Transverse Colon Cancer: Long-Term Survival Results of a Prospective Single Centre Non-Randomized Study.

    Science.gov (United States)

    Storli, Kristian Eeg; Eide, Geir Egil

    2016-01-01

    Laparoscopic complete mesocolic excision (CME) used in the treatment of transverse colon cancer has been questioned on the basis of the technical challenges. The aim of this study was to evaluate the medium- and long-term clinical and survival outcomes after laparoscopic and open CME for transverse colon cancer and to compare the 2 approaches. This study was a retrospective non-randomized study of patients with prospectively registered data on open and laparoscopic CME for transverse colon cancer tumour-node-metastasis stages I-III operated on between 2007 and 2014. This was a single-centre study in a community teaching hospital. A total of 56 patients with transverse colon cancer were included, excluding those with tumours in the colonic flexures. The outcome aims were 4-year time to recurrence (TTR) and cancer-specific survival (CSS). Morbidity was also measured. The 4-year TTR was 93.9% in the laparoscopic group and 91.3% in the open group (p = 0.71). The 4-year CSS was 97.0% in the laparoscopic group and 91.3% in the open group (p = 0.42). This was a prospective single-institution study with a small sample size. Results of the study suggest that the laparoscopic CME approach might be the preferred approach for transverse colon cancer, especially regarding its benefits in terms of short-term morbidity, length of stay and oncological outcome. © 2016 S. Karger AG, Basel.

  19. No Love Lost Between Viruses and Interferons.

    Science.gov (United States)

    Fensterl, Volker; Chattopadhyay, Saurabh; Sen, Ganes C

    2015-11-01

    The interferon system protects mammals against virus infections. There are several types of interferons, which are characterized by their ability to inhibit virus replication and resultant pathogenesis by triggering both innate and cell-mediated immune responses. Virus infection is sensed by a variety of cellular pattern-recognition receptors and triggers the synthesis of interferons, which are secreted by the infected cells. In uninfected cells, cell surface receptors recognize the secreted interferons and activate intracellular signaling pathways that induce the expression of interferon-stimulated genes; the proteins encoded by these genes inhibit different stages of virus replication. To avoid extinction, almost all viruses have evolved mechanisms to defend themselves against the interferon system. Consequently, a dynamic equilibrium of survival is established between the virus and its host, an equilibrium that can be shifted to the host's favor by the use of exogenous interferon as a therapeutic antiviral agent.

  20. Prediction of response to interferon therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Søndergaard, Helle Bach; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5...... genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β. METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed...... prospectively after the initiation of their first treatment with IFN-β. RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk...

  1. An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands.

    Science.gov (United States)

    van Gorkom, T; Sankatsing, S U C; Voet, W; Ismail, D M; Muilwijk, R H; Salomons, M; Vlaminckx, B J M; Bossink, A W J; Notermans, D W; Bouwman, J J M; Kremer, K; Thijsen, S F T

    2018-04-01

    Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using Borrelia burgdorferi strain B31 and various recombinant antigens, and subsequently, the number of Borrelia -specific interferon gamma (IFN-γ)-secreting T cells was measured. We included 33 active and 37 treated Lyme neuroborreliosis patients, 28 healthy individuals treated for an early manifestation of LB in the past, and 145 untreated healthy individuals. The median numbers of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs did not differ between active Lyme neuroborreliosis patients (6.0; interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9) ( P = 1.000); however, the median number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs among untreated healthy individuals was lower (2.0; IQR, 0.5 to 3.9) ( P ≤ 0.016). We conclude that the Borrelia ELISpot assay, measuring the number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs, correlates with exposure to the Borrelia bacterium but cannot be used for the diagnosis of active Lyme neuroborreliosis. Copyright © 2018 van Gorkom et al.

  2. A Prospective Open-label Pilot Study of Fluvastatin on Pro-inflammatory and Pro-thrombotic Biomarkers in Antiphospholipid Antibody Positive Patients

    Science.gov (United States)

    Erkan, Doruk; Willis, Rohan; Murthy, Vijaya L.; Basra, Gurjot; Vega, JoAnn; Ruiz Limón, Patricia; Carrera, Ana Laura; Papalardo, Elizabeth; Martínez-Martínez, Laura Aline; González, Emilio B.; Pierangeli, Silvia S.

    2014-01-01

    Objective: To determine if pro-inflammatory and pro-thrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: a) Primary Antiphospholipid Syndrome (PAPS); b) Systemic Lupus Erythematosus (SLE) with APS (SLE/APS); c) Persistent aPL positivity without SLE or APS (Primary aPL); and d) Persistent aPL positivity with SLE but no APS (SLE/aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for three months. At three months, patients stopped the study medication and they were followed for another three months. Blood samples for 12 pro-inflammatory and pro-thrombotic biomarkers were collected monthly for six months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin [IL]-6, IL1β, vascular endothelial growth factor [VEGF], tumor necrosis factor [TNF]-□α, interferon [IFN]-α, inducible protein-10 [IP10], soluble CD40 ligand [sCD40L], soluble tissue factor [sTF], and intracellular cellular adhesion molecule [ICAM]-1) were significantly elevated. Twenty-four patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L, and sTF). Conclusion: Our prospective mechanistic study demonstrates that pro-inflammatory and pro-thrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients. PMID:23933625

  3. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy.

    Science.gov (United States)

    Poynard, Thierry; Colombo, Massimo; Bruix, Jordi; Schiff, Eugene; Terg, Ruben; Flamm, Steven; Moreno-Otero, Ricardo; Carrilho, Flair; Schmidt, Warren; Berg, Thomas; McGarrity, Thomas; Heathcote, E Jenny; Gonçales, Fernando; Diago, Moises; Craxi, Antonio; Silva, Marcelo; Bedossa, Pierre; Mukhopadhyay, Pabak; Griffel, Louis; Burroughs, Margaret; Brass, Clifford; Albrecht, Janice

    2009-05-01

    Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy. This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 microg/kg/wk) plus weight-based ribavirin (800-1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator's request. Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P 600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups. Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.

  4. A prospective 3-year follow-up trial of implantation of two trabecular microbypass stents in open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Donnenfeld ED

    2015-11-01

    Full Text Available Eric D Donnenfeld,1 Kerry D Solomon,2 Lilit Voskanyan,3 David F Chang,4 Thomas W Samuelson,5 Iqbal Ike K Ahmed,6 L Jay Katz7 1Ophthalmic Consultants of Long Island, Rockville Centre, NY, 2Carolina Eyecare Physicians, Mt Pleasant, SC, USA; 3S.V. Malayan Ophthalmology Centre, Yerevan, Armenia; 4Altos Eye Physicians, Los Altos, CA, 5Minnesota Eye Consultants, Minneapolis, MN, USA; 6University of Toronto, Toronto, ON, Canada; 7Wills Eye Hospital, Jefferson Medical College, Philadelphia, PA, USA Purpose: To evaluate 3-year safety and intraocular pressure (IOP following two trabecular microbypass stents in phakic and pseudophakic subjects with open-angle glaucoma (OAG not controlled on preoperative medication. Patients and methods: In this prospective pilot study, phakic or pseudophakic subjects with OAG and IOP between 18 mmHg and 30 mmHg on one preoperative topical ocular hypotensive medication underwent medication washout. Thirty-nine qualified subjects with preoperative unmedicated IOP ≥22 mmHg and ≤38 mmHg received two stents. Postoperative examinations were scheduled at Day 1, Week 1, Months 1, 3, 6, and 12, and semiannually through Month 60. Ocular hypotensive medication was considered if postoperative IOP exceeded 21 mmHg. IOP, medication use, and safety were assessed at each visit. Subject follow-up through Month 36 was completed. Results: Thirty-six eyes (92.3%; 95% confidence interval [CI] 79.1%, 98.4% achieved the primary efficacy end point of Month 12 reduction in IOP ≥20% from baseline (unmedicated IOP without ocular hypotensive medication. Four subjects required medication during the Month 36 follow-up period. Mean IOP at 36 months for subjects not taking medication was 15.2 mmHg. At 36 months, subjects sustained mean IOP decrease of 9.1±2.7 mmHg (95% CI 8.0 mmHg, 10.14 mmHg, or 37% IOP reduction, from unmedicated baseline IOP. Compared to preoperative medicated IOP, subjects had mean reduction at Month 36 of 5.5±2

  5. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.

    Science.gov (United States)

    Bolaman, Zahit; Kadikoylu, Gurhan; Yukselen, Vahit; Yavasoglu, Irfan; Barutca, Sabri; Senturk, Taskin

    2003-12-01

    Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p

  6. Interferon Treatment of Multiple Sclerosis

    OpenAIRE

    Alajbegovic, Azra; Deljo, Dervis; Alajbegovic, Salem; Djelilovic-Vranic, Jasminka; Todorovic, Ljubica; Tiric-Campara, Merita

    2012-01-01

    Introduction: In the treatment of Multiple Sclerosis (MS) differ: treatment of relapse, treatment slow the progression of the disease (immunomodulators and immunosuppression), and symptomatic treatment. The aim: The aim of this study is to analyze the application of interferon therapy in the treatment of MS-E: Process the disease, patients with multiple sclerosis who have passed the commission for multiple sclerosis at the Neurology Clinic of Clinical Center of Sarajevo University as a refere...

  7. The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial.

    LENUS (Irish Health Repository)

    Neary, Peter M

    2012-01-01

    Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours.

  8. Open versus closed lateral internal anal sphincterotomy in the management of chronic anal fissures: A prospective randomized study

    Directory of Open Access Journals (Sweden)

    Vivek Gupta

    2014-10-01

    Conclusion: Closed lateral internal sphincterotomy is the treatment of choice for chronic fissures as it is effective, safe, less expensive, and associated with a lower rate of complications than the open sphincterotomy technique.

  9. Type 1 Diabetes and Interferon Therapy

    OpenAIRE

    Nakamura, Kan; Kawasaki, Eiji; Imagawa, Akihisa; Awata, Takuya; Ikegami, Hiroshi; Uchigata, Yasuko; Kobayashi, Tetsuro; Shimada, Akira; Nakanishi, Koji; Makino, Hideichi; Maruyama, Taro; Hanafusa, Toshiaki

    2011-01-01

    OBJECTIVE Interferon therapy can trigger induction of several autoimmune diseases, including type 1 diabetes. To assess the clinical, immunologic, and genetic characteristics of type 1 diabetes induced by interferon therapy, we conducted a nationwide cross-sectional survey. RESEARCH DESIGN AND METHODS Clinical characteristics, anti-islet autoantibodies, and HLA-DR typing were examined in 91 patients for whom type 1 diabetes developed during or shortly after interferon therapy. RESULTS Median ...

  10. DMPD: Type I interferon [corrected] gene induction by the interferon regulatory factorfamily of transcription factors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16979567 Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...ng) (.svg) (.html) (.csml) Show Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...orrected] gene induction by the interferon regulatory factorfamily of transcription factors. Authors Honda K

  11. Interferon in chronic myeloid leukaemia: past and future.

    Science.gov (United States)

    Guilhot, François; Roy, Lydia; Saulnier, Pierre-Jean; Guilhot, Joëlle

    2009-09-01

    Imatinib has revolutionized the therapy of chronic myeloid leukaemia. However the complete eradication of leukaemic stem cells is still a matter of discussion. Interferon (IFN) has been used in the past with success. However the proportion of patients who achieved sustained complete cytogenetic response was small. Recently, in addition to its direct antineoplastic effect and immunomodulatory activity, IFN has been shown to stimulate the quiescent leukaemic stem cells. Thus there is now a rational for combining Imatinib and IFN. Large prospective phase III trials are in good progress to demonstrate in humans the usefullness of a combination therapy using Imatinib and IFN.

  12. The Effect of Medicinal Cannabis on Pain and Quality-of-Life Outcomes in Chronic Pain: A Prospective Open-label Study.

    Science.gov (United States)

    Haroutounian, Simon; Ratz, Yael; Ginosar, Yehuda; Furmanov, Karina; Saifi, Fayez; Meidan, Ronit; Davidson, Elyad

    2016-12-01

    The objective of this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain. The primary outcome was the change in the pain symptom score on the S-TOPS (Treatment Outcomes in Pain Survey-Short Form) questionnaire at the 6-month follow-up in an intent-to-treat population. Secondary outcomes included the change in S-TOPS physical, social, and emotional disability scales, the pain severity, and pain interference on the Brief Pain Inventory, sleep problems, and the change in opioid consumption. A total of 274 participants were approved for treatment; complete baseline data were available for 206 (intent-to-treat), and complete follow-up data for 176 participants. At follow-up, the pain symptom score improved from median 83.3 (95% confidence interval [CI], 79.2-87.5) to 75.0 (95% CI, 70.8-79.2) (Pmedicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. Results suggest long-term benefit of cannabis treatment in this group of patients, but the study's noncontrolled nature should be considered when extrapolating the results.

  13. Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

    Science.gov (United States)

    Sugimoto, Shinya; Naganuma, Makoto; Kiyohara, Hiroki; Arai, Mari; Ono, Keiko; Mori, Kiyoto; Saigusa, Keiichiro; Nanki, Kosaku; Takeshita, Kozue; Takeshita, Tatsuya; Mutaguchi, Makoto; Mizuno, Shinta; Bessho, Rieko; Nakazato, Yoshihiro; Hisamatsu, Tadakazu; Inoue, Nagamu; Ogata, Haruhiko; Iwao, Yasushi; Kanai, Takanori

    2016-01-01

    Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted. © 2016 S. Karger AG, Basel.

  14. Maximum mouth opening and trismus in 143 patients treated for oral cancer: a 1-year prospective study.

    Science.gov (United States)

    Wetzels, Jan-Willem G H; Merkx, Matthias A W; de Haan, Anton F J; Koole, Ron; Speksnijder, Caroline M

    2014-12-01

    Patients with oral cancer can develop restricted mouth opening (trismus) because of the oncologic treatment. Maximum mouth opening (MMO) was measured in 143 patients shortly before treatment and 0, 6, and 12 months posttreatment, and the results were analyzed using a linear mixed-effects model. In every patient, MMO decreased after treatment. The patients who underwent surgery, recovered partially by 6 and 12 months after treatment, whereas the patients who received both surgery and radiotherapy or primary radiotherapy did not recover. Tumor location, tumor size, and alcohol consumption had independent effects on MMO. Having trismus (MMO oral cancer treatment. © 2014 Wiley Periodicals, Inc.

  15. A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study

    Directory of Open Access Journals (Sweden)

    van Duivendijk Peter

    2010-06-01

    Full Text Available Abstract Background The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing? Method/design The Tapas-study is a three-arm multicenter prospective cohort study. All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1. Open surgery with ERAS recovery (cohort 2 and laparoscopic surgery with ERAS recovery (cohort 3 are the alternative exposures. Three separate time periods are used in order to prevent attrition bias. Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation and the indirect non medical costs (friction method. Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life. Based on an estimated difference in direct medical costs (highest cost factor of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05, a group size of 3×40 = 120 patients is calculated. Discussion The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals. Trial registration ISRCTN44649165.

  16. A prospective randomized trial of open surgery versus endourological stone removal in patients of staghorn stones with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Anant Kumar

    2001-01-01

    Conclusion: In view of the better clearance rate and lesser cost of treatment, open surgery still has a place in the management of staghorn stones with chronic renal failure even in a tertiary urological center. However postoperative pain and a larger scar cannot be ignored.

  17. Unexpected difficulties in randomizing patients in a surgical trial: A prospective study comparing extracorporeal shock wave lithotripsy with open cholecystectomy

    NARCIS (Netherlands)

    P.W. Plaisier; M.Y. Berger (Marjolein); R.L. van der Hul (René); H.G. Nijs (Huub); R. den Toom (Rene); O.T. Terpstra (Onno); H.A. Bruining (Hajo); S.M. Strasberg (S.)

    1994-01-01

    textabstractShortly after extracorporeal shock wave lithotripsy (ESWL) was introduced as a promising new treatment modality for gallstone disease, a randomized controlled study was performed to assess the cost-effectiveness of ESWL compared to open cholecystectomy, the gold standard. During the

  18. Independent predictors of enteric fistula and abdominal sepsis after damage control laparotomy: results from the prospective AAST Open Abdomen registry.

    Science.gov (United States)

    Bradley, Matthew J; Dubose, Joseph J; Scalea, Thomas M; Holcomb, John B; Shrestha, Binod; Okoye, Obi; Inaba, Kenji; Bee, Tiffany K; Fabian, Timothy C; Whelan, James F; Ivatury, Rao R

    2013-10-01

    Enterocutaneous fistula (ECF), enteroatmospheric fistula (EAF), and intra-abdominal sepsis/abscess (IAS) are major challenges for surgeons caring for patients undergoing damage control laparotomy after trauma. To determine independent predictors of ECF, EAF, or IAS in patients undergoing damage control laparotomy after trauma, using the AAST Open Abdomen Registry. The AAST Open Abdomen registry of patients with an open abdomen following damage control laparotomy was used to identify patients who developed ECF, EAF, or IAS and to compare these patients with those without these complications. Univariate analyses were performed to compare these groups of patients. Variables from univariate analyses differing at P IAS. Fourteen level I trauma centers. A total of 517 patients with an open abdomen following damage control laparotomy. Complication of ECF, EAF, or IAS. More patients in the ECF/EAF/IAS group than in the group without these complications underwent bowel resection (63 of 111 patients [57%] vs 133 of 406 patients [33%]; P 48 hours after surgery, the ECF/EAF/IAS group received more colloids (P IAS group underwent almost twice as many abdominal reexplorations as did the group without these complications (mean [SD] number, 4.1 [4.1] vs 2.2 [3.4]; P IAS were a large bowel resection (adjusted odds ratio [AOR], 3.56 [95% CI, 1.88-6.76]; P 48 hours of between 5 and 10 L (AOR, 2.11 [95% CI, 1.15-3.88]; P = .02) or more than 10 L (AOR, 1.93 [95% CI, 1.04-3.57]; P = .04), and an increasing number of reexplorations (AOR, 1.14 [95% CI, 1.06-1.21]; P IAS in patients with an open abdomen after damage control laparotomy.

  19. Does osteoporosis increase complication risk in surgical fracture treatment? A protocol combining new endpoints for two prospective multicentre open cohort studies

    Directory of Open Access Journals (Sweden)

    Marent Marta

    2010-11-01

    Full Text Available Abstract Background With an ever-increasing elderly population, orthopaedic surgeons are faced with treating a high number of fragility fractures. Biomechanical tests have demonstrated the potential role of osteoporosis in the increased risk of fracture fixation complications, yet this has not been sufficiently proven in clinical practice. Based on this knowledge, two clinical studies were designed to investigate the influence of local bone quality on the occurrence of complications in elderly patients with distal radius and proximal humerus fractures treated by open reduction and internal fixation. Methods/Design The studies were planned using a prospective multicentre open cohort design and included patients between 50 and 90 years of age. Distal radius and proximal humerus fractures were treated with locking compression 2.4 mm and proximal humerus internal locking plates, respectively. Follow-up examinations were planned for 6 weeks, 3 and 12 months as well as a telephone interview at 6 months. The primary outcome focuses on the occurrence of at least one local bone quality related complication. Local bone quality is determined by measuring bone mineral density and bone mineral content at the contralateral radius. Primary complications are categorised according to predefined factors directly related to the bone/fracture or the implant/surgical technique. Secondary outcomes include the documentation of soft tissue/wound or general/systemic complications, clinical assessment of range of motion, and patient-rated evaluations of upper limb function and quality of life using both objective and subjective measures. Discussion The prospective multicentre open cohort studies will determine the value of local bone quality as measured by bone mineral density and content, and compare the quality of local bone of patients who experience a complication (cases following surgery with that of patients who do not (controls. These measurements are novel and

  20. Interferon-α treatment in systemic mastocytosis

    DEFF Research Database (Denmark)

    Bjerrum, Ole Weis

    2011-01-01

    classification need treatment. This review on interferon treatment in systemic mastocytosis documents an effect of this biological agent in some patients with mastocytosis. However, the place of interferon-a, as mono- or combination therapy, in the treatment algorithm may only be definitely established...

  1. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial.

    Science.gov (United States)

    Bazinet, Michel; Pântea, Victor; Cebotarescu, Valentin; Cojuhari, Lilia; Jimbei, Pavlina; Albrecht, Jeffrey; Schmid, Peter; Le Gal, Frédéric; Gordien, Emmanuel; Krawczyk, Adalbert; Mijočević, Hrvoje; Karimzadeh, Hadi; Roggendorf, Michael; Vaillant, Andrew

    2017-12-01

    REP 2139 clears circulating hepatitis B virus (HBV) surface antigen (HBsAg), enhancing the restoration of functional control of HBV infection by immunotherapy. We assessed the safety and efficacy of REP 2139 and pegylated interferon alfa-2a in patients with chronic HBV and hepatitis D virus (HDV) co-infection. In this open-label, non-randomised, phase 2 trial, patients aged 18-55 years, who were treatment naive, hepatitis B e antigen [HBeAg] negative, anti-hepatitis D antigen [HDAg] positive, and HDV RNA positive, with serum HBsAg concentrations of more than 1000 IU/mL, and a history of HDV infection for 6 months or more before treatment, were recruited at Toma Ciorbă Hospital of Infectious Diseases in Chișinău, Moldova. Patients were excluded if they had HDV superinfection, liver infections other than HBV and HDV, or liver cirrhosis. Patients received 500 mg intravenous REP 2139 once per week for 15 weeks, followed by combined therapy with 250 mg intravenous REP 2139 and 180 μg subcutaneous pegylated interferon alfa-2a once per week for 15 weeks, then monotherapy with 180 μg pegylated interferon alfa-2a once per week for 33 weeks. The primary endpoints assessed at the end of treatment were the safety and tolerability of the treatment regimen, analysed in the intention-to-treat population. Secondary outcomes included the proportion of patients with serum HBsAg less than 50 IU/mL, the proportion of patients with suppressed HBV DNA, and the proportion of patients who maintained these responses through follow-up. The REP 301 trial is registered with ClinicalTrials.gov, number NCT02233075. We also did an additional follow-up at 1 year after the end of treatment, as an interim analysis of the REP 301-LTF trial (planned duration 3 years), registered with ClinicalTrials.gov, number NCT02876419, which is ongoing but not recruiting patients. Between Sept 8, 2014, and Jan 27, 2015, we enrolled 12 patients into the REP 301 study. All 12 patients experienced at least one

  2. Interferon-γ Inhibits Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Bethany A Rhein

    Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  3. Interferon-γ Inhibits Ebola Virus Infection.

    Science.gov (United States)

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  4. Studies on Brucella interferon: Chromatographic behaviour and purification

    International Nuclear Information System (INIS)

    Bousquet-Ucla, C.; Wietzerbin, J.; Falcoff, E.

    1980-01-01

    Interferon was induced by infecting mice with Brucella suis. Serum containing interferon activity was analyzed by chromatography on Concanavalin A-Sepharose and Phenyl-Sepharose CL-4B columns. Antiviral activity was completely retained by the lectin column indicating that all the interferon molecules are glycosylated. The chromatographic behaviour of Brucella interferon on Phenyl-Sepharose CL-4B show that, like other interferons, Brucella interferon displays hydrophobic properties. However, the hydrophobicity of the interferon molecule was masked in the crude preparation and was only detectable when purified Brucella interferon was used for chromatography. The antigenic properties of Brucella interferon provided the means for developing an affinity chromatographic method resulting in about 60.000 fold purification. As in the case of viral interferon, treatment of L cells with Brucella interferon induced specific enhanced in vitro phosphorylation of a 67.000 molecular weight protein after incubation of cell extracts with doublestranded RNA and [γ- 32 p]ATP. (auth.)

  5. Laparoscopic versus open liver segmentectomy: prospective, case-matched, intention-to-treat analysis of clinical outcomes and cost effectiveness.

    Science.gov (United States)

    Polignano, Francesco M; Quyn, Aaron J; de Figueiredo, Rodrigo S M; Henderson, Nikola A; Kulli, Christoph; Tait, Iain S

    2008-12-01

    Reduction in hospital stay, blood loss, postoperative pain and complications are common findings after laparoscopic liver resection, suggesting that the laparoscopic approach may be a suitable alternative to open surgery. Some concerns have been raised regarding cost effectiveness of this procedure and potential implications of its large-scale application. Our aim has been to determine cost effectiveness of laparoscopic liver surgery by a case-matched, case-control, intention-to-treat analysis of its costs and short-term clinical outcomes compared with open surgery. Laparoscopic liver segmentectomies and bisegmentectomies performed at Ninewells Hospital and Medical School between 2005 and 2007 were considered. Resections involving more than two Couinaud segments, or involving any synchronous procedure, were excluded. An operation-magnitude-matched control group was identified amongst open liver resections performed between 2004 and 2007. Hospital costs were obtained from the Scottish Health Service Costs Book (ISD Scotland) and average national costs were calculated. Cost of theatre time, disposable surgical devices, hospital stay, and high-dependency unit (HDU) and intensive care unit (ICU) usage were the main endpoints for comparison. Secondary endpoints were morbidity and mortality. Statistical analysis was performed with Student's t-test, chi(2) and Fisher exact test as most appropriate. Twenty-five laparoscopic liver resections were considered, including atypical resection, segmentectomy and bisegmentectomy, and they were compared to 25 matching open resections. The two groups were homogeneous by age, sex, coexistent morbidity, magnitude of resection, prevalence of liver cirrhosis and indications. Operative time (p < 0.03), blood loss (p < 0.0001), Pringle manoeuvre (p < 0.03), hospital stay (p < 0.003) and postoperative complications (p < 0.002) were significantly reduced in the laparoscopic group. Overall hospital cost was significantly lower in the

  6. The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study.

    Science.gov (United States)

    Ghandi, Sedigheh; Aflatoonian, Abbas; Tabibnejad, Nasim; Moghaddam, Mohammad Hossein Sojoodi

    2011-07-01

    Comparing the effects of metformin or orlistat on hormone, lipid profile and ovulation status in obese women with polycystic ovary syndrome. A total of 80 women were prospectively recruited to receive either metformin (n = 40) or orlistat (n = 40). Weight, BMI, waist, serum LH, total serum testosterone and lipid profile were assessed at baseline and after 3 months. The subjects' ovulatory status was assessed after 3 months. There was no significant difference in ovulation between the two treatment groups (30% vs 15%). Treatment with either drug showed a significant decline in body weight, BMI (Body Mass Index), and waist circumference, but the degree of decline in both groups was the same. Patients who were treated with orlistat, showed a significant reduction in total testosterone and serum lipid. Women in metformin group showed a significant reduction in serum LH. Both metformin and orlistat showed a similar effect on weight loss and ovulation rates.

  7. An open prospective study evaluating efficacy and safety of a new medical device for rectal application of activated carbon in the treatment of chronic, uncomplicated perianal fistulas

    DEFF Research Database (Denmark)

    Zawadzki, Antoni; Johnson, Louis Banka; Bohe, Måns

    2017-01-01

    PURPOSE: It has been proposed that biological/chemical substances in the intestine might play a role in the occurrence and deterioration of perianal fistulas. Elimination of such unidentified factors from the lower gastrointestinal tract might offer a new strategy for the management of anal...... fistulas. The aim of this study was to evaluate the clinical effects on non-Crohn's disease perianal fistula healing, and the safety and tolerability of a new medical device that applies high-purity, high-activity granular activated carbon locally into the rectum twice daily of patients with perianal...... fistulas without any concomitant medication. METHODS: An open, single-arm, prospective study with active treatment for 8 weeks and an optional follow-up until week 24 ( ClinicalTrial.gov identifier NCT01462747) among patients with chronic, uncomplicated perianal fistulas scheduled for surgery was conducted...

  8. The preventive effect of tamsulosin on voiding dysfunction after prostate biopsy: a prospective, open-label, observational study.

    Science.gov (United States)

    Chung, Seung Jun; Jung, Seung Il; Ryu, Ji Won; Hwang, Eu Chang; Kwon, Dong Deuk; Park, Kwangsung; Kim, Jin Woong

    2015-05-01

    To evaluate the association of prostate biopsy with voiding impairment and to investigate whether tamsulosin treatment given before prostate biopsy could improve voiding dysfunction after the procedure. The study included 88 consecutive patients who underwent transrectal ultrasound-guided prostate biopsy without prior BPH medication and were prospectively randomized. Of these 88 patients, 44 patients underwent prostate biopsy only without tamsulosin treatment and served as the control group. The remaining 44 patients were treated with tamsulosin (0.2 mg daily) beginning the day before the biopsy procedure for 7 days. The International Prostate Symptom Score (IPSS) was recorded in all patients before the procedure and on postbiopsy day 7. Maximal flow rate (Q(max)) and postvoid residual urine volume were recorded in all patients before the procedure and on postbiopsy days 1 and 7. No difference was found in baseline characteristics between the two groups. The IPSS (total, storage, and voiding symptom) was not significantly changed after biopsy in both groups. In the control group, the postvoid residual urine volume was increased on postbiopsy days 1 (P tamsulosin group, Q(max) was significantly increased on postbiopsy days 1 and 7 (P tamsulosin group, but it developed in two patients (4.5%) of the control group. The results of our study show that prostate biopsy leads to objective voiding impairment. Therefore, the use of alpha-1 blocker tamsulosin before biopsy in patients without prior BPH medication may decrease this morbidity.

  9. An open-label, prospective, observational study of the efficacy of bisphosphonate therapy for painful osteoid osteoma

    Energy Technology Data Exchange (ETDEWEB)

    Bousson, Valerie; Parlier-Cuau, Caroline; Laredo, Jean-Denis [AP-HP, Hopital Lariboisiere, Service de Radiologie Osteo-Articulaire, Paris (France); Universite Paris Diderot, Sorbonne Paris Cite, Paris (France); Leturcq, Tifenn; Ea, Hang-Korng; Orcel, Philippe [AP-HP, Hopital Lariboisiere, Service de Rhumatologie, Paris (France); Universite Paris Diderot, Sorbonne Paris Cite, Paris (France); Hauger, Olivier [CHU Pellegrin Bordeaux, Service d' Imagerie Diagnostique et Therapeutique de l' Adulte, Bordeaux (France); Mehsen-Cetre, Nadia; Schaeverbeke, Thierry [CHU Pellegrin Bordeaux, Service de Rhumatologie, Bordeaux (France); Hamze, Bassam [AP-HP, Hopital Lariboisiere, Service de Radiologie Osteo-Articulaire, Paris (France)

    2018-02-15

    To assess the efficacy of bisphosphonate therapy on bone pain in patients with osteoid osteoma (OO) (main objective), and to describe bisphosphonate-induced changes in nidus mineralisation and regional bone-marrow oedema (BMO). A prospective, observational study was conducted from 2011 to 2014. Patients with risk factors for complications of percutaneous or surgical ablation or recurrence after ablation, were offered once monthly intravenous bisphosphonate treatment until significant pain alleviation was achieved. We included 23 patients. The first two patients received pamidronate and the next 21 zoledronic acid (mean, 2.95 infusions per patient). Bisphosphonate therapy was successful in 19 patients (83%), whose mean pain visual analogue scale score decreased by 76.7%; this pain-relieving effect persisted in 17 patients (74%) with a mean follow-up time of 36 months. Computed tomography (CT) demonstrated a mean nidus density increase of 177.7% (p = 0.001). By magnetic resonance imaging (MRI), mean decreases were 38.4% for BMO surface area and 30.3% for signal intensity (p = 0.001 and p = 0.000, respectively). In 17/23 patients with painful OO managed conservatively with bisphosphonates, long-term final success was achieved. Bisphosphonates may accelerate the spontaneous healing of OO. (orig.)

  10. The life-extension and upgrade program of the Tsing Hua Open-pool Reactor (THOR) and its research prospectives

    International Nuclear Information System (INIS)

    Kai, J.-J.

    1992-01-01

    The Tsing Hua Open-Pool Reactor (THOR) has been operated for thirty years. It is the regulations of the ROCAEC that any reactor shall be decommissioned after forty-year operation since the first fuel loading. Therefore, for extending the lifetime of THOR, it is necessary to have a life-extension program to be approved by the ROCAEC and also completed by the year of 1997. At the same time, for proceeding new research purposes, it is planed to upgrade the thermal power of THOR from 1 Wth up to 3 Wth and hopefully to reach the maximum thermal neutron flux of 5x10 13 n/cm 2 .s and the fast flux close to that order. New research directions involve (a) boron-captured neutron cancer therapy (BNCT) (b) small-angle neutron scattering (SANS). (author)

  11. Prospective assessment of chronic multisymptom illness reporting possibly associated with open-air burn pit smoke exposure in Iraq.

    Science.gov (United States)

    Powell, Teresa M; Smith, Tyler C; Jacobson, Isabel G; Boyko, Edward J; Hooper, Tomoko I; Gackstetter, Gary D; Phillips, Christopher J; Smith, Besa

    2012-06-01

    To investigate the relationship between chronic multisymptom illness (CMI) and possible exposure to an open-air burn pit at three selected bases among those deployed to operations in Iraq and Afghanistan. Chronic multisymptom illness (reporting at least one symptom in at least two of the following symptom constructs: general fatigue; mood and cognition problems; and musculoskeletal discomfort) was assessed, differentiating by potential burn pit exposure, among deployers who completed 2004 and 2007 Millennium Cohort questionnaires. More than 21,000 Cohort participants were deployed in support of the current operations, including more than 3000 participants with at least one deployment within a 3-mile radius of a documented burn pit. After adjusting for covariates, no elevated risk of CMI was observed among those exposed. There was no increase in CMI symptom reporting in those deployed to three selected bases with documented burn pits compared with other deployers.

  12. Interferon-induced central retinal vein thrombosis

    International Nuclear Information System (INIS)

    Nazir, L.; Husain, A.; Haroon, W.; Shaikh, M.I.; Mirza, S.A.; Khan, Z.

    2012-01-01

    A middle-aged lady presented with sudden onset of unilateral central retinal vein thrombosis after completing 6 months course of interferon and ribavirin for chronic hepatitis C infection. She had no risk factors and all her thrombophilia workup was normal, however, she was found to be dyslipidemic which may have contributed to atherosclerosis and predispose to thrombosis. Despite anticoagulation, her visual acuity deteriorated. This case illustrates the possibility of unpredictable visual complication of interferon. Frequent eye examination should be undertaken in patients having underlying risk factors like diabetes, hypertension or dyslipidemia undergoing interferon therapy. (author)

  13. Interferon-induced central retinal vein thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Nazir, L; Husain, A; Haroon, W; Shaikh, M I; Mirza, S A; Khan, Z

    2012-11-15

    A middle-aged lady presented with sudden onset of unilateral central retinal vein thrombosis after completing 6 months course of interferon and ribavirin for chronic hepatitis C infection. She had no risk factors and all her thrombophilia workup was normal, however, she was found to be dyslipidemic which may have contributed to atherosclerosis and predispose to thrombosis. Despite anticoagulation, her visual acuity deteriorated. This case illustrates the possibility of unpredictable visual complication of interferon. Frequent eye examination should be undertaken in patients having underlying risk factors like diabetes, hypertension or dyslipidemia undergoing interferon therapy. (author)

  14. Review of the recombinant human interferon gamma as an immunotherapeutic: Impacts of production platforms and glycosylation.

    Science.gov (United States)

    Razaghi, Ali; Owens, Leigh; Heimann, Kirsten

    2016-12-20

    Human interferon gamma is a cytokine belonging to a diverse group of interferons which have a crucial immunological function against mycobacteria and a wide variety of viral infections. To date, it has been approved for treatment of chronic granulomatous disease and malignant osteopetrosis, and its application as an immunotherapeutic agent against cancer is an increasing prospect. Recombinant human interferon gamma, as a lucrative biopharmaceutical, has been engineered in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. Human interferon gamma is commonly expressed in Escherichia coli, marketed as ACTIMMUNE ® , however, the resulting product of the prokaryotic expression system is unglycosylated with a short half-life in the bloodstream; the purification process is tedious and makes the product costlier. Other expression systems also did not show satisfactory results in terms of yields, the biological activity of the protein or economic viability. Thus, the review aims to synthesise available information from previous studies on the production of human interferon gamma and its glycosylation patterns in different expression systems, to provide direction to future research in this field. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Efficacy of 10% sucralfate ointment in the reduction of acute postoperative pain after open hemorrhoidectomy: a prospective, double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Ala, Shahram; Saeedi, Majid; Eshghi, Fariborz; Rafati, Mohamadreza; Hejazi, Vahid; Hadianamrei, Roja

    2013-01-01

    The aim of the present study was to evaluate the efficacy of 10 % sucralfate ointment in the reduction of acute postoperative pain after open hemorrhoidectomy. A total of 48 patients (24 men and 24 women) between 20 and 70 years of age who underwent open hemorrhoidectomy were included in this prospective, double-blind, randomized, controlled trial and were randomly divided into two groups (24 in each group), receiving either sucralfate ointment or placebo immediately after surgery and then every 12 h for 14 days. The primary outcome measure was pain intensity measured by a visual analogue scale at different time points after hemorrhoidectomy. The sucralfate group had significantly less pain than the placebo group at 24th h and the 48th h after hemorrhoidectomy (4 ± 1.14 vs 5.08 ± 0.97; P = 0.001 and 3 ± 0.72 vs 4.41 ± 0.8; P < 0.001, respectively), and they consumed lower amounts of analgesics at the same time intervals (12.50 ± 16.48 vs 21.87 ± 15.30 mg of pethidine; P = 0.047 and 152 ± 23 vs 172 ± 29 mg of diclofenac; P = 0.009, respectively). The same trend continued until the end of the trial. Sucralfate ointment reduced the acute postoperative pain after hemorrhoidectomy.

  16. A unilateral open door laminoplasty technique: prospective analysis of the relationship between midline extensor muscle preservation and postoperative neck pain.

    Science.gov (United States)

    Park, Jin Hoon; Jeong, Eui-Kyun; Lee, Moon Kyu; Chul Rhim, Seung; Roh, Sung Woo; Kim, Jeoung Hee; Jeon, Sang Ryong

    2015-02-01

    Since laminoplasty was first introduced, several techniques have been developed to reduce postoperative neck pain and progressive kyphosis following this procedure. We describe the importance of deep muscle preservation to prevent postoperative neck pain following cervical posterior surgery, using the inter-muscular plane. We performed cervical laminoplasty on 10 patients from March to July 2012. The mean follow-up duration was 14.6 (range 12-18) months, and the mean age was 58.8 (48-68) years. There were eight men and two women in the study cohort, which consisted of eight cases of cervical spondylotic myelopathy and two cases of ossification of the posterior longitudinal ligament. The Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) score were assessed before and at 6 and 12 months after surgery. The numeric rating scale (NRS) for neck pain was evaluated at 1, 3, 6, and 12 months after surgery. CT scan was performed immediately after the operation, and a radiograph was performed preoperatively and during the follow-up evaluation at 1, 3, 6, and 12 months after surgery. The preoperative JOA and NDI scores improved in all patients. Although there were two patients who complained of moderate postoperative neck pain (NRS 4 and 5), their condition gradually improved. Seven patients had mild or no neck pain (below NRS 3) at the 12 month follow-up. In addition, the cervical alignment was well maintained in all but one patient. Although larger prospective cohorts, longer follow-up periods, and comparative analyses are still needed, the clinical and radiological outcomes observed in the short 12 month period in this small cohort are promising. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Characteristics of plasmids in multi-drug-resistant Enterobacteriaceae isolated during prospective surveillance of a newly opened hospital in Iraq.

    Directory of Open Access Journals (Sweden)

    Xiao-Zhe Huang

    Full Text Available BACKGROUND: Gram-negative multidrug-resistant (MDR bacteria are major causes of nosocomial infections, and antibiotic resistance in these organisms is often plasmid mediated. Data are scarce pertaining to molecular mechanisms of antibiotic resistance in resource constrained areas such as Iraq. METHODOLOGY/PRINCIPAL FINDINGS: In this study, all MDR Enterobacteriaceae (n = 38 and randomly selected non-MDR counterparts (n = 41 isolated from patients, healthcare workers and environmental surfaces in a newly opened hospital in Iraq were investigated to characterize plasmids found in these isolates and determine their contribution to antibiotic resistance. Our results demonstrated that MDR E. coli and K. pneumoniae isolates harbored significantly more (≥ 3 plasmids compared to their non-MDR counterparts, which carried ≤ 2 plasmids (p<0.01. Various large plasmids (~52 to 100 kb from representative isolates were confirmed to contain multiple resistance genes by DNA microarray analysis. Aminoglycoside (acc, aadA, aph, strA/B, and ksgA, β-lactam (bla(TEM1, bla(AMPC, bla(CTX-M-15, bla(OXA-1, bla(VIM-2 and bla(SHV, sulfamethoxazole/trimethoprim (sul/dfr, tetracycline (tet and chloramphenicol (cat resistance genes were detected on these plasmids. Additionally, multiple plasmids carrying multiple antibiotic resistance genes were found in the same host strain. Genetic transfer-associated genes were identified on the plasmids from both MDR and non-MDR isolates. Seven plasmid replicon types (FII, FIA, FIB, B/O, K, I1 and N were detected in the isolates, while globally disseminated IncA/C and IncHI1 plasmids were not detected in these isolates. CONCLUSIONS/SIGNIFICANCE: This is the first report of the characteristics of the plasmids found in Enterobacteriaceae isolated following the opening of a new hospital in Iraq. The information provided here furthers our understanding of the mechanisms of drug resistance in this specific region and their evolutionary

  18. Cost-effectiveness of microendoscopic discectomy versus conventional open discectomy in the treatment of lumbar disc herniation: a prospective randomised controlled trial [ISRCTN51857546

    Directory of Open Access Journals (Sweden)

    Brand Ronald

    2006-05-01

    Full Text Available Abstract Background Open discectomy is the standard surgical procedure in the treatment of patients with long-lasting sciatica caused by lumbar disc herniation. Minimally invasive approaches such as microendoscopic discectomy have gained attention in recent years. Reduced tissue trauma allows early ambulation, short hospital stay and quick resumption of daily activities. A comparative cost-effectiveness study has not been performed yet. We present the design of a randomised controlled trial on cost-effectiveness of microendoscopic discectomy versus conventional open discectomy in patients with lumbar disc herniation. Methods/Design Patients (age 18–70 years presenting with sciatica due to lumbar disc herniation lasting more than 6–8 weeks are included. Patients with disc herniation larger than 1/3 of the spinal canal diameter, or disc herniation less than 1/3 of the spinal canal diameter with concomitant lateral recess stenosis or sequestration, are eliglible for participation. Randomisation into microendoscopic discectomy or conventional unilateral transflaval discectomy will take place in the operating room after induction of anesthesia. The length of skin incision is equal in both groups. The primary outcome measure is the functional assessment of the patient, measured by the Roland Disability Questionnaire for Sciatica, at 8 weeks and 1 year after surgery. We will also evaluate several other outcome parameters, including perceived recovery, leg and back pain, incidence of re-operations, complications, serum creatine kinase, quality of life, medical consumption, absenteeism and costs. The study is a randomised prospective multi-institutional trial, in which two surgical techniques are compared in a parallel group design. Patients and research nurses are kept blinded of the allocated treatment during the follow-up period of 2 years. Discussion Currently, open discectomy is the golden standard in the surgical treatment of lumbar disc

  19. Laboratory evaluation of commercial interferon preparations

    International Nuclear Information System (INIS)

    Schoub, B.D.; Lyons, S.F.; Crespi, M.; Chiu, M.-N.; Lomnitzer, R.

    1983-01-01

    The antiviral, antiproliferative and natural killer-cell (NKC) stimulatory activities of four commercial therapeutic interferon preparations were assayed in a laboratory. The antiviral and antiproliferative activities of each preparation were relatively similar, but an unexpectedly high NKC stimulatory activity was found in one of them. In-house determination of antiviral activity and evaluation of the antiproliferative and NKC stimulation potential of interferon preparations are essential before rational clinical trials of this agent are carried out

  20. Redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study.

    Science.gov (United States)

    Garre, Aurora; Martinez-Masana, Gemma; Piquero-Casals, Jaime; Granger, Corinne

    2017-01-01

    Skin aging is accelerated by multiple extrinsic factors: ultraviolet radiation, smoking and pollution increase oxidative activity, damaging cellular and extracellular components such as DNA, proteins, and lipids. With age, collagen and hyaluronic acid levels decline, resulting in loss of elasticity and moisture of the skin. Over time this damage leads to characteristic signs that make the skin look older: altered facial contour, sagging skin, wrinkles, and an uneven complexion. This study evaluated the anti-aging effects of a new facial cream formulated with carnosine, Alteromonas ferment extract, crosspolymer hyaluronic acid, and a tripeptide. An open-label intra-individual study to assess the anti-aging efficacy of the investigational product in 33 women aged 45 to 65 years. The product was applied twice daily for 56 days. Facial contour and skin deformation, elasticity, hydration, and complexion were measured with specialized equipment at baseline and days 28 and 56. Additionally, subjects completed questionnaires at days 28 and 56 on the perceived efficacy and cosmetic characteristics of the product. After 56 days of use of the investigational product, a redefining effect was observed, with a significant decrease in sagging jawline (7%). Skin was significantly more hydrated (12%), firmer (29%), and more elastic (20%) ( P <0.001 for all). On complexion assessment, skin texture (a measure of skin smoothness) and spots (brown and red skin lesions) also improved significantly (12% and 6% decrease, respectively). In the subjective self-evaluation, the majority of subjects reported that the skin was visibly tightened and more elastic, flexible, and moisturized (91%, 88%, 91%, and 90%, respectively). The product was well tolerated with no adverse events reported during the study. This new cosmetic product demonstrated anti-aging effects after 56 days of use, most notably a redefined facial contour and improved complexion. It is a safe and effective anti-aging product.

  1. Redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study

    Directory of Open Access Journals (Sweden)

    Garre A

    2017-11-01

    Full Text Available Aurora Garre,1 Gemma Martinez-Masana,1 Jaime Piquero-Casals,2 Corinne Granger1 1Innovation and Development, ISDIN S.A., Barcelona, Spain; 2Dermik Clinic, Barcelona, Spain Background: Skin aging is accelerated by multiple extrinsic factors: ultraviolet radiation, smoking and pollution increase oxidative activity, damaging cellular and extracellular components such as DNA, proteins, and lipids. With age, collagen and hyaluronic acid levels decline, resulting in loss of elasticity and moisture of the skin. Over time this damage leads to characteristic signs that make the skin look older: altered facial contour, sagging skin, wrinkles, and an uneven complexion. This study evaluated the anti-aging effects of a new facial cream formulated with carnosine, Alteromonas ferment extract, crosspolymer hyaluronic acid, and a tripeptide. Methods: An open-label intra-individual study to assess the anti-aging efficacy of the investigational product in 33 women aged 45 to 65 years. The product was applied twice daily for 56 days. Facial contour and skin deformation, elasticity, hydration, and complexion were measured with specialized equipment at baseline and days 28 and 56. Additionally, subjects completed questionnaires at days 28 and 56 on the perceived efficacy and cosmetic characteristics of the product. Results: After 56 days of use of the investigational product, a redefining effect was observed, with a significant decrease in sagging jawline (7%. Skin was significantly more hydrated (12%, firmer (29%, and more elastic (20% (P<0.001 for all. On complexion assessment, skin texture (a measure of skin smoothness and spots (brown and red skin lesions also improved significantly (12% and 6% decrease, respectively. In the subjective self-evaluation, the majority of subjects reported that the skin was visibly tightened and more elastic, flexible, and moisturized (91%, 88%, 91%, and 90%, respectively. The product was well tolerated with no adverse events reported

  2. Alpha interferon therapy in Danish haemophiliac patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Laursen, A L; Scheibel, E; Ingerslev, Jørgen

    1998-01-01

    Following a survey among all Danish haemophiliac patients 49 HIV-negative patients with chronic hepatitis C were offered enrollment in a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment. Dose modifications...... and biochemical response after 6 months of follow up. Overall, the individualized treatment regimen did not seem to offer any advantage over the fixed dose regimen. The response to alpha interferon treatment in Danish haemophiliac patients with chronic hepatitis C immediately after treatment is comparable...... and treatment discontinuation were based upon changes in transaminase levels. Forty-seven patients enrolled received 3 MU of alpha interferon thrice weekly (TIW) for 3 months. Twenty-six nonresponders had their dose increased to 6 MU TIW for an additional 3 months, while 21 responding patients continued on 3 MU...

  3. Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial.

    Science.gov (United States)

    Demiroglu, H; Ozcebe, O I; Barista, I; Dündar, S; Eldem, B

    2000-02-19

    Sight-threatening eye involvement is a serious complication of Behçet's disease. Extraocular complications such as arthritis, vascular occlusive disorders, mucocutaneous lesions, and central-nervous-system disease may lead to morbidity and even death. We designed a prospective study in newly diagnosed patients without previous eye disease to assess whether prevention of eye involvement and extraocular manifestations, and preservation of visual acuity are possible with combination treatments with and without interferon alfa-2b. Patients were randomly assigned 3 million units interferon alfa-2b subcutaneously every other day for the first 6 months plus 1.5 mg colchicine orally daily and 1.2 million units benzathine penicillin intramuscularly every 3 weeks (n=67), or colchicine and benzathine penicillin alone (n=68). The primary endpoint was visual-acuity loss. Analysis was by intention to treat. Significantly fewer patients who were treated with interferon had eye involvement than did patients who did not receive interferon (eight vs 27, relative risk 0.21 [95% CI 0.09-0.50], p<0.001). Ocular attack rate was 0.2 (SD 0.62) per year with interferon therapy and 1.02 (1.13) without interferon therapy (p=0.0001). Visual-acuity loss was significantly lower among patients treated with interferon than in those without interferon (two vs 13, relative risk 0.13 [95% CI 0.03-0.60], p=0.003). Arthritis episodes, vascular events, and mucocutaneous lesions were also less frequent in patients treated with interferon than in those not receiving interferon. No serious side-effects were reported. Therapy with interferon alfa-2b, colchicine, and benzathine penicillin seems to be an effective regimen in Behçet's disease for the prevention of recurrent eye attacks and extraocular complications, and for the protection of vision.

  4. Health-related quality of life from a prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy.

    Science.gov (United States)

    Messer, Jamie C; Punnen, Sanoj; Fitzgerald, John; Svatek, Robert; Parekh, Dipen J

    2014-12-01

    To compare health-related quality-of-life (HRQoL) outcomes for robot-assisted laparoscopic radical cystectomy (RARC) with those of traditional open radical cystectomy (ORC) in a prospective randomised fashion. This was a prospective randomised clinical trial evaluating the HRQoL for ORC vs RARC in consecutive patients from July 2009 to June 2011. We administered the Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index questionnaire, validated to assess HRQoL, preoperatively and then at 3, 6, 9 and 12 months postoperatively. Scores for each domain and total scores were compared in terms of deviation from preoperative values for both the RARC and the ORC cohorts. Multivariate linear regression was used to assess the association between the type of radical cystectomy and HRQoL. At the time of the study, 47 patients had met the inclusion criteria, with 40 patients being randomised for analysis. The cohorts consisted of 20 patients undergoing ORC and 20 undergoing RARC, who were balanced with respect to baseline demographic and clinical features. Univariate analysis showed a return to baseline scores at 3 months postoperatively in all measured domains with no statistically significant difference among the various domains between the RARC and the ORC cohorts. Multivariate analysis showed no difference in HRQoL between the two approaches in any of the various domains, with the exception of a slightly higher physical well-being score in the RARC group at 6 months. There were no significant differences in the HRQoL outcomes between ORC and RARC, with a return of quality of life scores to baseline scores 3 months after radical cystectomy in both cohorts. © 2014 The Authors. BJU International © 2014 BJU International.

  5. Type I Interferons Direct Gammaherpesvirus Host Colonization.

    Directory of Open Access Journals (Sweden)

    Cindy S E Tan

    2016-05-01

    Full Text Available Gamma-herpesviruses colonise lymphocytes. Murid Herpesvirus-4 (MuHV-4 infects B cells via epithelial to myeloid to lymphoid transfer. This indirect route entails exposure to host defences, and type I interferons (IFN-I limit infection while viral evasion promotes it. To understand how IFN-I and its evasion both control infection outcomes, we used Mx1-cre mice to tag floxed viral genomes in IFN-I responding cells. Epithelial-derived MuHV-4 showed low IFN-I exposure, and neither disrupting viral evasion nor blocking IFN-I signalling markedly affected acute viral replication in the lungs. Maximising IFN-I induction with poly(I:C increased virus tagging in lung macrophages, but the tagged virus spread poorly. Lymphoid-derived MuHV-4 showed contrastingly high IFN-I exposure. This occurred mainly in B cells. IFN-I induction increased tagging without reducing viral loads; disrupting viral evasion caused marked attenuation; and blocking IFN-I signalling opened up new lytic spread between macrophages. Thus, the impact of IFN-I on viral replication was strongly cell type-dependent: epithelial infection induced little response; IFN-I largely suppressed macrophage infection; and viral evasion allowed passage through B cells despite IFN-I responses. As a result, IFN-I and its evasion promoted a switch in infection from acutely lytic in myeloid cells to chronically latent in B cells. Murine cytomegalovirus also showed a capacity to pass through IFN-I-responding cells, arguing that this is a core feature of herpesvirus host colonization.

  6. The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

    Science.gov (United States)

    Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

    2016-04-01

    Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  7. A PROSPECTIVE STUDY ON FUNCTIONAL OUTCOME OF HUMERUS SHAFT FRACTURES TREATED WITH OPEN REDUCTION AND INTERNAL FIXATION WITH DYNAMIC COMPRESSION PLATE AND SCREWS

    Directory of Open Access Journals (Sweden)

    Vidyadhar S. Donimath

    2017-12-01

    Full Text Available BACKGROUND Fracture of the humerus shaft accounts to 3% to 5% of all fractures. Majority of the fractures are unstable due to distraction force of the gravity in the upper limb and strong muscle contraction leading to displacement. Internal fixation and early mobilisation is more stressed on than splinting and prolonged immobilisation to allow earlier mobilisation and rapid return to work. The aim of the study was to study the union rates and the functional outcome and complications associated with shaft humerus fractures in KIMS Hospital. MATERIALS AND METHODS A prospective study which was carried out from October 2015 to September 2017 in Karnataka Institute of Medical Sciences, Hubballi, Karnataka State, India. In this study period, 25 cases of fracture shaft of the humerus were treated by open reduction and internal fixation using DCP. Skeletally mature patients with fresh humerus diaphysis fractures were included in the study. Pathological fractures and Tscherne grade 2 and above, Gustilo Anderson type2 and above were excluded from the study. RESULTS In our series of 25 cases, there were 21 men and 4 women with average age of 42.5 years. Sixteen (64% cases were due to RTA and with predominance of right side. Transverse fractures were most common that is 15 (60% patients. Eleven (31% cases were having associated injuries. 92% of the fractures united with good to excellent outcome. There were 2 (8% cases of non-union due to infection and comminution. CONCLUSION Open reduction and internal fixation with dynamic compression plate is still the standard treatment of choice for fracture shaft of humerus achieving excellent to good functional outcome.

  8. Low-Dose Total Skin Electron Beam Therapy as a Debulking Agent for Cutaneous T-Cell Lymphoma: An open-label prospective phase II study

    DEFF Research Database (Denmark)

    Kamstrup, M R; Lindahl, Lise Maria; Gniadecki, R

    2012-01-01

    Background: Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphomas (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36 Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited...... due to the cumulative toxicity. Complete response rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III. Objectives: To evaluate prospectively the efficacy of low-dose TSEBT (10 Gy) in terms of complete cutaneous response rate, overall response rate...... and response duration in CTCL. Methods: Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with 4 fractions of 1 Gy/week TSEB to a total skin dose of 10 Gy. Treatment responses were assessed at 1 and 3 months after treatment and subsequently at least every 6 months...

  9. The success of opening single chronic total occlusion lesions to improve myocardialviabilitytrial (SOS-COMEDY): Study protocol of a prospective multicenter study.

    Science.gov (United States)

    Huang, Rongchong; Song, Xiantao; Zhang, Haishan; Tian, Wen; Huang, Zheng; Zhang, Xingwei; Yang, Junqing; Zhang, Dongfeng; Wu, Jian; Zhong, Lei; Ting, Henry H

    2018-04-01

    Success of opening single (SOS)-comedy is a prospective multicenter study to compare the improvement in the decrease of myocardial viability by percutaneous coronary intervention (PCI) with that by optimal medical therapy (OMT) alone in patients with chronic total occlusion (CTO) of a single coronary artery. The risks and the benefits of both options (PCI and OMT) were listed in a CTO decision aid (DA). Eligible participants detected by invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) were divided into PCI or OMT groups according to patients' choice after shared-decision making process with DA. Participants will undergo positron emission tomography/computed tomography (PET/CT), cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE), and proceed to ICA and revascularization if possible. Blinded core laboratory interpretation will be performed for ICA, CCTA, PET/CT, CMR, and TTE. All participants will be followed up for 12 months. The primary endpoint is the improvement to the decrease of myocardial viability from baseline assessed with the use of PET/CT after 12-month follow-up. All of the patients are appropriately consented before enrolling in this study, which has been approved by the Ethics Committee. Results of SOS-COMEDY will be helpful to develop a strategy for single CTO patients.

  10. Long-term weight loss observed with olanzapine orally disintegrating tablets in overweight patients with chronic schizophrenia. A 1 year open-label, prospective trial.

    Science.gov (United States)

    Chawla, Bharat; Luxton-Andrew, Heather

    2008-04-01

    To investigate the long-term weight loss outcomes during usual clinical practice after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In this open-label prospective study, 26 patients with schizophrenia who were clinically stable on olanzapine SOT treatment were switched to olanzapine ODT. All other aspects of treatment remained constant. Weight was recorded at 3, 6, and 12 months. Patients incurred an average weight loss of 2.7 +/- 0.7 kg (p = 0.001) after switching patients from olanzapine SOT to olanzapine ODT at 12 months. Peak weight loss was observed at 6 months; however, significant weight loss was achieved as early as 3 months. The majority (81.9%) of patients lost weight, while 18.1% had no weight change or weight gain. Body mass index (BMI) significantly decreased by 1.0 +/- 0.3 kg/m(2) (p = 0.001). Interestingly, patients treated with higher doses of olanzapine (> or = 20 mg) incurred a greater weight loss of their body weight (5.6%), compared to those treated with lower doses (< 20 mg), who lost 1.9% of their body weight (p = 0.04). This study demonstrated that, in usual clinical practice, switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained over 12 months. 2008 John Wiley & Sons, Ltd.

  11. Sublingual Immunotherapy with a Five-Grass Pollen Tablet in Adult Patients with Allergic Rhinitis: An Open, Prospective, Noninterventional, Multicenter Study

    Directory of Open Access Journals (Sweden)

    Oliver Pfaar

    2015-01-01

    Full Text Available Background. Although the safety and efficacy of sublingual immunotherapy (SLIT with a five-grass pollen tablet have been demonstrated in randomized clinical trials (RCTs, these outcomes must always be evaluated in real-life medical practice. Methods. In a prospective, open-label, noninterventional, “real-life” study in Germany, we evaluated the safety, tolerability, and effectiveness of SLIT with a five-grass pollen tablet in adults with grass-pollen-induced allergic rhinoconjunctivitis. Results. 808 adults were enrolled between September 2008 and December 2009. 35.3% of the participants experienced at least one adverse drug reaction (ADR, the most common of which were mild-to-moderate gastrointestinal and respiratory disorders. Serious ADRs considered causally related to SLIT treatment occurred in four patients. Overall, the five-grass pollen tablet was considered to have good or very good tolerability by most investigators and patients. Treatment was associated with the relief of nasal, ocular, and bronchial symptoms and decreased symptomatic medication use. However, interpretation of clinical improvements was limited by lower atmospheric grass pollen levels during the study season (relative to the preceding season. Conclusions. In a large population of patients treated in real-life medical practice, SLIT with a five-grass pollen tablet was safe and well tolerated. The patient-reported symptom relief suggests that SLIT was associated with clinical benefits.

  12. [Use of itopride in the symptoms of functional dyspepsia in Russia: results of a phase IV prospective open-label multicenter clinical trial].

    Science.gov (United States)

    Kas'ianenko, V I; Denisov, N L; Vasil'ev, Iu V

    2014-01-01

    To evaluate the efficacy and safety of itopride used to treat the symptoms of functional dyspepsia (FD) of the upper gastrointestinal tract. A prospective, open-label, multicenter trial using as a control the placebo response obtained in the previous investigations enrolled 96 adult patients. The diagnosis of FD corresponded to its Rome II criteria. Patients received itopride (Ganaton) oral tablets (50 mg) 3 times daily for 8 weeks. When included into the trial, the patients were orally given itopride (ganaton) tablets (50 mg) thrice daily before meals for 8 weeks. The patients' status was evaluated during (at weeks 4 and 8) and after (at week 12) treatment. Treatment response was assessed using the Global Patient Assessment (GPA) and the Leeds Dyspepsia Questionnaire (LDQ). To evaluate the safety of itopride use, the investigators studied the frequency of adverse events and carried out laboratory tests (renal and liver function tests) and electrocardiography (ECG). The GPA showed that 53.76, 85.71, and 82.22% of the patients achieved a therapeutic effect of itopride at weeks 4, 8, and 12, respectively. The proportion of the patients who achieved the therapeutic effect (86%) at week 8 was higher than the historical placebo controls in the previous studies--45% (86% vs 45%; X2 = 68.868, df = 3; p Itopride is an effective and well-tolerated drug in the treatment of functional dyspepsia in the Russian patients.

  13. Postural and Balance Disorders in Patients with Parkinson's Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment

    Science.gov (United States)

    Santamato, Andrea; Ranieri, Maurizio; Cinone, Nicoletta; Stuppiello, Lucia Anna; Valeno, Giovanni; De Sanctis, Jula Laura; Fortunato, Francesca; Solfrizzi, Vincenzo; Greco, Antonio; Seripa, Davide; Panza, Francesco

    2015-01-01

    Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson's disease (PD) to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy) for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients. PMID:26798551

  14. Postural and Balance Disorders in Patients with Parkinson’s Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment

    Directory of Open Access Journals (Sweden)

    Andrea Santamato

    2015-01-01

    Full Text Available Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson’s disease (PD to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients.

  15. Polymorphism in the interferon-{alpha} gene family

    Energy Technology Data Exchange (ETDEWEB)

    Golovleva, I.; Lundgren, E.; Beckman, L. [Univ. of Umea (Sweden); Kandefer-Szerszen, M. [Maria Curie-Sklodowska Univ., Lublin (Poland)

    1996-09-01

    A pronounced genetic polymorphism of the interferon type I gene family has been assumed on the basis of RFLP analysis of the genomic region as well as the large number of sequences published compared to the number of loci. However, IFNA2 is the only locus that has been carefully analyzed concerning gene frequency, and only naturally occurring rare alleles have been found. We have extended the studies on a variation of expressed sequences by studying the IFNA1, IFNA2, IFNA10, IFNA13, IFNA14, and IFNA17 genes. Genomic white-blood-cell DNA from a population sample of blood donors and from a family material were screened by single-nucleotide primer extension (allele-specific primer extension) of PCR fragments. Because of sequence similarities, in some cases {open_quotes}nested{close_quotes} PCR was used, and, when applicable, restriction analysis or control sequencing was performed. All individuals carried the interferon-{alpha} 1 and interferon-{alpha} 13 variants but not the LeIF D variant. At the IFNA2 and IFNA14 loci only one sequence variant was found, while in the IFNA10 and IFNA17 groups two alleles were detected in each group. The IFNA10 and IFNA17 alleles segregated in families and showed a close fit to the Hardy-Weinberg equilibrium. There was a significant linkage disequilibrium between IFNA10 and IFNA17 alleles. The fact that the extent of genetic polymorphism was lower than expected suggests that a majority of the previously described gene sequences represent nonpolymorphic rare mutants that may have arisen in tumor cell lines. 44 refs., 4 figs., 4 tabs.

  16. Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3?

    Institute of Scientific and Technical Information of China (English)

    Ijaz S Jamall; Shafaq Yusuf; Maimoona Azhar; Selene Jamall

    2008-01-01

    Over the past decade,significant improvements have been made in the treatment of chronic hepatitis C(CHC),especially with the introduction of combined therapy using both interferon and ribavarin.The optimal dose and duration of treatment is still a matter of debate and,importantly,the efficacy of this combined treatment varies with the viral genotype responsible for infection.In general,patients infected with viral genotypes 2 or 3 more readily achieve a sustained viral response than those infected with viral genotype 1.The introduction of a pegylated version of interferon in the past decade has produced better clinical outcomes in patients infected with viral genotype 1.However,the published literature shows no improvement in clinical outcomes in patients infected with viral genotypes 2 or 3 when they are treated with pegylated interferon as opposed to nonpegylated interferon,both given in combination with ribavarin.This is significant because the cost of a 24-wk treatment with pegylated interferon in lessdeveloped countries is between six and 30 times greater than that of treatment with interferon.Thus,clinicians need to carefully consider the cost-versusbenefit of using pegylated interferon to treat CHC,particularly when there is no evidence for clinically measurable benefits in patients with genotypes 2 and 3 infections.

  17. Interferon alfa with or without ribavirin for chronic hepatitis C

    DEFF Research Database (Denmark)

    Kjaergard, L L; Krogsgaard, K; Gluud, C

    2001-01-01

    To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C.......To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C....

  18. Dampened STING-Dependent Interferon Activation in Bats.

    Science.gov (United States)

    Xie, Jiazheng; Li, Yang; Shen, Xurui; Goh, Geraldine; Zhu, Yan; Cui, Jie; Wang, Lin-Fa; Shi, Zheng-Li; Zhou, Peng

    2018-03-14

    Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Interferon Lambda: A New Sword in Cancer Immunotherapy

    Science.gov (United States)

    Lasfar, Ahmed; Abushahba, Walid; Balan, Murugabaskar; Cohen-Solal, Karine A.

    2011-01-01

    The discovery of the interferon-lambda (IFN-λ) family has considerably contributed to our understanding of the role of interferon not only in viral infections but also in cancer. IFN-λ proteins belong to the new type III IFN group. Type III IFN is structurally similar to type II IFN (IFN-γ) but functionally identical to type I IFN (IFN-α/β). However, in contrast to type I or type II IFNs, the response to type III IFN is highly cell-type specific. Only epithelial-like cells and to a lesser extent some immune cells respond to IFN-λ. This particular pattern of response is controlled by the differential expression of the IFN-λ receptor, which, in contrast to IFN-α, should result in limited side effects in patients. Recently, we and other groups have shown in several animal models a potent antitumor role of IFN-λ that will open a new challenging era for the current IFN therapy. PMID:22190970

  20. Time to initial operative treatment following open fracture does not impact development of deep infection: a prospective cohort study of 736 subjects.

    Science.gov (United States)

    Weber, Donald; Dulai, Sukhdeep K; Bergman, Joseph; Buckley, Richard; Beaupre, Lauren A

    2014-11-01

    To evaluate the association between time to surgery, antibiotic administration, Gustilo grade, fracture location, and development of deep infection in open fractures. Prospective cohort between 2001 and 2009. Three Level 1 Canadian trauma centers. A total of 736 (791 fractures) subjects were enrolled and 686 subjects (93%; 737 fractures) provided adequate follow-up data (1-year interview and/or clinical follow-up >90 days). Demographics, injury information, time to surgery, and antibiotics were recorded. Subjects were evaluated using standardized data forms until the fracture(s) healed. Phone interviews were undertaken 1 year after the fracture. Infection requiring unplanned surgical debridement and/or sustained antibiotic therapy. Tibia/fibula fractures were most common (n = 413, 52%), followed by upper extremity (UE) (n = 285, 36%), and femoral (n = 93, 12%) fractures. Infection developed in 46 fractures (6%). The median time to surgery was 9 hours 4 minutes (interquartile range, 6 hours 39 minutes to 12 hours 33 minutes) and 7 hours 39 minutes (interquartile range, 6 hours 10 minutes to 9 hours 54 minutes) for those without and with infection, respectively (P = 0.04). Gustilo grade 3B/3C fractures accounted for 17 of 46 infections (37%) (P developed infections (P = 0.001). Multivariate regression found no association between infection and time to surgery [odds ratio (OR), 0.97; 95% confidence interval (95% CI), 0.90-1.06] or antibiotics (OR, 1.0; 95% CI, 0.90-1.05). Grades 3A (OR, 6.37; 95% CI, 1.37-29.56) and 3B/3C (OR, 12.87; 95% CI, 2.72-60.95) relative to grade 1 injuries and tibia/fibula (OR, 3.91; 95% CI, 1.33-11.53) relative to UE fractures were significantly associated with infection. Infection after open fracture was associated with increasing Gustilo grade or tibia/fibula fractures but not time to surgery or antibiotics. Prognostic level I. See instructions for authors for a complete description of levels of evidence.

  1. The effect of ziprasidone on metabolic syndrome risk factors in subjects with schizophrenia: a 1 year, open-label, prospective study.

    Science.gov (United States)

    Chue, Pierre; Mandel, Francine S; Therrien, François

    2014-06-01

    Metabolic syndrome (MetS) is prevalent in subjects with schizophrenia-related psychotic disorders and contributes to increased rates of premature death due to cardiovascular disease. This study examined the impact of switching from another antipsychotic to ziprasidone on the distribution of the number of risk factors for MetS in subjects with schizophrenia or related psychotic disorders. In this 1 year, open-label, prospective study, all subjects received ziprasidone 40-160 mg/day. Standard exclusion criteria included treatment resistance, physical health disorders, and substance abuse. The primary end point was the percentage of subjects achieving a reduction from baseline of at least one risk factor for MetS at end point (week 52 or premature discontinuation) in the per-protocol population (treated for at least 16 weeks). Secondary end points included the mean change from baseline in number of MetS risk factors, the prevalence of MetS, individual MetS risk factors (waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and glucose), and 10 year coronary heart disease (Framingham score) risk. www.clinicaltrials.gov: NCT00748566. Of 114 evaluable subjects, 58.77% demonstrated one less MetS risk factor at week 52 (last observation carried forward) compared with baseline. Secondary end points also improved, with reductions in other metabolic parameters (fasting low-density lipoprotein cholesterol, total cholesterol and serum insulin, weight, body mass index and glycosylated hemoglobin [HbA1c]). The 10 year coronary heart disease risk decreased continually over time. The open-label and uncontrolled design is a limitation of the study. Ziprasidone treatment reduced both the rate of MetS and its individual risk factors in subjects with schizophrenia and related psychotic disorders. The results have implications for the selection of first-line treatments in schizophrenia and related psychotic disorders, and provide treatment

  2. Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yi; GONG Mei-en; YIN Qing-yun; MAI Jian-ning; JING Jin; LUO Xiang-yang; MA Hong-wei; LI Hai-bo; XIE Ling; LI Yan; Kuang Gui-fang; WANG Yu-feng; YI Ming-ji; WANG Feng; ZHU Xiao-hua; YAO Yah-bin; QIN Jiong; WANG Li-wen; ZOU Li-ping; JIN Xing-ming; XU Tong; WANG Yi; QI Yuan-li

    2011-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood,characterized by the core symptoms of hyperactivity,impulsivity and inattention and puts great burden on children themselves,their families and the society.Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH).It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles.The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.Methods This 6-week,multi-center,prospective,open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg,36 mg or 54 mg) treatment.The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales,physician-rated CGI-I and parent-rated global efficacy assessment scale.Blood pressure,pulse rate measurement,adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.Results A total of 1447 children with ADHD (mean age (9.52±2.36) years) were enrolled in this trial.Totally 96.8%children received an OROS-MPH modal dose of 18 mg,3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study.The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P <0.001) improvement with OROS-MPH (mean:6.95±2.71) versus the score at baseline (10.45±2.72).The change in the parent IOWA Conners O/D subscale,CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment.Fewer than half of 1447 patients (511 (35.3%)) reported AEs,and the majority of the events reported were mild (68.2

  3. Some biological properties of the human amniotic membrane interferon

    Directory of Open Access Journals (Sweden)

    P. C. P. Ferreira

    1992-03-01

    Full Text Available Human amniotic interferon was investigated to define the species specificity of its antiviral action and compare its anti-cellular and NK cell stimulating activities with those of other human interferons. The antiviral effect was titrated in bovine (RV-IAL and monkey (VERO cells. Amniotic interferon exhibited, in bovine cells, 5% of the activity seen in monkey cells, while alpha interferon displayed 200%. No effect was detected with either beta or gamma interferon in bovine cells. Daudi cells were exposed to different concentrations of various interferons and the cell numbers were determined. The anticellular effect of the amniotic interferon reached its peak on the third day of incubation. Results suggested a higher activity for alpha and gamma interferons and a lower activity for beta when compared to amniotic interferon. Using total mononuclear cells as effector cells and K 562 as target cell in a 51Cr release assay, it was demonstrated that low concentrations of amniotic interferon consistently stimulated NK cell activity in cells derived from several donors, the results indicating a higher level of activity with this interferon than with alpha and beta interferons.

  4. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

    NARCIS (Netherlands)

    Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

    2006-01-01

    BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.

  5. The Efficacy and Tolerability of the Clonidine Transdermal Patch in the Treatment for Children with Tic Disorders: A Prospective, Open, Single-Group, Self-Controlled Study.

    Science.gov (United States)

    Song, Pan-Pan; Jiang, Li; Li, Xiu-Juan; Hong, Si-Qi; Li, Shuang-Zi; Hu, Yue

    2017-01-01

    To evaluate the efficacy and tolerability of a clonidine transdermal patch in the treatment of children with tic disorders (TD) and to establish a predictive model for patients. Forty-one patients who met the inclusion criteria entered into 12 weeks of prospective, open, single-group, self-controlled treatment with a clonidine transdermal patch. The Yale Global Tic Severity Scale (YGTSS) was employed before therapy (baseline) and at 4, 8, and 12 weeks after therapy. (1) The total effect rates of treatment with a clonidine transdermal patch were 29.27, 53.66, and 63.41% at 4, 8, and 12 weeks, respectively. Compared with the baseline, the differences were significant at three different observation periods. (2) Compared to the level of 25% reduction, there were significant decreases in the score-reducing rate of motor tic and total tic severities at 12 weeks. (3) If the disease course was ≤24 months and the motor tic score was tic score was >16, there was an effective rate of 57.1%. If the disease course was >24 months and the clinical classification was chronic TD, there was an effective rate of 62.5%. If the disease course was >24 months and the clinical classification was Tourette's syndrome, 90% of the patients were invalid. (4) The main adverse events were rash, slight dizziness, and headache. (1) When patients were pretreated with a D2-dopamine receptor antagonist that was ineffective or not tolerated well, switching to a clonidine transdermal patch treatment was effective and safe. (2) A clonidine transdermal patch could be a first-line medication for mild and moderate TD cases that are characterized by motor tics.

  6. Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements.

    Science.gov (United States)

    Smith, David H; Neutel, Joel M; Lacourcière, Yves; Kempthorne-Rawson, Joan

    2003-07-01

    This meta-analysis aimed to determine whether ambulatory blood pressure monitoring (ABPM) results from double-blind, placebo-controlled (DBPC) and prospective, randomized, open-label, blinded-endpoint (PROBE) hypertension trials are statistically comparable. Two DBPC and three PROBE parallel-group studies were selected from an angiotensin II receptor blocker clinical programme. These were fixed-dose studies involving similar mild to moderate hypertensive patient populations. All used SpaceLabs 90207 ABPM devices, and each comprised a 4-week placebo period and a 4-8-week treatment period. Data from patients receiving telmisartan 80 mg were used to compare the results of DBPC (126 patients) and PROBE (734 patients) trials. The analysis had approximately 87% power to show equivalence between the two design types in terms of ruling out differences of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. Office blood pressure was also compared. The change from baseline in mean 24-h ambulatory SBP was -12.2 mmHg in DBPC trials and -12.3 mmHg in PROBE trials, a rounded difference of 0.2 mmHg [95% confidence interval (CI): -1.8, 2.1]. The change from baseline in mean 24-h ambulatory DBP was -7.7 mmHg in DBPC trials versus -7.9 mmHg in PROBE trials, a difference of 0.2 mmHg (95% CI: -1.1, 1.5). Ambulatory pulse pressure results were identical. Thus, changes in mean 24-h ambulatory blood pressure from the DBPC and PROBE trials in this meta-analysis are statistically equivalent in terms of ruling out a difference of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. This supports the validity of the PROBE design in assessing antihypertensive efficacy based on blinded ABPM measurements.

  7. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

    Science.gov (United States)

    Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

    2015-06-27

    The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Clinical effectiveness and safety of OROS® hydromorphone in break-through cancer pain treatment: a multicenter, prospective, open-label study in Korean patients.

    Science.gov (United States)

    Lee, Kyung Hee; Kim, Min Kyoung; Hyun, Myung Soo; Kim, Jin Young; Park, Keon Uk; Song, Hong Suk; Lee, Sun Ah; Lee, Won Sik; Bae, Sung Hwa; Ryoo, Hun Mo; Cho, Yoon Young

    2012-01-01

    To evaluate the effectiveness of OROS® hydromorphone in reducing breakthrough pain (BTP) medication frequency in Korean patients with chronic cancer pain. Multicenter, prospective, open-label, phase IV study. Patients with chronic malignant pain using immediate-release oxycodone more than two times per day for BTP. Patients were stabilized on their ongoing drug for 3 days immediately before baseline measurements (day 0). Medication was changed to OROS® hydromorphone at a dose equianalgesic to oxycodone using a 2.5:1 controlled-release oxycodone to hydromorphone hydrochloride conversion ratio; the patients were observed for 7 days. Dose was titrated, if required, and the patients were observed for another 7 days. Effectiveness and safety parameters were measured at baseline, day 7, and day 14. BTP medication frequency on days 7 and 14, compared to baseline. Of the 141 patients screened, 114 received study drug and 98 completed the study. Compared to day 0, daily BTP medication frequency on day 14 decreased from 2.93 to 2.00 (p > 0.0001), daily BTP frequency decreased from 3.67 to 2.44 (p > 0.0001), and end-of-dose pain frequency decreased by 44 percent. Pain was controlled adequately during daytime and night-time. Pain intensity decreased by 11 percent as assessed using the Korean Brief Pain Inventory and by 17 percent as assessed using the numerical rating scale. About 61.2 percent patients and 60.2 percent physicians were satisfied with the treatment. Common adverse events, which occurred in 91.2 percent patients, were constipation, somnolence, and dizziness. Once-daily OROS® hydromorphone is efficient in the reduction of cancer pain-related BTP episodes, including end-of-dose pain.

  9. Modest blood pressure reduction with valsartan in acute ischemic stroke: a prospective, randomized, open-label, blinded-end-point trial.

    Science.gov (United States)

    Oh, Mi Sun; Yu, Kyung-Ho; Hong, Keun-Sik; Kang, Dong-Wha; Park, Jong-Moo; Bae, Hee-Joon; Koo, Jaseong; Lee, Juneyoung; Lee, Byung-Chul

    2015-07-01

    To assess the efficacy and safety of modest blood pressure (BP) reduction with valsartan within 48 h after symptom onset in patients with acute ischemic stroke and high BP. This was a multicenter, prospective, randomized, open-label, blinded-end-point trial. A total of 393 subjects were recruited at 28 centers and then randomly assigned in a 1:1 ratio to receive valsartan (n = 195) or no treatment (n = 198) for seven-days after presentation. The primary outcome was death or dependency, defined as a score of 3-6 on the modified Rankin Scale (mRS) at 90 days after symptom onset. Early neurological deterioration (END) within seven-days and 90-day major vascular events were also assessed. There were 372 patients who completed the 90-day follow-up. The valsartan group had 46 of 187 patients (24·6%) with a 90-day mRS 3-6, compared with 42 of 185 patients (22·6%) in the control group (odds ratio [OR], 1·11; 95% confidence interval [CI], 0·69-1·79; P = 0·667). The rate of major vascular events did not differ between groups (OR, 1·41; 95% CI, 0·44-4·49; P = 0·771). There was a significant increase of END in the valsartan group (OR, 2·43; 95% CI, 1·25-4·73; P = 0·008). Early reduction of BP with valsartan did not reduce death or dependency and major vascular events at 90 days, but increased the risk of END. © 2015 World Stroke Organization.

  10. Feasibility of a cardiologist-only approach to sedation for electrical cardioversion of atrial fibrillation: a randomized, open-blinded, prospective study.

    Science.gov (United States)

    Guerra, Federico; Pavoni, Ilaria; Romandini, Andrea; Baldetti, Luca; Matassini, Maria Vittoria; Brambatti, Michela; Luzi, Mario; Pupita, Giuseppe; Capucci, Alessandro

    2014-10-20

    Sedation with propofol should be administered by personnel trained in advanced airway management. To overcome this limitation, the use of short acting benzodiazepines by cardiologists spread widely, causing concerns about the safety of this procedure in the absence of anesthesiology assistance. The aim of the study was to compare feasibility of a cardiologist-only approach with an anesthesiologist-assisted sedation protocol during elective direct-current cardioversion (DCC) of persistent atrial fibrillation (AF). This prospective, open-blinded, randomized study included 204 patients, which were admitted for scheduled cardioversion of persistent AF, and randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the propofol group underwent DCC with anesthesiologist assistance, while patients in the midazolam group saw the cardiologist as the only responsible for both sedation and DCC. Twenty-three adverse events occurred: 13 in the propofol group and 10 in the midazolam group (p=NS). Most of them were related to bradyarrhythmias and respiratory depressions. There was no need of intubation or other advanced resuscitation techniques in any of these patients. No differences were found regarding procedure tolerability and safety endpoints between the two groups. DCC procedures with anesthesiology support were burdened by higher delay from scheduled time and higher costs. Sedation with midazolam administered by cardiologist-only appears to be as safe as sedation with propofol and anesthesiologist assistance. Adverse events were few in both groups and easily handled by the cardiologist alone. A cardiologist-only approach to sedation provides less procedural delay, thus being easier to schedule and correlated with fewer costs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Efficacy and safety of Vitex agnus-castus extract for treatment of premenstrual syndrome in Japanese patients: a prospective, open-label study.

    Science.gov (United States)

    Momoeda, Mikio; Sasaki, Hidetaka; Tagashira, Eiko; Ogishima, Masayuki; Takano, Yuichi; Ochiai, Kazunori

    2014-03-01

    Herbal medicine containing Vitex agnus-castus (VAC) extract is widely used by women with premenstrual syndrome (PMS) in Europe, however, in Japan, clinical evidence remains to be determined. This study attempted to investigate the efficacy and safety profiles of VAC extract in Japanese patients with PMS. A multi-center, prospective, open-label, single-arm, phase 3 study was performed in Japanese women with PMS and aged 18-44 years. The patients received Prefemin® (Max Zeller Söhne AG, Romanshorn, Switzerland), containing 20 mg of VAC extract, once daily for three menstrual cycles. The efficacy profile was examined based on the intensity of ten PMS symptoms-irritability, depressed mood, anger, headache, bloating, breast fullness, skin disorder, fatigue, drowsiness, and sleeplessness-recorded by patients via a visual analog scale (VAS). In addition, the responder rate was calculated based on the total VAS score defined by the sum of the VAS scores of the first six symptoms mentioned above. Furthermore, physician's global assessment (PGA) scores were recorded. Adverse events including vital signs and laboratory test values were monitored as safety evaluation. Sixty-nine patients received Prefemin®. After the first menstrual cycle, a statistically significant decrease in total VAS score was observed (P<0.001), and the score continued to diminish for the following two cycles. Each of the ten symptom scores decreased significantly in this manner. In addition, the responder rate increased in a time-dependent manner; the rate at the third menstrual cycle was 91.0%, and almost all of the patients were without symptoms or exhibited only mild symptoms based on PGA. Eight patients exhibited non-serious adverse events, one of which was allergic dermatitis whose causal relationship with VAC was not ruled out. VAC extract improved PMS symptoms in Japanese patients, with no substantial adverse events. This is the first study to report the effect of VAC extract in Japanese

  12. Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15.

    Science.gov (United States)

    Cambau, E; Saunderson, P; Matsuoka, M; Cole, S T; Kai, M; Suffys, P; Rosa, P S; Williams, D; Gupta, U D; Lavania, M; Cardona-Castro, N; Miyamoto, Y; Hagge, D; Srikantam, A; Hongseng, W; Indropo, A; Vissa, V; Johnson, R C; Cauchoix, B; Pannikar, V K; Cooreman, E A W D; Pemmaraju, V R R; Gillini, L

    2018-03-01

    Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. A Prospective Randomized Study on Operative Treatment for Simple Distal Tibial Fractures-Minimally Invasive Plate Osteosynthesis Versus Minimal Open Reduction and Internal Fixation.

    Science.gov (United States)

    Kim, Ji Wan; Kim, Hyun Uk; Oh, Chang-Wug; Kim, Joon-Woo; Park, Ki Chul

    2018-01-01

    To compare the radiologic and clinical results of minimally invasive plate osteosynthesis (MIPO) and minimal open reduction and internal fixation (ORIF) for simple distal tibial fractures. Randomized prospective study. Three level 1 trauma centers. Fifty-eight patients with simple and distal tibial fractures were randomized into a MIPO group (treatment with MIPO; n = 29) or a minimal group (treatment with minimal ORIF; n = 29). These numbers were designed to define the rate of soft tissue complication; therefore, validation of superiority in union time or determination of differences in rates of delayed union was limited in this study. Simple distal tibial fractures treated with MIPO or minimal ORIF. The clinical outcome measurements included operative time, radiation exposure time, and soft tissue complications. To evaluate a patient's function, the American Orthopedic Foot and Ankle Society ankle score (AOFAS) was used. Radiologic measurements included fracture alignment, delayed union, and union time. All patients acquired bone union without any secondary intervention. The mean union time was 17.4 weeks and 16.3 weeks in the MIPO and minimal groups, respectively. There was 1 case of delayed union and 1 case of superficial infection in each group. The radiation exposure time was shorter in the minimal group than in the MIPO group. Coronal angulation showed a difference between both groups. The American Orthopedic Foot and Ankle Society ankle scores were 86.0 and 86.7 in the MIPO and minimal groups, respectively. Minimal ORIF resulted in similar outcomes, with no increased rate of soft tissue problems compared to MIPO. Both MIPO and minimal ORIF have high union rates and good functional outcomes for simple distal tibial fractures. Minimal ORIF did not result in increased rates of infection and wound dehiscence. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

  14. Clinical and radiographic outcomes of medial open-wedge high tibial osteotomy with Anthony-K plate: prospective minimum five year follow-up data.

    Science.gov (United States)

    Altay, Mehmet Akif; Ertürk, Cemil; Altay, Nuray; Mercan, Ahmet Şükrü; Sipahioğlu, Serkan; Kalender, Ali Murat; Işıkan, Uğur Erdem

    2016-07-01

    The purpose of this study was to prospectively evaluate the clinical and radiographic outcomes, and complication rates, after a minimum of five years of follow-up after medial open wedge high tibial osteotomy (MOWHTO) using an Anthony-K plate. MOWHTO was performed on 35 knees of 34 consecutive patients. A visual analogue scale (VAS), and Western Ontario and McMaster University Osteoarthritis (WOMAC) and Lysholm scores, were used in clinical evaluation. Upon radiographic assessment, alignment was expressed as the femorotibial angle (FTA). The posterior tibial slope (PTS) and the Insall-Salvati Index (ISI) were also measured. VAS, WOMAC, and Lysholm scores improved significantly upon follow-up (p FTA was 4.68 ± 4.39° varus pre-operatively; at the last post-operative follow-up, the value was 8.43 ± 2.02° valgus. The mean correction angle was 13.1 ± 2.7°. A significant increase in PTS was evident (p < 0.01), as was a significant decrease in the ISI (p < 0.01). The overall complication rate was 8.6 %. The Anthony-K plate affords accurate correction, initially stabilises the osteotomy after surgery, and maintains such stability until the osteotomy gap is completely healed, without correction loss. The plate survival rate was 97.2 % after a minimum of five years of follow-up. The plate increased the PTS, as do other medial osteotomy fixation plates.

  15. Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

    Science.gov (United States)

    Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

    2013-04-01

    Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

  16. Health risk factors and the incidence of hypertension: 4-year prospective findings from a national cohort of 60 569 Thai Open University students.

    Science.gov (United States)

    Thawornchaisit, Prasutr; de Looze, Ferdinandus; Reid, Christopher M; Seubsman, Sam-Ang; Sleigh, Adrian C

    2013-06-25

    This study evaluates the impact of a number of demographic, biological, behavioural and lifestyle health risk factors on the incidence of hypertension in Thailand over a 4-year period. A 4-year prospective study of health risk factors and their effects on the incidence of hypertension in a national Thai Cohort Study from 2005 to 2009. As Thailand is transitioning from a developing to a middle-income developed country, chronic diseases (particularly cardiovascular disease) have emerged as major health issues. Hypertension is a major risk factor for heart attack and stroke and cross-sectional studies have indicated that the prevalence is increasing. A total of 57 558 Sukhothai Thammathirat Open University students who participated in both the 2005 and 2009 questionnaire surveys and who were normotensive in 2005 were included in the analysis. Adjusted relative risks associating each risk factor and incidence of hypertension by sex, after controlling for confounders such as age, socioeconomic status, body mass index (BMI) and underlying diseases. The overall 4-year incidence of hypertension was 3.5%, with the rate in men being remarkably higher than that in women (5.2% vs 2.1%). In both sexes, hypertension was associated with age, higher BMI and comorbidities but not with income and education. In men, hypertension was associated with physical inactivity, smoking, alcohol and fast food intake. In women, hypertension was related to having a partner. In both men and women, hypertension was strongly associated with age, obesity and comorbidities while it had no association with socioeconomic factors. The cohort patterns of socioeconomy and hypertension reflect that the health risk transition in Thais is likely to be at the middle stage. Diet and lifestyle factors associate with incidence of hypertension in Thais and may be amenable targets for hypertension control programmes.

  17. A prospective study on fetal posterior cranial fossa assessment for early detection of open spina bifida at 11-13 weeks.

    Science.gov (United States)

    Kose, Semir; Altunyurt, Sabahattin; Keskinoglu, Pembe

    2018-01-01

    The objective of this study was to test three measurements: brain stem (BS), intracranial translucency (IT) and brain stem to occipital bone distance (BSOB), as well as one landmark: cisterna magna (CM) visibility, for early diagnosis of open spina bifida (OSB) in a low risk population. A prospective observational study was undertaken in a university hospital. A sample of 1479 women consented to participate between 20 September 2013 and 30 June 2015. Measurements were performed from the mid-sagittal view, as is routinely used for nuchal thickness assessment. CM visibility was assessed qualitatively as the third anechoic band in the posterior cranial fossa (PCF). All pregnancies were screened with a combination of maternal serum alpha-fetoprotein and second trimester anomaly scan and followed until delivery. Predictive values were calculated for each marker. We were able to diagnose two OSB cases and highly suspect one Dandy-Walker malformation case at the first trimester scan by the observation of PCF. PCF characteristics of OSB cases were increased BS diameter, increased BS-BSOB ratio and non-visualization of the CM. All the markers demonstrated high sensitivity and specificity but CM visibility reached the highest positive predictive value. Due to relatively high false positive rates, PCF measurements could not reach a satisfactory performance to validate their clinical use as a single marker. CM visibility has the advantage of being a qualitative marker and reduces the need for sophisticated and time-consuming measurements. Intracranial translucency and BS-BSOB ratio measurements should be used when the CM visibility is absent or in doubt. © 2017 Japanese Teratology Society.

  18. Intradialytic parenteral nutrition in maintenance hemodialysis patients suffering from protein-energy wasting. Results of a multicenter, open, prospective, randomized trial.

    Science.gov (United States)

    Marsen, Tobias A; Beer, Justinus; Mann, Helmut

    2017-02-01

    Protein-energy wasting (PEW) is increasingly becoming a clinical problem in maintenance hemodialysis patients and guidelines call for nutritional interventions. Serum prealbumin (transthyretin) represents a critical nutritional marker positively correlated with patient survival and negatively correlated with morbidity. Nutritional counseling, oral supplementation as well as intradialytic parenteral nutrition (IDPN) are recommended to fight PEW, however clinical trials on their use are scarce. We conducted a prospective, multicenter, randomized, open-label, controlled, parallel-group Phase IV clinical trial in 107 maintenance hemodialysis patients suffering from PEW to assess the impact of IDPN on prealbumin and other biochemical and clinical parameters reflecting nutritional status. Patients randomized to the intervention group received standardized nutritional counseling plus IDPN three times weekly over 16 weeks followed by a treatment-free period of 12 weeks. The control group received standardized nutritional counseling only. Main trial inclusion criteria included moderate to severe malnutrition (SGA score B or C), maintenance hemodialysis therapy (3 times per week) for more than six months, and presence of two out of the following three criteria: albumin 30 mg/L at week 16 (48.7% vs. 31.8%). Prealbumin response to IDPN therapy was more prominent in patients suffering from moderate malnutrition (SGA score B) compared to patients with severe malnutrition (SGA score C). The results of this trial demonstrate for the first time that IDPN therapy, given three times weekly in a 16-week short-term intervention, results in a statistically significant and clinically relevant increase in mean serum prealbumin, a surrogate marker for outcome and survival in hemodialysis patients suffering from PEW, and is superior to nutritional counseling. Clinical trial registry:www.clinicaltrials.gov (NCT00501956). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights

  19. A prospective, observational, open-label, multicentre study to investigate the daily treatment practice of ranibizumab in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    van Asten, Freekje; Evers-Birkenkamp, Kim U; van Lith-Verhoeven, Janneke J C; de Jong-Hesse, Yvonne; Hoppenreijs, Vincent P T; Hommersom, Richard F; Scholten, Agnes M; Hoyng, Carel B; Klaver, Johannes H J

    2015-03-01

    The HELIOS (Health Economics with Lucentis in Observational Settings) study was designed on request of the Dutch Health Authority for an observational study to assess the effectiveness and safety of ranibizumab for neovascular age-related macular degeneration (wet AMD) in daily practice. The HELIOS study was a 2-year prospective, observational, open-label, multicentre study involving 14 sites. Patients with wet AMD were enrolled and observed for a period of 24 months. The data were collected at baseline and at the visits closest around the time-points 3, 6, 12, 18 and 24 months after inclusion. Treatment with ranibizumab resulted in prevention of vision loss. The mean ETDRS score increased from 45.1 letters at baseline to 48.5 letters at 24 months. This was achieved with a mean of 7.8 injections over 24 months. Stabilization of visual acuity was also reflected by the scores on the quality of life EQ-5D questionnaire, which did not significantly change over the study period. The more subjective EQ-VAS questionnaire showed an overall improvement. The VFQ-25 questionnaire was also mostly stable over time. After 24 months, 32.2% of the patients gained ≥1 letter and 17.1% gained >15 letters. Patients completing the loading phase were better responders, as demonstrated by increased long-term visual acuity. In addition, ranibizumab was well tolerated and had a safety profile commonly seen in routine clinical practice. This study demonstrates that also in daily practice ranibizumab was effective in preventing vision loss over a period of 24 months. No new safety findings were identified. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  20. [Calcaneal fractures treated by open reduction and internal fixation with a locking compression plate (LCP). A prospective study. part I: basic analysis of the group].

    Science.gov (United States)

    Svatoš, F; Bartoška, R; Skála-Rosenbaum, J; Douša, P; Pacovský, V; Krbec, M

    2011-01-01

    In a prospective study of patients with calcaneal fractures treated by open reduction from an extensile lateral approach and LCP osteosynthesis, the authors evaluated the basic epidemiological data, mechanism of injury, type of fracture, essential data on surgery, days of hospital stay and the number of complications. In the period from September 1, 2006 to July 31, 2010, a total of 230 patients with 243 calcaneal fractures were treated. The fractures were classified as either open or closed and according to the Essex-Lopresti system. Of the total number of patients, 135 (55.6 % of all fractures) were indicated for conservative treatment and 108 (44.4% of all fractures) for surgical intervention. Indications for surgery based on the generally accepted criteria enabled us to select 77 patients with 82 fractures (33.7 % of all fractures) for treatment by the method of open reduction and LCP osteosynthesis. These patients constituted the group evaluated here. The other patients were treated using other techniques (21 fractures, i.e., 8.6 % of all fractures, by the Stehlík-Štulík transfixation method and further five [2.1 %] by screw osteosynthesis). Six surgeons were involved in the treatment of this group. For the diagnosis of fractures, plain radiographs in lateral and axial projection and axial and coronal CT images were used. All fractures were treated after subsidence of oedema by the method of open reduction and LCP fixation from an extensile lateral approach, with the use of a tourniquet. The follow-up period for the evaluation of functional outcome and bone union was 3 to 48 months. Fifty patients were followed up for over one year. The group evaluated comprised 58 men (75.3 %) with 63 fractures (76.8 %) and 19 women (24.7 %) with 19 fractures (23.2 %). The average age of the group was 42 years, with 41 years (range, 22-61 years) in men and 47 years (range, 30-70 years) in women. The most frequent cause of injury was a fall from a height below 1 metre and

  1. [Pegylation and interferons in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Diego Centonze

    2016-07-01

    Full Text Available Pegylation is a procedure used for drug development since the 1970s and consists of the conjugation of a polyethylene glycol molecule (PEG to a drug. PEG has shown to be safe and effective in improving the pharmacokinetic and pharmacodynamic profile of drugs. Recently, a 20 kDa linear chain of PEG was conjugated to interferon beta-1a with the aim to offer a new treatment option to relapsing-remitting multiple sclerosis (RRMS patients. Due to a prolonged bioavailability, this new drug can be administered less frequently (every two weeks than the other interferons beta available, thus allowing to hypothesize a better adherence to the treatment, which, in turn, should result in better clinical and economic outcomes. A phase III clinical trial has proven its effectiveness compared to placebo in RRMS patients, as well as a safety profile comparable to that found in other interferon beta preparations. The immunogenicity of this new molecule is < 1%, thus minimizing the suppression or reduction of interferon beta biological activity that could come from the development of Neutralizing Antibodies (NAbs. [Article in Italian

  2. Interferon alfa and ribavirin induced hair changes

    International Nuclear Information System (INIS)

    Amir, S.; Taj, A.; Muhamud, T.H.; Iqbal, Z.; Yaqub, F.

    2007-01-01

    Combination therapy of Interferon alfa and ribavirin in chronic hepatitis C has well documented cutaneous adverse effects. Most interesting of these has been reported on hair physiology. This study was conducted to determine the frequency and pattern of adverse effects involving hair in patients receiving combination of interferon alfa 2a and ribavirin for chronic hepatitis C. The study was conducted in Department of Dermatology, Division of Medicine Shaikh Zayed Hospital. Thirty Eight patients who completed treatment with interferon alfa (3 MIU subcutaneously thrice weekly) and 1200 mg ribavirin daily for 24 weeks were enrolled in this single-center study. The patient's response and examination finding particularly regarding involvement of hair was noted on a Proforma. Thirty Two out of thirty eight (84%) patients noted adverse effects involving hair. The most frequent was diffuse hair loss and occurred in 27 patients (71%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 18 (47%) and 16 (42%) patients respectively. Graying of hair was noted in 4 patients (11%), while discoloration of moustache hair was seen in 2 patients (5%). Epilation at the site of subcutaneous injection was noted in 10 patients (26%). Alopecia areata was reported in 2 patients (5%). It is concluded that adverse effects involving hair are frequent and varied (hair loss to excess hair growth) during combination therapy with Interferon alfa-2a and Ribavirin for chronic hepatitis C. (author)

  3. Interferon alpha association with neuromyelitis optica

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Voss, Anne; Steenstrup, Troels

    2013-01-01

    Interferon-alpha (IFN- α ) has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN- α in neuromyelitis optica (NMO) patients. Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population...

  4. Interferons in the central nervous system

    DEFF Research Database (Denmark)

    Owens, Trevor; Khorooshi, Reza M. H.; Wlodarczyk, Agnieszka

    2014-01-01

    Interferons (IFNs) are implicated as an important component of the innate immune system influencing viral infections, inflammation, and immune surveillance. We review here the complex biological activity of IFNs in the central nervous system (CNS) and associated glial–immune interactions...

  5. Opening remarks

    International Nuclear Information System (INIS)

    Kyd, D.R.

    1993-11-01

    In his opening remarks Mr. David R. Kyd briefly described the IAEA mission. Then he outlined main aim of the seminar which is bring together journalists, educators, officials and other specialists to let them hear and put questions to experts on various aspects of nuclear energy and techniques. Further he analyzed problems and prospects of energy development in Asia and particularly in China, including environmental considerations. The final part of the remarks was devoted comparative evaluation of different energy production technologies

  6. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.

    Science.gov (United States)

    Rice, Gillian I; Forte, Gabriella M A; Szynkiewicz, Marcin; Chase, Diana S; Aeby, Alec; Abdel-Hamid, Mohamed S; Ackroyd, Sam; Allcock, Rebecca; Bailey, Kathryn M; Balottin, Umberto; Barnerias, Christine; Bernard, Genevieve; Bodemer, Christine; Botella, Maria P; Cereda, Cristina; Chandler, Kate E; Dabydeen, Lyvia; Dale, Russell C; De Laet, Corinne; De Goede, Christian G E L; Del Toro, Mireia; Effat, Laila; Enamorado, Noemi Nunez; Fazzi, Elisa; Gener, Blanca; Haldre, Madli; Lin, Jean-Pierre S-M; Livingston, John H; Lourenco, Charles Marques; Marques, Wilson; Oades, Patrick; Peterson, Pärt; Rasmussen, Magnhild; Roubertie, Agathe; Schmidt, Johanna Loewenstein; Shalev, Stavit A; Simon, Rogelio; Spiegel, Ronen; Swoboda, Kathryn J; Temtamy, Samia A; Vassallo, Grace; Vilain, Catheline N; Vogt, Julie; Wermenbol, Vanessa; Whitehouse, William P; Soler, Doriette; Olivieri, Ivana; Orcesi, Simona; Aglan, Mona S; Zaki, Maha S; Abdel-Salam, Ghada M H; Vanderver, Adeline; Kisand, Kai; Rozenberg, Flore; Lebon, Pierre; Crow, Yanick J

    2013-12-01

    Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials. In this case-control study, samples were collected prospectively from patients with mutation-proven AGS. The expression of six interferon-stimulated genes (ISGs) was measured by quantitative PCR, and the median fold change, when compared with the median of healthy controls, was used to create an interferon score for each patient. Scores higher than the mean of controls plus two SD (>2·466) were designated as positive. Additionally, we collated historical data for interferon activity, measured with a viral cytopathic assay, in CSF and serum from mutation-positive patients with AGS. We also undertook neutralisation assays of interferon activity in serum, and looked for the presence of autoantibodies against a panel of interferon proteins. 74 (90%) of 82 patients had a positive interferon score (median 12·90, IQR 6·14-20·41) compared with two (7%) of 29 controls (median 0·93, IQR 0·57-1·30). Of the eight patients with a negative interferon score, seven had mutations in RNASEH2B (seven [27%] of all 26 patients with mutations in this gene). Repeat sampling in 16 patients was consistent for the presence or absence of an interferon signature on 39 of 41 occasions. Interferon activity (tested in 147 patients) was negatively correlated with age (CSF, r=-0·604; serum, r=-0·289), and was higher in CSF than in serum in 104 of 136 paired samples. Neutralisation assays suggested that measurable antiviral activity was related to interferon α production. We did not record significantly increased concentrations of autoantibodies to interferon subtypes in patients with AGS, or an association between the presence

  7. Effects of Interferon Therapy on Heart

    International Nuclear Information System (INIS)

    Faisal, A. W. K.; Ali, S. A.; Nisar, S.; Ahmad, F.

    2016-01-01

    Background: Hepatitis C virus (HCV) infection is a major health problem worldwide. Around 185 million people are suffering from HCV infection all over the world, out of which 10 million people are residing in Pakistan. 4.7 percent (2-14 percent by different studies) of Pakistanis are suffering from this deadly disease. Interferon+Ribavarin IFN/RIB is the mainstay of treatment for this infection. Various cardiovascular adverse reactions have been reported of this therapy. We conducted this study at Punjab Institute of cardiology to look for the cardiac safety of interferon therapy in our population. Methods: We studied HCV infected patients planned for interferon therapy between 21st of November 2012 to 20th of August 2014. Echocardiography was performed before, during and after the completion of therapy. Pegylated interferon once a week plus ribavirin therapy was given to the patients. Patients received 16-40 injections of pegylated interferon depending upon the decision of hepatologist. Patients with prior structural heart disease, patients who did not start the treatment or patients who did not turn up on follow up were excluded from the study. Results: A total of 102 patients planned to have interferon therapy were screened echocardiographically. One patient died after 5 injections due to infection (a non-cardiac cause). 46 patients completed the treatment and the follow up. None of the patients had any acute cardiac event. All patients had normal biventricular systolic function at the end of study. None of the patients had significant valvular heart disease or pulmonary hypertension. Reversal of E/A ratio or E/A ratio>2, parameters of diastolic dysfunction and mild pericardial effusion were noted in a statistically significant number of patients. Conclusion: Interferon therapy for HCV infection is cardiac safe in patients who have structurally normal heart. Female patients have propensity of adverse events like severe diastolic dysfunction and mild pericardial

  8. Literature systematic review on the ophthalmological side effects of interferons

    Directory of Open Access Journals (Sweden)

    Yara Dadalti Fragoso

    2011-08-01

    Full Text Available Interferons alpha and beta have been used worldwide for a few decades, altering the natural history of several severe diseases including hepatitis C, cancer and immune-mediated conditions such as multiple sclerosis. The adverse events profile of interferons is well established, but only isolated reports of ophthalmological complications of interferon therapy have been published. The objective of this study was to carry out a literature systematic review on the subject, bringing to light the need for careful ophthalmological monitoring of patients undergoing interferon treatment. Nearly 500 cases of ophthalmological complications related to interferon have been reported. The most frequent findings were soft exudates, hemorrhages and retina ischemia.

  9. Cystic craniopharyngioma: intratumoral chemotherapy with alpha interferon

    Directory of Open Access Journals (Sweden)

    Patrícia Alessandra Dastoli

    2011-02-01

    Full Text Available OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.

  10. Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN.

    Science.gov (United States)

    Kilday, John-Paul; Caldarelli, Massimo; Massimi, Luca; Chen, Robert Hsin-Hung; Lee, Yi Yen; Liang, Muh-Lii; Parkes, Jeanette; Naiker, Thuran; van Veelen, Marie-Lise; Michiels, Erna; Mallucci, Conor; Pettorini, Benedetta; Meijer, Lisethe; Dorfer, Christian; Czech, Thomas; Diezi, Manuel; Schouten-van Meeteren, Antoinette Y N; Holm, Stefan; Gustavsson, Bengt; Benesch, Martin; Müller, Hermann L; Hoffmann, Anika; Rutkowski, Stefan; Flitsch, Joerg; Escherich, Gabriele; Grotzer, Michael; Spoudeas, Helen A; Azquikina, Kristian; Capra, Michael; Jiménez-Guerra, Rolando; MacDonald, Patrick; Johnston, Donna L; Dvir, Rina; Constantini, Shlomi; Kuo, Meng-Fai; Yang, Shih-Hung; Bartels, Ute

    2017-10-01

    Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years. Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted. © The Author(s) 2017. Published by Oxford University Press on behalf of

  11. Similarities of cellular receptors for interferon and cortisol

    International Nuclear Information System (INIS)

    Filipic, B.; Schauer, P.; Likar, M.

    1977-01-01

    Cellular receptors are molecules located on the cell membrane. Their function is to bind different molecules to the cell surface. These molecules can penetrate into the cytoplasm and trigger cellular changes. One kind of such bound molecules are interferons and corticosteroids. Until very recently very little was known about interferon's receptors on the cell surface, mechanisms of interferon's binding to them or about kinetics of such binding. On the basis of results published elsewhere and on the basis of experimental results, the authors suggest: receptors for interferon and cortisol are glycoproteins located on the cell surface, in analogy with PHA receptors they are chemically sialoglycoproteins, binding kinetics of cortisol and interferon is similar, interferon and cortisol compete for cellular receptors, binding of cortisol or interferon is dependent on allosteric configuration of receptor molecules. (author)

  12. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial.

    Science.gov (United States)

    Laing, Richard W; Mergental, Hynek; Yap, Christina; Kirkham, Amanda; Whilku, Manpreet; Barton, Darren; Curbishley, Stuart; Boteon, Yuri L; Neil, Desley A; Hübscher, Stefan G; Perera, M Thamara P R; Muiesan, Paolo; Isaac, John; Roberts, Keith J; Cilliers, Hentie; Afford, Simon C; Mirza, Darius F

    2017-11-28

    The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres. Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival. The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. NCT02740608

  13. Dentoskeletal outcomes of a rapid maxillary expander with differential opening in patients with bilateral cleft lip and palate: A prospective clinical trial

    Science.gov (United States)

    Garib, Daniela; De Cássia Moura Carvalho Lauris, Rita; Calil, Louise Resti; De Medeiros Alves, Arthur César; Janson, Guilherme; De Almeida, Araci Malagodi; Cevidanes, Lúcia Helena Soares; Lauris, José Roberto Pereira

    2017-01-01

    Introduction The purpose of this 2-arm parallel study was to evaluate the dentoskeletal effects of rapid maxillary expansion with differential opening (EDO) compared with the hyrax expander in patients with complete bilateral cleft lip and palate. Methods A sample of patients with complete bilateral cleft lip and palate was prospectively and consecutively recruited. Eligibility criteria included participants in the mixed dentition with lip and palate repair performed during early childhood and maxillary arch constriction with a need for maxillary expansion before the alveolar bone graft procedure. The participants were consecutively divided into 2 study groups. The experimental and control groups comprised patients treated with rapid maxillary expansion using EDO and the hyrax expander, respectively. Cone-beam computed tomography examinations and digital dental models of the maxillary dental arches were obtained before expansion and 6 months postexpansion. Standardized cone-beam computed tomography coronal sections were used for measuring maxillary transverse dimensions and posterior tooth inclinations. Digital dental models were used for assessing maxillary dental arch widths, arch perimeters, arch lengths, palatal depths, and posterior tooth inclinations. Blinding was used only during outcome assessment. The chi-square test was used to compare the sex ratios between groups (P <0.05). Intergroup comparisons were performed using independent t tests with the Bonferroni correction for multiple tests. Results Fifty patients were recruited and analyzed in their respective groups. The experimental group comprised 25 patients (mean age, 8.8 years), and the control group comprised 25 patients (mean age, 8.6 years). No intergroup significant differences were found for age, sex ratio, and dentoskeletal variables before expansion. No significant differences were found between the EDO and the hyrax expander groups regarding skeletal changes. The EDO promoted significantly

  14. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Schnitzbauer, Andreas A; Adam, Rene; Bechstein, Wolf O; Becker, Thomas; Beckebaum, Susanne; Chazouillères, Olivier; Cillo, Umberto; Colledan, Michele; Fändrich, Fred; Gugenheim, Jean; Hauss, Johann P; Zuelke, Carl; Heise, Michael; Hidalgo, Ernest; Jamieson, Neville; Königsrainer, Alfred; Lamby, Philipp E; Lerut, Jan P; Mäkisalo, Heikki; Margreiter, Raimund; Mazzaferro, Vincenzo; Mutzbauer, Ingrid; Graeb, Christian; Otto, Gerd; Pageaux, Georges-Philippe; Pinna, Antonio D; Pirenne, Jacques; Rizell, Magnus; Rossi, Giorgio; Rostaing, Lionel; Roy, Andre; Turrion, Victor Sanchez; Schmidt, Jan; Rochon, Justine; Troisi, Roberto I; Hoek, Bart van; Valente, Umberto; Wolf, Philippe; Wolters, Heiner; Mirza, Darius F; Scholz, Tim; Steininger, Rudolf; Soderdahl, Gunnar; Strasser, Simone I; Bilbao, Itxarone; Jauch, Karl-Walter; Neuhaus, Peter; Schlitt, Hans J; Geissler, Edward K; Burra, Patrizia; Jong, Koert P de; Duvoux, Christophe; Kneteman, Norman M

    2010-01-01

    The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2 1/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from

  15. Comparison of toxin removal outcomes in online hemodiafiltration and intra-dialytic exercise in high-flux hemodialysis: A prospective randomized open-label clinical study protocol

    Directory of Open Access Journals (Sweden)

    Maheshwari Vaibhav

    2012-11-01

    Full Text Available Abstract Background Maintenance hemodialysis (HD patients universally suffer from excess toxin load. Hemodiafiltration (HDF has shown its potential in better removal of small as well as large sized toxins, but its efficacy is restricted by inter-compartmental clearance. Intra-dialytic exercise on the other hand is also found to be effective for removal of toxins; the augmented removal is apparently obtained by better perfusion of skeletal muscles and decreased inter-compartmental resistance. The aim of this trial is to compare the toxin removal outcome associated with intra-dialytic exercise in HD and with post-dilution HDF. Methods/design The main hypothesis of this study is that intra-dialytic exercise enhances toxin removal by decreasing the inter-compartmental resistance, a major impediment for toxin removal. To compare the HDF and HD with exercise, the toxin rebound for urea, creatinine, phosphate, and β2-microglobulin will be calculated after 2 hours of dialysis. Spent dialysate will also be collected to calculate the removed toxin mass. To quantify the decrease in inter-compartmental resistance, the recently developed regional blood flow model will be employed. The study will be single center, randomized, self-control, open-label prospective clinical research where 15 study subjects will undergo three dialysis protocols (a high flux HD, (b post-dilution HDF, (c high flux HD with exercise. Multiple blood samples during each study session will be collected to estimate the unknown model parameters. Discussion This will be the first study to investigate the exercise induced physiological change(s responsible for enhanced toxin removal, and compare the toxin removal outcome both for small and middle sized toxins in HD with exercise and HDF. Successful completion of this clinical research will give important insights into exercise effect on factors responsible for enhanced toxin removal. The knowledge will give confidence for implementing

  16. Open abdominal management after damage-control laparotomy for trauma: a prospective observational American Association for the Surgery of Trauma multicenter study.

    Science.gov (United States)

    Dubose, Joseph J; Scalea, Thomas M; Holcomb, John B; Shrestha, Binod; Okoye, Obi; Inaba, Kenji; Bee, Tiffany K; Fabian, Timothy C; Whelan, James; Ivatury, Rao R

    2013-01-01

    We conducted a prospective observational multi-institutional study to examine the natural history of the open abdomen (OA) after trauma and identify risk factors for failure to achieve definitive primary fascial closure (DPC) after OA use in trauma. Adults requiring OA for trauma were enrolled during a 2-year period. Demographics, presentation, and management variables were used to compare primary fascial closure and non-primary fascial closure patients, with logistic regression used to identify independent risk factors for failure to achieve primary fascial closure. A total of 572 patients from 14 American College of Surgeons-verified Level I trauma centers were enrolled. The majority were male (79%), mean (SD) age 39 (17) years. Injury Severity Score (ISS) was 15 or greater in 85% of patients and 84% had an abdominal Abbreviated Injury Scale (AIS) score of 3 or greater. Overall mortality was 23%. Initial primary fascial closure with unaltered native fascia was achieved in 379 patients (66%). Patients surviving at least 48 hours were grouped into those achieving DPC and those who did not achieve DPC after OA use. After logistic regression, independent risk factors for failure to achieve DPC included the number of reexplorations required (adjusted odds ratio [AOR], 1.3; 95% confidence interval (CI), 1.2-1.6; p < 0.001) the development of intra-abdominal abscess/sepsis (AOR, 2.4; 95% CI, 1.2-4.8; p = 0.011) bloodstream infection (AOR, 2.6; 95% CI, 1.2-5.7; p = 0.017), acute renal failure (AOR, 2.3; 95% CI, 1.2-5.7; p = 0.007), enteric fistula (AOR, 6.4; 95% CI, 1.2-32.8; p = 0.010) and ISS of greater than 15 (AOR, 2.5; 95% CI, 1.1-5.9; p = 0.037). Our study identifies independent risk factors associated with failure to achieve primary fascial closure during initial hospitalization after OA use for trauma. Additional study is required to validate appropriate algorithms that optimize the opportunity to achieve primary fascial closure and outcomes in this population

  17. Accelerated rehabilitation compared with a standard protocol after distal radial fractures treated with volar open reduction and internal fixation: a prospective, randomized, controlled study.

    Science.gov (United States)

    Brehmer, Jess L; Husband, Jeffrey B

    2014-10-01

    There are relatively few studies in the literature that specifically evaluate accelerated rehabilitation protocols for distal radial fractures treated with open reduction and internal fixation (ORIF). The purpose of this study was to compare the early postoperative outcomes (at zero to twelve weeks postoperatively) of patients enrolled in an accelerated rehabilitation protocol with those of patients enrolled in a standard rehabilitation protocol following ORIF for a distal radial fracture. We hypothesized that patients with accelerated rehabilitation after volar ORIF for a distal radial fracture would have an earlier return to function compared with patients who followed a standard protocol. From November 2007 to November 2010, eighty-one patients with an unstable distal radial fracture were prospectively randomized to follow either an accelerated or a standard rehabilitation protocol after undergoing ORIF with a volar plate for a distal radial fracture. Both groups began with gentle active range of motion at three to five days postoperatively. At two weeks, the accelerated group initiated wrist/forearm passive range of motion and strengthening exercises, whereas the standard group initiated passive range of motion and strengthening at six weeks postoperatively. Patients were assessed at three to five days, two weeks, three weeks, four weeks, six weeks, eight weeks, twelve weeks, and six months postoperatively. Outcomes included Disabilities of the Arm, Shoulder and Hand (DASH) scores (primary outcome) and measurements of wrist flexion/extension, supination, pronation, grip strength, and palmar pinch. The patients in the accelerated group had better mobility, strength, and DASH scores at the early postoperative time points (zero to eight weeks postoperatively) compared with the patients in the standard rehabilitation group. The difference between the groups was both clinically relevant and statistically significant. Patients who follow an accelerated rehabilitation

  18. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Roy Andre

    2010-05-01

    Full Text Available Abstract Background The potential anti-cancer effects of mammalian target of rapamycin (mTOR inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC-free patient survival in liver transplant (LT recipients with a pre-transplant diagnosis of HCC. Methods/Design The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously

  19. The head impulse test as a predictor of videonystagmography caloric test lateralization according to the level of examiner experience: A prospective open-label study.

    Science.gov (United States)

    Awadie, Ashraf; Holdstein, Yehuda; Kaminer, Margalit; Shupak, Avi

    2018-01-01

    We conducted a study to compare how well the head impulse test (HIT), without and with eye-movement recordings, would predict videonystagmographic (VNG) caloric test lateralization when performed by a resident and an experienced otoneurologist. This prospective, open-label, blinded study was conducted in an ambulatory tertiary care referral center. Our study population was made up of 60 patients-29 men and 31 women, aged 20 to 82 years (mean: 56.4 ± 11.4)-with peripheral vestibulopathy who underwent HIT and VNG caloric testing. The HIT was conducted in two protocols: HIT0 and HIT1. The HIT0 was performed with passive brisk movements of the patient's head from the 0° null position to 20° sideways, and the HIT1 was performed toward the center while the null position was a 20° head rotation to the right and to the left. Each protocol was carried out without video eye-movement recordings (HIT0 and HIT1) and with such recordings (rHIT0 and rHIT1). The primary outcome measures were (1) a comparison of the HIT's sensitivity and specificity when performed by the resident and by the experienced otoneurologist and (2) the ability of video-recorded HIT to predict VNG caloric test lateralization. The sensitivity and specificity obtained by the resident were 41 and 81%, respectively, for HIT0 and 41 and 90% for HIT1. The sensitivity and specificity obtained by the experienced otoneurologist were 18 and 89% for HIT0 and 32 and 85% for HIT1. Analysis of the recorded eye-movement clips of the HIT0 and HIT1 obtained by a second experienced otoneurologist found a sensitivity and specificity of 32 and 63% for rHIT0 and 33 and 82% for rHIT1. We conclude that the HIT yields high false-negative rates in predicting significant caloric lateralization. Analysis of the eye-movement recordings was no better than normal testing alone for detecting saccades. The experience of the examining physician had no impact on test performance characteristics.

  20. Oromucosal Administration of Interferon to Humans

    Directory of Open Access Journals (Sweden)

    Manfred W. Beilharz

    2010-01-01

    Full Text Available The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNa therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.

  1. Mouth-opening device as a treatment modality in trismus patients with head and neck cancer and oral submucous fibrosis: a prospective study.

    Science.gov (United States)

    Li, Yu-Hsuan; Chang, Wei-Chin; Chiang, Tien-En; Lin, Chiun-Shu; Chen, Yuan-Wu

    2018-04-26

    This study investigated the clinical effectiveness of intervention with an open-mouth exercise device designed to facilitate maximal interincisal opening (MIO) and improve quality of life in patients with head and neck (H&N) cancer and oral submucous fibrosis (OSF). Sixty patients with H&N cancer, OSF, and trismus (MIO cancer and OSF and improve mouth-opening range and quality of life.

  2. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

    2012-07-18

    Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0

  3. Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial.

    Science.gov (United States)

    Kalra, Lalit; Irshad, Saddif; Hodsoll, John; Simpson, Matthew; Gulliford, Martin; Smithard, David; Patel, Anita; Rebollo-Mesa, Irene

    2015-11-07

    Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in patients with dysphagia after acute stroke. We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com, number ISRCTN37118456. Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 [13%] of 564 patients in antibiotics group vs 52

  4. Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study.

    Science.gov (United States)

    Timmermann, Lars; Jain, Roshini; Chen, Lilly; Maarouf, Mohamed; Barbe, Michael T; Allert, Niels; Brücke, Thomas; Kaiser, Iris; Beirer, Sebastian; Sejio, Fernando; Suarez, Esther; Lozano, Beatriz; Haegelen, Claire; Vérin, Marc; Porta, Mauro; Servello, Domenico; Gill, Steven; Whone, Alan; Van Dyck, Nic; Alesch, Francois

    2015-07-01

    High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease. We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure

  5. Interferon synthesis in mouse peritoneal cells damaged by x irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Szolgay, E; T' alas, M

    1976-01-01

    NDV-induced interferon of peritoneal cells of irradiated (x-rays, 400 R) and control mice was investigated in vitro. Irradiation or treatment with hydroxyurea (10(-5) M) and mitomycin C (25 microng/ml) did not change interferon synthesis in spite of an 80 to 90% inhibition of 3H-thymidine incorporation. Increased doses of mitomycin C and treatment with actinomycin D and puromycin blocked interferon production. De novo interferon synthesis occurred in cells with damaged replicative activity of DNA caused by irradiation or by treatment with antimetabolites.

  6. Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Hegen, Harald; Adrianto, Indra; Lessard, Christopher J

    2016-01-01

    OBJECTIVE: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)-β treatment in patients with multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment...... were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays...

  7. Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

    Directory of Open Access Journals (Sweden)

    Debora Lucia Seguro Danilovic

    2011-01-01

    Full Text Available OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels, which occur despite stable free T4 and TSH levels. A thyroid

  8. A multicenter prospective study of patients undergoing open ventral hernia repair with intraperitoneal positioning using the monofilament polyester composite ventral patch

    DEFF Research Database (Denmark)

    Berrevoet, Frederik; Doerhoff, Carl; Muysoms, Filip

    2017-01-01

    PURPOSE: This study assessed the recurrence rate and other safety and efficacy parameters following ventral hernia repair with a polyester composite prosthesis (Parietex™ Composite Ventral Patch [PCO-VP]). PATIENTS AND METHODS: A single-arm, multicenter prospective study of 126 patients undergoing...

  9. How Extraverted, Open, Agreeable, Conscientious, and Neurotic Are Prospective Early Childhood Pedagogues? A Comparison with the German Socio-Economic Panel

    Science.gov (United States)

    Smidt, Wilfried; Roux, Susanna

    2015-01-01

    Against the background of theories and research, it is crucial to gather in-depth information about the Big Five personality traits of pedagogues as well as prospective pedagogues. Such information can be attained by comparing them with a cross section of the population. However, there is a research gap concerning the Big Five of early childhood…

  10. Combined adjuvant radiation and interferon-alpha 2B therapy in high-risk melanoma patients: the potential for increased radiation toxicity

    International Nuclear Information System (INIS)

    Hazard, Lisa J.; Sause, William T.; Noyes, R. Dirk

    2002-01-01

    Purpose: Surgically resected melanoma patients with high-risk features commonly receive adjuvant therapy with interferon-alpha 2b combined with radiation therapy; the purpose of our study was to evaluate the potential enhancement of radiation toxicity by interferon. Methods and Materials: Patients at LDS Hospital and the University of Utah Medical Center in Salt Lake City treated with interferon during radiotherapy or within 1 month of its completion were retrospectively identified, and their charts were reviewed. If possible, the patients were asked to return to the LDS Hospital radiation therapy department for follow-up. Results: Five of 10 patients receiving interferon-alpha 2b therapy during radiation therapy or within 1 month of its completion experienced severe subacute/late complications of therapy. Severe subacute/late complications included two patients with peripheral neuropathy, one patient with radiation necrosis in the brain, and two patients with radiation necrosis in the s.c. tissue. One patient with peripheral neuropathy and one patient with radiation necrosis also developed lymphedema. Conclusions: In vitro studies have identified a radiosensitizing effect by interferon-alpha on certain cell lines, which suggests the possibility that patients treated with interferon and radiation therapy may experience more severe radiation toxicities. We have observed severe subacute/late complications in five of 10 patients treated with interferon-alpha 2b during radiation therapy or within 1 month of its completion. Although an observational study of 10 patients lacks the statistic power to reach conclusions regarding the safety and complication rates of combined interferon and radiation therapy, it is sufficient to raise concerns and suggest the need for prospective studies

  11. Effectiveness of percutaneous laser disc decompression versus conventional open discectomy in the treatment of lumbar disc herniation; Design of a prospective randomized controlled trial

    NARCIS (Netherlands)

    P.A. Brouwer (Patrick); W.C. Peul (Wilco); R. Brand (René); M.P. Arts (Mark); B.W. Koes (Bart); A.A. van den Berg (Annette); M.A. van Buchem (Mark)

    2009-01-01

    textabstractBackground. The usual surgical treatment of refractory sciatica caused by lumbar disc herniation, is open discectomy. Minimally invasive procedures, including percutaneous therapies under local anesthesia, are increasingly gaining attention. One of these treatments is Percutaneous Laser

  12. Deregulation of Interferon Signaling in Malignant Cells

    Directory of Open Access Journals (Sweden)

    Leonidas C. Platanias

    2010-02-01

    Full Text Available Interferons (IFNs are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo, recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.

  13. Effectiveness of telemedicine and distance learning applications for patients with chronic heart failure. A protocol for prospective parallel group non-randomised open label study

    OpenAIRE

    Vanagas, Giedrius; Umbrasienė, Jelena; Šlapikas, Rimvydas

    2012-01-01

    Introduction Chronic heart failure in Baltic Sea Region is responsible for more hospitalisations than all forms of cancer combined and is one of the leading causes of hospitalisations in elderly patients. Frequent hospitalisations, along with other direct and indirect costs, place financial burden on healthcare systems. We aim to test the hypothesis that telemedicine and distance learning applications is superior to the current standard of home care. Methods and analysis Prospective parallel ...

  14. Renal failure after treatment with interferon alpha 2b

    NARCIS (Netherlands)

    Roeloffzen, WWH; Hospers, GAP; De Vries, EGE; Navis, GJ

    2002-01-01

    Although there has been considerable experience with interferons in the treatment of malignancy and viral illnesses, acute renal failure as a side-effect of interferon treatment has rarely been reported. We present the case of a patient who developed acute on chronic renal failure 16 months after

  15. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  16. Interferon-alpha in the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Khoo, T.L.; Joshua, D.; Gibson, J.

    2011-01-01

    Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the hematological malignancy multiple myeloma. Interferon has been used......-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous or allogeneic transplantation. Interferon as a single induction agent or co-induction agent with other chemotherapy agents appears only to have minimal benefit...... in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs" - thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment...

  17. Specificity, cross-talk and adaptation in Interferon signaling

    Science.gov (United States)

    Zilman, Anton

    Innate immune system is the first line of defense of higher organisms against pathogens. It coordinates the behavior of millions of cells of multiple types, achieved through numerous signaling molecules. This talk focuses on the signaling specificity of a major class of signaling molecules - Type I Interferons - which are also used therapeutically in the treatment of a number of diseases, such as Hepatitis C, multiple sclerosis and some cancers. Puzzlingly, different Interferons act through the same cell surface receptor but have different effects on the target cells. They also exhibit a strange pattern of temporal cross-talk resulting in a serious clinical problem - loss of response to Interferon therapy. We combined mathematical modeling with quantitative experiments to develop a quantitative model of specificity and adaptation in the Interferon signaling pathway. The model resolves several outstanding experimental puzzles and directly affects the clinical use of Type I Interferons in treatment of viral hepatitis and other diseases.

  18. Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone chronic hepatitis B. Protocol for a Cochrane Review

    DEFF Research Database (Denmark)

    Mellerup, M T; Krogsgaard, K; Mathurin, P

    2000-01-01

    Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon....

  19. Long-Term Adjustment after Surviving Open Heart Surgery: The Effect of Using Prayer for Coping Replicated in a Prospective Design

    Science.gov (United States)

    Ai, A. L.; Ladd, K. L.; Peterson, C.; Cook, C. A.; Shearer, M.; Koenig, H. G.

    2010-01-01

    Purpose: Despite the growing evidence for effects of religious factors on cardiac health in general populations, findings are not always consistent in sicker and older populations. We previously demonstrated that short-term negative outcomes (depression and anxiety) among older adults following open heart surgery are partially alleviated when…

  20. Open the "Black Box" Creativity and Innovation: A Study of Activities in R&D Departments. Some Prospects for Engineering Education

    Science.gov (United States)

    Millet, Charlyne; Oget, David; Cavallucci, Denis

    2017-01-01

    Innovation is a key component to the success and longevity of companies. Our research opens the "black box" of creativity and innovation in R&D teams. We argue that understanding the nature of R&D projects in terms of creativity/innovation, efficiency/inefficiency, is important for designing education policies and improving…

  1. UNEXPECTED DIFFICULTIES IN RANDOMIZING PATIENTS IN A SURGICAL TRIAL - A PROSPECTIVE-STUDY COMPARING EXTRACORPOREAL SHOCK-WAVE LITHOTRIPSY WITH OPEN CHOLECYSTECTOMY

    NARCIS (Netherlands)

    PLAISIER, PW; BERGER, MY; VANDERHUL, RL; NIJS, HGT; DENTOOM, R; TERPSTRA, OT; BRUINING, HA

    1994-01-01

    Shortly after extracorporeal shock wave lithotripsy (ESWL) was introduced as a promising new treatment modality for gallstone disease, a randomized controlled study was performed to assess the cost-effectiveness of ESWL compared to open cholecystectomy, the gold standard. During the performance of

  2. Pilot non dialysis chronic renal insufficiency study (P-ND-CRIS): a pilot study of an open prospective hospital-based French cohort.

    Science.gov (United States)

    Massol, Jacques; Janin, Gérard; Bachot, Camille; Gousset, Christophe; Deville, Geoffroy Sainte-Claire; Chalopin, Jean-Marc

    2017-02-01

    Before establishing a prospective cohort, an initial pilot study is recommended. However, there are no precise guidelines on this subject. This paper reports the findings of a French regional pilot study carried out in three nephrology departments, before realizing a major prospective Non Dialysis Chronic Renal Insufficiency study (ND-CRIS). We carried out an internal pilot study. The objectives of this pilot study were to validate the feasibility (regulatory approval, providing patients with information, availability of variables, refusal rate of eligible patients) and quality criteria (missing data, rate of patients lost to follow-up, characteristics of the patients included and non-included eligible patients, quality control of the data gathered) and estimate the human resources necessary (number of clinical research associates required). The authorizations obtained (CCTIRS - CNIL) and the contracts signed with hospitals have fulfilled the regulatory requirements. After validating the information on the study provided to patients, 1849 of them were included in three centres (university hospital, intercommunal hospital, town hospital) between April 2012 and September 2015. The low refusal rate (51 patients) and the characteristics of non-included patients have confirmed the benefit for patients of participating in the study and provide evidence of the feasibility and representativeness of the population studied. The lack of missing data on the variables studied, the quality of the data analyzed and the low number of patients lost to follow-up are evidence of the quality of the study. By taking into account the time spent by CRAs to enter data and to travel, as well as the annual patient numbers in each hospital, we estimate that five CRAs will be required in total. With no specific guidelines on how to realize a pilot study before implementing a major prospective cohort, we considered it pertinent to report our experience of P-ND-CRIS. This experience confirms

  3. Renal access in PNL under sonographic guidance: Do we really need to insert an open end ureteral catheter in dilated renal systems? A prospective randomized study.

    Science.gov (United States)

    Eryildirim, Bilal; Tuncer, Murat; Camur, Emre; Ustun, Fatih; Tarhan, Fatih; Sarica, Kemal

    2017-10-03

    To evaluate the true necessity of open end ureteral catheter insertion in patients with moderate to severe pelvicalyceal system dilation treated with percutaneous nephrolithotomy (PNL) under sonographic guidance. 50 cases treated with PNL under sonographic guidance in prone position for solitary obstructing renal stones were evaluated. Patients were randomly divided into two groups; Group 1: Patients in whom a open end ureteral catheter was inserted prior to the procedure; Group 2: Patients receiving no catheter before PNL. In addition to the duration of the procedure as a whole and also all relevant stages as well, radiation exposure time, hospitalization period, mean nephrostomy tube duration, mean drop in Hb levels and all intra and postoperative complications have been evaluated. Mean size of the stones was 308.5 ± 133.2 mm2. Mean total duration of the PNL procedure in cases with open end ureteral catheter was significantly longer than the other cases (p < 0.001). Evaluation of the outcomes of the PNL procedures revealed no statistically significant difference between two groups regarding the stone-free rates (86% vs 84%). Additionally, there was no significant difference with respect to the duration of nephrostomy tube, hospitalization period and secondary procedures needed, complication rates as well as the post-operative Hb drop levels in both groups (p = 0.6830). Our results indicate that the placement of an open end ureteral catheter prior to a PNL procedure performed under sonographic access may not be indicated in selected cases presenting with solitary obstructing renal pelvic and/or calyceal stones.

  4. Do Open Reduction and Internal Fixation With Articular Disc Anatomical Reduction and Rigid Anchorage Manifest a Promising Prospect in the Treatment of Intracapsular Fractures?

    Science.gov (United States)

    Cai, Bo-Lei; Ren, Rong; Yu, Hong-Bo; Liu, Peng-Chao; Shen, Steve G F; Shi, Jun

    2018-05-01

    In response to the increased attention to soft tissue reduction in the treatment of intracapsular condylar fractures (ICFs), a modified open reduction technique is proposed and its functional and radiographic outcomes were evaluated in this study. This is a retrospective case series study of patients with all ICF types that were treated with open reduction and internal fixation (ORIF) with articular disc anatomic reduction and rigid anchorage. Inclusion and exclusion criteria were strictly applied. Preoperative and postoperative clinical examinations of malocclusion, maximum incisor opening (MIO), laterotrusion, and temporomandibular disorder symptoms were recorded and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to assess articular position and condylar morphology and position. Thirty-four patients with ICFs (47 sides) were treated with the modified ORIF technique. At 6 months of follow-up, no malocclusion was found and the MIO considerably expanded to 3.56 ± 0.13 cm. Only 4 patients (12%) had temporomandibular joint discomfort with mouth opening. Interestingly, for unilateral type B ICFs, the laterotrusion distance to the ORIF sides was notably longer than to the non-ORIF sides. Postoperative CT and MRI showed that all fragments were properly reduced and the condyles were in the normal position. Postoperative anterior disc displacement occurred in 4 sides and condylar morphologic abnormalities (slight surface roughening and articular cartilage absorption) occurred in 3 sides (6.4%). This modified ORIF technique, which achieved good outcomes after treatment of all ICF types, shows promise for the treatment of ICFs. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

    Science.gov (United States)

    Mondal, Lakshmikanta; Baidya, Krishnapada; Choudhury, Himadri; Roy, Rupam

    2013-06-01

    The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

  6. Antiviral Activity of Lambda Interferon in Chickens

    Science.gov (United States)

    Reuter, Antje; Soubies, Sebastien; Härtle, Sonja; Schusser, Benjamin; Kaspers, Bernd

    2014-01-01

    Interferons (IFNs) are essential components of the antiviral defense system of vertebrates. In mammals, functional receptors for type III IFN (lambda interferon [IFN-λ]) are found mainly on epithelial cells, and IFN-λ was demonstrated to play a crucial role in limiting viral infections of mucosal surfaces. To determine whether IFN-λ plays a similar role in birds, we produced recombinant chicken IFN-λ (chIFN-λ) and we used the replication-competent retroviral RCAS vector system to generate mosaic-transgenic chicken embryos that constitutively express chIFN-λ. We could demonstrate that chIFN-λ markedly inhibited replication of various virus strains, including highly pathogenic influenza A viruses, in ovo and in vivo, as well as in epithelium-rich tissue and cell culture systems. In contrast, chicken fibroblasts responded poorly to chIFN-λ. When applied in vivo to 3-week-old chickens, recombinant chIFN-λ strongly induced the IFN-responsive Mx gene in epithelium-rich organs, such as lungs, tracheas, and intestinal tracts. Correspondingly, these organs were found to express high transcript levels of the putative chIFN-λ receptor alpha chain (chIL28RA) gene. Transfection of chicken fibroblasts with a chIL28RA expression construct rendered these cells responsive to chIFN-λ treatment, indicating that receptor expression determines cell type specificity of IFN-λ action in chickens. Surprisingly, mosaic-transgenic chickens perished soon after hatching, demonstrating a detrimental effect of constitutive chIFN-λ expression. Our data highlight fundamental similarities between the IFN-λ systems of mammals and birds and suggest that type III IFN might play a role in defending mucosal surfaces against viral intruders in most if not all vertebrates. PMID:24371053

  7. Carry on the glorious traditions and open up new prospects. A speech addressed to the celebration of the 45th anniversary of the founding of BRIUG

    International Nuclear Information System (INIS)

    Ma Fei

    2004-01-01

    This paper reviews the forty-five years' brilliant course of the Beijing Research Institute of Uranium Geology (BRIUG), puts emphasis on elaborating the gratifying achievements in fields of geology, geophysical and geochemical exploration, analytical and determining methods, remote sensing, high-level radioactive waste disposal, and so on; and shows some BRIUG's achievements in deepening reform unceasingly, carrying on the well-known trade-mark strategy, blazing a new trail in sciences and technologies, quickening the development of diversified economy, strengthening quality administrations in scientific researches. It makes a prospect of the wonderful future for creating the first-class technical and administrative personnel, raising the overall scientific research strength in order to establish an institute of the best quality. (author)

  8. Registro Absorb Italiano (BVS-RAI): an investigators-owned and -directed, open, prospective registry of consecutive patients treated with the Absorb™ BVS: study design

    Energy Technology Data Exchange (ETDEWEB)

    Cortese, Bernardo, E-mail: bcortese@gmail.com [Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milano (Italy); Ielasi, Alfonso [Azienda Ospedaliera Bolognini, Seriate (Italy); Varricchio, Attilio [Ospedale Monaldi, Napoli (Italy); Tarantini, Giuseppe [Azienda Ospedaliera Universitaria, Padova (Italy); LaVecchia, Luigi [Azienda Ospedaliera San Bortolo, Vicenza (Italy); Pisano, Francesco [Ospedale Regionale, Aosta (Italy); Facchin, Michela [Ospedale di Este (Italy); Gistri, Roberto [Ospedale S. Andrea, La Spezia (Italy); D’Urbano, Maurizio [Ospedale di Magenta (Italy); Lucci, Valerio [Ospedale di Avezzano (Italy); Loi, Bruno [Azienda Ospedaliera Brotzu, Cagliari (Italy); Tumminello, Gabriele [Ospedale Cardinal Massaia, Asti (Italy); Colombo, Alessandro [Ospedale Sacco, Milano (Italy); Limbruno, Ugo [Ospedale della Misericordia, Grosseto (Italy); Nicolino, Annamaria [Ospedale Santa Corona, Pietra Ligure (Italy); Calzolari, Diego [Azienda Ospedaliera Ca Foncello, Treviso (Italy); Tognoni, Gianni [Centro di Ricerche Farmacologiche e Biomediche ' Mario Negri' , Milano (Italy); Defilippi, Gianfranco [Ospedale Cardinal Massaia, Asti (Italy); Buccheri, Dario [Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milano (Italy); Tespili, Maurizio [Azienda Ospedaliera Bolognini, Seriate (Italy); and others

    2015-09-15

    Background: The Absorb™ BVS is a bioresorbable, everolimus-eluting scaffold approved and marketed for coronary use. Published data on long-term results after treatment are limited to a small number of patients, most of them with elective PCI of simple lesions. The importance of scaffold resorption is variably appreciated among cardiologists, and indications for use from health technology assessment bodies or guidelines are missing. Instruments are needed to collect, share and assess the experience being accumulated with this new device in several centres. Methods/Design: The BVS-RAI Registry is a spontaneous initiative of a group of Italian interventional cardiologists in cooperation with Centro di Ricerche Farmacologiche e Biomediche 'Mario Negri' Institute, and is not recipient of funding or benefits originating from the BVS manufacturer. It is a prospective registry with 5-year follow-up of all consecutive patients who have undergone successful implantation of 1 or more coronary BVS following the indications, techniques and protocols used in each of the participating institutions. Outcome measures are BVS target lesion failure within one year and device-oriented major adverse cardiac events within 5 years. The registry started in October 2012 and will extend enrolment throughout 2015, with the aim to include about 1000 patients. ClinicalTrials.gov identifier is CT02298413. Conclusions: The BVS-RAI Registry will contribute observational knowledge on the long-term safety and efficacy of the Absorb™ BVS as used in a number of Italian interventional centres in a broad spectrum of settings. Unrewarded and undirected consecutive patient enrolments are key-features of this observation, which is therefore likely to reflect common clinical practice in those centres. - Highlights: • prospective data collection of successful Absorb implantation; • expert Italian centers; • no restrictions for enrollment/no exclusion criteria; • clinical follow up;

  9. Do Stimulants Reduce the Risk for Alcohol and Substance Use in Youth With ADHD? A Secondary Analysis of a Prospective, 24-Month Open-Label Study of Osmotic-Release Methylphenidate.

    Science.gov (United States)

    Hammerness, Paul; Petty, Carter; Faraone, Stephen V; Biederman, Joseph

    2017-01-01

    The purpose of this study was to examine the impact of stimulant treatment on risk for alcohol and illicit drug use in adolescents with ADHD. Analysis of data derived from a prospective open-label treatment study of adolescent ADHD ( n = 115, 76% male), and a historical, naturalistic sample of ADHD ( n = 44, 68% male) and non-ADHD youth ( n = 52, 73% male) of similar age and sex. Treatment consisted of extended-release methylphenidate in the clinical trial or naturalistic stimulant treatment. Self-report of alcohol and drug use was derived from a modified version of the Drug Use Screening Inventory. Rates of alcohol and drug use in the past year were significantly lower in the clinical trial compared with untreated and treated naturalistic ADHD comparators, and similar to rates in non-ADHD comparators. Well-monitored stimulant treatment may reduce the risk for alcohol and substance use in adolescent ADHD.

  10. Comparative therapeutic response to pegylated interferon plus ribavirin versus interferon alpha-2b in chronic hepatitis C patients

    International Nuclear Information System (INIS)

    Ali, S.; Nazir, G.; Khan, S.A.; Fatima, F.; Iram, S.

    2010-01-01

    Background: Hepatitis C is an epidemic worldwide since discovery in 1989. Conventional interferon alpha-2b plus Ribavirin therapy was started in 1998 but over all sustained viral response (SVR) rates are much below the desired rates to eradicate the diseases and stopping its epidemic. This study was conducted to access the therapeutic and cost-effectiveness of long acting pegylated interferon alpha-2b plus Ribavirin therapy verses conventional interferon alpha-2b plus Ribavirin. Methods: This comparative study was done at PAF Hospital Shorkot Cantt from July 2005 to July 2008. One hundred anti-HCV positive patients were selected randomly for the study according to willingness due to cost afford ability of the patients for conventional interferon. Group-A was labelled as pegylated interferon alpha-2b plus Ribavirin group, and Group-B interferon alpha-2b plus Ribavirin group. Both groups were given treatment for 24 weeks. Early virological response (EVR) was accessed at 12 weeks of the treatment. Sustained virological response (SVR) in both the groups was done at 24 week during the treatment and 6 monthly after treatment for 2 years. Initially non-responders and relapsed patients within 2 years of treatment were re-treated for 24 weeks with the same treatment. In both groups non-responders and relapsed patients were labelled as resistant patients. Both groups were followed with same protocol for 2 years. Results: Out of 100 patients included in the study, 34% were females and 66% were males. Group-A patients over all showed 94% SVR as compare to 80% in Group-B in 2 year follow-up. Group-A showed 6% resistant patients as compare to Group-B (20%). Conventional interferons were better tolerated. Higher incidence of side-effects was seen in Group-A. Conclusion: Pegylated interferon plus Ribavirin showed 94% SVR in 2 years. Pegylated interferon plus Ribavirin is the treatment of choice.

  11. Aripiprazole for Irritability in Asian Children and Adolescents with Autistic Disorder: A 12-Week, Multinational, Multicenter, Prospective Open-Label Study.

    Science.gov (United States)

    Kim, Hyo-Won; Park, Eun-Jin; Kim, Ji-Hoon; Boon-Yasidhi, Vitharon; Tarugsa, Jariya; Reyes, Alexis; Manalo, Stella; Joung, Yoo-Sook

    2018-04-24

    We investigated the effectiveness and tolerability of aripiprazole in the treatment of irritability in Asian children and adolescents (6-17 years) with autistic disorder in a 12-week, multinational, multicenter, open-label study. Sixty-seven subjects (10.0 ± 3.1 years old, 52 boys) were enrolled and treated with flexibly dosed aripiprazole for 12 weeks (mean dose, 5.1 ± 2.5 mg; range 2-15 mg). Aripiprazole significantly reduced the mean caregiver-rated scores for the Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech subscales of the Aberrant Behavior Checklist from baseline to week 12 (p autistic disorder. Further studies with larger sample sizes and longer treatment durations are required.

  12. Open the `black box' creativity and innovation: a study of activities in R&D departments. Some prospects for engineering education

    Science.gov (United States)

    Millet, Charlyne; Oget, David; Cavallucci, Denis

    2017-11-01

    Innovation is a key component to the success and longevity of companies. Our research opens the 'black box' of creativity and innovation in R&D teams. We argue that understanding the nature of R&D projects in terms of creativity/innovation, efficiency/inefficiency, is important for designing education policies and improving engineering curriculum. Our research addresses the inventive design process, a lesser known aspect of the innovation process, in 197 R&D departments of industrial sector companies in France. One fundamental issue facing companies is to evaluate processes and results of innovation. Results show that the evaluation of innovation is confined by a lack of methodology of inventive projects. We will be establishing the foundations of a formal ontology for inventive design projects and finally some recommendations for engineering education.

  13. Time to reach tacrolimus maximum blood concentration,mean residence time, and acute renal allograft rejection: an open-label, prospective, pharmacokinetic study in adult recipients.

    Science.gov (United States)

    Kuypers, Dirk R J; Vanrenterghem, Yves

    2004-11-01

    The aims of this study were to determine whether disposition-related pharmacokinetic parameters such as T(max) and mean residence time (MRT) could be used as predictors of clinical efficacy of tacrolimus in renal transplant recipients, and to what extent these parameters would be influenced by clinical variables. We previously demonstrated, in a prospective pharmacokinetic study in de novo renal allograft recipients, that patients who experienced early acute rejection did not differ from patients free from rejection in terms of tacrolimus pharmacokinetic exposure parameters (dose interval AUC, preadministration trough blood concentration, C(max), dose). However, recipients with acute rejection reached mean (SD) tacrolimus T(max) significantly faster than those who were free from rejection (0.96 [0.56] hour vs 1.77 [1.06] hours; P clearance nor T(1/2) could explain this unusual finding, we used data from the previous study to calculate MRT from the concentration-time curves. As part of the previous study, 100 patients (59 male, 41 female; mean [SD] age, 51.4 [13.8] years;age range, 20-75 years) were enrolled in the study The calculated MRT was significantly shorter in recipients with acute allograft rejection (11.32 [031] hours vs 11.52 [028] hours; P = 0.02), just like T(max) was an independent risk factor for acute rejection in a multivariate logistic regression model (odds ratio, 0.092 [95% CI, 0.014-0.629]; P = 0.01). Analyzing the impact of demographic, transplantation-related, and biochemical variables on MRT, we found that increasing serum albumin and hematocrit concentrations were associated with a prolonged MRT (P calculated MRT were associated with a higher incidence of early acute graft rejection. These findings suggest that a shorter transit time of tacrolimus in certain tissue compartments, rather than failure to obtain a maximum absolute tacrolimus blood concentration, might lead to inadequate immunosuppression early after transplantation.

  14. Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria: a prospective open-label long-term study using frequency-volume chart.

    Science.gov (United States)

    Kojima, Yoshiyuki; Sasaki, Shoichi; Imura, Makoto; Kubota, Yasue; Hayashi, Yutaro; Kohri, Kenjiro

    2012-01-01

    The effects of tamsulosin treatment on changes in frequency-volume chart (FVC) data, especially nighttime urine production, over time were assessed, and the mechanisms underlying the improvement of nocturia in benign prostatic hyperplasia (BPH) patients with nocturnal polyuria (NP) are discussed. A total of 104 patients with lower urinary tract symptoms secondary to BPH were enrolled. After enrollment in the study, the patients were treated with tamsulosin (0.2 mg) once daily. Visits were scheduled every 4 weeks until week 12 (month 3) after study entry, and then every 12 weeks subsequently. All patients completed the International Prostate Symptom Score (IPSS), quality of life (QOL) index, and 3-day FVC, and underwent uroflowmetry at enrollment and on each visit. Eighty-two patients (mean age: 70.9 ± 7.1 years) were analyzed for 24 months after treatment. Patients were divided into two groups, NP and nonNP, based on FVC outcome. The IPSS, QOL index, and maximum flow rate improved during the 24-month period after treatment in both groups. Mean daytime urine volume significantly increased in the NP group, but no changes were detected in the nonNP group. Mean nighttime urine frequency significantly decreased in the NP group over a 24-month period, and was associated with a significant decrease in nighttime urine volume that was not found in the nonNP group. Maximum voided volume increased most months after treatment in both groups. The present long-term prospective study using FVC demonstrated that tamsulosin reduced nighttime urine production in BPH patients with NP. Copyright © 2011 Wiley Periodicals, Inc.

  15. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

    Science.gov (United States)

    Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

    2009-06-09

    Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

  16. Outcome of Sentinel Hospital-based and CDC-based ART Service Delivery: A Prospective Open Cohort of People Living with HIV in China.

    Science.gov (United States)

    Ning, Chuanyi; Smith, Kumi M; McCann, Chase D; Hu, Fengyu; Lan, Yun; Zhang, Fuchun; Liang, Hao; Zhao, Jinmin; Tucker, Joseph D; Cai, Weiping

    2017-02-14

    The primary objective of this study was to obtain insights into the outcomes of people living with HIV who accessed services through HIV/AIDS sentinel hospital-based and ART service delivery in China. Post-hoc analyses of an open cohort from an observational database of 22 qualified HIV/AIDS sentinel hospital-based and two CDC-based drug delivery facilities (DDFs) in Guangdong Province was completed. Linkage to care, mortality and survival rates were calculated according to WHO criteria. 12,966 individuals received ART from HIV/AIDS sentinel hospitals and 1,919 from DDFs, with linkage to care rates of 80.7% and 79.9%, respectively (P > 0.05). Retention rates were 94.1% and 84.0% in sentinel hospitals and DDFs, respectively (P hospitals (P ART from the DDFs than sentinel hospitals, with an adjusted HR of 3.3 (95% CI: 2.3, 4.6). A crude HR of treatment termination in DDFs was 7.5 fold higher (95% CI: 6.3, 9.0) compared to sentinel hospitals. HIV/AIDS sentinel hospital had better retention, and substantially lower mortality compared to DDFs.

  17. A prospective randomized trial comparing anterior cervical discectomy and fusion versus plate-only open-door laminoplasty for the treatment of spinal stenosis in degenerative diseases.

    Science.gov (United States)

    Jiang, Yun-Qi; Li, Xi-Lei; Zhou, Xiao-Gang; Bian, Chong; Wang, Han-Ming; Huang, Jian-Ming; Dong, Jian

    2017-04-01

    For three or more involved cervical levels, there is a debate over which approach yields the best outcomes for the treatment of multilevel cervical degenerative disease. Our objective is to compare the radiological and clinical outcomes of two treatments for multilevel cervical degenerative disease: anterior cervical discectomy and fusion (ACDF) versus plate-only open-door laminoplasty (laminoplasty). Patients were randomized on a 1:1 randomization schedule with 17 patients in the ACDF group and 17 patients in the laminoplasty group. Clinical outcomes were assessed by a visual analog scale (VAS), Japanese Orthopedic Association (JOA) scores, operative time, blood loss, rates of complications, drainage volume, discharge days after surgery, and complications. The cervical spine curvature index (CI) and range of motion (ROM) were assessed with radiographs. The mean VAS score, the mean JOA score, and the rate of complications did not differ significantly between groups. The laminoplasty group had greater blood loss, a longer operative time, more drainage volume, and a longer hospital stay than the ACDF group. There were no significant differences in the CI and ROM between the two groups at baseline and at each follow-up time point. ROM in both groups decreased significantly after surgery. Both ACDF and laminoplasty are effective and safe treatments for multilevel cervical degenerative disease. ACDF causes fewer traumas than laminoplasty.

  18. Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: A Prospective Study.

    Science.gov (United States)

    Kang, Jae H; Loomis, Stephanie J; Rosner, Bernard A; Wiggs, Janey L; Pasquale, Louis R

    2015-04-01

    We explored whether risk factor associations differed by primary open-angle glaucoma (POAG) subtypes defined by visual field (VF) loss pattern (i.e., paracentral or peripheral). We included 77,157 women in the Nurses' Health Study (NHS) and 42,773 men in the Health Professionals Follow-up Study (HPFS 1986-2010), and incident medical record confirmed cases of paracentral (n = 440) and peripheral (n = 865) POAG subtypes. We evaluated African heritage, glaucoma family history, body mass index (BMI), mean arterial blood pressure, diabetes mellitus, physical activity, smoking, caffeine intake, and alcohol intake. We used competing risk Cox regression analyses modeling age as the metameter and stratified by age, cohort, and event type. We sequentially identified factors with the least significant differences in associations with POAG subtypes ("stepwise down" approach with P for heterogeneity [P-het] 0.10) adverse associations with both POAG subtypes were observed with glaucoma family history, diabetes, African heritage, greater caffeine intake, and higher mean arterial pressure. These data indicate that POAG with early paracentral VF loss has distinct as well as common determinants compared with POAG with peripheral VF loss.

  19. [What is the situation with human rights of the elderly? : UN Open-ended Working Group on Ageing - review and prospects].

    Science.gov (United States)

    Mahler, Claudia

    2017-06-01

    In November 2010 the United Nations General Assembly set up a working group to strengthen the protection of human rights for older persons (UN Open-ended Working Group on Ageing) with the United Nations Resolution A/C.3/65/L.8/Rev.1. In December 2016 the members of the working group met for the seventh time and discussed how they can approach the fulfillment of the mandate. In addition to better implementation, the strengthening of rights can consist of closing existing gaps or further differentiation of the rights in order to give the member states better guidance on how to implement them. To improve the human rights of older persons a task of the members of the working group would be to examine the existing rights and, where possible, adjust them to the real needs of the group. One of the major challenges facing the working group is already apparent: who belongs to the group of older persons and how could the group be described? This article deals with the presentation of the international process, new developments at the regional level and the attitudes of the member states and the civil society. A further aim is to present the possibilities and effects of a comprehensive legally binding instrument.

  20. Interferon α subtypes in HIV infection.

    Science.gov (United States)

    Sutter, Kathrin; Dickow, Julia; Dittmer, Ulf

    2018-02-13

    Type I interferons (IFN), which are immediately induced after most virus infections, are central for direct antiviral immunity and link innate and adaptive immune responses. However, several viruses have evolved strategies to evade the IFN response by preventing IFN induction or blocking IFN signaling pathways. Thus, therapeutic application of exogenous type I IFN or agonists inducing type I IFN responses are a considerable option for future immunotherapies against chronic viral infections. An important part of the type I IFN family are 12 IFNα subtypes, which all bind the same receptor, but significantly differ in their biological activities. Up to date only one IFNα subtype (IFNα2) is being used in clinical treatment against chronic virus infections, however its therapeutic success rate is rather limited, especially during Human Immunodeficiency Virus (HIV) infection. Recent studies addressed the important question if other IFNα subtypes would be more potent against retroviral infections in in vitro and in vivo experiments. Indeed, very potent IFNα subtypes were defined and their antiviral and immunomodulatory properties were characterized. In this review we summarize the recent findings on the role of individual IFNα subtypes during HIV and Simian Immunodeficiency Virus infection. This includes their induction during HIV/SIV infection, their antiretroviral activity and the regulation of immune response against HIV by different IFNα subtypes. The findings might facilitate novel strategies for HIV cure or functional cure studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Evolution of vertebrate interferon inducible transmembrane proteins

    Directory of Open Access Journals (Sweden)

    Hickford Danielle

    2012-04-01

    Full Text Available Abstract Background Interferon inducible transmembrane proteins (IFITMs have diverse roles, including the control of cell proliferation, promotion of homotypic cell adhesion, protection against viral infection, promotion of bone matrix maturation and mineralisation, and mediating germ cell development. Most IFITMs have been well characterised in human and mouse but little published data exists for other animals. This study characterised IFITMs in two distantly related marsupial species, the Australian tammar wallaby and the South American grey short-tailed opossum, and analysed the phylogeny of the IFITM family in vertebrates. Results Five IFITM paralogues were identified in both the tammar and opossum. As in eutherians, most marsupial IFITM genes exist within a cluster, contain two exons and encode proteins with two transmembrane domains. Only two IFITM genes, IFITM5 and IFITM10, have orthologues in both marsupials and eutherians. IFITM5 arose in bony fish and IFITM10 in tetrapods. The bone-specific expression of IFITM5 appears to be restricted to therian mammals, suggesting that its specialised role in bone production is a recent adaptation specific to mammals. IFITM10 is the most highly conserved IFITM, sharing at least 85% amino acid identity between birds, reptiles and mammals and suggesting an important role for this presently uncharacterised protein. Conclusions Like eutherians, marsupials also have multiple IFITM genes that exist in a gene cluster. The differing expression patterns for many of the paralogues, together with poor sequence conservation between species, suggests that IFITM genes have acquired many different roles during vertebrate evolution.

  2. Interferon Alpha Association with Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Nasrin Asgari

    2013-01-01

    Full Text Available Interferon-alpha (IFN-α has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN-α in neuromyelitis optica (NMO patients. Thirty-six NMO and 41 multiple sclerosis (MS patients from a population-based retrospective case series were included. Expanded Disability Status Scale (EDSS score and MRI findings determined disease activity. Linear regression was used to assess the effects of the level of IFN-α on disability (EDSS. IFN-α was determined by sensitive ELISA assays. IFN-α was detectable in sera from 9/36 NMO patients, significantly more often than in the MS group (2/41 (P=0.0197. A higher frequency of IFN-α was observed in NMO patients with acute relapse compared to NMO patients in remission (P<0.001 and compared to the MS patients with relapse (P=0.010. In NMO patients, the levels of IFN-α were significantly associated with EDSS (P=0.0062. It may be concluded that IFN-α was detectable in a subgroup of NMO patients. Association of IFN-α levels with clinical disease activity and severity suggests a role for IFN-α in disease perpetuation and may provide a plausible explanation for a negative effect of IFN-1 treatment in NMO patients.

  3. How Ebola virus counters the interferon system.

    Science.gov (United States)

    Kühl, A; Pöhlmann, S

    2012-09-01

    Zoonotic transmission of Ebola virus (EBOV) to humans causes a severe haemorrhagic fever in afflicted individuals with high case-fatality rates. Neither vaccines nor therapeutics are at present available to combat EBOV infection, making the virus a potential threat to public health. To devise antiviral strategies, it is important to understand which components of the immune system could be effective against EBOV infection. The interferon (IFN) system constitutes a key innate defence against viral infections and prevents development of lethal disease in mice infected with EBOV strains not adapted to this host. Recent research revealed that expression of the host cell IFN-inducible transmembrane proteins 1-3 (IFITM1-3) and tetherin is induced by IFN and restricts EBOV infection, at least in cell culture model systems. IFITMs, tetherin and other effector molecules of the IFN system could thus pose a potent barrier against EBOV spread in humans. However, EBOV interferes with signalling events required for human cells to express these proteins. Here, we will review the strategies employed by EBOV to fight the IFN system, and we will discuss how IFITM proteins and tetherin inhibit EBOV infection. © 2012 Blackwell Verlag GmbH.

  4. MiDAS I (mild Decompression Alternative to Open Surgery): a preliminary report of a prospective, multi-center clinical study.

    Science.gov (United States)

    Chopko, Bohdan; Caraway, David L

    2010-01-01

    Neurogenic claudication due to lumbar spinal stenosis is a common problem that can be caused by many factors including hypertrophic ligamentum flavum, facet hypertrophy, and disc protrusion. When standard medical therapies such as pain medication, epidural steroid injections, and physical therapy fail, or when the patient is unwilling, unable, or not severe enough to advance to more invasive surgical procedures, both physicians and patients are often left with a treatment dilemma. Patients in this study were treated with mild, an ultra-minimally invasive lumbar decompression procedure using a dorsal approach. The mild procedure is performed under fluoroscopic imaging to resect bone adjacent to, and achieve partial resection of, the hypertrophic ligamentum flavum with minimal disruption of surrounding muscular and skeletal structure. To assess the clinical application and patient safety and functional outcomes of the mild lumbar decompression procedure in the treatment of symptomatic central canal spinal stenosis. Multi-center, non-blinded, prospective clinical study. Fourteen US spine specialist practices. Between July 2008 and January 2010, 78 patients were enrolled in the MiDAS I Study and treated with the mild procedure for lumbar decompression. Of these patients, 6-week follow-up was available for 75 patients. Visual Analog Score (VAS), Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and SF-12v2 Health Survey. Outcomes were assessed at baseline and 6 weeks post-treatment. There were no major device or procedure-related complications reported in this patient cohort. At 6 weeks, the MiDAS I Study showed statistically and clinically significant reduction of pain as measured by VAS, ZCQ, and SF-12v2. In addition, improvement in physical function and mobility as measured by ODI, ZCQ, and SF-12v2 was statistically and clinically significant in this study. This is a preliminary report encompassing 6-week follow-up. There was no control group

  5. Superiority of Interferon-Free Regimens for Chronic Hepatitis C

    Science.gov (United States)

    Younossi, Zobair M.; Stepanova, Maria; Esteban, Rafael; Jacobson, Ira; Zeuzem, Stefan; Sulkowski, Mark; Henry, Linda; Nader, Fatema; Cable, Rebecca; Afendy, Mariam; Hunt, Sharon

    2017-01-01

    Abstract Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients. Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy—Fatigue, Chronic Liver Disease Questionnaire— HCV, Work Productivity and Activity—Specific Health Problem) before, during, and after treatment. A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to −24.4% by treatment week 12, up to −8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to −7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs. IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores. PMID:28207507

  6. Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study.

    Science.gov (United States)

    Huang, Fenglei; Marzin, Kristell; Koenen, Rüdiger; Kammerer, Klaus Peter; Strelkowa, Natalja; Elgadi, Mabrouk; Quinson, Anne-Marie; Haertter, Sebastian

    2017-10-01

    Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by 240 mg faldaprevir once daily from day 6 to day 10, with an additional single dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples for the statins were collected on days 1-3 and days 10-12. Concomitant administration with faldaprevir led to approximately 9-fold and 34-fold increases in AUC 0-∞ and C max , respectively, of atorvastatin and approximately 15-fold and 33-fold increases in AUC 0-∞ and C max , respectively, of rosuvastatin, compared with the statins given alone. Exposure to the major metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased to a similar magnitude as that of the parent compounds. The marked drug-drug interaction observed is most likely related to the inhibitory effects of faldaprevir on transporters, particularly hepatic uptake transporters such as OTAP1B1 and OATP1B3. Given the significant increase in exposure to statins in healthy volunteers, coadministration of faldaprevir with statins should be avoided. © 2017, The American College of Clinical Pharmacology.

  7. INFLUENCE OF GRADED AEROBIC EXERCISE ON QUALITY OF LIFE IN POST SURGICAL MITRAL VALVE DISEASE INDIVIDUAL A PROSPECTIVE RANDOMIZED OPEN LABEL STUDY

    Directory of Open Access Journals (Sweden)

    Shanthi C

    2016-10-01

    Full Text Available Background: Post surgical mitral valve disease individual focus their cardiac rehabilitation training on two major goal that is to improve cardiac output response exercises and place an important role in determining exercise tolerance and to improve quality of life. Cardiac rehabilitation programs involve prescribed exercise and education however various other method are being used to improve quality of life. But our study to find out the effectiveness of graded aerobic exercise protocol on ejection fraction and quality of life in post surgical mitral valve disease individuals. Methods: The study design was open label studies total of 100 post surgical mitral valve disease individuals patients from the age group of 20-60 years were recruited from SVIMS hospital. They were randomly divided into two groups. Group I underwent a twelve week structured graded individually tailored exercises. The group II received only none graded (not individualized exercise training. The ejection fraction and quality of life was measured before and after 12 weeks of exercise training for two groups. Results: Repeated measures ANOVA was used to compare mean values of continuous variables between baseline and at the time of discharge and three months after surgery for each parameter. Comparison of means between groups was done by the unpaired student t test. Mean age of the subjects was 40.18±10.29. There was a significant increase in the ejection fraction in the group I(61.34±2.49 to 64.4±3.31 compared to with the group II (61.06±2.51. to 61.62 ±2.37. QOL had improved in group I than group II at p<0.05. Conclusion: A 12 week structured graded aerobic exercise training significantly improved ejection fraction and quality of life in post surgical mitral valve disease individuals.

  8. Prevention of hypothermia in patients undergoing orthotopic liver transplantation using the humigard® open surgery humidification system: a prospective randomized pilot and feasibility clinical trial.

    Science.gov (United States)

    Weinberg, Laurence; Huang, Andrew; Alban, Daniel; Jones, Robert; Story, David; McNicol, Larry; Pearce, Brett

    2017-01-23

    Perioperative thermal disturbances during orthotopic liver transplantation (OLT) are common. We hypothesized that in patients undergoing OLT the use of a humidified high flow CO 2 warming system maintains higher intraoperative temperatures when compared to standardized multimodal strategies to maintain thermoregulatory homeostasis. We performed a randomized pilot study in adult patients undergoing primary OLT. Participants were randomized to receive either open wound humidification with a high flow CO 2 warming system in addition to standard care (Humidification group) or to standard care alone (Control group). The primary end point was nasopharyngeal core temperature measured 5 min immediately prior to reperfusion of the donor liver (Stage 3 - 5 min). Secondary endpoints included intraoperative PaCO 2 , minute ventilation and the use of vasoconstrictors. Eleven patients were randomized to each group. Both groups were similar for age, body mass index, MELD, SOFA and APACHE II scores, baseline temperature, and duration of surgery. Immediately prior to reperfusion (Stage 3 - 5 min) the mean (SD) core temperature was higher in the Humidification Group compared to the Control Group: 36.0 °C (0.13) vs. 35.4 °C (0.22), p = 0.028. Repeated measured ANOVA showed that core temperatures over time during the stages of the transplant were higher in the Humidification Group compared to the Control Group (p < 0.0001). There were no significant differences in the ETCO 2 , PaCO 2 , minute ventilation, or inotropic support. The humidified high flow CO 2 warming system was superior to standardized multimodal strategies in maintaining normothermia in patients undergoing OLT. Use of the device was feasible and did not interfere with any aspects of surgery. A larger study is needed to investigate if the improved thermoregulation observed is associated with improved patient outcomes. ACTRN12616001631493 . Retrospectively registered 25 November 2016.

  9. Opposing roles for interferon regulatory factor-3 (IRF-3 and type I interferon signaling during plague.

    Directory of Open Access Journals (Sweden)

    Ami A Patel

    Full Text Available Type I interferons (IFN-I broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-β was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-β following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-β signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-β production.

  10. Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

    Science.gov (United States)

    Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

    2016-01-01

    The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

  11. Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon

    NARCIS (Netherlands)

    Poupon, R. E.; Bonnand, A. M.; Queneau, P. E.; Trépo, C.; Zarski, J. P. A.; Vetter, D.; Raabe, J. J.; Thieffin, G.; Larrey, D.; Grangé, J. D.; Capron, J. P.; Serfaty, L.; Chrétien, Y.; St Marc Girardin, M. F.; Mathiex-Fortunet, H.; Zafrani, E. S.; Guéchot, J.; Beuers, U.; Paumgartner, G.; Poupon, R.

    2000-01-01

    Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus

  12. Efficacy and tolerability of escitalopram in treatment of major depressive disorder with anxiety symptoms: a 24-week, open-label, prospective study in Chinese population

    Directory of Open Access Journals (Sweden)

    Jiang KD

    2017-02-01

    Full Text Available Kaida Jiang,1 Lingjiang Li,2 Xueyi Wang,3 Maosheng Fang,4 Jianfei Shi,5 Qiuyun Cao,6 Jincai He,7 Jinan Wang,8 Weihao Tan,8 Cuili Hu8 1Psychiatry Department, Shanghai Mental Health Center, Shanghai, 2Psychiatry Department,The Second Xiangya Hospital, Central South University, Changsha, 3Psychiatry Department, First affiliated Hospital of Hebei Medical University, Shijiazhuang, 4Psychiatry Department, Wuhan Mental Health Center, Wuhan, 5Psychiatry Department, Hangzhou the 7th Hospital, Hangzhou, 6Psychology Department, Nanjing Drum Tower Hospital, Nanjing, 7Neurology Department, First affiliated Hospital of Wenzhou Medical University, Wenzhou, 8Medical Affairs Department, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Background: Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD. This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods: Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14 were enrolled and received escitalopram (10–20 mg/day treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results: Overall, 200 of 318 (66.2% enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7 rate in the full analysis set (N=285 was 73.3% (95% confidence interval: 67.80, 78.38 at week 24. Mean (± standard deviation MADRS total score was 33.4 (±7.13 and HAM-A score was 27.6 (±7.26 at baseline, which reduced to 6.6 (±10.18 and 6.0 (±8

  13. Prospective, randomized study of one, two, or three trabecular bypass stents in open-angle glaucoma subjects on topical hypotensive medication

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    Katz LJ

    2015-12-01

    Full Text Available L Jay Katz,1 Carl Erb,2 Amadeu Carceller Guillamet,3 Antonio M Fea,4 Lilit Voskanyan,5 Jeffrey M Wells,6 Jane Ellen Giamporcaro6 1Wills Eye Hospital, Jefferson Medical College, Philadelphia, PA, USA; 2Eye Clinic Wittenbergplatz, Berlin, Germany; 3Department of Ophthalmology, Hospital d’Hebron, Barcelona, Spain; 4University Eye Clinic of the University of Turin, Turin, Italy; 5SV Malayan Opthalmology Centre, Yerevan, Armenia; 6Glaukos Corporation, Laguna Hills, CA, USA Purpose: To assess the safety and efficacy of one, two, or three trabecular microbypass stents in eyes with primary open-angle glaucoma (OAG not controlled on ocular hypotensive medication. A total of 119 subjects were followed for 18 months postoperatively.Materials and methods: Subjects with medicated intraocular pressure (IOP 18–30 mmHg and postmedication-washout baseline IOP 22–38 mmHg were randomized to implantation of one, two, or three stents. Ocular hypotensive medication was to be used if postoperative IOP exceeded 18 mmHg.Results: A total of 38 subjects were implanted with one stent, 41 subjects with two stents, and 40 subjects with three stents. Both month 12 IOP reduction ≥20% without ocular hypotensive medication vs baseline unmedicated IOP and month 12 unmedicated IOP ≤18 mmHg were achieved by 89.2%, 90.2%, and 92.1% of one-, two-, and three-stent eyes, respectively. Furthermore, 64.9%, 85.4%, and 92.1% of the three respective groups achieved unmedicated IOP ≤15 mmHg. Over the 18-month follow-up period, medication was required in seven one-stent subjects, four two-stent subjects, and three three-stent subjects. At 18 months, mean unmedicated IOP was 15.9±0.9 mmHg in one-stent subjects, 14.1±1.0 mmHg in two-stent subjects, and 12.2±1.1 mmHg in three-stent subjects. Month 18 IOP reduction was significantly greater (P<0.001 with implantation of each additional stent, with mean differences in reduction of 1.84 mmHg (95% confidence interval 0.96

  14. Prospective unmasked randomized evaluation of the iStent inject® versus two ocular hypotensive agents in patients with primary open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Fea AM

    2014-05-01

    Full Text Available Antonio M Fea,1 Jose I Belda,2 Marek Rękas,3 Anselm Jünemann,4 Lydia Chang,5 Luis Pablo,6 Lilit Voskanyan,7 L Jay Katz81Università degli Studi di Torino, Clinica Oculistica, Torino, Italy; 2Hospital Torrevieja Salud, UTE, Servicio de Oftalmologia, Alicante, Spain; 3Military Institute of Medicine, Department of Ophthalmology, Warsaw, Poland; 4Universitätsaugenklinik, Erlangen, Germany; 5Hinchingbrooke Hospital NHS Trust and Moorfields Bedford Hospital NHS Trust, United Kingdom; 6Hospital Universitario Miguel Servet, Servicio Oftalmologico, Zaragoza, Spain; 7SV Malayan Ophthalmological Center, Yerevan, Armenia; 8Wills Eye Institute, Jefferson Medical College, Philadelphia, PA, USAPurpose: The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG not controlled on one medication who underwent either implantation of two iStent inject® trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol.Patients and methods: Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject® devices in the treated eye and 98 to receive medical therapy.Results: At the month 12 visit, 94.7% of eyes (89/94 in the stent group reported an unmedicated intraocular pressure (IOP reduction of ≥20% versus baseline unmedicated IOP, and 91.8% of eyes (88/98 in the medical therapy group reported an IOP reduction ≥20% versus baseline unmedicated IOP. A 17.5% between-group treatment difference in favor of the iStent inject group was statistically significant (P=0.02 at the ≥50% level of IOP reduction. An IOP ≤18 mmHg was reported in 92.6% of eyes (87/94 in the iStent inject group and 89.8% of eyes (88/98 in the medical therapy group. Mean (standard deviation IOP decreases from screening of 8.1 (2.6 mmHg and 7.3 (2.2 mmHg were reported in the iStent inject and medical therapy groups, respectively. A high

  15. T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Birch, Carsten; Gaardbo, Julie C

    2015-01-01

    Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T......-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-α and ribavirin, and six patients were treated with an interferon-free regimen. All patients were...... compared to prior treatment values. Finally, a proportion of CD8+ effector memory was lower while proportion of apoptotic T cells was higher after sustained virologic response compared to prior treatment. Despite lymphopenia during interferon, alterations in T-cell homeostasis during treatment were...

  16. Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke

    2015-01-01

    Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for......-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.......Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used...... for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels...

  17. Efficacy of peg-interferon based treatment in patients with hepatitis C refractory to previous conventional interferon-based treatment

    International Nuclear Information System (INIS)

    Shaikh, S.; Devrajani, B.R.; Kalhoro, M.

    2012-01-01

    Objective: To determine the efficacy of peg-interferon-based therapy in patients refractory to previous conventional interferon-based treatment and factors predicting sustained viral response (SVR). Study Design: Analytical study. Place and Duration of Study: Medical Unit IV, Liaquat University Hospital, Jamshoro, from July 2009 to June 2011. Methodology: This study included consecutive patients of hepatitis C who were previously treated with conventional interferon-based treatment for 6 months but were either non-responders, relapsed or had virologic breakthrough and stage = 2 with fibrosis on liver biopsy. All eligible patients were provided peg-interferon at the dosage of 180 mu g weekly with ribavirin thrice a day for 6 months. Sustained Viral Response (SVR) was defined as absence of HCV RNA at twenty four week after treatment. All data was processed on SPSS version 16. Results: Out of 450 patients enrolled in the study, 192 were excluded from the study on the basis of minimal fibrosis (stage 0 and 1). Two hundred and fifty eight patients fulfilled the inclusion criteria and 247 completed the course of peg-interferon treatment. One hundred and sixty one (62.4%) were males and 97 (37.6%) were females. The mean age was 39.9 +- 6.1 years, haemoglobin was 11.49 +- 2.45 g/dl, platelet count was 127.2 +- 50.6 10/sup 3/ /mm/sup 3/, ALT was 99 +- 65 IU/L. SVR was achieved in 84 (32.6%). The strong association was found between SVR and the pattern of response (p = 0. 001), degree of fibrosis and early viral response (p = 0.001). Conclusion: Peg-interferon based treatment is an effective and safe treatment option for patients refractory to conventional interferon-based treatment. (author)

  18. Bilateral Ischemic Optic Neuropathy Developed under Interferon Therapy

    Directory of Open Access Journals (Sweden)

    Fatih Selcukbiricik

    2012-01-01

    Full Text Available Introduction. Interferon is a glycoprotein produced by assigned cells of immune system. It has been used in many different diseases. Although flu-like syndrome, myalgia, rash, hypotension, thrombocytopenia and peripheral neuropathy due to interferon use are encountered frequently, ocular side effects are rare, generally mild and transient. Case Report. 47-year-old female patient, presented with a mass lesion in right renal pelvis. Right radical nephrectomy was applied and the histopathological examination was consistent with papillary renal cell carcinoma. Interferon alpha treatment was started subcutaneously at the dose of 5 MIU/3 times in a week. Four weeks after the interferon therapy, suddenly bilateral visual loss developed. We discussed the diagnosis, followup, and treatment of the patient who developed irreversible ischemic optic neuropathy and had no previous known primary systemic disease to cause this condition. Conclusion. We suggest that patients should be screened for risk factors causing optic ischemic neuropathy, before interferon therapy. Although there was no adequate information in the literature for the followup, patients should be monitorized before, 1 month after, and 2 months after the treatment. And if there is no complication, we suggest that they should be followed up at 3-month intervals.

  19. Open environmental data sets - prospect of co-operation between public and private sector in water quality monitoring. Final report of Water Quality Service for Lakes -project; Avoin ympaeristoetieto - yhteistyoen kehittaeminen vesistoejen seurannassa. Jaervien vedenlaatupalvelu -hankkeen loppuraportti

    Energy Technology Data Exchange (ETDEWEB)

    Anttila, S.; Broeckl, M.; Herlevi, A. (and others)

    2012-04-15

    Data sets collected by the public sector are common property and should be freely available. Effective usage of this open data is anticipated to create new information and services, but also to develop welfare for humans. Insufficient usage of public and open environmental data sets in the private sector has been recognized as a problem. Reasons for this can be found from the non-commercial nature of environmental data, the way it is collected and archived, but also from the strong role of public sector in this field. In the Water Quality Service for Lakes -project (Tekes, 2009-2012), we wanted to advance the utilization of the public data sets in the private sector, as well as to promote the co-operation between these two sectors. Starting point was to develop local research infrastructure in the way that collected information would be easily accessible to private companies. This was realized by creating a data base that gathers water quality information from several data sources and provides a standardized interface for the data utilization. In addition, project provided a variety of research results including a questionnaire survey targeted to the users of water quality information, and the methods to increase the accuracy of collected data and to create forecasts from it. A concrete result from the project was also the development of 'laymans' water quality measurement device named as Secchi3000. A digital camera installed in e.g. mobile phones can be used with Secchi3000 device to measure water quality of different natural waters. This new innovation has great potential in e.g. citizen based monitoring. The challenges and opportunities to create business based on the public environmental data were revolved in two work shops. In this publication the prospects of co-operation between public and private sector are discussed based on the results of the Water Quality Service for lakes -project. (orig.)

  20. Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

    Science.gov (United States)

    Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H

    1989-10-05

    Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.

  1. Hepatitis C virus and the controversial role of the interferon sensitivity determining region in the response to interferon treatment.

    Science.gov (United States)

    Torres-Puente, Manuela; Cuevas, José M; Jiménez-Hernández, Nuria; Bracho, María A; García-Robles, Inmaculada; Carnicer, Fernando; del Olmo, Juan; Ortega, Enrique; Moya, Andrés; González-Candelas, Fernando

    2008-02-01

    The degree of variability of the interferon sensitivity determining region (ISDR) in the hepatitis C virus (HCV) genome has been postulated to predict the response to interferon therapy, mainly in patients infected with subtype 1b, although this prediction has been the subject of a long controversy. This prediction has been tested by analyzing a cohort of 67 Spanish patients infected with HCV genotype 1, 23 of which were infected with subtype 1a and 44 with subtype 1b. A sample previous to therapy with alpha-interferon plus ribavirin was obtained and several clones (between 25 and 96) including the ISDR were sequenced from each patient. A significant correlation between mutations at the ISDR and response to treatment for subtype 1b patients, but not for those infected with subtype 1a, has been detected. Although the results suggest that the same relationship holds true for subtype 1a, lack of statistical power because of the small sample size of this subtype prevented firmer conclusions. However, identical ISDR sequences were found in responder and non-responder patients, suggesting that the stability of the ISDR sequence can occasionally help HCV to evade interferon therapy, although this is not a sufficient condition. More complex interactions, including the ISDR or not, are likely to exist and govern the HCV response to interferon treatment. (Copyright) 2007 Wiley-Liss, Inc.

  2. Interferons and their potential in the treatment of ocular inflammation

    Directory of Open Access Journals (Sweden)

    Friederike Mackensen

    2009-10-01

    Full Text Available Friederike Mackensen,1 Regina Max,2 Matthias D Becker31Department of Ophthalmology, 2Department of Internal Medicine, Interdisciplinary Uveitis Center, University of Heidelberg, Germany; 3Department of Ophthalmology, Triemli Hospital Zürich, SwitzerlandAbstract: Since their discovery in the 1950s interferons have been the scope of investigation in many diseases as therapeutic as well as pathogenetic factors. We know they have immune stimulatory and immune regulatory effects. This apparently counter-intuitive mechanism can be summarized as immunomodulatory action and seems to be very effective in a number of ocular inflammatory diseases. We review the current knowledge of interferons in immunity and autoimmunity and show their use in clinical ophthalmologic practice.Keywords: interferon, uveitis, treatment, inflammation

  3. Role of interferon in resistance and immunity to protozoa

    Science.gov (United States)

    Sonnenfeld, G.; Degee, A. L. W.; Mansfield, J. M.; Newsome, A. L.; Arnold, R. R.

    1985-01-01

    Production of interferon (I) in response to protozoan infection, and the interferon-mediated inhibition of parasite replication were studied in order to determine if these effects may be related to immunologic-mediated resistance of the hosts. Two extracellular parasites-Trypanosoma brucei rhodesiense and Naegleria fowlei were used. Upon infection with the trypanosome, only resistant strains of mice produced I. An early peak of alpha/beta I is followed by appearance of gamma I, which coincided with antibody production and a drop in parasitemia. In case of the amoeba, pretreatment of its suspension with alpha/beta I inhibits its replication in vitro, and appears to protect mice from the infection and the disease. It is proposed that production of interferon, with its regulatory effect on the immune responses, may play a major role in regulating the processes of protozoan-caused diseases.

  4. Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens

    Directory of Open Access Journals (Sweden)

    Yuchen Nan

    2014-12-01

    Full Text Available Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR. Host PRR for RNA viruses include Toll-like receptors (TLR and retinoic acid-inducible gene I (RIG-I like receptors (RLR. Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses.

  5. Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity.

    Science.gov (United States)

    Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsøyr, Ole; Haavik, Jan; Peleikis, Dawn E

    2014-12-01

    How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, Ptreatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  6. Comparison of efficacy of transversus abdominis plane block and iliohypogastric/ilioinguinal nerve block for postoperative pain management in patients undergoing inguinal herniorrhaphy with spinal anesthesia: a prospective randomized controlled open-label study.

    Science.gov (United States)

    Okur, Onur; Tekgul, Zeki Tuncel; Erkan, Nazif

    2017-10-01

    The purpose of this study was to compare the effects of lateral abdominal transversus abdominis plane block (TAP block) and iliohypogastric/ilioinguinal nerve block (IHINB) under ultrasound guidance for postoperative pain management of inguinal hernia repair. Secondary purposes were to compare the complication rates of the two techniques and to examine the effects of TAP block and IHINB on chronic postoperative pain. This was a prospective randomized controlled open-label study. After approval of the Research Ethics Board, a total of 90 patients were allocated to three groups of 30 by simple randomized sampling as determined with a priori power analysis. Peripheral nerve blocks (TAP block or IHINB) were administered to patients following subarachnoid block according to their allocated group. Patient pain scores, additional analgesic requirements and complication rates were recorded periodically and compared. Pain scores were significantly lower in the study groups (p block group [GT] 266.6 ± 119.7 min; IHINB group [GI] 247.2 ± 128.7 min; and control group [GC] 79.1 ± 66.2 min; p block or IHINB for patients undergoing inguinal herniorrhaphy reduces the intensity of both acute and chronic postoperative pain and additional analgesic requirements.

  7. Functional Characterization of Canine Interferon-Lambda

    Science.gov (United States)

    Fan, Wenhui; Xu, Lei; Ren, Liqian; Qu, Hongren; Li, Jing; Liang, Jingjing; Liu, Wenjun

    2014-01-01

    In this study, we provide the first comprehensive annotation of canine interferon-λ (CaIFN-λ, type III IFN). Phylogenetic analysis based on genomic sequences indicated that CaIFN-λ is located in the same branch with Swine IFN-λ1 (SwIFN-λ), Bat IFN-λ1 (BaIFN-λ), and human IFN-λ1 (HuIFN-λ1). CaIFN-λ was cloned, expressed in Escherichia coli, and purified to further investigate the biological activity in vitro. The recombinant CaIFN-λ (rCaIFN-λ) displayed potent antiviral activity on both homologous and heterologous animal cells in terms of inhibiting the replication of the New Jersey serotype of vesicular stomatitis virus (VSV), canine parvovirus, and influenza virus A/WSN/33 (H1N1), respectively. In addition, we also found that rCaIFN-λ exhibits a significant antiproliferative response against A72 canine tumor cells and MDCK cells in a dose-dependent manner. Furthermore, CaIFN-λ activated the JAK-STAT signaling pathway. To evaluate the expression of CaIFN-λ induced by virus and the expression of IFN-stimulated genes (ISGs) induced by rCaIFN-λ in the MDCK cells, we measured the relative mRNA level of CaIFN-λ and ISGs (ISG15, Mx1, and 2′5′-OAS) by quantitative real-time PCR and found that the mRNA level of CaIFN-λ and the ISGs significantly increased after treating the MDCK cells with viruses and rCaIFN-λ protein, respectively. Finally, to evaluate the binding activity of rCaIFN-λ to its receptor, we expressed the extracellular domain of the canine IFN-λ receptor 1 (CaIFN-λR1-EC) and determined the binding activity via ELISA. Our results demonstrated that rCaIFN-λ bound tightly to recombinant CaIFN-λR1-EC (rCaIFN-λR1-EC). PMID:24950142

  8. Interferon Lambda: Modulating Immunity in Infectious Diseases.

    Science.gov (United States)

    Syedbasha, Mohammedyaseen; Egli, Adrian

    2017-01-01

    Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis . Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage

  9. Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A B; Døssing, Kristina B V; Aabakke, Anna JM

    2011-01-01

    To investigate if and how the proinflammatory cytokine interferon ¿ (IFN¿) affects ghrelin expression in mice.......To investigate if and how the proinflammatory cytokine interferon ¿ (IFN¿) affects ghrelin expression in mice....

  10. Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A B; Døssing, Kristina B V; Aabakke, Anna JM

    2011-01-01

    To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice.......To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice....

  11. Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study

    Directory of Open Access Journals (Sweden)

    Carbonell Dalia

    2004-10-01

    Full Text Available Abstract Background Tuberculosis (TB is increasing in the world and drug-resistant (DR disease beckons new treatments. Methods To evaluate the action of interferon (IFN gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 106 IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. Results Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. Conclusions These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged.

  12. DMPD: Molecular mechanisms of the anti-inflammatory functions of interferons. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18086388 Molecular mechanisms of the anti-inflammatory functions of interferons. Ko....csml) Show Molecular mechanisms of the anti-inflammatory functions of interferons. PubmedID 18086388 Title ...Molecular mechanisms of the anti-inflammatory functions of interferons. Authors K

  13. Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice

    NARCIS (Netherlands)

    Poosti, Fariba; Bansal, Ruchi; Yazdani, Saleh; Prakash, Jai; Beljaars, Leonie; van den Born, Jacob; de Borst, Martin H.; van Goor, Harry; Hillebrands, Jan-Luuk; Poelstra, Klaas

    2016-01-01

    Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is lacking. Interferon-gamma is a pro-inflammatory cytokine with anti-fibrotic properties. Clinical use of interferon-gamma is hampered due to inflammation-mediated systemic side effects. We used an interferon-gamma

  14. Kaposi's sarcoma after alpha-interferon treatment for HIV-negative T ...

    African Journals Online (AJOL)

    Although interferon was successful in controlling the lymphoma the clinical course was complicated by the rapid development of aggressive, fatal Kaposi's sarcoma shortly after cessation of interferon treatment. It is suggested that the immunosuppressive effect of interferon therapy (or the T -cell lymphoma or both) may have ...

  15. DMPD: Interferon gene regulation: not all roads lead to Tolls. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16095970 Interferon gene regulation: not all roads lead to Tolls. Jefferies CA, Fit...zgerald KA. Trends Mol Med. 2005 Sep;11(9):403-11. (.png) (.svg) (.html) (.csml) Show Interferon gene regulation: not all roads... lead to Tolls. PubmedID 16095970 Title Interferon gene regulation: not all roads lead to

  16. Lessons, open questions, and future prospects

    Directory of Open Access Journals (Sweden)

    Grupe D.

    2012-12-01

    Full Text Available We summarize some of the highlights of this workshop, the first of its kind dedicated to observing and modeling the tidal disruption of stars by black holes in the centers of galaxies (or star clusters. We review the lessons learned from recent observations and from theory and identify outstanding questions and areas where more theoretical and observational work is needed. We also consider upcoming observing facilities that can be used to study tidal disruption events and speculate what these new facilities may contribute to the field.

  17. Safety, Tolerability, and Immunogenicity of Interferons

    Directory of Open Access Journals (Sweden)

    Michael G. Tovey

    2010-04-01

    Full Text Available Interferons (IFNs are class II cytokines that are key components of the innate immune response to virus infection. Three IFN sub-families, type I, II, and III IFNs have been identified in man, Recombinant analogues of type I IFNs, in particular IFNα2 and IFNβ1, have found wide application for the treatment of chronic viral hepatitis and remitting relapsing multiple sclerosis respectively. Type II IFN, or IFN gamma, is used principally for the treatment of chronic granulomatous disease, while the recently discovered type III IFNs, also known as IFN lambda or IL-28/29, are currently being evaluated for the treatment of chronic viral hepatitis. IFNs are in general well tolerated and the most common adverse events observed with IFNα or IFNβ therapy are “flu-like” symptoms such as fever, headache, chills, and myalgia. Prolonged treatment is associated with more serious adverse events including leucopenia, thrombocytopenia, increased hepatic transaminases, and neuropsychiatric effects. Type I IFNs bind to high-affinity cell surface receptors, composed of two transmembrane polypeptides IFNAR1 and IFNAR2, resulting in activation of the Janus kinases Jak1 and Tyk2, phosphorylation and activation of the latent cytoplasmic signal transducers and activators of transcription (STAT1 and STAT2, formation of a transcription complex together with IRF9, and activation of a specific set of genes that encode the effector molecules responsible for mediating the biological activities of type I IFNs. Systemic administration of type I IFN results in activation of IFN receptors present on essentially all types of nucleated cells, including neurons and hematopoietic stem cells, in addition to target cells. This may well explain the wide spectrum of IFN associated toxicities. Recent reports suggest that certain polymorphisms in type I IFN signaling molecules are associated with IFN-induced neutropenia and thrombocytopenia in patients with chronic hepatitis C. IFN

  18. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis

    2011-01-01

    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-a) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-a compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  19. Osteopontin as a marker for response to pegylated interferon Alpha ...

    African Journals Online (AJOL)

    Osteopontin as a marker for response to pegylated interferon Alpha-2b treatment in Chronic HCV Saudi patients. Yousri Mostafa Hussein1,2, Ayman Alhazmi1, Saad Alzahrani3, Ahmad El-Askary1,4,. Abdulrahman Alghamdy5, Eman Bayomy4, Assmaa Selim6, Mohammed Alghamdy1. 1. Medical Laboratories Department ...

  20. Antiproliferative activity of recombinant human interferon-λ2 ...

    African Journals Online (AJOL)

    Antiproliferative activity of recombinant human interferon-λ2 expressed in stably ... The representing 26 kDa protein band of IFN-λ2 was detected by SDS-PAGE and ... The antiproliferative activity of hIFN-λ2 was determined by MTT assay.

  1. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...

  2. Tumor inherent interferons: Impact on immune reactivity and immunotherapy.

    Science.gov (United States)

    Brockwell, Natasha K; Parker, Belinda S

    2018-04-19

    Immunotherapy has revolutionized cancer treatment, with sustained responses to immune checkpoint inhibitors reported in a number of malignancies. Such therapeutics are now being trialed in aggressive or advanced cancers that are heavily reliant on untargeted therapies, such as triple negative breast cancer. However, responses have been underwhelming to date and are very difficult to predict, leading to an inability to accurately weigh up the benefit-to-risk ratio for their implementation. The tumor immune microenvironment has been closely linked to immunotherapeutic response, with superior responses observed in patients with T cell-inflamed or 'hot' tumors. One class of cytokines, the type I interferons, are a major dictator of tumor immune infiltration and activation. Tumor cell inherent interferon signaling dramatically influences the immune microenvironment and the expression of immune checkpoint proteins, hence regulators and targets of this pathway are candidate biomarkers of immunotherapeutic response. In support of a link between IFN signaling and immunotherapeutic response, the combination of type I interferon inducers with checkpoint immunotherapy has recently been demonstrated critical for a sustained anti-tumor response in aggressive breast cancer models. Here we review evidence that links type I interferons with a hot tumor immune microenvironment, response to checkpoint inhibitors and reduced risk of metastasis that supports their use as biomarkers and therapeutics in oncology. Copyright © 2018. Published by Elsevier Ltd.

  3. Interferon-gamma treatment kinetics among patients with active ...

    African Journals Online (AJOL)

    Introduction: Interferon-γ (IFN-γ) is essential for defence against Mycobacterium tuberculosis; however, levels in patients with active tuberculosis (TB) and changes during treatment have not been documented in our tuberculosis patients in Nigeria, hence this study has been carried out. Objective: To determine variations, ...

  4. Interferon α treatment of molluscum contagiosum in immunodeficiency

    OpenAIRE

    Hourihane, J.; Hodges, E.; Smith, J.; Keefe, M.; Jones, A.; Connett, G.

    1999-01-01

    A sister (aged 6 years) and brother (aged 8 years) presented four months apart with severe molluscum contagiosum. Both children demonstrated clinical and laboratory evidence of combined immunodeficiency. The extent of skin involvement by molluscum contagiosum precluded conventional treatment as well as intralesional interferon α (IFNα). Both subjects responded well to subcutaneous IFNα.



  5. Guarding the frontiers: the biology of type III interferons

    DEFF Research Database (Denmark)

    Wack, Andreas; Terczynska-Dyla, Ewa; Hartmann, Rune

    2015-01-01

    Type III interferons (IFNs) or IFN-λs regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-λs primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-λs thereby help to maintain...

  6. Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK).

    Science.gov (United States)

    Mueller, Ruediger B; Gengenbacher, Michael; Richter, Symi; Dudler, Jean; Möller, Burkhard; von Kempis, Johannes

    2016-04-14

    Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks. This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included. The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in

  7. Results of a Prospective Randomized, Open-Label, Noninferiority Study of Tbo-Filgrastim (Granix) versus Filgrastim (Neupogen) in Combination with Plerixafor for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma.

    Science.gov (United States)

    Bhamidipati, Pavan Kumar; Fiala, Mark A; Grossman, Brenda J; DiPersio, John F; Stockerl-Goldstein, Keith; Gao, Feng; Uy, Geoffrey L; Westervelt, Peter; Schroeder, Mark A; Cashen, Amanda F; Abboud, Camille N; Vij, Ravi

    2017-12-01

    Autologous hematopoietic stem cell transplantation (auto-HSCT) improves survival in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen; recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, a biosimilar recombinant G-CSF (Tevagrastim) has been approved for various indications similar to those of reference filgrastim, including stem cell mobilization for auto-HSCT; however, in the United States, tbo-filgrastim (Granix) is registered under the original biological application and is not approved for stem cell mobilization. In retrospective studies, stem cell mobilization with tbo-filgrastim has shown similar efficacy and toxicity as filgrastim, but no prospective studies have been published to date. We have conducted the first prospective randomized trial comparing the safety and efficacy of tbo-filgrastim in combination with plerixafor with that of filgrastim in combination with plerixafor for stem cell mobilization in patients with MM and NHL. This is a phase 2 prospective randomized (1:1) open-label single-institution noninferiority study of tbo-filgrastim and filgrastim with plerixafor in patients with MM or NHL undergoing auto-HSCT. Here 10 µg/kg/day of tbo-filgrastim/filgrastim was administered s.c. for 5 days (days 1 to 5). On day 4 at approximately 1800 hours, 0.24 mg/kg of plerixafor was administered s.c. Apheresis was performed on day 5 with a target cumulative collection goal of at least 5.0 × 10 6 CD34 + cells/kg. The primary objective was to compare day 5 CD34 +  cells/kg collected. Secondary objectives included other mobilization endpoints, safety, engraftment outcomes, and hospital readmission rate. A total of 97 evaluable patients were enrolled (tbo-filgrastim, n = 46; filgrastim, n = 51). Tbo-filgrastim was not inferior to filgrastim in terms of day 5 CD34 +  cell collection (mean, 11.6 ± 6.7 CD34

  8. Newer Clinical Strategies for Combining Interferon and Cytotoxic Agents Against Solid Tumours and Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Scott Wadler

    1994-01-01

    Full Text Available The role of interferons in the treatment of cancer continues to evolve. Despite limited single agent activity against solid tumours, interferons now appear to have an important role as modulators of the activity of a variety of cytotoxic drugs. Clinical benefits have been observed for combinations of interferons and alkylating agents against low grade lymphomas, interferons and dacarbazine against malignant melanoma, and interferons and 5-fluorouracil against gastrointestinal and genitourinary malignancies. Further progress will depend on a grealer understanding of the biology of the interaction.

  9. Neuromyelitis optica-like pathology is dependent on type I interferon response.

    Science.gov (United States)

    Khorooshi, Reza; Wlodarczyk, Agnieszka; Asgari, Nasrin; Owens, Trevor

    2013-09-01

    Neuromyelitis optica is an antibody-mediated autoimmune inflammatory disease of the central nervous system. Reports have suggested that interferon beta which is beneficial for multiple sclerosis, exacerbates neuromyelitis optica. Our aim was to determine whether type I interferon plays a role in the formation of neuromyelitis optica lesions. Immunoglobulin G from a neuromyelitis optica patient was injected intracerebrally with human complement to type I interferon receptor deficient and wildtype mice. Loss of aquaporin-4 and glial fibrillary acidic protein was reduced in type I interferon receptor deficient mice brain. Our findings suggest that type I interferon signaling contributes to neuromyelitis optica pathogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Study design of the influence of SErotonin inhibition on patients with RENAl impairment or diabetes undergoing drug-eluting stent implantation (SERENADE) study: A multicenter, open-label, prospective, randomized study.

    Science.gov (United States)

    Lee, Seung-Ah; Suh, Jung-Won; Park, Jin Joo; Yoon, Chang-Hwan; Cho, Young-Suk; Youn, Tae-Jin; Chae, In-Ho; Kim, Hyo-Soo; Kim, Sang-Hyun; Choi, Dong-Ju

    2015-07-01

    The rates of stent failure after percutaneous coronary intervention have decreased since the introduction of the drug-eluting stent (DES). However, chronic kidney disease (CKD) and diabetes mellitus (DM) remain strong clinical predictors of poor prognosis despite DES implantation. Sarpogrelate, a selective serotonin (5-hydroxytryptamine (HT)2a [5-HT2A]) receptor antagonist, has antiproliferative effects, reducing neointimal hyperplasia and smooth muscle cell proliferation, as well as potent antiplatelet action, inhibiting 5-HT-induced platelet aggregation. However, efficacy and safety data for sarpogrelate in patients with CKD or DM are limited. We aim to determine whether sarpogrelate has beneficial effects in patients with CDK or DM treated with DES implantation. The SERENADE trial is a multicenter, open-label, prospective, randomized study that will test the superiority of triple anti-platelet therapy (TAT; aspirin, clopidogrel, and sarpogrelate) to conventional dual antiplatelet therapy (DAT; aspirin and clopidogrel) in preventing late lumen loss 9 months after the index procedure in patients with CKD or DM. A total of 220 patients diagnosed with coronary artery disease with DM or CKD will be randomized to the TAT or DAT groups (1:1 ratio) after DES implantation. The primary endpoint is late lumen loss at 9 months assessed by quantitative coronary angiography. Secondary efficacy endpoints are composites of major adverse cardiovascular events including cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Secondary safety endpoints are major bleeding events and hepatic or renal impairment. The SERENADE trial will provide insight on the efficacy of adjunctive therapy with sarpogrelate after DES implantation for patients with high-risk profiles such as CKD or DM. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov NCT02294643). Copyright © 2015. Published by Elsevier Inc.

  11. Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study.

    Science.gov (United States)

    Mackenzie, Isla S; Ford, Ian; Walker, Andrew; Hawkey, Chris; Begg, Alan; Avery, Anthony; Taggar, Jaspal; Wei, Li; Struthers, Allan D; MacDonald, Thomas M

    2016-09-08

    Ischaemic heart disease (IHD) is one of the most common causes of death in the UK and treatment of patients with IHD costs the National Health System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase inhibitor used to prevent gout that also has several positive effects on the cardiovascular system. The ALL-HEART study aims to determine whether allopurinol improves cardiovascular outcomes in patients with IHD. The ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and over with IHD. Patients are followed up by electronic record linkage and annual questionnaires for an average of 4 years. The primary outcome is the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes include all-cause mortality, quality of life and cost-effectiveness of allopurinol. The study will end when 631 adjudicated primary outcomes have occurred. The study is powered at 80% to detect a 20% reduction in the primary end point for the intervention. Patient recruitment to the ALL-HEART study started in February 2014. The study received ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2 (13/ES/0104). The study is event-driven and results are expected after 2019. Results will be reported in peer-reviewed journals and at scientific meetings. Results will also be disseminated to guideline committees, NHS organisations and patient groups. 32017426, pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Rationale, Design, and Baseline Characteristics of the Utopia Trial for Preventing Diabetic Atherosclerosis Using an SGLT2 Inhibitor: A Prospective, Randomized, Open-Label, Parallel-Group Comparative Study.

    Science.gov (United States)

    Katakami, Naoto; Mita, Tomoya; Yoshii, Hidenori; Shiraiwa, Toshihiko; Yasuda, Tetsuyuki; Okada, Yosuke; Umayahara, Yutaka; Kaneto, Hideaki; Osonoi, Takeshi; Yamamoto, Tsunehiko; Kuribayashi, Nobuichi; Maeda, Kazuhisa; Yokoyama, Hiroki; Kosugi, Keisuke; Ohtoshi, Kentaro; Hayashi, Isao; Sumitani, Satoru; Tsugawa, Mamiko; Ohashi, Makoto; Taki, Hideki; Nakamura, Tadashi; Kawashima, Satoshi; Sato, Yasunori; Watada, Hirotaka; Shimomura, Iichiro

    2017-10-01

    Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker. The Study of Using Tofogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, blinded-endpoint, multicenter, and parallel-group comparative study. The aim was to recruit a total of 340 subjects with T2DM but no history of apparent CVD at 24 clinical sites and randomly allocate these to a tofogliflozin treatment group or a conventional treatment group using drugs other than SGLT2 inhibitors. As primary outcomes, changes in mean and maximum IMT of the common carotid artery during a 104-week treatment period will be measured by carotid echography. Secondary outcomes include changes in glycemic control, parameters related to β-cell function and diabetic nephropathy, the occurrence of CVD and adverse events, and biochemical measurements reflecting vascular function. This is the first study to address the effects of SGLT2 inhibitors on the progression of carotid IMT in subjects with T2DM without a history of CVD. The results will be available in the very near future, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent CVD. Kowa Co., Ltd. UMIN000017607.

  13. Effect of doxazosin gastrointestinal therapeutic system 4 mg vs tamsulosin 0.2 mg on nocturia in Chinese men with lower urinary tract symptoms: a prospective, multicenter, randomized, open, parallel study.

    Science.gov (United States)

    Zhang, Kai; Yu, Wei; Jin, Jie; Ye, Haiyun; Wang, Xiaofeng; Zhang, Ning; Yang, Yong; Zhong, Chenyang; Wan, Ben

    2011-09-01

    To compare the efficacy of the doxazosin gastrointestinal therapeutic system (doxazosin-GITS) 4 mg and tamsulosin 0.2 mg on nocturia in Chinese men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Data were analyzed from a prospective, multicenter, randomized, open, parallel study of Chinese men aged 50-84 years with LUTS/BPH. Two hundred patients were randomized to receive daily treatment with 4 mg doxazosin-GITS (n=100) or 0.2 mg tamsulosin (n=100) for 8 weeks. Nocturia was assessed by question 7 of the International Prostate Symptom Score (IPSS-question 7) and a frequency-volume chart (FVC) at weeks 4 and 8. Self-reported quality of sleep and quality of life by the last question of the IPSS questionnaire were also evaluated. A total of 189 patients (94 receiving doxazosin-GITS, 95 tamsulosin) completed the study. The reduction from baseline in mean nocturia was greater with doxazosin-GITS than tamsulosin by the FVC (1.7 vs 1.3 at week 4; 2.1 vs 1.7 at week 8, both P=.001) and by the IPSS-question 7 (1.5 vs 1.1 at 4 weeks, P=.001; 2.0 vs 1.6 at 8 weeks, Psleep was significantly more with doxazosin-GITS than tamsulosin (43.6% vs 27.4% at 4 weeks, P=.020; 81.9% vs 67.4% at 8 weeks, P=.022), and quality of life was better with doxazosin-GITS (2.5 vs 2.8 at 4 weeks, P=.001; 2.1 vs 2.5 at 8 weeks, P<.001). In Chinese patients with LUTS/BPH, doxazosin-GITS is slightly better than tamsulosin in reducing the frequency of nocturia. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Biotechnology: challenges and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Sasson, A.

    1985-04-01

    Rapidly occurring technological breakthroughs in the wake of numerous discoveries in different fields, such as biochemistry, genetic engineering as well as cellular and molecular biology as described in this paper have a variety of industrial applications, and forcasts covering these and various other fields have been made. The emerging bio-industry, covering diverse industries, such as chemical, food, pharmaceutical, etc., as well as the domains of health, environmental protection and abatement of pollution present challenging prospects. Several biotechnology processes relating to bioenergy, fermentation, waste transformation, vaccines, etc. are of particular interest to the developing countries. The 'functioning systems' resulting from the breakthrouth in genetic engineering, entailing extraordinary refinement of analytical techniques and technological progress, pose the challenging task of harnessing them to the advantage of mankind. Providing effective legal protection, conducive to the development of biotechnologies-their innovative process and technological change-is a matter of serious concern, involving practical and economical considerations. Several other issues and questions, such as risk prevention and management of potential dangers and hazards in genetic recombination operation by way of safety regulations and necessary guidelines, questions relating to the clinical trials of the interferons-the wonder drug-as well as questions of professional ethics are raised by biotechnologies. Industry-funded research in biotechnology, where scientific and commercial imperatives are interlocked, has for instance, its repercussions on the traditional thrust of university system, specially the sanctity of autonomy for basic research.

  15. Differential expression of interferon-gamma and interferon-gamma-inducing cytokines in Thai patients with scrub typhus or leptospirosis

    NARCIS (Netherlands)

    Chierakul, Wirongrong; de Fost, Maaike; Suputtamongkol, Yupin; Limpaiboon, Roongreung; Dondorp, Arjen; White, Nicholas J.; van der Poll, Tom

    2004-01-01

    Interferon (IFN)-gamma plays an important role in the induction of a type 1 immune response against intracellular pathogens. We compared the plasma levels of IFN-gamma and IFN-gamma-inducing cytokines in adult Thai patients with scrub typhus, caused by the obligate intracellular bacterium Orientia

  16. Interferon gamma, interferon-gamma-induced-protein 10, and tuberculin responses of children at high risk of tuberculosis infection

    DEFF Research Database (Denmark)

    Petrucci, Roberta; Abu Amer, Nabil; Gurgel, Ricardo Queiroz

    2008-01-01

    BACKGROUND: Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-gamma (INF-gamma) release assays. Ot...

  17. Interferon gamma, interferon-gamma-induced-protein 10, and tuberculin responses of children at high risk of tuberculosis infection

    DEFF Research Database (Denmark)

    Petrucci, Roberta; Abu Amer, Nabil; Gurgel, Ricardo Queiroz

    2008-01-01

    BACKGROUND: Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-gamma (INF-gamma) release assays...

  18. Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway

    International Nuclear Information System (INIS)

    Song, Wuqi; Kao, Wenping; Zhai, Aixia; Qian, Jun; Li, Yujun; Zhang, Qingmeng; Zhao, Hong; Hu, Yunlong; Li, Hui; Zhang, Fengmin

    2013-01-01

    Highlights: •IRF7 nuclear localisation was inhibited by BDV persistently infected. •BDV N protein resistant to IFN induction both in BDV infected OL cell and N protein plasmid transfected OL cell. •BDV N protein is related to the inhibition of IRF7 nuclear localisation. -- Abstract: The expression of type I interferon (IFN) is one of the most potent innate defences against viral infection in higher vertebrates. Borna disease virus (BDV) establishes persistent, noncytolytic infections in animals and in cultured cells. Early studies have shown that the BDV phosphoprotein can inhibit the activation of type I IFN through the TBK1–IRF3 pathway. The function of the BDV nucleoprotein in the inhibition of IFN activity is not yet clear. In this study, we demonstrated IRF7 activation and increased IFN-α/β expression in a BDV-persistently infected human oligodendroglia cell line following RNA interference-mediated BDV nucleoprotein silencing. Furthermore, we showed that BDV nucleoprotein prevented the nuclear localisation of IRF7 and inhibited endogenous IFN induction by poly(I:C), coxsackie virus B3 and IFN-β. Our findings provide evidence for a previously undescribed mechanism by which the BDV nucleoprotein inhibits type I IFN expression by interfering with the IRF7 pathway

  19. Esophagectomy - open

    Science.gov (United States)

    ... Lewis esophagectomy, Blunt esophagectomy; Esophageal cancer - esophagectomy - open; Cancer of the esophagus - esophagectomy - open ... lining of the esophagus that can lead to cancer ( Barrett esophagus ) Severe trauma Destroyed esophagus Severely damaged stomach

  20. Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon

    Science.gov (United States)

    Akiyama, Hisashi; Ramirez, Nora-Guadalupe Pina; Gibson, Gregory; Kline, Christopher; Watkins, Simon; Ambrose, Zandrea

    2017-01-01

    ABSTRACT A hallmark of human immunodeficiency virus type 1 (HIV-1) infection in vivo is chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicate in vivo via mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein, CD169, as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4+ T cells in trans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4+ T cells in trans and thus offset antiviral effects of type I IFN. In support of this hypothesis, infection of HIV-1 or murine leukemia virus Env (MLV-Env)-pseudotyped HIV-1 particles was enhanced in IFN-α-treated THP-1 monocytoid cells, and this enhancement was primarily dependent on CD169-mediated enhancement at the virus entry step, a phenomenon phenocopied in HIV-1 infections of IFN-α-treated primary monocyte-derived macrophages (MDMs). Furthermore, expression of CD169, a marker of type I IFN-induced immune activation in vivo, was enhanced in lymph nodes from pigtailed macaques infected with simian immunodeficiency virus (SIV) carrying HIV-1 reverse transcriptase (RT-SHIV), compared to uninfected macaques, and interestingly, there was extensive colocalization of p27gag and CD169, suggesting productive infection of CD169+ myeloid cells in vivo. While cell-free HIV-1 infection of IFN-α-treated CD4+ T cells was robustly decreased, initiation of infection in trans via coculture with CD169+ IFN-α-treated DCs restored infection, suggesting that HIV-1 exploits CD169 in cis and in trans to attenuate a type I IFN-induced antiviral state. IMPORTANCE HIV-1 infection in humans causes immune activation characterized by elevated levels of proinflammatory cytokines, including type I interferons (IFN

  1. Kallikrein–Kinin System Suppresses Type I Interferon Responses: A Novel Pathway of Interferon Regulation

    Directory of Open Access Journals (Sweden)

    Alecia Seliga

    2018-02-01

    Full Text Available The Kallikrein–Kinin System (KKS, comprised of kallikreins (klks, bradykinins (BKs angiotensin-converting enzyme (ACE, and many other molecules, regulates a number of physiological processes, including inflammation, coagulation, angiogenesis, and control of blood pressure. In this report, we show that KKS regulates Type I IFN responses, thought to be important in lupus pathogenesis. We used CpG (TLR9 ligand, R848 (TLR7 ligand, or recombinant IFN-α to induce interferon-stimulated genes (ISGs and proteins, and observed that this response was markedly diminished by BKs, klk1 (tissue kallikrein, or captopril (an ACE inhibitor. BKs significantly decreased the ISGs induced by TLRs in vitro and in vivo (in normal and lupus-prone mice, and in human PBMCs, especially the induction of Irf7 gene (p < 0.05, the master regulator of Type I IFNs. ISGs induced by IFN-α were also suppressed by the KKS. MHC Class I upregulation, a classic response to Type I IFNs, was reduced by BKs in murine dendritic cells (DCs. BKs decreased phosphorylation of STAT2 molecules that mediate IFN signaling. Among the secreted pro-inflammatory cytokines/chemokines analyzed (IL-6, IL12p70, and CXCL10, the strongest suppressive effect was on CXCL10, a highly Type I IFN-dependent cytokine, upon CpG stimulation, both in normal and lupus-prone DCs. klks that break down into BKs, also suppressed CpG-induced ISGs in murine DCs. Captopril, a drug that inhibits ACE and increases BK, suppressed ISGs, both in mouse DCs and human PBMCs. The effects of BK were reversed with indomethacin (compound that inhibits production of PGE2, suggesting that BK suppression of IFN responses may be mediated via prostaglandins. These results highlight a novel regulatory mechanism in which members of the KKS control the Type I IFN response and suggest a role for modulators of IFNs in the pathogenesis of lupus and interferonopathies.

  2. Regulation of interferon receptor expression in human blood lymphocytes in vitro and during interferon therapy

    International Nuclear Information System (INIS)

    Lau, A.S.; Hannigan, G.E.; Freedman, M.H.; Williams, B.R.

    1986-01-01

    Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. The binding characteristics of IFN to human lymphocytes were studied using IFN alpha 2 labeled with 125 I to high specific activity. The specific binding curves generated were analyzed by the LIGAND program of Munson and Rodbard to determine receptor numbers. The number of receptors in peripheral blood lymphocytes (PBL) and tonsillar B-lymphocytes (TBL) from normal individuals were 505 +/- 293 (n = 10) and 393 +/- 147 (n = 3) respectively. When these cells were preincubated in vitro with unlabeled IFN alpha 2, the receptor number decreased to 82 +/- 45 and 61 +/- 16 respectively. Receptor binding activities recovered gradually over a period of 72 h when the cells were incubated in IFN-free medium. This recovery of receptors could be blocked by the addition of actinomycin D to the incubation medium. A similar decrease in receptor expression was observed in vivo in PBL from patients being treated daily with 5 X 10(6) units/m2 per d of IFN alpha 2 by subcutaneous injection, for acute lymphoblastic leukemia or papilloma virus infections. Receptor numbers in PBL in vivo were further reduced concurrent with the progression of IFN therapy. Thus, the reduction in IFN receptor expression observed in vitro can be demonstrated in vivo. These studies indicate that monitoring IFN receptor expression in vivo can provide information regarding the availability of IFN receptors at the cell surface for the mediation of IFN actions during the course of IFN therapy

  3. Persistent interferon transgene expression by RNA interference-mediated silencing of interferon receptors.

    Science.gov (United States)

    Takahashi, Yuki; Vikman, Elin; Nishikawa, Makiya; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

    2010-09-01

    The in vivo half-life of interferons (IFNs) is very short, and its extension would produce a better therapeutic outcome in IFN-based therapy. Delivery of IFN genes is one solution for providing a sustained supply. IFNs have a variety of functions, including the suppression of transgene expression, through interaction with IFN receptors (IFNRs). This suppression could prevent IFNs from being expressed from vectors delivered. Silencing the expression of IFNAR and IFNGR, the receptors for type I and II IFNs, respectively, in cells expressing IFNs may prolong transgene expression of IFNs. Mouse melanoma B16-BL6 cells or mouse liver were selected as a site expressing IFNs (not a target for IFN gene therapy) and IFN-expressing plasmid DNA was delivered with or without small interfering RNA (siRNA) targeting IFNRs. Transfection of B16-BL6 cells with siRNA targeting IFNAR1 subunit (IFNAR1) resulted in the reduced expression of IFNAR on the cell surface. This silencing significantly increased the IFN-beta production in cells that were transfected with IFN-beta-expressing plasmid DNA. Similar results were obtained with the combination of IFN-gamma and IFNGR. Co-injection of IFN-beta-expressing plasmid DNA with siRNA targeting IFNAR1 into mice resulted in sustained plasma concentration of IFN-beta. These results provide experimental evidence that the RNAi-mediated silencing of IFNRs in cells expressing IFN, such as hepatocytes, is an effective approach for improving transgene expression of IFNs when their therapeutic target comprises cells other than those expressing IFNs.

  4. Open access

    NARCIS (Netherlands)

    Valkenburg, P.M.

    2015-01-01

    Open access week Van 19 tot en met 25 oktober 2015 vond wereldwijd de Open Access Week plaats. Tijdens deze week werden er over de hele wereld evenementen georganiseerd waar open access een rol speelt. Ook in Nederland zijn er diverse symposia, workshops en debatten georganiseerd zoals het debat in

  5. TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Lee Adam Wheeler

    2016-05-01

    Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

  6. Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study.

    Science.gov (United States)

    Rorie, David A; Rogers, Amy; Mackenzie, Isla S; Ford, Ian; Webb, David J; Willams, Bryan; Brown, Morris; Poulter, Neil; Findlay, Evelyn; Saywood, Wendy; MacDonald, Thomas M

    2016-02-09

    Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing. The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10,269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power. TIME has ethical approval in the UK, and results will be published in a peer-reviewed journal. UKCRN17071; Pre-results. Published by the BMJ

  7. SmartPill® as an objective parameter for determination of severity and duration of postoperative ileus: study protocol of a prospective, two-arm, open-label trial (the PIDuSA study).

    Science.gov (United States)

    Vilz, Tim O; Pantelis, Dimitrios; Lingohr, Philipp; Fimmers, Rolf; Esmann, Anke; Randau, Thomas; Kalff, Jörg C; Coenen, Martin; Wehner, Sven

    2016-07-08

    Postoperative ileus (POI) is a frequent complication after abdominal surgery (AS). Until today, neither a prophylaxis nor an evidence-based therapy exists. This originates from the absence of objective parameters evaluating the severity and duration of POI resulting in clinical trials of modest quality. The SmartPill(®), a capsule which frequently measures pH value, temperature and intraluminal pressure after swallowing, offers an elegant option for analysing gastrointestinal (GI) transit times and smooth muscle activity in vivo. As the use in patients in the first months after AS is not covered by the marketing authorisation, we aim to investigate the safety and feasibility of the SmartPill(®) immediately after surgery. Additionally, we analyse the influence of prokinetics and laxatives as well as standardised physiotherapy on postoperative bowel contractility, as scientific evidence of its effects is still lacking. The PIDuSA study is a prospective, single-centre, two-arm, open-label trial. The SmartPill(®) will be applied to 55 patients undergoing AS having a high risk for POI and 10 patients undergoing extra-abdominal surgery rarely developing POI. The primary objective is the safety of the SmartPill(®) in patients after surgery on the basis of adverse device effects/serious adverse device effects (ADE/SADE). The sample size suggests that events with a probability of 3% could be seen with a certainty of 80% for at least once in the sample. Secondary objective is the analysis of postoperative intestinal activity in the GI tract in both groups. Furthermore, clinical signs of bowel motility disorders will be correlated to the data measured by the SmartPill(®) to evaluate its significance as an objective parameter for assessing POI severity. Additionally, effects of prokinetics, laxatives and physiotherapy on postoperative peristaltic activity recorded by the SmartPill(®) will be analysed. The protocol was approved by the federal authority (94

  8. Symptom-modifying effects of oral avocado/soybean unsaponifiables in routine treatment of knee osteoarthritis in Poland. An open, prospective observational study of patients adherent to a 6-month treatment

    Directory of Open Access Journals (Sweden)

    Piotr Głuszko

    2016-11-01

    Full Text Available Objectives: Observational studies provide insights into real-life situations. Therefore, we assessed the effects of oral avocado/soybean unsaponifiable (ASU capsules on pain relief and functional ability in patients, while they were receiving a routine treatment for knee osteoarthritis (OA. Material and methods : An open, prospective, observational 6-month study was conducted in 99 centers in Poland in a group of 4822 patients with symptomatic knee OA receiving one 300 mg ASU capsule/day as a routine medication. The patients had no diagnoses of other rheumatic diseases and were not treated with other symptomatic slow-acting drugs for osteoarthritis (SYSADOAs. Data on OA symptoms and therapy were collected from the initiation of ASU treatment (visit 0 and during 3 consecutive control visits performed every 2 months (visits 1–3. Functional Lequesne index, severity of joint pain of one symptomatic knee (Laitinen index and VAS, use of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs, adherence to treatment and adverse events were evaluated and recorded using electronic Case Report Forms. Results : Four thousand one hundred and eighty-six patients (86.8% attended all 4 visits. In 94.2% of patients (mean age 60.7 ±11.6 years SD, 73.4% female at least one OA risk factor was identified. There was a significant improvement in functional ability between the last and baseline visits as evidenced by the median Lequesne index decreasing from 8 to 4 points (p < 0.001. Measures of pain intensity also fell significantly (p < 0.001 throughout the study: median Laitinen score decreased from 6 to 3 points, median pain at rest VAS – from 1.8 to 0 cm and median pain during walking VAS – from 5.6 to 1.9 cm. The significant differences were also noted between consecutive visits. The proportion of patients using analgesics and NSAIDs declined from 58.8% at the baseline visit to 24.9% at the last visit 3 (p < 0.001. Defined daily dose of NSAIDs

  9. A single-center, prospective, randomized, open-label, clinical trial of ceramide 2-containing hydrocolloid dressings versus polyurethane film dressings for pressure ulcer prevention in high-risk surgical patients

    Directory of Open Access Journals (Sweden)

    Kohta M

    2015-11-01

    Full Text Available Masushi Kohta,1 Kazumi Sakamoto,2 Yasuhiro Kawachi,3 Tsunao Oh-i4 1Medical Engineering Laboratory, ALCARE Co, Ltd, Tokyo, 2Department of Nursing, 3Department of Dermatology, Tokyo Medical University Ibaraki Medical Center, Ibaraki, 4Department of Dermatology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan Purpose: There have been previous clinical studies regarding the impact of dressings on the prevention of pressure ulcer development. However, it remains unclear whether one type of dressing is better than any other type for preventing ulcer development during surgery. Therefore, we compared the effects of ceramide 2-containing hydrocolloid dressing with film dressings in high-risk patients with regard to reducing the incidence of pressure ulcer development during surgery. Patients and methods: A prospective, randomized, open-label, clinical trial was conducted involving patients who were at a high risk of developing pressure ulcers at a Japanese hospital. The intervention group received ceramide 2-containing hydrocolloid dressings (n=66, and the control group received film dressings (n=64. The primary end point was the incidence rate of pressure ulcer development in both groups; skin damage, such as blanchable erythema, skin discoloration, contact dermatitis, and stripped skin, was recorded as the secondary end point. The relative risk (RR and 95% confidence interval (CI were assessed to compare the probability ratios of pressure ulcer development between the groups. Results: There were significantly fewer patients who developed pressure ulcers in the intervention group than in the control group (RR, 0.37; 95% CI, 0.05–0.99; P=0.04. In the post hoc subgroup analysis, the superiority of the intervention group was more marked when patients had a lower body mass index (P=0.02, lower albumin values (P=0.07, and operation time of 3 hours or more and less than 6 hours (P=0.03. There was no evidence of any statistically significant

  10. Hypothyroidism In Hepatitis C Patients On Pegylated Interferon Therapy.

    Science.gov (United States)

    Hameed, Muhammad Asim; Mehmood, Asif; Farooq, Muhammad Ahsan; Tayyab, Ghias Un Nabi; Haq Toor, Israr Ul

    2016-01-01

    Chronic hepatitis has become a major health problem all over the world especially in the third world countries. The most common cause of chronic hepatitis in Pakistan is hepatitis C which can lead Toliver cirrhosis and hepatocellular carcinoma. In Pakistan Pegylated Interferon Alpha is still corner stone of therapy for chronic hepatitis C. One of the major side effects of this therapy is the development of thyroid dysfunction, i.e., hypothyroidism and hyperthyroidism. This study was done to assess the frequency of hypothyroidism in hepatitis C patients after three months of pegylated interferon therapy. This study was conducted from 1st October 2013 to 31st march 2014 at outpatients department (OPD) of Gastroenterology and Hepatology, Lahore General Hospital Lahore. Descriptive case series study design was used. The sample of 200 patients was taken from the patients who visited OPD and fulfil the inclusion criteria of the study. Serum thyroid stimulating hormone level (TSH) was done before and after completion of three months therapy at centre for Nuclear Medicine (CENUM) laboratory, Mayo Hospital, Lahore by immune-radiometric assay (IRMA) and patients having TSH>4.0 mIU/L (normal range: 0.2-4.0 mIU/L) were considered hypothyroid. The mean age of the patients was 36.29±8.5 years. One hundred and twenty-three (61.5%) were male and 77 (38.5%) were female. After 3 months of interferon therapy, 163 (81.5%) patients were euthyroid and 37(18.5%) patients were having thyroid dysfunction. There were total 29 (14.5%) hypothyroid patients; 8 (27.6%) were male and 21 (72.4%) female. It is concluded from this study that frequency of hypothyroidism in patients with chronic hepatitis C was 14.5% after treatment with pegylated interferon therapy for 3 months. Female patients were more prone to develop hypothyroidism as compared to male patients.

  11. Interferon γ-inducible protein (IFI) 16 transcriptionally regulates type i interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses.

    Science.gov (United States)

    Thompson, Mikayla R; Sharma, Shruti; Atianand, Maninjay; Jensen, Søren B; Carpenter, Susan; Knipe, David M; Fitzgerald, Katherine A; Kurt-Jones, Evelyn A

    2014-08-22

    The interferon γ-inducible protein 16 (IFI16) has recently been linked to the detection of nuclear and cytosolic DNA during infection with herpes simplex virus-1 and HIV. IFI16 binds dsDNA via HIN200 domains and activates stimulator of interferon genes (STING), leading to TANK (TRAF family member-associated NF-κB activator)-binding kinase-1 (TBK1)-dependent phosphorylation of interferon regulatory factor (IRF) 3 and transcription of type I interferons (IFNs) and related genes. To better understand the role of IFI16 in coordinating type I IFN gene regulation, we generated cell lines with stable knockdown of IFI16 and examined responses to DNA and RNA viruses as well as cyclic dinucleotides. As expected, stable knockdown of IFI16 led to a severely attenuated type I IFN response to DNA ligands and viruses. In contrast, expression of the NF-κB-regulated cytokines IL-6 and IL-1β was unaffected in IFI16 knockdown cells, suggesting that the role of IFI16 in sensing these triggers was unique to the type I IFN pathway. Surprisingly, we also found that knockdown of IFI16 led to a severe attenuation of IFN-α and the IFN-stimulated gene retinoic acid-inducible gene I (RIG-I) in response to cyclic GMP-AMP, a second messenger produced by cyclic GMP-AMP synthase (cGAS) as well as RNA ligands and viruses. Analysis of IFI16 knockdown cells revealed compromised occupancy of RNA polymerase II on the IFN-α promoter in these cells, suggesting that transcription of IFN-stimulated genes is dependent on IFI16. These results indicate a broader role for IFI16 in the regulation of the type I IFN response to RNA and DNA viruses in antiviral immunity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Inflammation Activates the Interferon Signaling Pathways in Taste Bud Cells

    OpenAIRE

    Wang, Hong; Zhou, Minliang; Brand, Joseph; Huang, Liquan

    2007-01-01

    Patients with viral and bacterial infections or other inflammatory illnesses often experience taste dysfunctions. The agents responsible for these taste disorders are thought to be related to infection-induced inflammation, but the mechanisms are not known. As a first step in characterizing the possible role of inflammation in taste disorders, we report here evidence for the presence of interferon (IFN)-mediated signaling pathways in taste bud cells. IFN receptors, particularly the IFN-γ rece...

  13. Peripheral Vasculitis, Intermediate Uveitis and Interferon Use in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Haluk Esgin

    2016-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system. A 40-year-old female patient with a 12-year history of MS was admitted to our clinic with blurred vision and floaters in her right eye for about 1 month. Here, we share the findings and the management of intermediate uveitis and retinal periphlebitis in an MS case being treated with interferon beta-1a for 7 years.

  14. Interferon Lambda Genetics and Biology in Regulation of Viral Control

    Directory of Open Access Journals (Sweden)

    Emily A. Hemann

    2017-12-01

    Full Text Available Type III interferons, also known as interferon lambdas (IFNλs, are the most recent addition to the IFN family following their discovery in 2003. Initially, IFNλ was demonstrated to induce expression of interferon-stimulated genes and exert antiviral properties in a similar manner to type I IFNs. However, while IFNλ has been described to have largely overlapping expression and function with type I IFNs, it has become increasingly clear that type III IFNs also have distinct functions from type I IFNs. In contrast to type I IFNs, whose receptor is ubiquitously expressed, type III IFNs signal and function largely at barrier epithelial surfaces, such as the respiratory and gastrointestinal tracts, as well as the blood–brain barrier. In further support of unique functions for type III IFNs, single nucleotide polymorphisms in IFNL genes in humans are strongly associated with outcomes to viral infection. These biological linkages have also been more directly supported by studies in mice highlighting roles of IFNλ in promoting antiviral immune responses. In this review, we discuss the current understanding of type III IFNs, and how their functions are similar to, and different from, type I IFN in various immune cell subtypes and viral infections.

  15. Interferon alpha for the adjuvant treatment of cutaneous melanoma.

    Science.gov (United States)

    Mocellin, Simone; Lens, Marko B; Pasquali, Sandro; Pilati, Pierluigi; Chiarion Sileni, Vanna

    2013-06-18

    Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists. To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma. We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials. We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II). Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates

  16. How Flaviviruses Activate and Suppress the Interferon Response

    Directory of Open Access Journals (Sweden)

    Brenda L. Fredericksen

    2010-02-01

    Full Text Available The flavivirus genus includes viruses with a remarkable ability to produce disease on a large scale. The expansion and increased endemicity of dengue and West Nile viruses in the Americas exemplifies their medical and epidemiological importance. The rapid detection of viral infection and induction of the innate antiviral response are crucial to determining the outcome of infection. The intracellular pathogen receptors RIG-I and MDA5 play a central role in detecting flavivirus infections and initiating a robust antiviral response. Yet, these viruses are still capable of producing acute illness in humans. It is now clear that flaviviruses utilize a variety of mechanisms to modulate the interferon response. The non-structural proteins of the various flaviviruses reduce expression of interferon dependent genes by blocking phosphorylation, enhancing degradation or down-regulating expression of major components of the JAK/STAT pathway. Recent studies indicate that interferon modulation is an important factor in the development of severe flaviviral illness. This suggests that an increased understanding of viral-host interactions will facilitate the development of novel therapeutics to treat these viral infections and improved biological models to study flavivirus pathogenesis.

  17. Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion

    Directory of Open Access Journals (Sweden)

    Ren Song

    2016-02-01

    Full Text Available Infection by alphaherpesviruses, including herpes simplex virus (HSV and pseudorabies virus (PRV, typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS. Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs. The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β or gamma interferon (IFN-γ significantly diminished the number of herpes simplex virus 1 (HSV-1 and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1 only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion.

  18. Open Content in Open Context

    Science.gov (United States)

    Kansa, Sarah Whitcher; Kansa, Eric C.

    2007-01-01

    This article presents the challenges and rewards of sharing research content through a discussion of Open Context, a new open access data publication system for field sciences and museum collections. Open Context is the first data repository of its kind, allowing self-publication of research data, community commentary through tagging, and clear…

  19. Combined pegylated interferon and ribavirin for the management of chronic hepatitis C in a prison setting.

    Science.gov (United States)

    Sabbatani, Sergio; Giuliani, Ruggero; Manfredi, Roberto

    2006-08-01

    The elevated frequency of chronic hepatitis C virus (HCV) infection found among prison inmates, and the availability of improved pharmacological cure for this potentially life-threatening disorder, make investigations conducted in this somewhat neglected area very relevant, since only a few, open-label experiences have been reported till now. In the metropolitan prison of Bologna (Italy), HCV seroprevalence was found to be over 31% in 2003, so that a pilot feasibility study based on treatment with pegylated interferon plus ribavirin was initiated, after careful counseling carried out by a joint commission of health care personnel of the correctional facility and infectious diseases consultants. Thirty-nine patients were enrolled, and despite expected dropouts due to difficulty in maintaining the same level of counseling pressure over time, and the particularly unfavorable climatic conditions during Summer 2003, a sustained virological response was obtained for 8 out of the 21 patients who remained evaluable after the first three month follow-up, although we need to take into account that a high percentage of subjects (67%) were selected for therapy due to their favorable HCV genotypes (types 2 and 3). Our preliminary experience shows that an intrinsically complicated therapy, such as the administration of pegylated interferon plus ribavirin, can attain a relatively high success rate, even in a very unfavorable and uncomfortable context, such as a prison, where only enforced counseling, active participation of institutional health care operators, and patient's willingness to maintain an elevated level of co-operation and adherence, can overcome most structural and relational difficulties.

  20. Pancreatitis versus open epiphysiodesis

    International Nuclear Information System (INIS)

    Al-Zahrani, Adnan G.; Al-Hossain, Mohammad H.; Aab, F.; Yaser, M.; Alammari, A.

    2003-01-01

    Epiphysiodesis is used for treatment of leg -length discrepancy in skeletally immature patients.Phemister described an open technique that requires surgical dissection with potential morbidity. Recently minimally invasive approaches that utilize intraoperative fluoroscopy have been introduced. The aim of this study is to compare our experience using the open and the minimally invasive percutaneous techniques. A prospective follow-up of 87 consecutive patients undergoing epiphysiodesis for correction of post traumetic leg-length discrepancy using either the open or the percutaneous technique at the Armed Forces Hospital ,Riyadh,Kingdom of Saudi Arabia between January 1993 and December 2000. Out of 87 patients , 52 were carried out using the open technique and 35 were utilized by this percutaneous technique.There was no statistically significant between two groups in terms of demographic date ,operative time,perioperative complications or time required to achieve the growth arrest. However there was a significant difference in the hospital stay and postoperative need for physiotherapy .The percutaneous group had a short hospitalization (average 2.5 days )compared to open technique group (average 4 days). Our experience is similarto what is reported in the literature and confirms that the percutaneous technique has an advatage over the open technique with shorter hospitalization and less duration of physiotherapy. (author) =

  1. Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease.

    Science.gov (United States)

    Rice, Gillian I; Melki, Isabelle; Frémond, Marie-Louise; Briggs, Tracy A; Rodero, Mathieu P; Kitabayashi, Naoki; Oojageer, Anthony; Bader-Meunier, Brigitte; Belot, Alexandre; Bodemer, Christine; Quartier, Pierre; Crow, Yanick J

    2017-02-01

    Increased type I interferon is considered relevant to the pathology of a number of monogenic and complex disorders spanning pediatric rheumatology, neurology, and dermatology. However, no test exists in routine clinical practice to identify enhanced interferon signaling, thus limiting the ability to diagnose and monitor treatment of these diseases. Here, we set out to investigate the use of an assay measuring the expression of a panel of interferon-stimulated genes (ISGs) in children affected by a range of inflammatory diseases. A cohort study was conducted between 2011 and 2016 at the University of Manchester, UK, and the Institut Imagine, Paris, France. RNA PAXgene blood samples and clinical data were collected from controls and symptomatic patients with a genetically confirmed or clinically well-defined inflammatory phenotype. The expression of six ISGs was measured by quantitative polymerase chain reaction, and the median fold change was used to calculate an interferon score (IS) for each subject compared to a previously derived panel of 29 controls (where +2 SD of the control data, an IS of >2.466, is considered as abnormal). Results were correlated with genetic and clinical data. Nine hundred ninety-two samples were analyzed from 630 individuals comprising symptomatic patients across 24 inflammatory genotypes/phenotypes, unaffected heterozygous carriers, and controls. A consistent upregulation of ISG expression was seen in 13 monogenic conditions (455 samples, 265 patients; median IS 10.73, interquartile range (IQR) 5.90-18.41), juvenile systemic lupus erythematosus (78 samples, 55 patients; median IS 10.60, IQR 3.99-17.27), and juvenile dermatomyositis (101 samples, 59 patients; median IS 9.02, IQR 2.51-21.73) compared to controls (78 samples, 65 subjects; median IS 0.688, IQR 0.427-1.196), heterozygous mutation carriers (89 samples, 76 subjects; median IS 0.862, IQR 0.493-1.942), and individuals with non-molecularly defined autoinflammation (89 samples, 69

  2. Weak openness and almost openness

    Directory of Open Access Journals (Sweden)

    David A. Rose

    1984-01-01

    Full Text Available Weak openness and almost openness for arbitrary functions between topological spaces are defined as duals to the weak continuity of Levine and the almost continuity of Husain respectively. Independence of these two openness conditions is noted and comparison is made between these and the almost openness of Singal and Singal. Some results dual to those known for weak continuity and almost continuity are obtained. Nearly almost openness is defined and used to obtain an improved link from weak continuity to almost continuity.

  3. Response of interferon alone and with ribavirin inpatients of chronic hepatitis C

    International Nuclear Information System (INIS)

    Niaz, A.

    2003-01-01

    Objective: The aim of the study was to compare the response of interferon alone and interferon plus ribavirin in patients of chronic hepatitis C. Results: At completion of treatment HCV-RNA levels in serum were not detectable in 15 of 20 (75%) patients who received interferon alpha and ribavirin combination therapy as compared to 10 of 20 (50%) patients who received interferon alpha alone. Only 1 patient became HCV RNA negative in the control group. Normalization of ALT concentration and histologic response was proportionate to the virological response. Conclusion: Combination therapy of interferon and ribavirin is more effective than treatment with interferon alone for minimizing viral load, improving ALT levels and histology. (author)

  4. Silybin supplementation during HCV therapy with pegylated interferon-α plus ribavirin reduces depression and anxiety and increases work ability.

    Science.gov (United States)

    Malaguarnera, Giulia; Bertino, Gaetano; Chisari, Giuseppe; Motta, Massimo; Vecchio, Michele; Vacante, Marco; Caraci, Filippo; Greco, Carmela; Drago, Filippo; Nunnari, Giuseppe; Malaguarnera, Michele

    2016-11-15

    Hepatitis C virus infection and interferon treatment are often associated with anxiety, depressive symptoms and poor health-related quality of life. To evaluate the Silybin-vitamin E-phospholipids complex effect on work ability and whether health related factors (anxiety and depression) were associated with work ability in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b (Peg-IFN) and Ribavirin (RBV). Thirty-one patients (Group A) with chronic hepatitis and other 31 subjects in Group B were recruited in a randomized, prospective, placebo controlled, double blind clinical trial. Group A received 1.5 mg/kg per week of Peg-IFN plus RBV and placebo, while Group B received the same dosage of Peg-IFN plus RBV plus association of Silybin 94 mg + vitamin E 30 mg + phospholipids 194 mg in pills for 12 months. All subjects underwent to laboratory exams and questionnaires to evaluate depression (Beck Depression Inventory - BDI), anxiety (State-trait anxiety inventory - STAI) and work ability (Work ability Index - WAI). The comparison between group A and group B showed significant differences after 6 months in ALT (P work ability and reduced depression and anxiety in patients treated with Peg-IFN and RBV. NCT01957319 , First received: September 25, 2013. Last updated: September 30, 2013 (retrospectively registered).

  5. Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Chiaki Okuse; Hiroshi Yotsuyanagi; Yoshihiko Nagase; Yuhtaro Kobayashi; Kiyomi Yasuda; Kazuhiko Koike; Shiro Iino; Michihiro Suzuki; Fumio Itoh

    2006-01-01

    AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy.METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy.RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%)despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension,or pretreatment arteriosclerotic changes in the optic fundj. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P=0.004,OR=245.918, 95% CI=5.6-10786.2).CONCLUSION: Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.

  6. Interferon Response and Viral Evasion by Members of the Family Rhabdoviridae

    OpenAIRE

    Matthias J. Schnell; Elizabeth J. Faul; Douglas S. Lyles

    2009-01-01

    Like many animal viruses, those of the Rhabdoviridae family, are able to antagonize the type I interferon response and cause disease in mammalian hosts. Though these negative-stranded RNA viruses are very simple and code for as few as five proteins, they have been seen to completely abrogate the type I interferon response early in infection. In this review, we will discuss the viral organization and type I interferon evasion of rhabdoviruses, focusing on vesicular stomatitis virus (VSV) and r...

  7. Interferon induction in bovine and feline monolayer cultures by four bluetongue virus serotypes.

    OpenAIRE

    Fulton, R W; Pearson, N J

    1982-01-01

    The interferon inducing ability of bluetongue viruses was studied in bovine and feline monolayer cultures inoculated with each of four bluetongue virus serotypes. Interferon was assayed by a plaque reduction method in monolayer cultures with vesicular stomatitis virus as challenge virus. Interferon was produced by bovine turbinate, Georgia bovine kidney, and Crandell feline kidney monolayer cultures in response to bluetongue virus serotypes 10, 11, 13 and 17. The antiviral substances produced...

  8. Mechanisms of regulation in the interferon factor 3 (IRF- 3) pathway

    OpenAIRE

    Limmer, Kirsten

    2008-01-01

    Interferon regulatory factor 3 (IRF-3) plays a critical role in the host cell response to both bacterial and viral infection. IRF-3 is activated by Toll-like receptors (TLRs) and cytoplasmic nucleic acid sensors, and serves to upregulate interferon beta and interferon stimulated genes (ISGs), thereby providing a quick and effective response to infection. In this work, two novel mechanisms of regulation in the IRF-3 pathway are revealed. The first part of this thesis work shows that upon bindi...

  9. Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis

    DEFF Research Database (Denmark)

    Dalbjerg, Sara Maria; Tsakiri, Anna; Fredriksen, Jette Lautrup

    2016-01-01

    Background Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis...... associated with Interferon-beta treatment. Case presentation We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved...... Interferon-beta-1-alpha therapy in patients with multiple sclerosis....

  10. Epidemiology, risk factors and prognosis of Interferon alpha induced thyroid disorders. A Prospective Clinical Study

    Directory of Open Access Journals (Sweden)

    Łukasz Obołończyk

    2017-09-01

    In conclusion: Thyroid disorders are common during IFN-α therapy. Previous epidemiological data seem to be underestimated. Important risk factors for IITD development are: female sex, elevated serum TSH concentration (≥2.5 μU/mL, positive TPO-Ab and increased blood velocity in thyroid arteries.

  11. Effects of preventive versus "on-demand" nutritional support on paid labour productivity, physical exercise and performance status during PEG-interferon-containing treatment for hepatitis C.

    Science.gov (United States)

    Huisman, Ellen J; van Meer, Suzanne; van Hoek, Bart; van Soest, Hanneke; van Nieuwkerk, Karin M J; Arends, Joop E; Siersema, Peter D; van Erpecum, Karel J

    2016-04-01

    Deterioration of nutritional status during PEG-interferon containing therapy for chronic hepatitis C can be ameliorated by preventive nutritional support. We aimed to explore whether such support also affects paid labour productivity, physical exercise and performance status. In this prospective randomized controlled trial (J Hepatol 2012;57:1069-75), 53 patients with chronic hepatitis C had been allocated to "on demand" support (n=26: nutritional intervention if weight loss>5%) or preventive support (n=27: regular dietary advice plus energy- and protein-rich evening snack) during PEG-interferon-containing therapy. Paid labour productivity, physical exercise and performance status were evaluated at baseline, after 24 and (if applicable) after 48 weeks of treatment. At baseline, 46% of patients performed paid labour and 62% performed some kind of physical exercise. Furthermore, most patients were able to carry out normal activity with only minor symptoms of disease (mean Karnofsky performance score: 94). Decreases of paid labour productivity (-21% vs. -70%, P=0.003), physical exercise activity (-43% vs. -87%, P=0.005) and Karnofsky performance scores (-12% vs. -24%, Plabour productivity, physical exercise and performance status during PEG-interferon-containing treatment for chronic hepatitis C. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study.

    Science.gov (United States)

    Krupp, Lauren B; Pohl, Daniela; Ghezzi, Angelo; Boyko, Alexey; Tenembaum, Silvia; Chen, Liang; Aycardi, Ernesto; Banwell, Brenda

    2016-04-15

    To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon β-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Opening Address

    Science.gov (United States)

    Yamada, T.

    2014-12-01

    Ladies and Gentlemen, it is my great honor and pleasure to present an opening address of the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3). On the behalf of the organizing committee, I certainly welcome all your visits to KGU Kannai Media Center belonging to Kanto Gakuin University, and stay in Yokohama. In particular, to whom come from abroad more than 17 countries, I would appreciate your participations after long long trips from your homeland to Yokohama. The first international workshop on "State of the Art in Nuclear Cluster Physics", called SOTANCP, was held in Strasbourg, France, in 2008, and the second one was held in Brussels, Belgium, in 2010. Then the third workshop is now held in Yokohama. In this period, we had the traditional 10th cluster conference in Debrecen, Hungary, in 2012. Thus we have the traditional cluster conference and SOTANCP, one after another, every two years. This obviously shows our field of nuclear cluster physics is very active and flourishing. It is for the first time in about 10 years to hold the international workshop on nuclear cluster physics in Japan, because the last cluster conference held in Japan was in Nara in 2003, about 10 years ago. The president in Nara conference was Prof. K. Ikeda, and the chairpersons were Prof. H. Horiuchi and Prof. I. Tanihata. I think, quite a lot of persons in this room had participated at the Nara conference. Since then, about ten years passed. So, this workshop has profound significance for our Japanese colleagues. The subjects of this workshop are to discuss "the state of the art in nuclear cluster physics" and also discuss the prospect of this field. In a couple of years, we saw significant progresses of this field both in theory and in experiment, which have brought better and new understandings on the clustering aspects in stable and unstable nuclei. I think, the concept of clustering has been more important than ever. This is true also in the

  14. Open hardware for open science

    CERN Multimedia

    CERN Bulletin

    2011-01-01

    Inspired by the open source software movement, the Open Hardware Repository was created to enable hardware developers to share the results of their R&D activities. The recently published CERN Open Hardware Licence offers the legal framework to support this knowledge and technology exchange.   Two years ago, a group of electronics designers led by Javier Serrano, a CERN engineer, working in experimental physics laboratories created the Open Hardware Repository (OHR). This project was initiated in order to facilitate the exchange of hardware designs across the community in line with the ideals of “open science”. The main objectives include avoiding duplication of effort by sharing results across different teams that might be working on the same need. “For hardware developers, the advantages of open hardware are numerous. For example, it is a great learning tool for technologies some developers would not otherwise master, and it avoids unnecessary work if someone ha...

  15. Open Access

    Science.gov (United States)

    Suber, Peter

    2012-01-01

    The Internet lets us share perfect copies of our work with a worldwide audience at virtually no cost. We take advantage of this revolutionary opportunity when we make our work "open access": digital, online, free of charge, and free of most copyright and licensing restrictions. Open access is made possible by the Internet and copyright-holder…

  16. Open innovation

    DEFF Research Database (Denmark)

    Bogers, Marcel; Chesbrough, Henry; Moedas, Carlos

    2018-01-01

    Open innovation is now a widely used concept in academia, business, and policy making. This article describes the state of open innovation at the intersection of research, practice, and policy. It discusses some key trends (e.g., digital transformation), challenges (e.g., uncertainty...

  17. A prospective, parallel group, open-labeled, comparative, multi-centric, active controlled study to evaluate the safety, tolerability and benefits of fixed dose combination of acarbose and metformin versus metformin alone in type 2 diabetes.

    Science.gov (United States)

    Jayaram, S; Hariharan, R S; Madhavan, R; Periyandavar, I; Samra, S S

    2010-11-01

    The present study was a prospective, parallel group, open-labeled, comparative, multicentric, active controlled study to evaluate the safety, tolerability and benefits of fixed dose combination of acarbose and metformin versus metformin alone in type 2 diabetic patients. A total of 229 patients with type 2 diabetes were enrolled at 5 medical centers across India. They received either acarbose (50 mg) + metformin (500 mg) bid/tid (n=115) or metformin monotherapy (500 mg) bid/ tid (n=114) for 12 weeks. Primary objective was to evaluate safety and tolerability based on the adverse events reported. Secondary objective was efficacy assessment based on changes in fasting, post prandial blood glucose and HbA1c values. In the acarbose + metformin group 10 patients reported 14 adverse events while in metformin group 9 patients reported 10 adverse events. No patient reported any serious adverse event or was withdraw from study because of adverse events. In the acarbose plus metformin group fasting blood glucose (FBG) decreased from a baseline of 158.85 +/- 18.14 mg/dl to 113.55 +/- 19.38 mg/dl (p fasting blood glucose decreased from a baseline of 158.31 +/- 26.53 mg/dl to 130.55 +/- 28.31 mg/dl (p < 0.0001) (decrease of 27.76 +/- 22.91 mg/dl) at 12 weeks. In the acarbose plus metformin group postprandial blood glucose (PPBG) decreased from a baseline of 264.65 +/- 34.03 mg/dl to 173.22 +/- 31.40 mg/dl (p < 0.0001) (decrease of 91.43 +/- 28.65 mg/dl) at 12 weeks, while in the metformin group PPBG decreased from a baseline of 253.56 +/- 36.28 mg/dl to 205.36 +/- 39.49 mg/dl (p < 0.0001) (decrease of 48.20 +/- 32.72 mg/dl) at 12 weeks. In the acarbose plus metformin group glycosylated haemoglobin (HbA1c) decreased from a baseline of 9.47 +/- 0.69% to 7.71 +/- 0.85% (p < 0.0001) (% decrease of 1.76 +/- 1.11) at 12 weeks, while in the metformin group HbAlc decreased from a baseline of 9.32 +/- 0.65% to 8.26 +/- 0.68% (p < 0.0001) (% decrease of 1.06 +/- 0.66) at 12 weeks. The

  18. Acetaminophen modulates the transcriptional response to recombinant interferon-beta.

    Directory of Open Access Journals (Sweden)

    Aaron Farnsworth

    Full Text Available BACKGROUND: Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-beta treatment. CD-1 mice were administered acetaminophen (APAP, interferon-beta (IFN-beta or a combination of IFN-beta+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-beta. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IkappaBK/NF-kappaB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points. CONCLUSIONS/SIGNIFICANCE: A significant change in the transcriptional response was observed following co-administration of IFN-beta+APAP relative to IFN-beta treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-beta treatment.

  19. Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

    Science.gov (United States)

    Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y

    2017-10-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

  20. Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

    Science.gov (United States)

    Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

    1992-04-01

    The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.

  1. Job Prospects for Metallurgical Engineering.

    Science.gov (United States)

    Basta, Nicholas

    1985-01-01

    Job prospects in mining, metal-extraction, steel, and refining industries are depressed, but technological discoveries are opening up new fields for metallurgical engineers. Enrollment/employment opportunities and salaries in these areas are discussed a well as the roles of foreign competition, plastics applications, and ceramics research and…

  2. Type I interferon signature in systemic lupus erythematosus.

    Science.gov (United States)

    Bezalel, Shira; Guri, Keren Mahlab; Elbirt, Daniel; Asher, Ilan; Sthoeger, Zev Moshe

    2014-04-01

    Type I interferons (IFN) are primarily regarded as an inhibitor of viral replication. However, type I IFN, mainly IFNalpha, plays a major role in activation of both the innate and adaptive immune systems. Systemic lupus erythematosus (SLE) is a chronic, multi-systemic, inflammatory autoimmune disease with undefined etiology. SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE. We review here the role of IFNalpha in the pathogenesis and course of SLE and the possible role of IFNalpha inhibition as a novel treatment for lupus patients.

  3. The Role of Interferons in Inflammation and Inflammasome Activation.

    Science.gov (United States)

    Kopitar-Jerala, Nataša

    2017-01-01

    Inflammation is an essential physiological process, which enables survival during infection and maintains tissue homeostasis. Interferons (IFNs) and pro- and anti-inflammatory cytokines are crucial for appropriate response to pathogens, damaged cells, or irritants in inflammatory response. The inflammasom is multiprotein complex, which initiates cleavage of pro-inflammatory cytokines IL-1β and IL-18 into active forms. In addition, inflammasomes initiate pyroptotic cell death. In the present review, I summarize and analyze recent findings regarding the cross talk of IFNs and inflammasomes.

  4. The Role of Interferons in Inflammation and Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Nataša Kopitar-Jerala

    2017-07-01

    Full Text Available Inflammation is an essential physiological process, which enables survival during infection and maintains tissue homeostasis. Interferons (IFNs and pro- and anti-inflammatory cytokines are crucial for appropriate response to pathogens, damaged cells, or irritants in inflammatory response. The inflammasom is multiprotein complex, which initiates cleavage of pro-inflammatory cytokines IL-1β and IL-18 into active forms. In addition, inflammasomes initiate pyroptotic cell death. In the present review, I summarize and analyze recent findings regarding the cross talk of IFNs and inflammasomes.

  5. Hypothyroidism in hepatitis c patients on pegylated interferon therapy

    International Nuclear Information System (INIS)

    Hameed, M.A.; Mehmood, A.; Farooq, M.A.; Nabi, G.U.; Toor, I. H.

    2017-01-01

    Chronic hepatitis has become a major health problem all over the world especially in the third world countries. The most common cause of chronic hepatitis in Pakistan is hepatitis C which can lead to liver cirrhosis and hepatocellular carcinoma. In Pakistan Pegylated Interferon Alpha is still corner stone of therapy for chronic hepatitis C. One of the major side effect of this therapy is the development of thyroid dysfunction, i.e., hypothyroidism and hyperthyroidism. This study was done to assess the frequency of hypothyroidism in hepatitis C patients after three months of pegylated interferon therapy. Method: This study was conducted from 1st October 2013 to 31st march 2014 at outpatients department (OPD) of Gastroenterology and Hepatology, Lahore General Hospital Lahore. Descriptive case series study design was used. The sample of 200 patients was taken from the patients who visited OPD and fulfil the inclusion criteria of the study. Serum thyroid stimulating hormone level (TSH) was done before and after completion of three months therapy at centre for Nuclear Medicine (CENUM) laboratory, Mayo Hospital, Lahore by immune-radiometric assay (IRMA) and patients having TSH>4.0 mIU/L (normal range: 0.2-4.0 mIU/L) were considered hypothyroid. Results: The mean age of the patients was 36.29+-8.5 years. One hundred and twenty-three (61.5 percent) were male and 77 (38.5 percent) were female. After 3 months of interferon therapy, 163 (81.5 percent) patients were euthyroid and 37(18.5 percent) patients were having thyroid dysfunction. There were total 29 (14.5 percent) hypothyroid patients; 8 (27.6 percent) were male and 21 (72.4 percent) female. Conclusion: It is concluded from this study that frequency of hypothyroidism in patients with chronic hepatitis C was 14.5 percent after treatment with pegylated interferon therapy for 3 months. Female patients were more prone to develop hypothyroidism as compared to male patients. (author)

  6. [Solubilization Specificities Interferon beta-1b from Inclusion Bodies].

    Science.gov (United States)

    Zhuravko, A S; Kononova, N V; Bobruskin, A I

    2015-01-01

    A new solubilization method of recombinant interferon beta-1b (IFNβ-1b) from the inclusion bodies was developed. This method allows to extract the target protein selectively in the solutions of different alcohols, such as ethanol, propanol and isopropanol. It was shown that the more effective IFNβ-1b solubilization was achieved in the 55% propanol solution. This method allowed to extract the target protein from inclusion bodies around 85-90%, and significantly reduced Escherichia coli content in the solubilizate, in comparison with standard methods.

  7. Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

    Directory of Open Access Journals (Sweden)

    Luis Jesuino de Oliveira Andrade

    Full Text Available OBJECTIVE: To investigate the frequency of thyroid disorders (TD in patients with chronic hepatitis C before and during interferon-alpha (IFN-α and ribavirin (RIB treatment. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: We prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab were systematically tested at entry (m0, week 12 (m3 and week 24 (m6 of treatment. RESULTS: Mean age of the 65 patients (38 females and 27 males was 49.61 ± 11.83 years. Seven (10.76% patients presented baseline thyroid disorders (m0, three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92% patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3. A total of 18 patients (27.69% developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6. The relative risk of developing hypothyroidism found in this study was 1.3 (95% CI: 1.1 to 1.6, hyperthyroidism 1.2 (95% CI: 1.1 to 1.4, and TPO-Ab positivity 7.6 (95% CI: 3.9 to 14.5. The study showed a significant association between female sex and thyroid disease (p = 0.009. CONCLUSION: Thyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.

  8. SVX b physics prospects

    International Nuclear Information System (INIS)

    Dell'Agnello, S.

    1992-11-01

    CDF has enhanced its capabilities for b-physics with the installation of a silicon vertex detector (SVX), which provides precise 2-dimensional tracking. The SVX impact parameter (IP) resolution (∼ 13μm for P t > 10 GeV) is well suited to detecting displaced secondary vertices (SV) from b-hadron decays (cτ B ≅ 390μm). In this paper we show evidence of SV detection using the Ψ → μ + μ - sample, which is b-enriched, and describe some prospects of b physics opened by the SVX with 25 pb -1 , the goal integrated luminosity of present run

  9. Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy.

    Science.gov (United States)

    Schmidt, M; Hochhaus, A; König-Merediz, S A; Brendel, C; Proba, J; Hoppe, G J; Wittig, B; Ehninger, G; Hehlmann, R; Neubauer, A

    2000-10-01

    Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-alpha) treatment in CML. Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro-stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-alpha therapy and in 47 additional CML samples taken during IFN-alpha therapy. IRF4 expression was then correlated with cytogenetic response to IFN-alpha. IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-alpha therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-alpha therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-alpha, a good response was associated with high IRF4 expression. IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-alpha therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-alpha in CML.

  10. Identification and isolation of stimulator of interferon genes (STING): an innate immune sensory and adaptor gene from camelids.

    Science.gov (United States)

    Premraj, A; Aleyas, A G; Nautiyal, B; Rasool, T J

    2013-10-01

    The mechanism by which type I interferon-mediated antiviral response is mounted by hosts against invading pathogen is an intriguing one. Of late, an endoplasmic reticulum transmembrane protein encoded by a gene called stimulator of interferon genes (STING) is implicated in the innate signalling pathways and has been identified and cloned in few mammalian species including human, mouse and pig. In this article, we report the identification of STING from three different species of a highly conserved family of mammals - the camelids. cDNAs encoding the STING of Old World camels - dromedary camel (Camelus dromedarius) and bactrian camel (Camelus bactrianus) and a New World camel - llama (Llama glama) were amplified using conserved primers and RACE. The complete STING cDNA of dromedary camel is 2171 bp long with a 706-bp 5' untranslated regions (UTR), an 1137-bp open reading frame (ORF) and a 328-bp 3' UTR. Sequence and phylogenetic analysis of the ORF of STING from these three camelids indicate high level of similarity among camelids and conservation of critical amino acid residues across different species. Quantitative real-time PCR analysis revealed high levels of STING mRNA expression in blood, spleen, lymph node and lung. The identification of camelid STING will help in better understanding of the role of this molecule in the innate immunity of the camelids and other mammals. © 2013 John Wiley & Sons Ltd.

  11. Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter.

    Science.gov (United States)

    Jääskeläinen, Kirsi M; Kaukinen, Pasi; Minskaya, Ekaterina S; Plyusnina, Angelina; Vapalahti, Olli; Elliott, Richard M; Weber, Friedemann; Vaheri, Antti; Plyusnin, Alexander

    2007-10-01

    The S RNA genome segment of hantaviruses carried by Arvicolinae and Sigmodontinae rodents encodes the nucleocapsid (N) protein and has an overlapping (+1) open reading frame (ORF) for a putative nonstructural protein (NSs). The aim of this study was to determine whether the ORF is functional. A protein corresponding to the predicted size of Tula virus (TULV) NSs was detected using coupled in vitro transcription and translation from a cloned S segment cDNA, and a protein corresponding to the predicted size of Puumala virus (PUUV) NSs was detected in infected cells by Western blotting with an anti-peptide serum. The activities of the interferon beta (IFN-beta) promoter, and nuclear factor kappa B (NF-kappaB)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta mRNA levels in IFN-competent MRC5 cells either infected with TULV or transiently expressing NSs were decreased. These data demonstrate that Tula and Puumala hantaviruses have a functional NSs ORF. The findings may explain why the NSs ORF has been preserved in the genome of most hantaviruses during their long evolution and why hantavirus-infected cells secrete relatively low levels of IFNs. (c) 2007 Wiley-Liss, Inc.

  12. Open Bibliography

    OpenAIRE

    Murray-Rust, Peter; Pollock, Rufus; MacGillivray, Mark; O'Steen, Ben; Waites, William

    2011-01-01

    Poster presented at the VSMF Symposium held at the Unilever Centre on 2011-01-17. More research is published currently than can be understood or followed by a researcher without the aid of a computer. We need Open shareable information on research publications, an Open Bibliography, to build the services that enable researchers to explore their field and discover the research they need. Producers of bibliographic data such as libraries, publishers, universities, scholars or social referenc...

  13. Open IS

    DEFF Research Database (Denmark)

    Germonprez, Matt; Crowston, Kevin; Avital, Michel

    2013-01-01

    The collective intelligence and collective action of “open” communities have produced a variety of complex knowledge goods and radical social change. The Information Systems (IS) community has invested significant effort into researching open communities and the ecosystems in which they operate...... therefore seeks to stimulate a thoughtful and dynamic discussion around the proposition that becoming a more open community will enhance the IS discipline’s scholarly inquiry and global impact....

  14. Neuromyelitis optica-like pathology is dependent on type I interferon response

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Wlodarczyk, Agnieszka; Asgari, Nasrin

    2013-01-01

    Neuromyelitis optica is an antibody-mediated autoimmune inflammatory disease of the central nervous system. Reports have suggested that interferon beta which is beneficial for multiple sclerosis, exacerbates neuromyelitis optica. Our aim was to determine whether type I interferon plays a role in ...

  15. DMPD: Signalling pathways mediating type I interferon gene expression. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17904888 Signalling pathways mediating type I interferon gene expression. Edwards M...hways mediating type I interferon gene expression. PubmedID 17904888 Title Signalling pathways...R, Slater L, Johnston SL. Microbes Infect. 2007 Sep;9(11):1245-51. Epub 2007 Jul 1. (.png) (.svg) (.html) (.csml) Show Signalling pat

  16. DMPD: Fifty years of interferon research: aiming at a moving target. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available mmunity. 2006 Sep;25(3):343-8. (.png) (.svg) (.html) (.csml) Show Fifty years of interferon research: aiming at a moving target. Pubm...edID 16979566 Title Fifty years of interferon research: aiming at a moving target.

  17. DMPD: Toll-like receptors and Type I interferons. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available m. 2007 May 25;282(21):15319-23. Epub 2007 Mar 29. (.png) (.svg) (.html) (.csml) Show Toll-like receptors and Type I interferons. Pub...medID 17395581 Title Toll-like receptors and Type I interferons. Authors Uematsu S,

  18. Delirium after interleukin-2 and alpha-interferon therapy for renal cell carcinoma

    NARCIS (Netherlands)

    Van Steijn, JHM; Nieboer, P; Hospers, GAP; De Vries, EGE; Mulder, NH

    2001-01-01

    A 55-year-old man receiving alpha-interferon and interieukin-2 therapy for renal cell carcinoma presented with seizures and delirium. A CT-scan of the cerebrum did not reveal any disorder. Both alpha-interferon and interleukin-2 were stopped Treatment with steroids led to complete regression of

  19. A prospective clinical, economic, and quality-of-life analysis comparing endovascular aneurysm repair (EVAR), open repair, and best medical treatment in high-risk patients with abdominal aortic aneurysms suitable for EVAR: the Irish patient trial.

    LENUS (Irish Health Repository)

    Hynes, Niamh

    2007-12-01

    To report the results of a trial comparing endovascular aneurysm repair (EVAR) to open repair (OR) and best medical therapy (BMT) involving high-risk patients with abdominal aortic aneurysms (AAA) suitable for EVAR.

  20. Gallbladder removal - open

    Science.gov (United States)

    Cholecystectomy - open; Gallbladder - open cholecystectomy; Cholecystitis - open cholecystectomy; Gallstones - open cholecystectomy ... a medical instrument called a laparoscope ( laparoscopic ... Open gallbladder surgery is used when laparoscopic surgery cannot ...

  1. Hepatitis B, interferon, and acne fulminans in a young girl

    Directory of Open Access Journals (Sweden)

    Sandeep Arora

    2016-01-01

    Full Text Available Acne fulminans (AF is a very rare severe form of acne seen in young males, characterized by a sudden and explosive onset of hemorrhagic pustules and ulceration on the trunk, systemic features in the form of fever, polyarthropathy, malaise, erythema nodosum and painful osteolytic bone involvement with leukocytosis, and an elevated erythrocyte sedimentation rate. Conventional treatment of AF includes corticosteroids or immunosuppressive agents for the initial phase followed by isotretinoin. Active hepatitis B infection with a high viral load precludes the administration of any immunosuppressive drugs. We present the case of an 18-year-old girl with a history of occasional acne who presented with AF of sudden onset following administration of interferon-alpha-2a for her recently detected hepatitis B infection. Management of hepatitis B was withheld in view of her general condition. The patient was managed with low dose isotretinoin with subsidence of lesions. AF in a young female precipitated by interferon and its management with isotretinoin in the presence of active hepatitis B infection make the case unique.

  2. The interferon response to intracellular DNA: why so many receptors?

    Science.gov (United States)

    Unterholzner, Leonie

    2013-11-01

    The detection of intracellular DNA has emerged to be a key event in the innate immune response to viruses and intracellular bacteria, and during conditions of sterile inflammation and autoimmunity. One of the consequences of the detection of DNA as a 'stranger' and a 'danger' signal is the production of type I interferons and pro-inflammatory cytokines. Much work has been dedicated to the elucidation of the signalling cascades that activate this DNA-induced gene expression programme. However, while many proteins have been proposed to act as sensors for intracellular DNA in recent years, none has been met with universal acceptance, and a theory linking all the recent observations is, as yet, lacking. This review presents the evidence for the various interferon-inducing DNA receptors proposed to date, and examines the hypotheses that might explain why so many different receptors appear to be involved in the innate immune recognition of intracellular DNA. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Interferon Action on Parental Semliki Forest Virus Ribonucleic Acid

    Science.gov (United States)

    Friedman, Robert M.; Fantes, Karl H.; Levy, Hilton B.; Carter, William B.

    1967-01-01

    Actinomycin D-treated chick fibroblasts were infected with purified 32P-labeled Semliki forest virus, and ribonucleic acid (RNA) was extracted after 1 or 2 hr. Within 1 hr, viral RNA forms sedimenting in sucrose gradients at 42S, 30S, and 16S were present. The 42S form corresponded to the RNA of the virion. The 16S form appeared to be a double-stranded template for the formation of new viral RNA, since nascent RNA was associated with it and the molecule could be heat-denatured and subsequently reannealed by slow cooling. Interferon treatment before infection, or puromycin (50 μg/ml) or cycloheximide (200 μg/ml) added at the time of virus infection, had no effect on the formation of the 30S RNA but inhibited the production of the 16S form. Several findings made it unlikely that these results were due to breakdown of parental RNA and reincorporation of 32P into progeny structures. The results suggested that the mechanism of interferon action involves inhibition of protein synthesis by parental viral RNA, since a specific viral RNA polymerase had previously been demonstrated to be necessary for production of 16S RNA. No protein synthesis appears necessary for formation of 30S RNA from parental virus RNA. PMID:5621488

  4. Interferon induced IFIT family genes in host antiviral defense.

    Science.gov (United States)

    Zhou, Xiang; Michal, Jennifer J; Zhang, Lifan; Ding, Bo; Lunney, Joan K; Liu, Bang; Jiang, Zhihua

    2013-01-01

    Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.

  5. Environmental triggers of thyroiditis: hepatitis C and interferon-α.

    Science.gov (United States)

    Menconi, F; Hasham, A; Tomer, Y

    2011-01-01

    Autoimmune thyroid diseases (AITD) are postulated to develop as a result of a complex interplay between several genetic and environmental influences. The pathogenesis of AITD is still not clearly defined. However, among the implicated triggers (e.g. iodine, infections, medications), more recent data confirmed strong associations of AITD with the hepatitis C virus (HCV) infection and interferon-α (IFNα) therapy. Moreover, it is likely that HCV and IFN act in synergism to trigger AITD in patients. Indeed, approximately 40% of HCV patients develop either clinical or subclinical disease while receiving IFNα. Interferon induced thyroiditis (IIT) can manifest as non-autoimmune thyroiditis (presenting as destructive thyroiditis, or non-autoimmune hypothyroidism), or autoimmune thyroiditis [presenting with clinical features of Graves' disease (GD) or Hashimoto's thyroiditis (HT)]. Although not yet clearly understood, it is thought that IFNα can induce thyroiditis via both immune stimulatory and direct toxic effects on the thyroid. In view of the high frequency of IIT, routine screening and surveillance of HCV patients receiving IFNα is recommended to avoid the complications, such as cardiac arrhythmias, associated with thyrotoxicosis. In summary, IIT is a common clinical problem that can be readily diagnosed with routine thyroid function screening of HCV patients receiving IFN. The treatment of IIT consists of the standard therapy for differing clinical manifestations of IIT such as GD, HT, or destructive thyroiditis. However, anti-thyroid medications are not recommended in this setting since they can potentially be hepatotoxic.

  6. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  7. Role for herpes simplex virus 1 ICP27 in the inhibition of type I interferon signaling

    International Nuclear Information System (INIS)

    Johnson, Karen E.; Song, Byeongwoon; Knipe, David M.

    2008-01-01

    Host cells respond to viral infection by many mechanisms, including the production of type I interferons which act in a paracrine and autocrine manner to induce the expression of antiviral interferon-stimulated genes (ISGs). Viruses have evolved means to inhibit interferon signaling to avoid induction of the innate immune response. Herpes simplex virus 1 (HSV-1) has several mechanisms to inhibit type I interferon production, the activities of ISGs, and the interferon signaling pathway itself. We report that the inhibition of the Jak/STAT pathway by HSV-1 requires viral gene expression and that viral immediate-early protein ICP27 plays a role in downregulating STAT-1 phosphorylation and in preventing the accumulation of STAT-1 in the nucleus. We also show that expression of ICP27 by transfection causes an inhibition of IFN-induced STAT-1 nuclear accumulation. Therefore, ICP27 is necessary and sufficient for at least some of the effects of HSV infection on STAT-1

  8. Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis - A case report.

    Science.gov (United States)

    Dalbjerg, Sara Maria; Tsakiri, Anna; Frederiksen, Jette Lautrup

    2016-07-01

    Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis associated with Interferon-beta treatment. We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved. Clinicians should be aware of the possibility of rhabdomyolysis occurring during Interferon-beta-1-alpha therapy. In cases where patients complain of severe myalgia, and in particular if weakness is reported, creatine kinase activity should be measured to prevent irreversible rhabdomyolysis during Interferon-beta-1-alpha therapy in patients with multiple sclerosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  10. The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives

    Directory of Open Access Journals (Sweden)

    Rodolfo Oliveira Leal

    2016-10-01

    Full Text Available Type I interferons (IFNs are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV and feline immunodeficiency virus (FIV. In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections.

  11. The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives.

    Science.gov (United States)

    Leal, Rodolfo Oliveira; Gil, Solange

    2016-10-27

    Type I interferons (IFNs) are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω) was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections.

  12. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

  13. DMPD: Interferons at age 50: past, current and future impact on biomedicine. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18049472 Interferons at age 50: past, current and future impact on biomedicine. Bor...975-90. (.png) (.svg) (.html) (.csml) Show Interferons at age 50: past, current and future impact on biomedicine.... PubmedID 18049472 Title Interferons at age 50: past, current and future impact on biomedicine

  14. Inhibition of interferon production in human fibroblasts by a tumor promoting phorbol ester

    International Nuclear Information System (INIS)

    Frankfort, H.M.; Vilcek, J.

    1982-01-01

    The effect of 12-0-tetradecanoylphorbol-13-acetate (TPA) on the induction of interferon in cultures of human fibroblasts was examined. TPA was found to inhibit polyinosinate-polycytidylate [poly(I) X poly(C)]-induced interferon production when added either before or with the inducer. A 3-hour pretreatment of FS-4 cells with TPA produced the greatest ihibitory effect. Partially inhibitory treatments with TPA caused a delay in interferon production. On the other hand, interferon yields were slightly enhanced by TPA added at 1 1/2 or 3 hours postinduction. No gross metabolic perturbations (e.g., inhibition of cellular protein or RNA synthesis) were detected which would explain the phenomenon. The inhibition of interferon production was a stereospecific event: biologically inactive derivatives of TPA (4-0-methyl TPA, 4-α-phorbol-12, 13-didecanoate and phorbol-12, 13-diacetate) had no effect on interferon production. Cellular proteases or nucleases did not appear to be involved in this process. The binding of labeled poly(I) X poly(C) to FS-4 cells was unaltered in TPA-treated cultures. In superinduced cultures (i.e., after enhancement of interferon yields by actinomycin D and cycloheximide), interferon production was generally less inhibited by TPA than after simple induction. Newcastle disease virus (NDV)-induced interferon synthesis in GM-258 cells was also inhibited by the phorbol ester. Both α (leukocyte) and β (fibroblast) interferon production was inhibited to a similar degree in TPA-treated cells inoculated with 0.1 or 1 plaque forming unit (PFU) of NDV per cell. Increasing the multiplicity of infection with NDV to 10 PFU per cell overcame the inhibitory action of TPA. We conclude that the site of TPA action is either the triggering (generation of the hypothetical inducing signal) or transcription of the interferom mRNA. (Author)

  15. Open access

    CERN Document Server

    Suber, Peter

    2012-01-01

    The Internet lets us share perfect copies of our work with a worldwide audience at virtually no cost. We take advantage of this revolutionary opportunity when we make our work "open access": digital, online, free of charge, and free of most copyright and licensing restrictions. Open access is made possible by the Internet and copyright-holder consent, and many authors, musicians, filmmakers, and other creators who depend on royalties are understandably unwilling to give their consent. But for 350 years, scholars have written peer-reviewed journal articles for impact, not for money, and are free to consent to open access without losing revenue. In this concise introduction, Peter Suber tells us what open access is and isn't, how it benefits authors and readers of research, how we pay for it, how it avoids copyright problems, how it has moved from the periphery to the mainstream, and what its future may hold. Distilling a decade of Suber's influential writing and thinking about open access, this is the indispe...

  16. Japanese encephalitis virus non-coding RNA inhibits activation of interferon by blocking nuclear translocation of interferon regulatory factor 3.

    Science.gov (United States)

    Chang, Ruey-Yi; Hsu, Ta-Wen; Chen, Yen-Lin; Liu, Shu-Fan; Tsai, Yi-Jer; Lin, Yun-Tong; Chen, Yi-Shiuan; Fan, Yi-Hsin

    2013-09-27

    Noncoding RNA (ncRNA) plays a critical role in modulating a broad range of diseases. All arthropod-borne flaviviruses produce short fragment ncRNA (sfRNA) collinear with highly conserved regions of the 3'-untranslated region (UTR) in the viral genome. We show that the molar ratio of sfRNA to genomic RNA in Japanese encephalitis virus (JEV) persistently infected cells is greater than that in acutely infected cells, indicating an sfRNA role in establishing persistent infection. Transfecting excess quantities of sfRNA into JEV-infected cells reduced interferon-β (IFN-β) promoter activity by 57% and IFN-β mRNA levels by 52%, compared to mock-transfected cells. Transfection of sfRNA into JEV-infected cells also reduced phosphorylation of interferon regulatory factor-3 (IRF-3), the IFN-β upstream regulator, and blocked roughly 30% of IRF-3 nuclear localization. Furthermore, JEV-infected sfRNA transfected cells produced 23% less IFN-β-stimulated apoptosis than mock-transfected groups did. Taken together, these results suggest that sfRNA plays a role against host-cell antiviral responses, prevents cells from undergoing apoptosis, and thus contributes to viral persistence. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Turkish Prospective Chemistry Teachers' Alternative Conceptions about Acids and Bases

    Science.gov (United States)

    Boz, Yezdan

    2009-01-01

    The purpose of this study was to obtain prospective chemistry teachers' conceptions about acids and bases concepts. Thirty-eight prospective chemistry teachers were the participants. Data were collected by means of an open-ended questionnaire and semi-structured interviews. Analysis of data indicated that most prospective teachers did not have…

  18. Open innovation

    DEFF Research Database (Denmark)

    West, Joel; Bogers, Marcel

    2017-01-01

    Interest in open innovation (OI) as a field of research has grown exponentially since the phrase was coined by Chesbrough in his 2003 book, with numerous articles, special issues, books, and conference sessions. Various reviews of the literature have summarized prior work, offered new frameworks......, and identified opportunities for future research. Here we summarize these opportunities, which include more research on outbound OI, the role of open innovation in services, and network forms of collaboration such as consortia, communities, ecosystems, and platforms. Research should also examine the use of OI...... by small, new, and not-for-profit organizations, as well as the linkage of individual actions and motivations to open innovation. Other opportunities include better measuring the costs, benefits, antecedents, mediators and moderators of the effects of OI on performance, and understanding why and how OI...

  19. Tratamento de hemangioma gigante com interferon alfa: relato de dois casos Treatment of giant hemangioma with interferon-alpha: report of two cases

    Directory of Open Access Journals (Sweden)

    Ana Julia Balau

    2007-12-01

    Full Text Available O objetivo do trabalho é descrever o uso de interferon alfa no tratamento de pacientes com hemangioma gigante. Os autores relatam e analisam dois casos de hemangioma gigante em tratamento com interferon alfa. IBS, 3 anos, em acompanhamento no Ambulatório de Hematologia desde um ano de idade com quadro de lesão angiomatosa em praticamente toda hemiface direita, acompanhada de sangramentos gengivais importantes. Após a realização de exames complementares (Angiorressonância magnética e feito o diagnóstico de hemangioma gigante em face, foi iniciado tratamento com prednisona e, posteriormente, associação com interferon alfa e observada importante melhora do quadro, resultando na diminuição dos episódios de sangramento e no tamanho do tumor. C.N.P., 12 anos, apresentando nódulo em região lateral de joelho esquerdo há 2 anos, com aumento progressivo do tamanho e dor local. Fez uso de prednisona e, sem melhora do quadro, introduzido interferon alfa com regressão importante do tamanho do tumor. O tratamento com interferon alfa deve ser considerado no tratamento de hemangiomas, pois apresenta bons resultados em relação à diminuição do tamanho do tumor e, conseqüentemente, reduz as intercorrências clínicas associadas à sua presença, principalmente os sangramentos.The aim of this study is to describe the treatment using interferon-alpha of giant hemangiomas in children. The authors report two cases of children presenting with giant hemangiomas treated using interferon-alpha and analyze the results. IBS, 3 years-old, has been followed up in Famema Hemathology Service since she was 1 year-old with a tumor on the face and persistent bleeding. After clinical and radiologic evaluations and suggested the diagnosis of giant hemangioma, she started treatment with interferon-alpha. A great clinical improvement was observed a reducing of the number of episodes of bleedings and a decrease in of the tumor size. CNP, 12 years-old, came to

  20. MOLECULAR CLONING, SEQUENCING, EXPRESSION AND BIOLOGICAL ACTIVITY OF GIANT PANDA (AILUROPODA MELANOLEUCA) INTERFERON-GAMMA.

    Science.gov (United States)

    Zhu, Hui; Wang, Wen-Xiu; Wang, Bao-Qin; Zhu, Xiao-Fu; Wu, Xu-Jin; Ma, Qing-Yi; Chen, De-Kun

    2012-06-29

    The giant panda (Ailuropoda melanoleuca) is an endangered species and indigenous to China. Interferon-gamma (IFN-γ) is the only member of type □ IFN and is vital for the regulation of host adapted immunity and inflammatory response. Little is known aboutthe FN-γ gene and its roles in giant panda.In this study, IFN-γ gene of Qinling giant panda was amplified from total blood RNA by RT-CPR, cloned, sequenced and analysed. The open reading frame (ORF) of Qinling giant panda IFN-γ encodes 152 amino acidsand is highly similar to Sichuan giant panda with an identity of 99.3% in cDNA sequence. The IFN-γ cDNA sequence was ligated to the pET32a vector and transformed into E. coli BL21 competent cells. Expression of recombinant IFN-γ protein of Qinling giant panda in E. coli was confirmed by SDS-PAGE and Western blot analysis. Biological activity assay indicated that the recombinant IFN-γ protein at the concentration of 4-10 µg/ml activated the giant panda peripheral blood lymphocytes,while at 12 µg/mlinhibited. the activation of the lymphocytes.These findings provide insights into the evolution of giant panda IFN-γ and information regarding amino acid residues essential for their biological activity.

  1. Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin

    DEFF Research Database (Denmark)

    Sperl, Jan; Horvath, Gabor; Halota, Waldemar

    2016-01-01

    daily (n=129) or sofosbuvir (400mg once daily) plus PR (n=128). Primary efficacy objective was sustained virologic response 12weeks after the end of therapy (SVR12, HCV RNA tier 1 safety event. RESULTS: The majority...... the lower bound of the 1-sided 1-sample exact test was greater than -10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference...... pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection. METHODS: This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000IU/ml were randomized to receive 12weeks of EBR/GZR 50mg/100mg once...

  2. Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome.

    Science.gov (United States)

    Nagtegaal, Gijsbert J A; Pohl, Christoph; Wattjes, Mike P; Hulst, Hanneke E; Freedman, Mark S; Hartung, Hans-Peter; Miller, David; Montalban, Xavier; Kappos, Ludwig; Edan, Gilles; Pleimes, Dirk; Beckman, Karola; Stemper, Brigitte; Polman, Christoph H; Sandbrink, Rupert; Barkhof, Frederik

    2014-02-01

    Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS. To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)). In the placebo-controlled phase, patients (n = 468) were initially randomised to IFNB-1b (n = 292) or placebo (n = 176) for two years or clinically definite MS (CDMS). In the open-label phase (n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year). A total of 435 patients were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (.42 vs .71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion. Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. NCT00544037.

  3. Evasion of interferon responses by Ebola and Marburg viruses.

    Science.gov (United States)

    Basler, Christopher F; Amarasinghe, Gaya K

    2009-09-01

    The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause frequently lethal viral hemorrhagic fever. These infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. Consistent with this, filoviruses have been found to encode proteins VP35 and VP24 that block host interferon (IFN)-alpha/beta production and inhibit signaling downstream of the IFN-alpha/beta and the IFN-gamma receptors, respectively. VP35, which is a component of the viral nucleocapsid complex and plays an essential role in viral RNA synthesis, acts as a pseudosubstrate for the cellular kinases IKK-epsilon and TBK-1, which phosphorylate and activate interferon regulatory factor 3 (IRF-3) and interferon regulatory factor 7 (IRF-7). VP35 also promotes SUMOylation of IRF-7, repressing IFN gene transcription. In addition, VP35 is a dsRNA-binding protein, and mutations that disrupt dsRNA binding impair VP35 IFN-antagonist activity while leaving its RNA replication functions intact. The phenotypes of recombinant EBOV bearing mutant VP35s unable to inhibit IFN-alpha/beta demonstrate that VP35 IFN-antagonist activity is critical for full virulence of these lethal pathogens. The structure of the VP35 dsRNA-binding domain, which has recently become available, is expected to provide insight into how VP35 IFN-antagonist and dsRNA-binding functions are related. The EBOV VP24 protein inhibits IFN signaling through an interaction with select host cell karyopherin-alpha proteins, preventing the nuclear import of otherwise activated STAT1. It remains to be determined to what extent VP24 may also modulate the nuclear import of other host cell factors and to what extent this may influence the outcome of infection. Notably, the Marburg virus VP24 protein does not detectably block STAT1 nuclear import, and, unlike EBOV, MARV infection inhibits STAT1 and STAT2 phosphorylation. Thus, despite their similarities, there are fundamental differences by which

  4. Open Education and the Open Science Economy

    Science.gov (United States)

    Peters, Michael A.

    2009-01-01

    Openness as a complex code word for a variety of digital trends and movements has emerged as an alternative mode of "social production" based on the growing and overlapping complexities of open source, open access, open archiving, open publishing, and open science. This paper argues that the openness movement with its reinforcing structure of…

  5. The Open

    Directory of Open Access Journals (Sweden)

    Saitya Brata Das

    2009-12-01

    Full Text Available In the Open darkness and light, remembrance and oblivion, coming into existence and disappearing in death play their originary co-belonging, or co-figuration. Existence belongs to this opening and is exposed to its coming to presence: it is on the basis of this originary opening, this originary historical which is revealed to this mortal being called ‘man,’ on the basis of this revelation, man founds something like politics and history. There thus comes into existence out of this freedom, out of this “play space”2, this field called ‘polis’3 where there takes place war and festival, where historical revolutions tear apart history, brings ruptures and discontinuities in the very mode of his existence, where man seeks the foundation of his own foundation (which is his metaphysical task , where occurs the dialectics of negativity between man and man, where man puts at stake his own death, his own dissolution, and by the power of his own dissolution stands in relation to the total world that he seeks to dominate. This means that man’s attempts to metaphysically found his own political and historical existence must presuppose a far more originary non-foundation, the differentiating revealing of the open, the ungrounded spacing play, or playing space of natality and mortality.

  6. Open data

    DEFF Research Database (Denmark)

    Bodum, Lars

    2017-01-01

    Everyone wants open data, but the road towards it can be both difficult and long. Implementation of data portals and ICT solutions for support of the data infrastructure can be initiated from the central government through legislation, regulation and public procurement. This is what you would call...

  7. Open Images

    DEFF Research Database (Denmark)

    Sanderhoff, Merete

    2013-01-01

    Museums around the world hold enormous troves of public domain artworks. In digitized form, they can be powerful tools for research and learning, as well as building blocks, in the hands of students, teachers, scholars, developers, and creative people. By opening up their digitized assets for reuse...

  8. Oxidative Modification of Blood Serum Proteins in Multiple Sclerosis after Interferon Beta and Melatonin Treatment

    Directory of Open Access Journals (Sweden)

    Monika Adamczyk-Sowa

    2017-01-01

    Full Text Available Multiple sclerosis (MS is a disease involving oxidative stress (OS. This study was aimed at examination of the effect of melatonin supplementation on OS parameters, especially oxidative protein modifications of blood serum proteins, in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS patients with the relapsing-remitting form of MS (RRMS, 36 patients with RRMS receiving interferon beta-1b (250 μg every other day, and 25 RRMS patients receiving interferon beta-1b plus melatonin (5 mg daily. The levels of N′-formylkynurenine, kynurenine, dityrosine, carbonyl groups, advanced glycation products (AGEs, advanced oxidation protein products (AOPP, and malondialdehyde were elevated in nontreated RRSM patients. N′-Formylkynurenine, kynurenine, AGEs, and carbonyl contents were decreased only in the group treated with interferon beta plus melatonin, while dityrosine and AOPP contents were decreased both in the group of patients treated with interferon beta and in the group treated with interferon beta-1b plus melatonin. These results demonstrate that melatonin ameliorates OS in MS patients supporting the view that combined administration of interferon beta-1b and melatonin can be more effective in reducing OS in MS patients than interferon beta-1b alone.

  9. Influence of Interferon-Alpha Combined with Chemo (Radio Therapy on Immunological Parameters in Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Svetlana Karakhanova

    2014-03-01

    Full Text Available Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio therapies with interferon-2α. Low doses of interferon-2α led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2α therapy on the dendritic cells and NK (natural killer cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-γ and IL-10 in the serum following the interferon-2α therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2α therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2α and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy.

  10. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon

    Science.gov (United States)

    Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K.; Alcami, Antonio

    2010-01-01

    Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. PMID:20019241

  11. Cutaneous Adverse Events Associated with Interferon-β Treatment of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Annette Kolb-Mäurer

    2015-07-01

    Full Text Available Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS patient treated with interferon-β who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.

  12. Prospective open randomized study comparing efficacies and safeties of a 3-day course of azithromycin and a 10-day course of erythromycin in children with community-acquired acute lower respiratory tract infections

    NARCIS (Netherlands)

    Roord, JJ; Goossens, MMHT; Kimpen, JLL; Wolf, B.H.

    1996-01-01

    The efficacies and safeties of a 3-day, 3-dose course of azithromycin (10 mg/kg of body weight per day) and a 10-day, 30-dose course of erythromycin (40 mg/kg/day) for the treatment of acute lower respiratory tract infections in children were compared in an open randomized multicenter study.

  13. Interferon treatment of neuroendocrine tumour xenografts as monitored by MRI

    International Nuclear Information System (INIS)

    Elvin, A.; Oeberg, K.; Lindgren, P.G.; Lundkvist, M.; Wilander, E.; Ericsson, A.; Hemmingsson, A.

    1994-01-01

    The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 nude mice (Balb/c). The purpose of the present study was to establish an animal model that would allow monitoring with magnetic resonance imaging (MRI) of changes induced by interferon (IFN) therapy and to evaluate whether the therapeutic response, as expressed by changes in MR signal characteristics and tumour proliferative activity, could be modulated by different IFN dosages. IFN did not seem to have any obvious antiproliferative effect on the LCC-18 tumour cell line transplanted to nude mice and no convincing treatment-related changes in rho values or T1 and T2 relaxation values were observed. The animal model was probably unsuitable for demonstration of IFN effects. (orig.)

  14. Respiratory syncytial virus mechanisms to interfere with type 1 interferons.

    Science.gov (United States)

    Barik, Sailen

    2013-01-01

    Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family that consists of viruses with nonsegmented negative-strand RNA genome. Infection by these viruses triggers the innate antiviral response of the host, mainly type I interferon (IFN). Essentially all other viruses of this family produce IFN suppressor functions by co-transcriptional RNA editing. In contrast, RSV has evolved two unique nonstructural proteins, NS1 and NS2, to effectively serve this purpose. Together, NS1 and NS2 degrade or sequester multiple signaling proteins that affect both IFN induction and IFN effector functions. While the mechanism of action of NS1 and NS2 is a subject of active research, their effect on adaptive immunity is also being recognized. In this review, we discuss various aspects of NS1 and NS2 function with implications for vaccine design.

  15. Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in mice

    DEFF Research Database (Denmark)

    Salem, Mohammad; Mony, Jyothi T; Lobner, Morten

    2011-01-01

    . Furthermore, IRF7-deficient mice developed more severe disease. Flow cytometric analysis showed that the extent of leukocyte infiltration into the CNS was higher in IRF7-deficient mice with significantly higher number of infiltrating macrophages and T cells, and the distribution of infiltrates within......ABSTRACT: BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with unknown etiology. Interferon-beta (IFN-beta), a member of the type I IFN family, is used as a therapeutic for MS and the IFN signaling pathway is implicated in MS susceptibility...... of MS-like disease in mice. Methods The role of IRF7 in development of EAE was studied by immunizing IRF7-KO and C57BL/6 (WT) mice with myelin oligodendrocyte glycoprotein using a standard protocol for the induction of EAE. We measured leukocyte infiltration and localization in the CNS using flow...

  16. Immune activation in multiple sclerosis and interferon-beta therapy

    DEFF Research Database (Denmark)

    Krakauer, Martin

    2007-01-01

    The PhD dissertation emanated from the Danish MS Research Centre, Rigshosptalet, Copenhagen. Multiple sclerosis (MS) is an inflammatory disease of the CNS. Inflammatory responses by T helper (Th)-lymphocytes are characterised by distinct cytokine expression profiles. In MS, activated Th1...... of inflammation or secondary lymphatic organs. Chemokine receptors are differentially expressed in T cells in blood and cerebrospinal fluid, indicating their role for in T-cell-recruitment to the CNS. Interferon (IFN)-beta is a first-line treatment for MS. The mechanism of action is unclear, but probably includes...... changes in lymphocyte activation, cytokine secretion, and trafficking. The aim of the studies was to shed more light on T-cell immunology in MS and IFN-beta treatment, as well as identifying putative biomarkers of treatment response and/or disease activity. In one study we identified a Th-cell subset...

  17. Induction of interferon by levamisole in mice. [X radiation

    Energy Technology Data Exchange (ETDEWEB)

    Matsubara, S.; Suzuki, F.; Ishida, N.

    1979-03-01

    Viral inhibitor(s) with the properties of interferon (IF) was found in the sera of DDI mice injected intraperitoneally with 5 to 10 mg/kg of levamisole. A significant level of IF activity appeared by 20 hr and reached a peak by 24 hr after the injection. The induction was abrogated when the mice were pretreated with either whole-body x irradiation of more than 500 R or 2.5 mg of hydrocortisone acetate but was not affected by macrophage-specific depressors such as carrageenan and trypan blue. Also, no induction was detected in thymus-defective nude mice. These results suggest that thymus-derived lymphocytes in the mouse may be required for IF induction by levamisole.

  18. [Conjunctival squamous cell carcinoma: paradoxical response to interferon eyedrops].

    Science.gov (United States)

    Mata, E; Conesa, E; Castro, M; Martínez, L; de Pablo, C; González, M L

    2014-07-01

    A 67 year-old male seen for a longstanding corneal-conjunctival tumor. topical interferon α2b (IFN-α2b) 10 U/ml. A significant increase in lesion size was observed after 8 weeks. A surgical excision with cryotherapy was then performed. Pathological examination confirmed the diagnosis of squamous cell carcinoma. At this time the patient was found to have a positive HIV serology. Conjunctival intraepithelial neoplasia (CIN) is a pre-cancerous lesion of the ocular surface. Medical treatment of CIN is essentially with IFN-α2b due to its antiviral/antitumor properties. In patients with HIV, treatment response could be paradoxical. We recommend serology for HIV before treatment with topical IFN-α2b. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  19. Interferon and the fear of needles: a case report.

    Science.gov (United States)

    López, Maria; Moreno, Laura; Dosal, Angelina; Pujol, Marta Maria; Vergara, Mercedes; Gil, Montserrat

    2011-01-01

    The treatment of viral hepatitis C infection uses a combination of pegylated interferon and ribavirin. Psychological preparation of the patient is vital to ensure adherence to the treatment. In our center, the nurse prepares this treatment according to an established educative protocol; however, some patients have special needs that require individualized attention. One such situation observed by the nurse is that the patients frequently admit to the fear of needle puncture (the peginterferon treatment is administered subcutaneously) and are unable to inject themselves. We describe a representative case and the care plan to manage the patient's fear so that the patient acquires confidence in his or her ability to self-inject. This facilitates autonomy and coresponsibility for the treatment, and the nurse can develop care approaches to combat the patient's fear of needles.

  20. Type I Interferon in the Pathogenesis of Lupus

    Science.gov (United States)

    Crow, Mary K.

    2014-01-01

    Investigations of patients with systemic lupus erythematosus (SLE) have applied insights from studies of the innate immune response to define type I interferon (IFN-I), with IFN-α the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFNI-induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained anti-virus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients. PMID:24907379

  1. Targeting Interferon Regulatory Factor for Cardiometabolic Diseases: Opportunities and Challenges.

    Science.gov (United States)

    Zhang, Yaxing; Zhang, Xiao-Jing; Li, Hongliang

    2017-01-01

    The pathological activation of innate immune system may contribute to the development of cardiometabolic diseases. The interferon regulatory factor (IRF) family members, which are the major transcription factors in innate immune signaling, are implicated in cardiometabolic diseases. The aim of this review is to summary the current knowledge of the biological functions of IRFs in innate immune responses and immune cell development, and highlight our contemporary understanding of the functions and molecular mechanisms of IRFs in metabolic diseases, cardiovascular remodeling, and stroke. IRFs are the essential regulators of cardiometabolic diseases via immune-dependent and - independent manners. IRFs signaling is the promising target to manage the initiation and progression of cardiometabolic disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections.

    Science.gov (United States)

    Lee, Sanghyun; Baldridge, Megan T

    2017-01-01

    Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule.

  3. Interferon lambda inhibits dengue virus replication in epithelial cells.

    Science.gov (United States)

    Palma-Ocampo, Helen K; Flores-Alonso, Juan C; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio; Flores-Mendoza, Lilian; Herrera-Camacho, Irma; Rosas-Murrieta, Nora H; Santos-López, Gerardo

    2015-09-28

    In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.

  4. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

    Directory of Open Access Journals (Sweden)

    Maura Manion

    Full Text Available Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment.The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006. These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy. As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001.Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

  5. Pharmacokinetic studies of the recombinant chicken interferon-α in broiler chickens.

    Science.gov (United States)

    Zhao, Jun; Yu, Hai-Yang; Zhang, Jun-Ling; Wang, Xing-Man; Li, Jin-Pei; Hu, Tao; Hu, Yong; Wang, Ming-Li; Shen, Yong-Zhou; Xu, Jing-Dong; Han, Guo-Xiang; Chen, Jason

    2017-02-14

    In this study, 24 male and female broiler chickens at 30-day-old were divided into three groups with 8 animals in each group. The animals were administered with recombinant chicken interferon-α (rChIFN-α) at a dose of 1.0 × 10 6 IU/kg intravenously, intramuscularly or subcutaneously, respectively. Serum samples were collected at different time points post administration, and the titers of rChIFN-α in the blood were determined by cytopathic effect inhibition assay. The results showed that the pharmacokinetic characteristics of rChIFN-α by intramuscular injection and subcutaneous injection were fitted to one compartment open model, and the T max was 3.21 ± 0.79 hr and 3.95 ± 0.85 hr, respectively, and the elimination half-life (T 1/2 ) was 6.20 ± 2.77 hr and 5.03 ± 3.70 hr, respectively. In contrast, the pharmacokinetics of rChIFN-α via intravenous injection was in line with the open model of two-compartment and was eliminated in the first order, and the elimination half-life (T 1/2 ) was 4.61 ± 0.84 hr. In addition, compared with those in the intravenous group and the subcutaneous group, the bioavailability of rChIFN-α in the intramuscular group was 82.80%. In conclusion, rChIFN-α was rapidly absorbed and slowly eliminated after intramuscular administration of single dose of rChIFN-α aqueous formulations. Thus, rChIFN-α can be used as a commonly-used therapeutic agent.

  6. Open Source, Open Access, Open Review, Open Data. Initiativen zu mehr Offenheit in der digitalen Welt

    OpenAIRE

    Herb, Ulrich

    2011-01-01

    The article discusses the principles of openess, open access and open availability of information based on the examples of open access to scientific information, open government data, open geographical data and open source software.

  7. Korea prospects

    International Nuclear Information System (INIS)

    Wyman, V.

    1990-01-01

    Contacts between the South Korean nuclear industry and a combined United Kingdom mission representing AEA Technology and British Nuclear Fuels Limited (BNFL) are reported. Prospects for entering the Korean market in two areas are perceived. The first is waste management and the second is the Safe Integral Reactor (SIR), an advanced pressurized water reactor design. AEA Technology and three collaborators have been promoting SIR as an inherently safe reactor design. Korean interest could be expressed in financial backing for the building of SIR stations in Korea and the opportunity could arise for BNFL to win fuel supply contracts. (UK)

  8. The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Madsen, Claus

    2017-01-01

    The introduction of interferon beta therapies more than 20 years ago marked a milestone in the treatment of relapsing-remitting multiple sclerosis (RRMS) with a significant impact on the approach to modern multiple sclerosis (MS) care. Key learnings and perspectives from the early days of disease...... modifying therapies in MS have improved the knowledge base of MS, need for treatment, and patient care. The continuous development of interferons over the past two decades outlines a journey with increased understanding of the pharmacodynamics and pharmacokinetic mechanisms of interferons, leading...

  9. Interferon status at the women with recurrent genital herpes in combined liposomal RNA treatment

    Directory of Open Access Journals (Sweden)

    A. Sh. Makhmutkhodzhayev

    2012-01-01

    Full Text Available The aim of this study was the estimation of the influence of liposomal ribonucleic acid (RNA medicine «Liprina» on interferon status of women with recurrent genital herpes. In this study 60 women were included, who combined (acyclovir and Liprina, n = 40 or monoterapy with acyclovir (n = 20 were received. The levels of serum interferon alpha and gamma along with cervical virus elimination were estimated. The medicine «Liprina» increased the therapy efficiency of the women with genital herpes, that perhaps related with endogen interferon production amplification.

  10. A Recombinant Adenovirus Expressing Ovine Interferon Tau Prevents Influenza Virus-Induced Lethality in Mice.

    Science.gov (United States)

    Martín, V; Pascual, E; Avia, M; Rangel, G; de Molina, A; Alejo, A; Sevilla, N

    2016-01-06

    Ovine interferon tau (IFN-τ) is a unique type I interferon with low toxicity and a broad host range in vivo. We report the generation of a nonreplicative recombinant adenovirus expressing biologically active IFN-τ. Using the B6.A2G-Mx1 mouse model, we showed that single-dose intranasal administration of recombinant Ad5-IFN-τ can effectively prevent lethality and disease induced by highly virulent hv-PR8 influenza virus by activating the interferon response and preventing viral replication. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Open areas and open access

    International Nuclear Information System (INIS)

    Thorndike, A.M.

    1979-01-01

    The main objective of the two open areas in the present ISABELLE design has been to provide flexibility with respect to the size and shape of experimental equipment that would eventually be installed there. No permanent building would be installed initially. One possibility would be to enclose each experiment in a temporary structure that would provide weatherproofing and shielding; another possibility would be to erect a permanent building at a later time, when experience has made the needs clearer than they are at present. The secondary objective of the design of open areas has been to keep initial costs as low as practicable. Another objective might be added, however, which we indicate by the term ''open access.'' This note will explore this idea and some design concepts based on it. In the ISABELLE 1977 summer workshop there was considerable discussion of the importance of techniques for inserting large pieces of experimental equipment quickly and removing them with equal ease and speed. Since enclosed halls have certain restrictions in this respect, open areas may be helpful in providing this feature. If the mechanical and electrical aspects could be handled quickly, one might even attempt to reduce the time spent on bureaucratic procedures in order to expedite the introduction of new experiments and new ideas in these areas

  12. The use aeroplanes and vehicles for prospecting. The technique of the detection radioactivity. The future opened up by the use of the discrimination of energies; Methodes de prospection autoportee et aeroportee. La technique de la detection des rayonnements. Les perspectives offertes par la discrimination des energies

    Energy Technology Data Exchange (ETDEWEB)

    Guitton, J; Berbezier, J; Blangy, B; Lallemant, C [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1958-07-01

    The idea of installing activity detectors on aeroplanes and vehicles has been widely applied by the CEA since the start of prospecting in the arid and tropical regions of the Communaute Francaise. Three systems of detection have been developed and compared in a systematic manner: a group of 50 G.M. tubes; the sodium iodide scintillator; the plastic scintillator. The sodium iodide scintillator is used as a standard reference; the results are compared by graphical recording. Airborne prospecting is carried out in two stages: the initial flights, which follow a kilometre square network, make possible the discovery of the most likely zones; these likely zones are then examined in greater detail using light aeroplanes or helicopters. The two types of airborne scintillation measuring devices which have been developed by the CEA are described in this article. The practical results obtained during systematic and detailed airborne prospecting campaigns in the Hoggar are described. The difficulty in airborne uranium prospecting is to be able to immediately distinguish while in flight, anomalies caused by uranium from those caused by thorium. (author) [French] L'idee de monter des detecteurs de rayonnements sur des avions ou des vehicules a ete largement appliquee par le CEA des le debut des prospections dans les pays sahariens et tropicaux de la Communaute Fran ise. On a realise et compare d'une maniere systematique trois moyens de detection: groupe de 50 tubes GM; scintillateur d'iodure de sodium, scintillateur plastique. L'appareil de reference sera le scintillateur d'iodure de sodium; les resultats sont compares par enregistrement graphique. La prospection aeroportee se fait en deux etapes; les premiers vols systematiques suivant un quadrillage kilometrique permettent de reperer les zones interessantes; ces dernieres font l'objet d'examens plus detailles effectues en avion leger ou en helicoptere. Dans cet article, on decrit les deux types de scintillometres aeroportes

  13. Open source posturography.

    Science.gov (United States)

    Rey-Martinez, Jorge; Pérez-Fernández, Nicolás

    2016-12-01

    The proposed validation goal of 0.9 in intra-class correlation coefficient was reached with the results of this study. With the obtained results we consider that the developed software (RombergLab) is a validated balance assessment software. The reliability of this software is dependent of the used force platform technical specifications. Develop and validate a posturography software and share its source code in open source terms. Prospective non-randomized validation study: 20 consecutive adults underwent two balance assessment tests, six condition posturography was performed using a clinical approved software and force platform and the same conditions were measured using the new developed open source software using a low cost force platform. Intra-class correlation index of the sway area obtained from the center of pressure variations in both devices for the six conditions was the main variable used for validation. Excellent concordance between RombergLab and clinical approved force platform was obtained (intra-class correlation coefficient =0.94). A Bland and Altman graphic concordance plot was also obtained. The source code used to develop RombergLab was published in open source terms.

  14. OpenAPC. Open-Access-Publikationskosten als Open Data

    OpenAIRE

    Tullney, Marco

    2015-01-01

    Präsentationsfolien zum Vortrag „OpenAPC. Open-Access-Publikationskosten als Open Data“ in der Session „Ausgestaltung eines wissenschaftsadäquaten APC-Marktes: Grundsätze, Finanzierungsansätze und Management“ der Open-Access-Tage 2015 in Zürich (https://www.open-access.net/community/open-access-tage/open-access-tage-2015-zuerich/programm/#c1974)

  15. Open Pneumothorax

    Directory of Open Access Journals (Sweden)

    Bart Paull

    2017-07-01

    Full Text Available History of present illness: A 27-year-old male was transported to the emergency department by emergency medical services after crashing his motorcycle into a guardrail. Upon presentation he was alert, normotensive, and tachypneic. Significant findings: A large chest wound was clinically obvious. A chest radiograph performed after intubation showed subcutaneous emphysema, an anterior rib fracture, and a right-sided pneumothorax. He was then taken to the operating room for further management. Discussion: Thoracic injuries are responsible for one-quarter of all trauma-related deaths. Following rib fracture, pneumothorax is the second most common thoracic injury, occurring in 30% of patients with thoracic trauma. An open pneumothorax occurs when a chest wall injury results in direct communication between the atmosphere and pleura.1-2 It is estimated that open pneumothorax occurs in 80% of all penetrating chest wounds, with stab wounds being more common than gunshot wounds or impalement. Open pneumothoraces can lead to ventilatory insufficiency and rapid respiratory decompensation.2 Advanced Trauma Life Support recommends that the initial management of an open pneumothorax is placement of an occlusive dressing taped on three sides to create a ‘flutter-valve’ mechanism. This should then be followed by tube thoracostomy and repair of the chest wall defect.3 The placement of an occlusive dressing or initial wound closure without subsequent tube thoracostomy may result in the development of a tension pneumothorax.2 The patient was intubated and mechanical ventilation was initiated without complication. Due to the large size of the wound, an occlusive dressing was not placed in the emergency department and the patient was rapidly transported to the operating room for further management. In the operating room two chest tubes were placed. Operative findings included a right hemopneumothorax, multiple rib fractures, and a manubrial fracture. After

  16. Opening address

    International Nuclear Information System (INIS)

    Ianko, L.

    1993-01-01

    This short talk was the opening remarks to the attendees at this conference, presented by the Scientific Secretary, IWG-LMNPP, of the IAEA. This meeting is an effort to aid research on problems related to the general area of nuclear plant aging and life management. In particular it addresses fracture properties of reactor materials and components, both as installed, and at end of service condition. A major concern is relating measurements made on laboratory samples to properties displayed by actual reactor components

  17. Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3

    Directory of Open Access Journals (Sweden)

    Aline Gonzalez Vigani

    Full Text Available BACKGROUND: Pegylated interferon (Peg-IFN and standard interferon (IFN play a significant role in the treatment of hepatitis C virus (HCV infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR rates following treatment with biosimilar standard IFN plus ribavirin (RBV versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7% patients with HCV genotype 2 infections. One hundred fourteen (66.3% were treated with biosimilar standard IFN plus RBV, whist 58 (33.7% patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172 patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58 had SVR compared to 49.1% (56/114 among those treated with biosimilar standard IFN plus RBV (p = 0.0001. CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.

  18. Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial.

    Science.gov (United States)

    Mackensen, Friederike; Jakob, Eva; Springer, Christina; Dobner, Bianca C; Wiehler, Ute; Weimer, Petra; Rohrschneider, Klaus; Fiehn, Christoph; Max, Regina; Storch-Hagenlocher, Brigitte; Becker, Matthias D

    2013-09-01

    To compare interferon (IFN) beta with methotrexate (MTX) in the treatment of intermediate uveitis with macular edema. Monocentric, prospective, randomized, controlled clinical trial. Specialized uveitis center at the University of Heidelberg. PATIENT OR STUDY POPULATION: Patients with either primary intermediate uveitis or uveitis associated with multiple sclerosis. MAIN INCLUSION CRITERIA: Visual acuity of 20/30 or worse (0.2 logarithm of the minimal angle of resolution) and macular edema of more than 250 μm (central 1-mm in optical coherence tomography; Stratus). Randomization into either IFN beta 44 μg subcutaneously 3 times weekly or 20 mg MTX subcutaneously once weekly. At 3 months, the primary outcome parameter of mean change in visual acuity was evaluated and efficacy was determined. Secondary parameters were macular edema by optical coherence tomography, inflammatory activity, and retinal sensitivity by microperimetry (MP-1; Nidek). In case of treatment failure, switching to the other treatment arm was possible. Nineteen patients were included. Ten were randomized to MTX, and 9 were randomized to IFN beta. At 3 months, visual acuity improved a mean 0.31 logarithm of the minimal angle of resolution (range, -0.02 to -0.96, 15.6 letters on the Early Treatment Diabetic Retinopathy Study chart) in the IFN beta group versus a mean 0.09 logarithm of the minimal angle of resolution (range, 0.12 to -0.38, 4.7 letters) in the MTX arm (P = .0435, Mann-Whitney U test). Macular thickness decreased by a mean of 206 μm (range, -41 to -416 μm) in the IFN arm, but increased by 47 μm (range, 108 to -28 μm) in the MTX group (P treatment of macular edema in the setting of intermediate uveitis. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Open access, open education resources and open data in Uganda ...

    African Journals Online (AJOL)

    As a follow up to OpenCon 2014, International Federation of Medical Students' Associations (IFMSA) students organized a 3 day workshop Open Access, Open Education Resources and Open Data in Kampala from 15-18 December 2014. One of the aims of the workshop was to engage the Open Access movement in ...

  20. Crystallization and preliminary X-ray analysis of Ebola VP35 interferon inhibitory domain mutant proteins

    International Nuclear Information System (INIS)

    Leung, Daisy W.; Borek, Dominika; Farahbakhsh, Mina; Ramanan, Parameshwaran; Nix, Jay C.; Wang, Tianjiao; Prins, Kathleen C.; Otwinowski, Zbyszek; Honzatko, Richard B.; Helgeson, Luke A.; Basler, Christopher F.; Amarasinghe, Gaya K.

    2010-01-01

    Three mutant forms of Ebola VP35 interferon inhibitory domain were crystallized in three different space groups. VP35 is one of seven structural proteins encoded by the Ebola viral genome and mediates viral replication, nucleocapsid formation and host immune suppression. The C-terminal interferon inhibitory domain (IID) of VP35 is critical for dsRNA binding and interferon inhibition. The wild-type VP35 IID structure revealed several conserved residues that are important for dsRNA binding and interferon antagonism. Here, the expression, purification and crystallization of recombinant Zaire Ebola VP35 IID mutants R312A, K319A/R322A and K339A in space groups P6 1 22, P2 1 2 1 2 1 and P2 1 , respectively, are described. Diffraction data were collected using synchrotron sources at the Advanced Light Source and the Advanced Photon Source

  1. An Assay in Microtitre Plates for Absolute Abundance of Chicken Interferon Alpha Transcripts

    Directory of Open Access Journals (Sweden)

    Renata Novak Kujundžić

    2010-01-01

    Full Text Available Immunosuppression of commercial chickens is a serious animal health and economic problem in the poultry industry. The major causes of the immunosuppression are viruses that suppress transcription of interferon genes, especially interferon alpha. There is a need for monitoring immunosuppression in commercially bred chickens. For this purpose, the absolute abundance of interferon alpha transcripts can be measured in blood of chickens by a suitable assay. Such an assay was used to estimate abundance of chicken interferon alpha in a sample of splenic cells induced with polyinosinic polycytidylic acid. The abundance measured was 29 ± 2 attomoles/µg total RNA. This assay can be performed in microtitre plates using samples collected from chickens in poultry houses.

  2. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria

    2003-01-01

    Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

  3. [Expression of gamma interferon during HPV and Chlamydia trachomatis infection in cervical samples].

    Science.gov (United States)

    Colín-Ferreyra, María Del Carmen; Mendieta-Zerón, Hugo; Romero-Figueroa, María Del Socorro; Martínez-Madrigal, Migdania; Martínez-Pérez, Sergio; Domínguez-García, María Victoria

    2015-02-01

    The aim of this study was to mesure the expression of gamma interferon in HPV and Chlamydia trachomatis infection in squamous intraepithelial lesions. Samples from 100 patients diagnosed by colposcopy with or without squamous intraepithelial lesions were used in the present study. Each patient was found to be infected by HPV and C.trachomatis. Relative gamma interferon mRNA expression was assessed using a real-time reverse transcriptase PCR assay (RT-PCR). The relative units of expression of gamma interferon mRNA were 13, 1.8 and 0.3, for HPV and C.trachomatis co-infection, or HPV or C.trachomatis infection, respectively. HPV and C.trachomatis could overstimulate the expression of gamma interferon. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  4. THE ROLE OF INTERFERON ALPHA-2b IN REDUCING OF VIRAL LOAD IN HPV INFECTED WOMEN

    Directory of Open Access Journals (Sweden)

    Кристина Владимировна Марочко

    2017-05-01

    Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.

  5. Product related factors influencing the immunogenicity of interferon beta-1b

    NARCIS (Netherlands)

    Haji Abdolvahab, M.

    2016-01-01

    Therapeutic interferon beta is the first line treatment of relapsing remitting Multiple Sclerosis. However, despite their success in improving patient wellbeing, all IFNβ products encounter a significant problem: immunogenicity. In some patients, IFNβ products induce the formation of antidrug

  6. Overlapping positive and negative regulatory domains of the human β-interferon gene

    International Nuclear Information System (INIS)

    Goodbourn, S.; Maniatis, T.

    1988-01-01

    Virus of poly(I) x poly(C) induction of human β-interferon gene expression requires a 40-base-pair DNA sequence designated the interferon gene regulatory element (IRE). Previous studies have shown that the IRE contains both positive and negative regulatory DNA sequences. To localize these sequences and study their interactions, the authors have examined the effects of a large number of single-base mutations within the IRE on β-interferon gene regulation. They find that the IRE consists of two genetically separable positive regulatory domains and an overlapping negative control sequence. They propose that the β-interferon gene is switched off in uninduced cells by a repressor that blocks the interaction between one of the two positive regulatory sequences and a specific transcription factor. Induction would then lead to inactivation or displacement of the repressor and binding of transcription factors to both positive regulatory domains

  7. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis.

    Science.gov (United States)

    Conrad, Curdin; Di Domizio, Jeremy; Mylonas, Alessio; Belkhodja, Cyrine; Demaria, Olivier; Navarini, Alexander A; Lapointe, Anne-Karine; French, Lars E; Vernez, Maxime; Gilliet, Michel

    2018-01-02

    Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2-5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis. Anti-TNF treatment prolongs type I interferon production by pDCs through inhibition of their maturation. The resulting type I interferon overexpression is responsible for the skin phenotype of paradoxical psoriasis, which, unlike classical psoriasis, is independent of T cells. These findings indicate that paradoxical psoriasis represents an ongoing overactive innate inflammatory process, driven by pDC-derived type I interferon that does not lead to T-cell autoimmunity.

  8. EFFICACY OF INTRAPERITONEAL INTERFERON-α ADMINISTRATION FOR TREATMENT OF ENDOMETRIOSIS IN RATS

    Directory of Open Access Journals (Sweden)

    R. V. Pavlov

    2006-01-01

    Full Text Available Abstract. The article presents the results of intraperitoneal administration of recombinant rat interferon-α to twenty Wistar rats with experimentally induced endometriosis. The following criteria of treatment efficiency were applied: presence of ectopic endometrium in transplanted segments of cornu uteri, proliferative activity of endometrioid cells, features of vascularization and leucocyte infiltration within endometrial foci. It was shown that local application of interferon-α caused regression of endometrioid epithelial heterotopias in 50 per cent of the cases. If endometrioid epithelium was retained, its proliferative activity did significantly drop under interferon-α application. In all transplants derived from rats treated with interferon-α, the degree of vascularization is reduced, accompanied by increased leucocytic infiltration (due to lymphocytes, along with decreased contents of macrophages within leucocytic infiltrates.

  9. Effects of adding ribavirin to interferon to treat chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2005-01-01

    Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40% of patients with chronic hepatitis C infection, but the effects on clinical outcomes are unclear. We evaluated the beneficial and harmful effects of ribavirin plus interferon...... vs interferon alone for treatment of patients with chronic hepatitis C infection. Randomized trials were included irrespective of blinding, language, or publication status. Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Library, MEDLINE....... In conclusion, the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection. However, combination therapy is associated with increased risk for adverse events....

  10. Open areas and open access

    International Nuclear Information System (INIS)

    Thorndike, A.M.

    1978-01-01

    One objective of the two open areas in the present ISABELLE design is to provide flexibility with respect to the size and shape of experimental equipment that would eventually be installed there. No permanent building would be installed initially. A second objective of the design of open areas is to keep initial costs as low as practicable. Another objective is open access. This note explores this idea and some design concepts based on it. It would permit inserting large pieces of experimental equipment quickly and removing them with equal ease and speed. Entire experiments would be moved in a single piece (or a few) by building them on movable platforms with capacities of up to about 1000 tons per platform. Most experiments could be built on a single platform or on a few. The shielding must also be moved. It must also be organized into a small number of large units. A scheme using large tanks filled with water is described. It is important to make the equipment on a given platform as complete and self-contained as possible, with a minimum of interconnections for power, coolant, controls, data transmission, etc. 5 figures

  11. Energy prospects

    International Nuclear Information System (INIS)

    Lyall, K.

    1991-01-01

    The Business Council of Australia's study on Prospects for Improved Energy Efficiency and the Application of Renewable Energy Resources is summarised. The study estimates that replacement of all off-peak electric units in Australia with solar gas boosted systems would reduce electricity consumption for residential water heating by approximately 25% and almost halve carbon dioxide emissions resulting from residential water heating. Furthermore, substitution of all water heating units in Australia with solar gas systems would reduce total emissions by about 80%. The study concludes that while substitution on such a scale could not readily be achieved even within several decades, the estimates do indicate the significant benefits that might be realised by a long term program. 2 refs., 3 tabs

  12. Opening remarks

    International Nuclear Information System (INIS)

    Southwood, Richard

    1987-01-01

    General opening remarks to a conference on the effects of low-level radiation on man, exploring particularly areas where disagreements have most frequently been voiced. The author comments on two approaches: a) the study, stepwise of putative cause and effect chains, using models which are tested by comparing calculated and observed effects. b) the epidemiological approach by extensive correlative study of cause, correlations and effect. Attention is drawn to the confidence to be accorded to any quantitative theory supported by both approaches, and the need for further analysis if the approaches give different indications. (U.K.)

  13. Open University

    CERN Multimedia

    Pentz,M

    1975-01-01

    Michel Pentz est née en Afrique du Sud et venu au Cern en 1957 comme physicien et président de l'associaion du personnel. Il est également fondateur du mouvement Antiapartheid de Genève et a participé à la fondation de l'Open University en Grande-Bretagne. Il nous parle des contextes pédagogiques, culturels et nationaux dans lesquels la méthode peut s'appliquer.

  14. Opening lecture

    International Nuclear Information System (INIS)

    Thomas, J.B.

    1997-01-01

    The opening lecture on the results of fifty years in the nuclear energy field, deals with the main principles underlying the CEA policy concerning the fission nuclear energy transformation, i.e. the design of a nuclear industry that is a safe, high-performance and reliable source of electric power, the development of an adaptive power generation tool with the capacity to progress according to new constraints, and the necessary anticipation for preparing to the effects of the next 50 year technological leaps

  15. Higher Serum Uric Acid Levels in Multiple Sclerosis Patients After Longterm Interferon Beta Treatment

    Directory of Open Access Journals (Sweden)

    Toncev Gordana

    2017-10-01

    Full Text Available Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS. However, there is some evidence that uric acid, a scavenger of peroxynitrite, is involved in MS pathology and that increasing serum uric acid levels might have beneficial therapeutic effects. The aim of this study is to investigate serum uric acid levels in MS patients before and after long-term interferon beta treatment. Blood samples from 101 MS patients (53 receiving interferon beta 1a treatment and 48 receiving interferon beta 1b treatment; 28 male and 73 female; mean age at treatment onset 32,4±7,3 years; mean duration of disease at treatment onset 5,1±3,2 years; mean EDSS 2±1,3 before and after interferon beta treatment (mean treatment duration 3±2 years were analysed. Serum uric acid levels were measured using a quantitative enzymatic assay (Elitech Diagnostic, Sees, France. MS patients had significantly increased serum uric acid levels after treatment compared with those at the beginning of treatment (272,31±78,21 μmol/l vs. 210,17±53,65 μmol/l; p=0,019, Wilcoxon Mann-Whitney U-test. We did not find significant differences in serum uric acid levels between the interferon beta 1a and interferon beta 1b groups (p=0.98. These results indicate that one of the beneficial effects of interferon beta in MS might be based on the elevation of serum uric acid levels as a natural scavenger of peroxynitrite.

  16. Kaposi's sarcoma after alpha-interferon treatment for HIV-negative T ...

    African Journals Online (AJOL)

    Abstract A 54-year-old HIV-negative patient suffering frOIn. T-cell lytnphoIna of Lennert's lytnphoIna (Lel) type was treated for 13 Inonths with interferon a-. 2b. While on treatment with interferon the patient. derrlOnstrated suppression of total and CD4+ lytn- phocytes to levels < 0,5 and 0,2 x 10911, respectively. Although ...

  17. Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells

    International Nuclear Information System (INIS)

    Miller, B.A.; Perrine, S.P.; Antognetti, G.; Perlmutter, D.H.; Emerson, S.G.; Sieff, C.; Faller, D.V.

    1987-01-01

    The effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes

  18. Results of interferon-based treatments in Alaska Native and American Indian population with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Stephen E. Livingston

    2016-03-01

    Full Text Available Background: There have been few reports of hepatitis C virus (HCV treatment results with interferon-based regimens in indigenous populations. Objective: To determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI population. Design: In an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined. Results: Sustained virologic response (SVR with standard interferon was 16.7% (3/18 and with standard interferon and ribavirin was 29.7% (11/37. Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%, including 10 of 46 with genotype 1 (21.7%, 38 of 51 with genotype 2 (74.5% and 13 of 22 with genotype 3 (59.1%. By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p=0.002, estimated duration of infection (p=0.034 and HCV genotype (p<0.0001. There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%. Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%. Conclusions: We had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1.

  19. Bim nuclear translocation and inactivation by viral interferon regulatory factor.

    Directory of Open Access Journals (Sweden)

    Young Bong Choi

    2010-08-01

    Full Text Available Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of the host cell. Human herpesvirus 8 (HHV-8 uses several strategies to block the host's innate antiviral defenses via interference with interferon and apoptotic signaling. Contributors include the four viral interferon regulatory factors (vIRFs 1-4, which function in dominant negative fashion to block cellular IRF activities in addition to targeting IRF signaling-induced proteins such as p53 and inhibiting other inducers of apoptosis such as TGFbeta receptor-activated Smad transcription factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim was identified in transfected cells, by both immunofluorescence assay and western analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim was detected in nuclei of lytically infected endothelial cells. In vitro co-precipitation assays using purified vIRF-1 and Bim revealed direct interaction between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion and point mutagenesis. Generation and experimental utilization of Bim-refractory vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically, in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking of the interaction with cell-permeable peptide corresponding to the Bim-binding region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro-replication activity. To our knowledge, this is the first report of an IRF protein that interacts with a Bcl-2 family member and of nuclear sequestration of Bim or any other member of the family as a means of inactivation. The data presented reveal a novel mechanism utilized by a virus to control

  20. Microassay for interferon, using [3H]uridine, microculture plates, and a multiple automated sample harvester.

    Science.gov (United States)

    Richmond, J Y; Polatnick, J; Knudsen, R C

    1980-01-01

    A microassay for interferon is described which uses target cells grown in microculture wells, [3H]uridine to measure vesicular stomatitis virus replication in target cells, and a multiple automated sample harvester to collect the radioactively labeled viral ribonucleic acid onto glass fiber filter disks. The disks were placed in minivials, and radioactivity was counted in a liquid scintillation spectrophotometer. Interferon activity was calculated as the reciprocal of the highest titer which inhibited the incorporation of [3H]uridine into viral ribonucleic acid by 50%. Interferon titers determined by the microassay were similar to the plaque reduction assay when 100 plaque-forming units of challenge vesicular stomatitis virus was used. However, it was found that the interferon titers decreased approximately 2-fold for each 10-fold increase in the concentration of challenge vesicular stomatitis virus when tested in the range of 10(2) to 10(5) plaque-forming units. Interferon titers determined by the microassay show a high degree of repeatability, and the assay can be used to measure small and large numbers of interferon samples. PMID:6155105

  1. Inhibition of interferon induction and action by the nairovirus Nairobi sheep disease virus/Ganjam virus.

    Science.gov (United States)

    Holzer, Barbara; Bakshi, Siddharth; Bridgen, Anne; Baron, Michael D

    2011-01-01

    The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV)). NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus). We have investigated the ability of NSDV to antagonise the induction and actions of interferon. Both pathogenic and apathogenic isolates could actively inhibit the induction of type 1 interferon, and also blocked the signalling pathways of both type 1 and type 2 interferons. Using transient expression of viral proteins or sections of viral proteins, these activities all mapped to the ovarian tumour-like protease domain (OTU) found in the viral RNA polymerase. Virus infection, or expression of this OTU domain in transfected cells, led to a great reduction in the incorporation of ubiquitin or ISG15 protein into host cell proteins. Point mutations in the OTU that inhibited the protease activity also prevented it from antagonising interferon induction and action. Interestingly, a mutation at a peripheral site, which had little apparent effect on the ability of the OTU to inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block the induction of type 1 and the action of type 2 interferons, but had a lesser effect on the ability to block type 1 interferon action, suggesting that targets other than ubiquitin and ISG15 may be involved in the actions of the viral OTU.

  2. Inhibition of interferon induction and action by the nairovirus Nairobi sheep disease virus/Ganjam virus.

    Directory of Open Access Journals (Sweden)

    Barbara Holzer

    Full Text Available The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV. NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus. We have investigated the ability of NSDV to antagonise the induction and actions of interferon. Both pathogenic and apathogenic isolates could actively inhibit the induction of type 1 interferon, and also blocked the signalling pathways of both type 1 and type 2 interferons. Using transient expression of viral proteins or sections of viral proteins, these activities all mapped to the ovarian tumour-like protease domain (OTU found in the viral RNA polymerase. Virus infection, or expression of this OTU domain in transfected cells, led to a great reduction in the incorporation of ubiquitin or ISG15 protein into host cell proteins. Point mutations in the OTU that inhibited the protease activity also prevented it from antagonising interferon induction and action. Interestingly, a mutation at a peripheral site, which had little apparent effect on the ability of the OTU to inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block the induction of type 1 and the action of type 2 interferons, but had a lesser effect on the ability to block type 1 interferon action, suggesting that targets other than ubiquitin and ISG15 may be involved in the actions of the viral OTU.

  3. Effect of alpha interferon on glucose and alanine transport by rat renal brush border membrane vesicles

    International Nuclear Information System (INIS)

    Batuman, V.; Chadha, I.

    1990-01-01

    To investigate the pathogenetic mechanisms of interferon nephrotoxicity, we studied the effect of recombinant interferon alfa-2b on the uptake of 14 C-D-glucose and 14 C-L-alanine by rat renal brush-border-membrane vesicles. Interferon significantly inhibited 20 sec. sodium-dependent and 5 and 10 min. equilibrium uptake of both glucose and alanine. The inhibitory effect was dose dependent with maximum effect achieved at interferon concentration of 5 x 10 -8 M in the uptake media. The half-maximal inhibitory concentrations, IC 50 , of interferon on glucose uptake was 1.8 x 10 -8 M, and 5.4 x 10 -9 M on alanine uptake. Dixon plot analysis of uptake data was consistent with pure non-competitive inhibition. The inhibition constants, K i , 1.5 x 10 -8 M for glucose uptake, and 7.3 x 10 -9 M for alanine uptake, derived from Dixon plots were in close agreement with the IC 50 s calculated from the semilog dose response curves. These observations reveal that direct interactions at the proximal tubule cell membrane are involved in the pathogenesis of interferon nephrotoxicity, and that its mechanism of nephrotoxicity is similar to that of other low molecular weight proteins

  4. A prospective international cooperative information technology platform built using open-source tools for improving the access to and safety of bone marrow transplantation in low- and middle-income countries.

    Science.gov (United States)

    Agarwal, Rajat Kumar; Sedai, Amit; Dhimal, Sunil; Ankita, Kumari; Clemente, Luigi; Siddique, Sulman; Yaqub, Naila; Khalid, Sadaf; Itrat, Fatima; Khan, Anwar; Gilani, Sarah Khan; Marwah, Priya; Soni, Rajpreet; Missiry, Mohamed El; Hussain, Mohamed Hamed; Uderzo, Cornelio; Faulkner, Lawrence

    2014-01-01

    Jagriti Innovations developed a collaboration tool in partnership with the Cure2Children Foundation that has been used by health professionals in Italy, Pakistan, and India for the collaborative management of patients undergoing bone marrow transplantation (BMT) for thalassemia major since August 2008. This online open-access database covers data recording, analyzing, and reporting besides enabling knowledge exchange, telemedicine, capacity building, and quality assurance. As of February 2014, over 2400 patients have been registered and 112 BMTs have been performed with outcomes comparable to international standards, but at a fraction of the cost. This approach avoids medical emigration and contributes to local healthcare strengthening and competitiveness. This paper presents the experience and clinical outcomes associated with the use of this platform built using open-source tools and focusing on a locally pertinent tertiary care procedure-BMT. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    Science.gov (United States)

    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    role of type III interferon (IFN)-mediated signaling, a host immune defense mechanism, in controlling YFV-17D infection and attenuation in different mouse models. We uncovered a critical role of type III IFN-mediated signaling in preserving the integrity of the blood-brain barrier and preventing viral brain invasion. Type III IFN also played a major role in regulating the induction of a potent but balanced immune response that prevented viral evasion of the host immune system. An improved understanding of the complex mechanisms regulating YFV-17D attenuation will provide insights into the key virus-host interactions that regulate host immune responses and infection outcomes as well as open novel avenues for the development of innovative vaccine strategies. Copyright © 2017 Douam et al.

  6. Comparative Evaluation of the Safety and Efficacy of Long-Term Use of Imidafenacin and Solifenacin in Patients with Overactive Bladder: A Prospective, Open, Randomized, Parallel-Group Trial (the LIST Study

    Directory of Open Access Journals (Sweden)

    Masayoshi Zaitsu

    2011-01-01

    Full Text Available Objectives. Overactive bladder (OAB is a chronic disease, but comparative trials of anticholinergics, which are commonly used for treatment of OAB, have generally been performed for up to 12 weeks only. There is no comparative study of a long-term intervention. Methods. We conducted a 52-week prospective randomized comparative study to evaluate the efficacy and tolerability of two anticholinergics. Results. Forty-one Japanese patients with untreated OAB were randomly assigned to imidafenacin and solifenacin groups. There was no difference in OABSS and KHQ scores between the two groups, but the severity and incidence of adverse events caused by the anticholinergics showed increased differences between the groups with time. The severity of dry mouth and the incidence of constipation were significantly lower in the imidafenacin group (=0.0092 and =0.0013, resp.. Conclusions. This study is the first long-term trial to show differences in the properties of anticholinergics that were not detected in short-term studies. Since OAB is a chronic disease, we conclude that imidafenacin is preferable to solifenacin from a perspective of safety.

  7. Fluoxetine regulates cell growth inhibition of interferon-α.

    Science.gov (United States)

    Lin, Yu-Min; Yu, Bu-Chin; Chiu, Wen-Tai; Sun, Hung-Yu; Chien, Yu-Chieh; Su, Hui-Chen; Yen, Shu-Yang; Lai, Hsin-Wen; Bai, Chyi-Huey; Young, Kung-Chia; Tsao, Chiung-Wen

    2016-10-01

    Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

  8. Type I interferons in tuberculosis: Foe and occasionally friend.

    Science.gov (United States)

    Moreira-Teixeira, Lúcia; Mayer-Barber, Katrin; Sher, Alan; O'Garra, Anne

    2018-05-07

    Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis. Since then, additional studies in human tuberculosis and experimental mouse models of M. tuberculosis infection support the concept that type I IFN promotes both bacterial expansion and disease pathogenesis. More recently, studies in a different setting have suggested a putative protective role for type I IFN. In this study, we discuss the mechanistic and contextual factors that determine the detrimental versus beneficial outcomes of type I IFN induction during M. tuberculosis infection, from human disease to experimental mouse models of tuberculosis. © 2018 Moreira-Teixeira et al.

  9. Bropirimine inhibits osteoclast differentiation through production of interferon

    International Nuclear Information System (INIS)

    Suzuki, Hiroaki; Mochizuki, Ayako; Yoshimura, Kentaro; Miyamoto, Yoichi; Kaneko, Kotaro; Inoue, Tomio; Chikazu, Daichi; Takami, Masamichi; Kamijo, Ryutaro

    2015-01-01

    Bropirimine is a synthetic agonist for toll-like receptor 7 (TLR7). In this study, we investigated the effects of bropirimine on differentiation and bone-resorbing activity of osteoclasts in vitro. Bropirimine inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) induced by receptor activator of nuclear factor κB ligand (RANKL) in a concentration-dependent manner. Furthermore, it suppressed the mRNA expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor for osteoclast differentiation, without affecting BMM viability. Bropirimine also inhibited osteoclast differentiation induced in co-cultures of mouse bone marrow cells (BMCs) and mouse osteoblastic UAMS-32 cells in the presence of activated vitamin D_3. Bropirimine partially suppressed the expression of RANKL mRNA in UAMS-32 cells induced by activated vitamin D_3. Finally, the anti-interferon-β (IFN-β) antibody restored RANKL-dependent differentiation of BMMs into osteoclasts suppressed by bropirimine. These results suggest that bropirimine inhibits differentiation of osteoclast precursor cells into osteoclasts via TLR7-mediated production of IFN-β.

  10. The nucleocapsid protein of measles virus blocks host interferon response

    International Nuclear Information System (INIS)

    Takayama, Ikuyo; Sato, Hiroki; Watanabe, Akira; Omi-Furutani, Mio; Sugai, Akihiro; Kanki, Keita; Yoneda, Misako; Kai, Chieko

    2012-01-01

    Measles virus (MV) belongs to the genus Morbillivirus of the family Paramyxoviridae. A number of paramyxoviruses inhibit host interferon (IFN) signaling pathways in host immune systems by various mechanisms. Inhibition mechanisms have been described for many paramyxoviruses. Although there are inconsistencies among previous reports concerning MV, it appears that P/V/C proteins interfere with the pathways. In this study, we confirmed the effects of MV P gene products of a wild MV strain on IFN pathways and examined that of other viral proteins on it. Interestingly, we found that N protein acts as an IFN-α/β and γ-antagonist as strong as P gene products. We further investigated the mechanisms of MV-N inhibition, and revealed that MV-N blocks the nuclear import of activated STAT without preventing STAT and Jak activation or STAT degradation, and that the nuclear translocation of MV-N is important for the inhibition. The inhibitory effect of the N protein was observed as a common feature of other morbilliviruses. The results presented in this report suggest that N protein of MV as well as P/V/C proteins is involved in the inhibition of host IFN signaling pathways.

  11. Development of a lion-specific interferon-gamma assay.

    Science.gov (United States)

    Maas, M; van Kooten, P J S; Schreuder, J; Morar, D; Tijhaar, E; Michel, A L; Rutten, V P M G

    2012-10-15

    The ongoing spread of bovine tuberculosis (BTB) in African free-ranging lion populations, for example in the Kruger National Park, raises the need for diagnostic assays for BTB in lions. These, in addition, would be highly relevant for zoological gardens worldwide that want to determine the BTB status of their lions, e.g. for translocations. The present study concerns the development of a lion-specific IFN-γ assay, following the production and characterization of monoclonal antibodies specific for lion interferon-gamma (IFN-γ). Recombinant lion IFN-γ (rLIFN-γ) was produced in mammalian cells and used to immunize mice to establish hybridoma cell lines producing monoclonal antibodies. These were used to develop a sensitive, lion IFN-γ-specific capture ELISA, able to detect rLIFN-γ to the level of 160 pg/ml. Recognition of native lion IFN-γ was shown in an initial assessment of supernatants of mitogen stimulated whole blood cultures of 11 known BTB-negative lions. In conclusion, the capture ELISA shows potential as a diagnostic assay for bovine tuberculosis in lions. Preliminary results also indicate the possible use of the test for other (feline) species. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. The interferon response circuit in antiviral host defense.

    Science.gov (United States)

    Haller, O; Weber, F

    2009-01-01

    Viruses have learned to multiply in the face of a powerful innate and adaptive immune response of the host. They have evolved multiple strategies to evade the interferon (IFN) system which would otherwise limit virus growth at an early stage of infection. IFNs induce the synthesis of a range of antiviral proteins which serve as cell-autonomous intrinsic restriction factors. For example, the dynamin-like MxA GTPase inhibits the multiplication of influenza and bunyaviruses (such as La Crosse virus, Hantaan virus, Rift Valley Fever virus, and Crimean-Congo hemorrhagic fever virus) by binding and sequestering the nucleocapsid protein into large perinuclear complexes. To overcome such intracellular restrictions, virulent viruses either inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Many viruses produce specialized proteins to disarm the danger signal or express virulence genes that target members of the IFN regulatory factor family (IRFs) or components of the JAK-STAT signaling pathway. An alternative evasion strategy is based on extreme viral replication speed which out-competes the IFN response. The identification of viral proteins with IFN antagonistic functions has great implications for disease prevention and therapy. Virus mutants lacking IFN antagonistic properties represent safe yet highly immunogenic candidate vaccines. Furthermore, novel drugs intercepting viral IFN-antagonists could be used to disarm the viral intruders.

  13. Interferon Gamma in African Trypanosome Infections: Friends or Foes?

    Science.gov (United States)

    Wu, Hui; Liu, Gongguan; Shi, Meiqing

    2017-01-01

    African trypanosomes cause fatal infections in both humans and livestock. Interferon gamma (IFN-γ) plays an essential role in resistance to African trypanosomes. However, increasing evidence suggests that IFN-γ, when excessively synthesized, also induces immunopathology, enhancing susceptibility to the infection. Thus, production of IFN-γ must be tightly regulated during infections with African trypanosomes to ensure that a robust immune response is elicited without tissue destruction. Early studies have shown that secretion of IFN-γ is downregulated by interleukin 10 (IL-10). More recently, IL-27 has been identified as a negative regulator of IFN-γ production during African trypanosome infections. In this review, we discuss the current state of our understanding of the role of IFN-γ in African trypanosome infections. We have focused on the cellular source of IFN-γ, its beneficial and detrimental effects, and mechanisms involved in regulation of its production, highlighting some recent advances and offering some perspectives on future directions.

  14. Bropirimine inhibits osteoclast differentiation through production of interferon

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Hiroaki [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Mochizuki, Ayako [Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Yoshimura, Kentaro; Miyamoto, Yoichi [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Kaneko, Kotaro [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023 (Japan); Inoue, Tomio [Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Chikazu, Daichi [Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023 (Japan); Takami, Masamichi [Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Kamijo, Ryutaro, E-mail: kamijor@dent.showa-u.ac.jp [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan)

    2015-11-06

    Bropirimine is a synthetic agonist for toll-like receptor 7 (TLR7). In this study, we investigated the effects of bropirimine on differentiation and bone-resorbing activity of osteoclasts in vitro. Bropirimine inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) induced by receptor activator of nuclear factor κB ligand (RANKL) in a concentration-dependent manner. Furthermore, it suppressed the mRNA expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor for osteoclast differentiation, without affecting BMM viability. Bropirimine also inhibited osteoclast differentiation induced in co-cultures of mouse bone marrow cells (BMCs) and mouse osteoblastic UAMS-32 cells in the presence of activated vitamin D{sub 3}. Bropirimine partially suppressed the expression of RANKL mRNA in UAMS-32 cells induced by activated vitamin D{sub 3}. Finally, the anti-interferon-β (IFN-β) antibody restored RANKL-dependent differentiation of BMMs into osteoclasts suppressed by bropirimine. These results suggest that bropirimine inhibits differentiation of osteoclast precursor cells into osteoclasts via TLR7-mediated production of IFN-β.

  15. Interferon therapy of acute respiratory viral infections in children

    Directory of Open Access Journals (Sweden)

    A.E. Abaturov

    2017-04-01

    end of therapy, we calculated the proportion of patients in groups, who didn’t have clinical signs of acute respiratory viral infection (more than 1 point after 5 days of treatment. The effectiveness of therapy with Laferobionum® was 100 %. The effectiveness of treatment with Laferobionum® depended to some extent on the etiology of the disease: in acute respiratory viral infections caused by the respiratory syncytial virus, there was less significant effect of interferon therapy on the course of the disease than in acute respiratory infections caused by influenza and parainfluenza viruses. Given the absence of subjective complaints from the examinees and negative changes in an objective and laboratory examination, tolerability of treatment in all patients receiving Laferobionum® was regarded as “good”. Conclusions. Interferon therapy, in particular the use of recombinant α-2b interferons (Laferobionum®, is one of the most important components of the treatment for acute respiratory viral diseases in children. The use of interferon for intranasal administration, which contributes to the sanogenesis of acute respiratory infections, will accelerate the process of recovery, prevent the development of bacterial complications.

  16. ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

    Science.gov (United States)

    Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

    2017-10-01

    Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Central Role of ULK1 in Type I Interferon Signaling

    Directory of Open Access Journals (Sweden)

    Diana Saleiro

    2015-04-01

    Full Text Available We provide evidence that the Unc-51-like kinase 1 (ULK1 is activated during engagement of the type I interferon (IFN receptor (IFNR. Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE and IFNγ activation site (GAS elements and controls expression of key IFN-stimulated genes (ISGs. We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK and establish that the regulatory effects of ULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway. Importantly, we demonstrate that ULK1 is essential for antiproliferative responses and type I IFN-induced antineoplastic effects against malignant erythroid precursors from patients with myeloproliferative neoplasms. Together, these data reveal a role for ULK1 as a key mediator of type I IFNR-generated signals that control gene transcription and induction of antineoplastic responses.

  18. Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

    Science.gov (United States)

    Denkinger, Claudia M.; Kik, Sandra V.; Rangaka, Molebogeng X.; Zwerling, Alice; Oxlade, Olivia; Metcalfe, John Z.; Cattamanchi, Adithya; Dowdy, David W.; Dheda, Keertan; Banaei, Niaz

    2014-01-01

    SUMMARY Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers. PMID:24396134

  19. The nucleocapsid protein of measles virus blocks host interferon response

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, Ikuyo; Sato, Hiroki; Watanabe, Akira; Omi-Furutani, Mio; Sugai, Akihiro; Kanki, Keita; Yoneda, Misako; Kai, Chieko, E-mail: ckai@ims.u-tokyo.ac.jp

    2012-03-01

    Measles virus (MV) belongs to the genus Morbillivirus of the family Paramyxoviridae. A number of paramyxoviruses inhibit host interferon (IFN) signaling pathways in host immune systems by various mechanisms. Inhibition mechanisms have been described for many paramyxoviruses. Although there are inconsistencies among previous reports concerning MV, it appears that P/V/C proteins interfere with the pathways. In this study, we confirmed the effects of MV P gene products of a wild MV strain on IFN pathways and examined that of other viral proteins on it. Interestingly, we found that N protein acts as an IFN-{alpha}/{beta} and {gamma}-antagonist as strong as P gene products. We further investigated the mechanisms of MV-N inhibition, and revealed that MV-N blocks the nuclear import of activated STAT without preventing STAT and Jak activation or STAT degradation, and that the nuclear translocation of MV-N is important for the inhibition. The inhibitory effect of the N protein was observed as a common feature of other morbilliviruses. The results presented in this report suggest that N protein of MV as well as P/V/C proteins is involved in the inhibition of host IFN signaling pathways.

  20. Role of interferon in lymphocyte recruitment into the skin

    International Nuclear Information System (INIS)

    Issekutz, T.B.; Stoltz, J.M.; Webster, D.M.

    1986-01-01

    Large numbers of lymphocytes are recruited from the blood into sites of cutaneous DTH reactions. Our goal was to investigate the factors controlling this recruitment. 111 In-labeled peritoneal exudate lymphocytes were injected iv and the accumulation of these cells in skin sites injected with a variety of stimuli, was used to measure lymphocyte recruitment in rats. Large numbers of lymphocytes migrated into vaccinia- and KLH-injected sites in sensitized animals, but only into the viral and not the KLH lesions in non-immune animals. Lymphocytes also migrated efficiently into sites injected with the alpha-interferon (IFN) inducers, uv-inactivated vaccinia virus and poly I:C, as well as into sites injected with IFN. In each case there was a dose-response relationship. Analysis of the kinetics of lymphocyte recruitment demonstrated that the peak rate of migration occurred most rapidly after the injection of IFN, later after poly I:C, and was slowest to be reached after vaccinia virus. Rabbit anti-IFN blocked the recruitment of lymphocytes by uv-inactivated vaccinia and by IFN. Histologically, all of these sites demonstrated a dense mononuclear cell infiltrate in the dermis. It is suggested that IFN may be an important mediator in the recruitment of lymphocytes into inflammatory reactions

  1. Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.

    Science.gov (United States)

    Kuo, Ping-Chang; Scofield, Barbara A; Yu, I-Chen; Chang, Fen-Lei; Ganea, Doina; Yen, Jui-Hung

    2016-01-08

    Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  2. Contact inhibition and interferon (IFN)-modulated gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kulesh, D.A.

    1986-01-01

    The relationship between cell morphology, proliferation and contact inhibition was studied in normal and malignant human cells which varied in their sensitivity to contact inhibition. Their ability to proliferate was examined under conditions where the cells were constrained into different shapes. Cell proliferation was quantitated by labeling indices, which were inferred by autoradiography, and by total cell counts. The normal cells (JHU-1, IMR-90) were dependent on cell shape for proliferation capability while the transformed cells (RT4, HT1080) were shape-dependent for proliferation. Interferon (IFN) induced shape-dependent proliferation and contact inhibition in the transformed cells when used at subantiproliferative concentrations. This ability of B-IFN to confer a level of proliferation control which is characteristic of normal fibroblasts suggests a possible relationship between gene expression mediated by IFN and those genes involved in the maintenance of regulated cell proliferation. To evaluate this possibility, cDNA libraries were constructed from IFN-treated and untreated HT1080 cells. The resulting 10 IFN-induced and 11 IFN-repressed sequences were then differentially rescreened using /sup 32/P-cDNA probes. This screening resulted in the identification of at least four cDNA sequences which appeared to be proliferation regulated as well as IFN-modulated. These cloned, regulated cDNA sequences were then used as /sup 32/P-labeled probes to study both the gene expression at the mRNA level employing Northern blotting and slot blotting techniques.

  3. The Peculiar Characteristics of Fish Type I Interferons

    Directory of Open Access Journals (Sweden)

    Pierre Boudinot

    2016-11-01

    Full Text Available Antiviral type I interferons (IFNs have been discovered in fish. Genomic studies revealed their considerable number in many species; some genes encode secreted and non-secreted isoforms. Based on cysteine motifs, fish type I IFNs fall in two subgroups, which use two different receptors. Mammalian type I IFN genes are intronless while type III have introns; in fish, all have introns, but structurally, both subgroups belong to type I. Type I IFNs likely appeared early in vertebrates as intron containing genes, and evolved in parallel in tetrapods and fishes. The diversity of their repertoires in fish and mammals is likely a convergent feature, selected as a response to the variety of viral strategies. Several alternative nomenclatures have been established for different taxonomic fish groups, calling for a unified system. The specific functions of each type I gene remains poorly understood, as well as their interactions in antiviral responses. However, distinct induction pathways, kinetics of response, and tissue specificity indicate that fish type I likely are highly specialized, especially in groups where they are numerous such as salmonids or cyprinids. Unravelling their functional integration constitutes the next challenge to understand how these cytokines evolved to orchestrate antiviral innate immunity in vertebrates.

  4. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

    Science.gov (United States)

    Kaufmann, Nathalie; Zeka, Bleranda; Schanda, Kathrin; Fujihara, Kazuo; Illes, Zsolt; Dahle, Charlotte; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID:26990978

  5. The type I interferon response during viral infections: a "SWOT" analysis.

    Science.gov (United States)

    Gaajetaan, Giel R; Bruggeman, Cathrien A; Stassen, Frank R

    2012-03-01

    The type I interferon (IFN) response is a strong and crucial moderator for the control of viral infections. The strength of this system is illustrated by the fact that, despite some temporary discomfort like a common cold or diarrhea, most viral infections will not cause major harm to the healthy immunocompetent host. To achieve this, the immune system is equipped with a wide array of pattern recognition receptors and the subsequent coordinated type I IFN response orchestrated by plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). The production of type I IFN subtypes by dendritic cells (DCs), but also other cells is crucial for the execution of many antiviral processes. Despite this coordinated response, morbidity and mortality are still common in viral disease due to the ability of viruses to exploit the weaknesses of the immune system. Viruses successfully evade immunity and infection can result in aberrant immune responses. However, these weaknesses also open opportunities for improvement via clinical interventions as can be seen in current vaccination and antiviral treatment programs. The application of IFNs, Toll-like receptor ligands, DCs, and antiviral proteins is now being investigated to further limit viral infections. Unfortunately, a common threat during stimulation of immunity is the possible initiation or aggravation of autoimmunity. Also the translation from animal models to the human situation remains difficult. With a Strengths-Weaknesses-Opportunities-Threats ("SWOT") analysis, we discuss the interaction between host and virus as well as (future) therapeutic options, related to the type I IFN system. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Evaluation of Interferon-gamma Application for Recognition of Patients Afflicted by Non-healing Cutaneous Leishmaniasis

    OpenAIRE

    Mohammad Moafi; Hossein Rezvan; Roya Sherkat; Sayyed Hamid Zarkesh-Esfahani; Roya Taleban; Ali Asilian; Mohammad Ali Nilforoushzadeh; Fariba Jaffary; Marjan Mansourian; Fatemeh Sokhanvari; Nazli Ansari

    2017-01-01

    Introduction:Different studies undertaken in the animal modeling show that Interferon-gamma deficiency impairs healing process of Leishmania infection. It seems that the level of Interferon-gamma production could also affect the healing duration of Leishmania lesion in humans. The current study aims to investigate the possibility of Interferon-gamma application for recognition of cases afflicted by non-healing Leishmaniasis. Materials and methods: Peripheral blood mononuclear cells (PBMCs) of...

  7. Stimulation of Inducible Nitric Oxide Synthase Expression by Beta Interferon Increases Necrotic Death of Macrophages upon Listeria monocytogenes Infection▿

    OpenAIRE

    Zwaferink, Heather; Stockinger, Silvia; Reipert, Siegfried; Decker, Thomas

    2008-01-01

    Murine macrophage death upon infection with Listeria monocytogenes was previously shown to be increased by beta interferon, produced by the infected cells. We saw that interferon-upregulated caspase activation or other interferon-inducible, death-associated proteins, including TRAIL, protein kinase R, and p53, were not necessary for cell death. Macrophage death was reduced when inducible nitric oxide synthase (iNOS) was inhibited during infection, and iNOS-deficient macrophages were less susc...

  8. Opening keynote

    International Nuclear Information System (INIS)

    Rae, B.

    1997-01-01

    In his opening address, the former premier of Ontario summarized the background of the Macdonald Committee which was appointed by his government after it became increasingly apparent that the infrastructure of Hydro Ontario was far bigger than the province and the economy could afford, and that the service that had once given Ontario tremendous competitive advantage, in the form of relatively cheap electric power, had become unsustainable in an era of economic downturn and zero inflation. He stated that the debate about Hydro is part of a broader issue, and it is no longer possible to manage our electricity system as if we were a self-enclosed universe. He predicted that the North American electricity grid will become increasingly interdependent, and that Hydro will have to develop competitive price structures, both to hold its domestic market share and to compete for export sales. He outlined the most pressing issues for Hydro as being debt reduction, while pursuing internal changes to make the organization more efficient. Organizational changes such as the creation of Ontario Hydro International, Ontario Hydro Research, separation of generation operations from the grid, and establishment of separate price and efficiency targets for the autonomous organizations within the utility family, were moves in the right direction. Equally important is to make sure that however Hydro might develop in the future, it is going to be fair to customers, and that the billions of dollars invested in Hydro by Ontario taxpayers over the years, are safeguarded

  9. Openness initiative

    International Nuclear Information System (INIS)

    Duncan, S.S.

    1995-01-01

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: open-quotes Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?close quotes To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts

  10. Openness initiative

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, S.S. [Los Alamos National Lab., NM (United States)

    1995-12-31

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: {open_quotes}Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?{close_quotes} To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts.

  11. Twelve-week, prospective, open-label, randomized trial on the effects of an anticholinergic agent or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms

    Directory of Open Access Journals (Sweden)

    Shin YS

    2014-07-01

    Full Text Available Yu Seob Shin,1 Li Tao Zhang,1 Chen Zhao,2 Young Gon Kim,1 Jong Kwan Park1 1Department of Urology, Chonbuk National University Medical School, and Institute for Medical Sciences, Chonbuk National University and Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, South Korea; 2Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai Institute of Andrology, Shanghai, People’s Republic of China Purpose: The effects of an anticholinergic or antidiuretic agent as add-on therapy to an ­alpha-blocker for lower urinary tract symptoms (LUTS according to a voiding diary in 3 days are unknown. We prospectively investigated the efficacy of an anticholinergic or antidiuretic agent as add-on therapy for nocturia in men previously treated with an alpha-blocker for LUTS.Subjects and methods: Patients were randomly subdivided into two groups. All patients had a 4-week washout. Group A had alpha-blocker for 4 weeks, then an alpha-blocker plus an anticholinergic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an antidiuretic agent. Group B had an alpha-blocker for 4 weeks, then an alpha-blocker plus an antidiuretic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an anticholinergic agent. In both groups, patients were subdivided into nocturnal polyuria, decreased nocturnal bladder capacity (NBC, or nocturia by both causes subgroups. A 3-day voiding diary, total International Prostate Symptom Score (IPSS, IPSS sub-scores, Overactive Bladder Symptom Score, uroflowmetry, and post-void residual urine volume, were assessed at baseline, and at 4, 8, and 12 weeks.Results: A total of 405 patients completed the study. During treatment, the changes from baseline in total IPSS and IPSS sub-scores were significantly decreased at 4 weeks and were maintained for 12 weeks. In the nocturnal polyuria subgroup of Groups A and B

  12. Opening Address

    Science.gov (United States)

    Crovini, L.

    1994-01-01

    Ladies and Gentlemen To quote Mr Jean Terrien: "Physics must be one step ahead of metrology". A long-serving Director of the BIPM, he said these words when visiting the IMGC in 1970 as a member of the scientific board of our Institute. At that time it was still an open question whether the IMGC should start research work on the absolute measurement of silicon lattice spacing. Mr Terrien underlined the revolutionary character of x-ray interferometry and, eventually, he caused the balance needle to lean towards the ... right direction. Mr Terrien correctly foresaw that, like Michelson's interferometer of 1880, x-ray interferometry could have a prominent place in today's science and technology. And while, in the first case, after more than a century we can see instruments based on electromagnetic wave interaction within every one's reach in laboratories and, sometimes, in workshops, in the second case, twenty-five years since the first development of an x-ray interferometer we can witness its role in nanometrology. Today and tomorrow we meet to discuss how to go beyond the sixth decimal place in the value of the Avogadro constant. We are aware that the quest for this achievement requires the cooperation of scientists with complementary capabilities. I am sure that the present workshop is a very good opportunity to present and discuss results and to improve and extend existing cooperation. The new adjustment of fundamental constants envisaged by the CODATA Task Group is redoubling scientists' efforts to produce competitive values of NA. The results of the measurements of the silicon lattice spacing in terms of an optical wavelength, which were available for the 1986 adjustment, combined with the determination of silicon molar volume, demonstrate how such an NA determination produces a consistent set of other constants and opens the way to a possible redefinition of the kilogram. We shall see in these two days how far we have progressed along this road. For us at the

  13. Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas

    Science.gov (United States)

    Holder, Tom; Clifford, Derek; Dexter, Ian; Brewer, Jacky; Smith, Noel; Waring, Laura; Crawshaw, Tim; Gillgan, Steve; Lyashchenko, Konstantin; Lawrence, John; Clarke, John; de la Rua-Domenech, Ricardo; Vordermeier, Martin

    2012-01-01

    We describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-γ) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas from Mycobacterium bovis culture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-γ and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-γ test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-γ test was at least in part due to undisclosed Mycobacterium microti infection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-γ positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-γ test with two antibody tests in a “test package,” although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations. PMID:22914362

  14. Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

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    Washington B. Cárdenas

    2010-01-01

    Full Text Available The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV and Ebola virus (EBOV, comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV, the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.

  15. Effects of interferon on cultured cells persistently infected with viruses

    Energy Technology Data Exchange (ETDEWEB)

    Crespi, M

    1986-01-01

    The role of interferon (IFN) in viral persistence at the cellular level was investigated. Two types of persistent infections were chosen. The first type was cell lines which contained hepatitis B virus (HBV) DNA (PLC/PRF/5 and Hep 3B cells) uninfected control hepatoma cells, (Mahlavu, HA22T and Hep G2 cells) or simian virus 40 (SV40) DNA (C2, C6, C11 cells) and control uninfected (CV-1 cells). In the second type of infection Vero cells persistently infected with SSPE or Sendai virus were used. The aim of this work was to determine what effect IFN had in these infections in terms of its antiviral and antiproliferative effects; which of the two major IFN-induced pathways, E enzyme or protein kinase were induced; whether there were any differences in sensitivity to IFN between the DNA and RNA virus persistent infections. The anti-viral effect of IFN was examined by its ability to inhibit Sindbis virus replication using a radioimmunoassay system. The antiproliferative effect of IFN was determined by cell counting and /sup 3/H-thymidine incorporation. The activation of the ribonuclease F, determined by the inhibition of /sup 3/H-leucine incorporation after introduction of 2-5 actin into the cells, was variable, being activated in all cell lines with the exception of the PLC/PRF/5, Hep 3B and Hep G2 cells. Major differences between the two DNA persistent infections and the two RNA persistent infections were found. No correlation was found between the presence of HBV or SV40 persistent infections and the sensitivity of the cell lines to IFN. Both the SSPE and Sendai virus persistent infections were resistant to the antiviral and antiproliferative effect of IFN.

  16. Type I interferons instigate fetal demise after Zika virus infection.

    Science.gov (United States)

    Yockey, Laura J; Jurado, Kellie A; Arora, Nitin; Millet, Alon; Rakib, Tasfia; Milano, Kristin M; Hastings, Andrew K; Fikrig, Erol; Kong, Yong; Horvath, Tamas L; Weatherbee, Scott; Kliman, Harvey J; Coyne, Carolyn B; Iwasaki, Akiko

    2018-01-05

    Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-deficient mice are highly susceptible to ZIKV infection. Severe fetal growth restriction with placental damage and fetal resorption is observed after ZIKV infection of type I IFN receptor knockout ( Ifnar1 -/- ) dams mated with wild-type sires, resulting in fetuses with functional type I IFN signaling. The role of type I IFNs in limiting or mediating ZIKV disease within this congenital infection model remains unknown. In this study, we challenged Ifnar1 -/- dams mated with Ifnar1 +/- sires with ZIKV. This breeding scheme enabled us to examine pregnant dams that carry a mixture of fetuses that express ( Ifnar1 +/- ) or do not express IFNAR ( Ifnar1 -/- ) within the same uterus. Virus replicated to a higher titer in the placenta of Ifnar1 -/- than within the Ifnar1 +/- concepti. Yet, rather unexpectedly, we found that only Ifnar1 +/- fetuses were resorbed after ZIKV infection during early pregnancy, whereas their Ifnar1 -/- littermates continue to develop. Analyses of the fetus and placenta revealed that, after ZIKV infection, IFNAR signaling in the conceptus inhibits development of the placental labyrinth, resulting in abnormal architecture of the maternal-fetal barrier. Exposure of midgestation human chorionic villous explants to type I IFN, but not type III IFNs, altered placental morphology and induced cytoskeletal rearrangements within the villous core. Our results implicate type I IFNs as a possible mediator of pregnancy complications, including spontaneous abortions and growth restriction, in the context of congenital viral infections. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. Structure of the Ebola VP35 interferon inhibitory domain.

    Science.gov (United States)

    Leung, Daisy W; Ginder, Nathaniel D; Fulton, D Bruce; Nix, Jay; Basler, Christopher F; Honzatko, Richard B; Amarasinghe, Gaya K

    2009-01-13

    Ebola viruses (EBOVs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. The Ebola VP35 protein is multifunctional, acting as a component of the viral RNA polymerase complex, a viral assembly factor, and an inhibitor of host interferon (IFN) production. Mutation of select basic residues within the C-terminal half of VP35 abrogates its dsRNA-binding activity, impairs VP35-mediated IFN antagonism, and attenuates EBOV growth in vitro and in vivo. Because VP35 contributes to viral escape from host innate immunity and is required for EBOV virulence, understanding the structural basis for VP35 dsRNA binding, which correlates with suppression of IFN activity, is of high importance. Here, we report the structure of the C-terminal VP35 IFN inhibitory domain (IID) solved to a resolution of 1.4 A and show that VP35 IID forms a unique fold. In the structure, we identify 2 basic residue clusters, one of which is important for dsRNA binding. The dsRNA binding cluster is centered on Arg-312, a highly conserved residue required for IFN inhibition. Mutation of residues within this cluster significantly changes the surface electrostatic potential and diminishes dsRNA binding activity. The high-resolution structure and the identification of the conserved dsRNA binding residue cluster provide opportunities for antiviral therapeutic design. Our results suggest a structure-based model for dsRNA-mediated innate immune antagonism by Ebola VP35 and other similarly constructed viral antagonists.

  18. Can pegylated interferon improve the outcome of polycythemia vera patients?

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    Elena Crisà

    2017-01-01

    Full Text Available Abstract Pegylated interferon (peg-IFN was proven by phase II trials to be effective in polycythemia vera (PV; however, it is not clear whether it could improve patient outcome compared to hydroxyurea (HU. Here, we present an observational study on 65 PV patients aged 65 years or younger, who received either peg-IFN (30 or HU (35 according to the physician choice. Median follow-up was 75 months. The two cohorts were comparable for patient and disease characteristics. Eighty-seven percent of the patients treated with peg-INF responded, with a CR rate of 70% as compared to 100 and 49% with HU, respectively. Discontinuation rate was similar in the two groups (20% in peg-IFN vs 17% in HU. JAK2 allele burden was monitored in peg-INF arm only, and a reduction was observed in 88% of the patients. No thrombotic events were observed during peg-IFN treatment compared to three on HU. Disease progression to myelofibrosis or acute myeloid leukemia occurred to a patient only in peg-INF, compared to three in HU. Overall, three second malignancies were observed during the study, two in patients who received HU only, and one in a patient largely treated HU who received also peg-IFN for 3 months. Overall survival was significantly better for peg-IFN patients compared to HU, p = 0.027. Our study, albeit limited by small patient and event number and lack of randomization, confirms the efficacy of peg-INF in PV and shows a significant survival advantage for peg-INF-treated patients. Waiting for confirming data from the ongoing phase III trials, our study can support peg-INF as a first-line treatment option for PV, at least for younger patients.

  19. Inflammation activates the interferon signaling pathways in taste bud cells.

    Science.gov (United States)

    Wang, Hong; Zhou, Minliang; Brand, Joseph; Huang, Liquan

    2007-10-03

    Patients with viral and bacterial infections or other inflammatory illnesses often experience taste dysfunctions. The agents responsible for these taste disorders are thought to be related to infection-induced inflammation, but the mechanisms are not known. As a first step in characterizing the possible role of inflammation in taste disorders, we report here evidence for the presence of interferon (IFN)-mediated signaling pathways in taste bud cells. IFN receptors, particularly the IFN-gamma receptor IFNGR1, are coexpressed with the taste cell-type markers neuronal cell adhesion molecule and alpha-gustducin, suggesting that both the taste receptor cells and synapse-forming cells in the taste bud can be stimulated by IFN. Incubation of taste bud-containing lingual epithelia with recombinant IFN-alpha and IFN-gamma triggered the IFN-mediated signaling cascades, resulting in the phosphorylation of the downstream STAT1 (signal transducer and activator of transcription protein 1) transcription factor. Intraperitoneal injection of lipopolysaccharide or polyinosinic:polycytidylic acid into mice, mimicking bacterial and viral infections, respectively, altered gene expression patterns in taste bud cells. Furthermore, the systemic administration of either IFN-alpha or IFN-gamma significantly increased the number of taste bud cells undergoing programmed cell death. These findings suggest that bacterial and viral infection-induced IFNs can act directly on taste bud cells, affecting their cellular function in taste transduction, and that IFN-induced apoptosis in taste buds may cause abnormal cell turnover and skew the representation of different taste bud cell types, leading to the development of taste disorders. To our knowledge, this is the first study providing direct evidence that inflammation can affect taste buds through cytokine signaling pathways.

  20. Interferon-γ-induced protein 10 in Lyme disease.

    Science.gov (United States)

    Fallahi, P; Elia, G; Bonatti, A

    2017-01-01

    Lyme disease is an infectious disease caused by bacteria of the Borrelia type, that affects about 300,000 people a year in the USA and 65,000 people a year in Europe. Borrelia infection, and Lyme disease, following occupational exposure has been frequently reported in USA, Europe and Asia. The manifestations of Lyme disease include erythema migrans (EM), arthritis, neuroborrelliosis (NB), and others. Cytokines and chemokines primarily orchestrate leukocyte recruitment to the areas of Borrelia infection, and they are critical mediators of immune and inflammatory responses, in particular of the induction of interferon (IFN)-γ and IFN-γ dependent chemokines. In EM high levels of T helper (Th) 1 cells chemoattranctants [monokine induced by IFN-γ (MIG), IFN-γ-induced protein 10 (IP- 10), and IFN-inducible T cell alpha chemoattractant (I-TAC)] have been shown. Synovial tissues and fluids of patients with Lyme Arthritis (LA) (overall with antibiotic-refractory LA) contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly MIG and IFN-γ. In NB concentrations of IP-10 and I-TAC in the cerebrospinal fluid (CSF) were significantly higher, suggesting that IP-10 and I-TAC create a chemokine gradient between the CSF and serum and recruite C-X-C chemokine receptor 3-expressing memory CD4+ T-cells into the CSF of these patients. A positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction has also been shown. These results suggest that IFN-γ dependent chemokines are important biomarkers to monitor the progression and diffusion of the disease in patients with Borrelia infection; further larger studies are needed.

  1. Interferon alpha induced cytogenetic remissions of chronic myelocytic leukemia

    International Nuclear Information System (INIS)

    Oguma, Nobuo; Shigeta, Chiharu; Tanaka, Kimio; Kamada, Nanao; Kuramoto, Atsushi; Ito, Chikako.

    1994-01-01

    In two heavily exposed A-bomb survivors, Philadelphia (Ph 1 ) chromosomes completed disappeared by the treatment with interferon (IFN)-α for chronic myelocytic leukemia (CML). One is a 55-year-old man exposed at 2.0 km in Hiroshima at the age of 13. Periodic mass screening in 1987 showed the presence of Ph 1 chromosomes, in addition to an increased number of leukocytes and the presence of neocytes. Subcutaneous injection of IFN-α (6,000,000 units/day) was started with a diagnosis of CML, and 5 months later Ph 1 chromosomes disappeared. Then, because Ph 1 chromosomes were found in 2.8% of 143 cells one year and 6 months after the termination of IFN-α, re-injection of IFN-α was started. The other patient is a 53-year-old woman exposed at 2.0 km in Hiroshima at the age of 6. She was pointed out to have leukocytosis in 1992; bone marrow examination showed the presence of Ph 1 chromosomes in 88.1% of 88 cells analyzed, leading to a diagnosis of CML. Subcutaneous injection of IFN-α (6,000,000 units/day) was started and 5 months later Ph 1 chromosomes disappeared. As of 11 months after the start of injection, no Ph 1 chromosomes were observed, but the patient is still treated with IFN-α injection. Effects of IFN-α and problems of residual Ph 1 chromosomes are discussed in a review of the literature. (N.K.)

  2. Immunomodulatory intervention with Gamma interferon in mice with sepsis.

    Science.gov (United States)

    Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong

    2017-09-15

    Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Pyrogenicity of interferon and its inducer in rabbits.

    Science.gov (United States)

    Won, S J; Lin, M T

    1988-03-01

    The effects of intracerebral administration of interferon (IFN) or its inducer polyriboinosinic acid-polyribocytidylic acid (poly I:C) on thermoregulatory responses were assessed in conscious rabbits. Administration of IFN (10(2)-10(6) IU) or poly I:C (0.012-12 micrograms) into the preoptic anterior hypothalamus or the third cerebral ventricle caused a dose-dependent fever in rabbits at three ambient temperatures (Ta) tested. In the cold (Ta = 8 degrees C), the fever was due to increased metabolism, whereas in the heat (Ta = 32 degrees C) the fever was due to a reduction in respiratory evaporative heat loss and ear skin blood flow. At the moderate environmental temperature (Ta = 22 degrees C), the fever was due to increased metabolism and cutaneous vasoconstriction. Compared with the febrile responses induced by cerebroventricular route injection of IFN or poly I:C, the hypothalamic route of injection required a much lower dose of IFN or poly I:C to produce a similar fever. Furthermore, the fever induced by intrahypothalamic injection of IFN or poly I:C was reduced by pretreatment of animals with a systemic dose of indomethacin (an inhibitor of all prostaglandins formation) or cycloheximide (an inhibitor of protein synthesis). The data indicate that IFN or its inducer may act through the endogenous release of a prostaglandin or a protein factor of an unknown chemical nature in the preoptic anterior hypothalamic region to induce fever in rabbits. The fever induced by IFN or its inducer is brought about by a decrease in heat loss and/or an increase in heat production in rabbits.

  4. Retinopatia em paciente portador de hepatite C tratado com interferon peguilado e ribavirina: relato de caso Retinopathy in a patient with hepatitis C treated with pegylated interferon and ribavirin: case report

    Directory of Open Access Journals (Sweden)

    Marcos Pereira de Ávila

    2006-04-01

    Full Text Available O interferon é uma citocina imunomoduladora utilizada no tratamento de diversas doenças, incluindo infecções crônicas pelo vírus da hepatite C. O interferon peguilado é uma nova forma de interferon, desenvolvida para aumentar o tempo de meia-vida da droga. Uma série de efeitos adversos têm sido associados ao uso do interferon, dentre eles a toxicidade ocular com desenvolvimento de retinopatia. As lesões oculares típicas incluem exsudatos algodonosos e hemorragias retinianas no pólo posterior, particularmente em torno do disco óptico. Descrevemos o caso de paciente tratado com associação de interferon peguilado e ribavirina com diminuição da acuidade visual e quadro oftalmológico compatível com retinopatia associada ao interferon. Quatro semanas após a suspensão do interferon, houve melhora da acuidade visual e diminuição importante das alterações retinianas.Interferon is an immunomodulating cytokine used to treat patients with different diseases, such as hepatitis C chronic infection. Pegylated interferon is a new type of interferon, developed to increase the half-life of the drug. Many side effects have been related to its use, including ocular toxicity and retinopathy. The most reported ocular findings are cotton-wool spots and hemorrhages located at the posterior pole and surrounding optic nerve head. We describe one case of pegylated interferon-associated retinopathy with visual loss. The patient had visual acuity improvement four weeks after discontinuation of the medication and the ocular findings became much more subtle.

  5. Open life science research, open software and the open century

    Directory of Open Access Journals (Sweden)

    Youhua Chen

    2015-05-01

    Full Text Available At the age of knowledge explosion and mass scientific information, I highlighted the importance of conducting open science in life and medical researches through the extensive usage of open software and documents. The proposal of conducting open science is to reduce the limited repeatability of researches in life science. I outlined the essential steps for conducting open life science and the necessary standards for creating, reusing and reproducing open materials. Different Creative Commons licenses were presented and compared of their usage scope and restriction. As a conclusion, I argued that open materials should be widely adopted in doing life and medical researches.

  6. Onset of Celiac Disease after Treatment of Chronic Hepatitis C with Interferon Based Triple Therapy

    Directory of Open Access Journals (Sweden)

    Amandeep Singh

    2015-01-01

    Full Text Available Background. Patients treated with interferon (IFN based therapies may develop exacerbation of autoimmune disease. We herein present the case of a 53-year-old female patient who developed celiac disease (CD as a result of triple therapy (interferon, ribavirin, and boceprevir for chronic HCV. Case. 53-year-old Caucasian female with past medical history of IV drug abuse was referred for abnormal LFTs. Laboratory data showed HCV RNA of 4,515,392 IU/mL, HCV genotype 1a, with normal LFTs. She was treated with 4 weeks of pegylated interferon alfa-2a plus ribavirin, followed by triple therapy using boceprevir for a total of 28 weeks. Approximately 4 weeks after initiation of triple therapy patient developed loose nonbloody bowel movements and was also found to have anemia. Biopsies from first and second portions of the duodenum were consistent with CD. The patient was treated with a gluten-free diet. Her intestinal symptoms improved and the hemoglobin returned to normal. Conclusion. Chronic HCV patients being treated with interferon alfa can develop celiac disease during or after therapy. For patients with positive autoantibodies, all-oral-IFN-free regimens should be considered. Celiac disease should be considered in patients who develop CD-like symptoms while on and shortly after cessation of interferon alfa therapy.

  7. Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Mahe J

    2013-08-01

    Full Text Available Julien Mahe,1 Aurélie Meurette,2 Anne Moreau,3 Caroline Vercel,2 Pascale Jolliet1,4 1Clinical Pharmacology Department, Institute of Biology, University Hospital, Nantes, France; 2Clinical Nephrology and Immunology Department, University Hospital, Nantes, France; 3Laboratory of Pathology, University Hospital, Nantes, France; 4EA 4275 Biostatistics, Pharmacoepidemiology and Subjective Measures in Health Sciences, University of Nantes, Nantes, France Abstract: Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. Keywords: thrombotic microangiopathy, interferon beta, hemolytic-uremic syndrome, antiangiogenic activity

  8. [Alpha interferon induced hyperthyroidism: a case report and review of the literature].

    Science.gov (United States)

    Maiga, I; Valdes-Socin, H; Thiry, A; Delwaide, J; Sidibe, A T; Beckers, A

    2015-01-01

    Treatment with alpha interferon in hepatitis C triggers a thyroid autoimmunity in a variable percentage of cases (2-8%). This complication raises some questions about its screening, the possibility to continue anti-viral therapy and thyroid treatment. Alpha interferon has an immunomodulatory effect on the thyroid, but also an inhibitory effect on thyroid hormone synthesis. This explains the occurrence of cases of thyroid dysfunction, which often remain undetected because of their latency. Factors predicting thyroid dysfunction with interferon use are: female sex, history of thyroid disease and previous autoimmunity. Several clinical aspects are encountered including hypothyroidism (the most frequent depending on the series) and hyperthyroidism related to Graves' disease. For their detection, a cooperation between general practionners, gastroenterologists and endocrinologists is mandatory thyroid function tests are requested before, during and after treatment,with alpha interferon. Therapeutic aspects of thyroid disorders range from simple monitoring to symptomatic treatment, such as thyroxine prescription in the presence of hypothyroidism. Antithyroid drugs radioactive iodine or thyroid surgery are used in cases of severe or persistent Graves' disease induced by alpha interferon.

  9. Pulmonary abnormalities caused by interferon with or without herbal drug. CT and radiographic findings

    International Nuclear Information System (INIS)

    Ikezoe, Junpei; Kohno, Nobuaki; Johkoh, Takeshi; Kozuka, Takahiro; Kawase, Ichiro; Ebara, Hidemi; Kamisako, Toshinori; Adachi, Yukihiko.

    1995-01-01

    Chest radiographic and CT findings of acute diffuse interstitial lung disease due to interferon administration were reviewed. The subjects were 5 patients who were treated with interferon alone (n=4) or combined with traditional herbal drug treatment (n=one) for chronic hepatitis C. Respiratory symptoms consisted of cough (n=4), fever (n=4), dyspnea (n=3), and chest pain (n=one). CT findings were peripherally predominant non-segmental consolidation (n=3) with or without ground-glass opacities, and intralobular reticulation with ground-glass opacities (n=2). Neither honeycombing nor lung distortion was observed on CT. Chest radiographs showed airspace consolidation with or without ground-glass opacities (n=4) and reticulonodular lesions with ground-glass opacities (n=one). Although radiological findings of interferon-induced lung abnormalities were not uniform, it appears that these findings reflect lung hypersensitivity to interferon. Recognizing radiographic and CT findings of interferon-induced lung abnormalities is required because they are likely to occur associated with increasing use of this drug in the clinical setting. (N.K.)

  10. Pulmonary abnormalities caused by interferon with or without herbal drug. CT and radiographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Ikezoe, Junpei; Kohno, Nobuaki; Johkoh, Takeshi; Kozuka, Takahiro; Kawase, Ichiro [Osaka Univ. (Japan). Faculty of Medicine; Ebara, Hidemi; Kamisako, Toshinori; Adachi, Yukihiko

    1995-02-01

    Chest radiographic and CT findings of acute diffuse interstitial lung disease due to interferon administration were reviewed. The subjects were 5 patients who were treated with interferon alone (n=4) or combined with traditional herbal drug treatment (n=one) for chronic hepatitis C. Respiratory symptoms consisted of cough (n=4), fever (n=4), dyspnea (n=3), and chest pain (n=one). CT findings were peripherally predominant non-segmental consolidation (n=3) with or without ground-glass opacities, and intralobular reticulation with ground-glass opacities (n=2). Neither honeycombing nor lung distortion was observed on CT. Chest radiographs showed airspace consolidation with or without ground-glass opacities (n=4) and reticulonodular lesions with ground-glass opacities (n=one). Although radiological findings of interferon-induced lung abnormalities were not uniform, it appears that these findings reflect lung hypersensitivity to interferon. Recognizing radiographic and CT findings of interferon-induced lung abnormalities is required because they are likely to occur associated with increasing use of this drug in the clinical setting. (N.K.).

  11. Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis.

    Science.gov (United States)

    Qi, Guoyan; Liu, Peng; Gu, Shanshan; Yang, Hongxia; Dong, Huimin; Xue, Yinping

    2018-04-01

    Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.

  12. Clinical Value of Thyrotropin Receptor Antibodies for the Differential Diagnosis of Interferon Induced Thyroiditis.

    Science.gov (United States)

    Benaiges, D; Garcia-Retortillo, M; Mas, A; Cañete, N; Broquetas, T; Puigvehi, M; Chillarón, J J; Flores-Le Roux, J A; Sagarra, E; Cabrero, B; Zaffalon, D; Solà, R; Pedro-Botet, J; Carrión, J A

    2016-01-01

    The clinical value of thyrotropin receptor antibodies for the differential diagnosis of thyrotoxicosis induced by pegylated interferon-alpha remains unknown. We analyzed the diagnostic accuracy of thyrotropin receptor antibodies in the differential diagnosis of thyrotoxicosis in patients with chronic hepatitis C (CHC) receiving pegylated interferon-alpha plus ribavirin. Retrospective analysis of 274 patients with CHC receiving pegylated interferon-alpha plus ribavirin. Interferon-induced thyrotoxicosis was classified according to clinical guidelines as Graves disease, autoimmune and non- autoimmune destructive thyroiditis. 48 (17.5%) patients developed hypothyroidism, 17 (6.2%) thyrotoxicosis (6 non- autoimmune destructive thyroiditis, 8 autoimmune destructive thyroiditis and 3 Graves disease) and 22 "de novo" thyrotropin receptor antibodies (all Graves disease, 2 of the 8 autoimmune destructive thyroiditis and 17 with normal thyroid function). The sensitivity and specificity of thyrotropin receptor antibodies for Graves disease diagnosis in patients with thyrotoxicosis were 100 and 85%, respectively. Patients with destructive thyroiditis developed hypothyroidism in 87.5% of autoimmune cases and in none of those with a non- autoimmune etiology (pthyroid scintigraphy for the differential diagnosis of thyrotoxicosis in CHC patients treated with pegylated interferon. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response-a prospective open-label study.

    Science.gov (United States)

    Hashimoto, Naoki; Toyomaki, Atsuhito; Honda, Minoru; Miyano, Satoru; Nitta, Nobuyuki; Sawayama, Hiroyuki; Sugawara, Yasufumi; Uemura, Keiichi; Tsukamoto, Noriko; Koyama, Tsukasa; Kusumi, Ichiro

    2015-01-01

    two additional subjects dropped out because of somnolence. In this open-label, single-arm study of 29 patients, quetiapine improved both the clinical symptoms and the neurocognitive impairment in chronic schizophrenia patients who failed to respond to prior antipsychotic treatment.

  14. Uranium project. Geochemistry prospection

    International Nuclear Information System (INIS)

    Lambert, J.

    1983-01-01

    Geochemistry studies the distribution of the chemicals elements in the terrestrial crust and its ways to migrate. The terminology used in this report is the following one: 1) Principles of the prospection geochemistry 2) Stages of the prospection geochemistry 3)utility of the prospection geochemistry 4) geochemistry of uranium 5) procedures used within the framework of uranium project 6) Average available 7) Selection of the zones of prospection geochemistry 8) Stages of the prospection, Sample preparation and analisis 9) Presentation of the results

  15. [Interferon α therapy in patients with chronic hepatitis C infection: biopsychosocial consequences].

    Science.gov (United States)

    Baranyi, A; Meinitzer, A; Stepan, A; Matejka, J; Stauber, R; Kapfhammer, H-P; Rothenhäusler, H-B

    2012-09-01

    Interferon α (IFN-alpha) is widely used in the treatment of viral infections, including hepatitis C. Unfortunately depression is a common side effect of IFN-alpha therapy. The presence of depressive symptoms is important because they have an adverse effect on the course of the illness and reduce the quality of life and the treatment adherence. The current prospective study examines the effects of IFN-alpha on the development of depressive disorders, on cognitive functioning and on quality of life. A total of 25 patients with chronic hepatitis C infection were investigated. All patients were treated in the Department of Gastroenterology and Hepatology, University of Medicine of Graz, Austria. Psychometric observer rating and self-rating scales were administered 1 month and 3 months after the beginning of the antiviral treatment to evaluate depressive symptoms [Beck Depression Inventory (BDI); Hamilton Depression Scale]. The data on life satisfaction before therapy and health-related quality of life were obtained from the Fragebogen zur Lebenszufriedenheit (FLZ) and the SF-36 (Health Status Questionnaire). Cognitive function was based on the SKT (Syndrom Kurztest). All patients completed the Social Support Questionnaire (SSS), a multidimensional self-report measure of social support. Three months after the initial IFN-alpha administration in the whole sample significant impairments in health-related quality of life were found in the health-related domains "physical functioning", "role physical", "role emotional", "social functioning" and "vitality". The whole sample showed cognitive impairments. No changes in social support were recorded. Three months after the first INF-alpha administration, 48% (n=12) of the sample suffered from moderate clinical depression. In comparison to patients without pathological affective findings, patients with INF-alpha-induced clinical depression showed decreased life satisfaction before the initial antiviral therapy. Impairments in

  16. Open Standards, Open Source, and Open Innovation: Harnessing the Benefits of Openness

    Science.gov (United States)

    Committee for Economic Development, 2006

    2006-01-01

    Digitization of information and the Internet have profoundly expanded the capacity for openness. This report details the benefits of openness in three areas--open standards, open-source software, and open innovation--and examines the major issues in the debate over whether openness should be encouraged or not. The report explains each of these…

  17. Atomoxetine Open-Label Trial in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available Atomoxetine (originally named tomoxetine, a new therapy for attention deficit hyperactivity disorder (ADHD marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

  18. Improving Open Access through Prior Learning Assessment

    Science.gov (United States)

    Yin, Shuangxu; Kawachi, Paul

    2013-01-01

    This paper explores and presents new data on how to improve open access in distance education through using prior learning assessments. Broadly there are three types of prior learning assessment (PLAR): Type-1 for prospective students to be allowed to register for a course; Type-2 for current students to avoid duplicating work-load to gain…

  19. Experience with predonated autologous blood transfusion in open ...

    African Journals Online (AJOL)

    Objectives: To find out the practicability, the acceptability, the effectiveness and the safety level of pre-donated, autologous blood transfusion (ABT) in patients who underwent open prostatectomy. Study design: Prospective. Patients and methods: It was a prospective study carried out in Nigeria over a 5-year period.

  20. Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin: a review

    Directory of Open Access Journals (Sweden)

    Luis Jesuíno de Oliveira Andrade

    Full Text Available Hepatitis C (HCV is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.

  1. Kinetic and metabolic studies on the priming effect of interferon in L cells

    International Nuclear Information System (INIS)

    Rosztoczy, I.

    1977-01-01

    In cultures primed by interferon pretreatment before stimulation by polyriboinosinic-polyribocytidylic acid interferon was detected one hour earlier, its production followed an enhanced pattern and became resistant to actinomycin D 30 min sooner than in unprimed cultures. The kinetics of development of the primed state was found to be a time- and dose-dependent phenomenon. The continuous presence of interferon during the pretreatment period was not required for the development of the primed state. Actinomycin D at a concentration inhibitory for nuclear RNA synthesis did not influence the development of priming. Higher concentrations of the drug and long term α-amanitin or cycloheximide pretreatments, inhibitory for heterogeneous nuclear RNA synthesis, prevented the establishment of the primed state. (author)

  2. IMMUNOMODULATING THERAPY BY RECOMBINANT ALPHA-2B INTERFERON AMONG CHILDREN WITH TIMOMEGALIA

    Directory of Open Access Journals (Sweden)

    L.A. Nikulin

    2007-01-01

    Full Text Available The study of the enlarged thymus gland syndrome is extremely important for understanding of the immune system formation and functioning mechanisms. the purpose of this study is to conduct clinical and immunological analysis of the children, suffering from the syndrome of the enlarged thymus gland II and III degrees, who received recombinant alpha2b interferon (in suppositories. The revealed changes in the immune sys tem during timomegalia are complex and conducive to the development of the infectious and inflammatory diseases among infants, thus, determining the necessity for the adequate immune correction. The application of the recombinant alpha 2b interferon among such children allows one to uncover the immunomodulating effects, normalizing the imbalances in the immune system of children with timomegalia.Key words: timomegalia, alpha 2b interferon, immunity, immune correction, children.

  3. Loss of prion protein induces a primed state of type I interferon-responsive genes

    DEFF Research Database (Denmark)

    Malachin, Giulia; Reiten, Malin R.; Salvesen, Øyvind

    2017-01-01

    The cellular prion protein (PrPC) has been extensively studied because of its pivotal role in prion diseases; however, its functions remain incompletely understood. A unique line of goats has been identified that carries a nonsense mutation that abolishes synthesis of PrPC. In these animals, the Pr...... genotypes. About 70% of these were classified as interferon-responsive genes. In goats without PrPC, the majority of type I interferon-responsive genes were in a primed, modestly upregulated state, with fold changes ranging from 1.4 to 3.7. Among these were ISG15, DDX58 (RIG-1), MX1, MX2, OAS1, OAS2...... and DRAM1, all of which have important roles in pathogen defense, cell proliferation, apoptosis, immunomodulation and DNA damage response. Our data suggest that PrPC contributes to the fine-tuning of resting state PBMCs expression level of type I interferon-responsive genes. The molecular mechanism...

  4. Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic low back pain with a neuropathic component: a blinded end point analysis of randomly selected routine data from 12-week prospective open-label observations.

    Science.gov (United States)

    Ueberall, Michael A; Mueller-Schwefe, Gerhard H H

    2016-01-01

    To evaluate the benefit-risk profile (BRP) of oxycodone/naloxone (OXN) and tapentadol (TAP) in patients with chronic low back pain (cLBP) with a neuropathic component (NC) in routine clinical practice. This was a blinded end point analysis of randomly selected 12-week routine/open-label data of the German Pain Registry on adult patients with cLBP-NC who initiated an index treatment in compliance with the current German prescribing information between 1st January and 31st October 2015 (OXN/TAP, n=128/133). Primary end point was defined as a composite of three efficacy components (≥30% improvement of pain, pain-related disability, and quality of life each at the end of observation vs baseline) and three tolerability components (normal bowel function, absence of either central nervous system side effects, and treatment-emergent adverse event [TEAE]-related treatment discontinuation during the observation period) adopted to reflect BRP assessments under real-life conditions. Demographic as well as baseline and pretreatment characteristics were comparable for the randomly selected data sets of both index groups without any indicators for critical selection biases. Treatment with OXN resulted formally in a BRP noninferior to that of TAP and showed a significantly higher primary end point response vs TAP (39.8% vs 25.6%, odds ratio: 1.93; P =0.014), due to superior analgesic effects. Between-group differences increased with stricter response definitions for all three efficacy components in favor of OXN: ≥30%/≥50%/≥70% response rates for OXN vs TAP were seen for pain intensity in 85.2%/67.2%/39.1% vs 83.5%/54.1%/15.8% ( P = ns/0.031/<0.001), for pain-related disability in 78.1%/64.8%/43.8% vs 66.9%/50.4%/24.8% ( P =0.043/0.018/0.001), and for quality of life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% ( P =0.026/0.022/0.017). Overall, OXN vs TAP treatments were well tolerated, and proportions of patients who either maintained a normal bowel function (68.0% vs 72

  5. Efficacy and tolerability of fixed-combination bimatoprost/timolol versus fixed-combination dorzolamide/brimonidine/timolol in patients with primary open-angle glaucoma or ocular hypertension: a multicenter, prospective, crossover study.

    Science.gov (United States)

    García-López, Alfonso; Paczka, José A; Jiménez-Román, Jesús; Hartleben, Curt

    2014-12-19

    Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension. In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively. Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P < 0.01) and dorz/brim/tim (P < 0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P < 0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P = 0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3

  6. Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells

    International Nuclear Information System (INIS)

    Lesinski, Gregory B; Zimmerer, Jason M; Kreiner, Melanie; Trefry, John; Bill, Matthew A; Young, Gregory S; Becknell, Brian; Carson, William E III

    2010-01-01

    Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells. Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr 701 -phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR. SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr 701 -phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation. These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ

  7. Modulation of gene expression in a human cell line caused by poliovirus, vaccinia virus and interferon

    Directory of Open Access Journals (Sweden)

    Hoddevik Gunnar

    2007-03-01

    Full Text Available Abstract Background The project was initiated to describe the response of a human embryonic fibroblast cell line to the replication of two different viruses, and, more specifically, to look for candidate genes involved in viral defense. For this purpose, the cells were synchronously infected with poliovirus in the absence or presence of interferon-alpha, or with vaccinia virus, a virus that is not inhibited by interferon. By comparing the changes in transcriptosome due to these different challenges, it should be possible to suggest genes that might be involved in defense. Results The viral titers were sufficient to yield productive infection in a majority of the cells. The cells were harvested in triplicate at various time-points, and the transcriptosome compared with mock infected cells using oligo-based, global 35 k microarrays. While there was very limited similarities in the response to the different viruses, a large proportion of the genes up-regulated by interferon-alpha were also up-regulated by poliovirus. Interferon-alpha inhibited poliovirus replication, but there were no signs of any interferons being induced by poliovirus. The observations suggest that the cells do launch an antiviral response to poliovirus in the absence of interferon. Analyses of the data led to a list of candidate antiviral genes. Functional information was limited, or absent, for most of the candidate genes. Conclusion The data are relevant for our understanding of how the cells respond to poliovirus and vaccinia virus infection. More annotations, and more microarray studies with related viruses, are required in order to narrow the list of putative defence-related genes.

  8. IRF3 and type I interferons fuel a fatal response to myocardial infarction.

    Science.gov (United States)

    King, Kevin R; Aguirre, Aaron D; Ye, Yu-Xiang; Sun, Yuan; Roh, Jason D; Ng, Richard P; Kohler, Rainer H; Arlauckas, Sean P; Iwamoto, Yoshiko; Savol, Andrej; Sadreyev, Ruslan I; Kelly, Mark; Fitzgibbons, Timothy P; Fitzgerald, Katherine A; Mitchison, Timothy; Libby, Peter; Nahrendorf, Matthias; Weissleder, Ralph

    2017-12-01

    Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections and cancer, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi-Goutières syndrome and STING-associated vasculopathy of infancy (SAVI). Myocardial infarction (MI) elicits inflammation, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production. In mice, single-cell RNA-seq analysis of 4,215 leukocytes isolated from infarcted and non-infarcted hearts showed that MI provokes activation of an IRF3-interferon axis in a distinct population of interferon-inducible cells (IFNICs) that were classified as cardiac macrophages. Mice genetically deficient in cyclic GMP-AMP synthase (cGAS), its adaptor STING, IRF3, or the type I IFN receptor IFNAR exhibited impaired interferon-stimulated gene (ISG) expression and, in the case of mice deficient in IRF3 or IFNAR, improved survival after MI as compared to controls. Interruption of IRF3-dependent signaling resulted in decreased cardiac expression of inflammatory cytokines and chemokines and decreased inflammatory cell infiltration of the heart, as well as in attenuated ventricular dilation and improved cardiac function. Similarly, treatment of mice with an IFNAR-neutralizing antibody after MI ablated the interferon response and improved left ventricular dysfunction and survival. These results identify IRF3 and the type I IFN response as a potential therapeutic target for post-MI cardioprotection.

  9. Interferon-Beta in Pediatric Multiple Sclerosis Patients: Safety in Short-Term Prescription

    Directory of Open Access Journals (Sweden)

    Amir Hadi Maghzi

    2012-02-01

    Full Text Available Introduction: None of the approved immunomodulatory drugs in adults Multiple Sclerosis (MS patients have been officially approved for the pediatric patients and are currently used off-label in this population. Objectives: In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a (Avonex® and subcutaneously injected interferon beta1-b (Betaferon® in children with definite relapsing-remitting MS (RRMS. Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonalds criteria, were enrolled in this study. Six patients were treated with Avonex® 30 μg, intramuscularly every week, and seven patients were treated with Betaferon® 250 μg, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Results: Eleven girls and two boys, mean (SD age of 14.7 (1.9 years, were studied. Following nine months of using interferon-beta, nine patients (69.2% had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. Conclusion: The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children.

  10. Adaptation of enterovirus 71 to adult interferon deficient mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Caine

    Full Text Available Non-polio enteroviruses, including enterovirus 71 (EV71, have caused severe and fatal cases of hand, foot and mouth disease (HFMD in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN receptor deficient and AG129 (α/β, γ IFN receptor deficient mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p. into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m. in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05. The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection

  11. DMPD: The role of the interferon regulatory factor (IRF) family in dendritic celldevelopment and function. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17702640 The role of the interferon regulatory factor (IRF) family in dendritic celldevelopment and function...in dendritic celldevelopment and function. PubmedID 17702640 Title The role of th...e interferon regulatory factor (IRF) family in dendritic celldevelopment and function. Authors Gabriele L, O

  12. Interferon-induced transcription of a gene encoding a 15-kDA protein depends on an upstream enhancer element

    International Nuclear Information System (INIS)

    Reich, N.; Evans, B.; Levy, D.; Fahey, D.; Knight, E. Jr.; Darnell, J.E. Jr.

    1987-01-01

    A human gene encoding an interferon-induced 15-kDa protein has been isolated from a genomic library. The gene appears to be single-copy and is composed of two exons, the first of which contains the ATG translation initiation codon. In vitro nuclear run-on assays showed that the transcription rate of the gene is stimulated after interferon treatment. To analyze transcriptional regulatory sequences, the authors constructed recombinant plasmids for use in transient transfection assays of HeLa cells. Constructs containing 115 nucleotides 5' to the transcription initiation site were found to be fully inducible by interferon. Assays of deletion mutants identified a critical element for interferon induction located between -115 and -96, just upstream of the CCAAT box. Moreover, a DNA fragment including this region can confer interferon inducibility on a heterologous promoter (thymidine kinase) when cloned in either orientation upstream of the gene or downstream of the gene. These are properties characteristic of an enhancer element that is active only after treatment with interferon. This regulatory sequence may be shared by a group of interferon-induced genes, since a very similar sequence is present within the functional region near the RNA start site of another interferon-induced gene

  13. Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi's sarcoma

    NARCIS (Netherlands)

    de Wit, R.; Schattenkerk, J. K.; Boucher, C. A.; Bakker, P. J.; Veenhof, K. H.; Danner, S. A.

    1988-01-01

    The effectiveness and antiretroviral activities of interferon-alpha in AIDS-related Kaposi's sarcoma was assessed in a non-randomised, phase-II clinical trial. 28 patients were treated with high-dose (27-36 MU) human recombinant interferon-alpha 2a subcutaneously every day for 8 weeks. In patients

  14. DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

  15. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia chromos...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

  16. Increased expression of beta 2-microglobulin and histocompatibility antigens on human lymphoid cells induced by interferon

    DEFF Research Database (Denmark)

    Hokland, M; Heron, I; Berg, K

    1982-01-01

    Normal human peripheral blood lymphocytes were incubated in the presence of different concentrations of interfero