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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

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    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. Current prospects for interferon-free treatment of hepatitis C in 2012.

    Science.gov (United States)

    Stedman, Catherine A M

    2013-01-01

    Present interferon-based therapy for chronic hepatitis C is limited by both efficacy and tolerability. Telaprevir and boceprevir are the first two direct-acting antiviral drugs (DAAs) that inhibit hepatitis C virus replication to be licensed for use in conjunction with pegylated interferon and ribavirin. Numerous other DAAs are in clinical development, and phases 2 and 3 trials are evaluating interferon-free combination DAA therapy. Interferon-free sustained virologic responses have now been achieved with combinations of asunaprevir and daclatasvir; sofosbuvir and ribavirin; sofosbuvir and daclatasvir; faldaprevir and BI207127; ABT-450, ritonovir and ABT-333; ABT-450, ritonovir and ABT-072; miracitabine, danoprevir and ritonavir; and alisporivir and ribavirin. Some drugs are genotype-specific in their activity, whereas others are pan-genotypic, and differential responses for the genotype 1 subtypes 1a and 1b have emerged with many DAA combinations. Viral breakthrough and resistance are important considerations for future trial design. The prospect of interferon-free combination DAA therapy for hepatitis C virus is now finally becoming a reality. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  5. COMBINED THERAPY OF VIRAL DIARRHEA IN CHILDREN: FIRST RESULTS OF AN OPEN COMPARATIVE RANDOMIZED CLINICAL TRIAL OF INTERFERON EFFICIENCY

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    A.V. Gorelov

    2011-01-01

    Full Text Available The article presents an interim statistical analysis of the open multicenter randomized clinical trial, whose goal was to evaluate the efficiency and safety of immunomodulatory therapy of acute intestinal infections of viral etiology in children. Patients and methods: at this stage 28 children aged 6 months to 6 years with a clinically diagnosed viral diarrhea were included in the study. Children were randomly assigned to two groups: basic, where for the treatment was used the suppository preparation of recombinant human interferon alpha-2b in combination with taurine, and a control group, where the patients admitted the drug as the recombinant human interferon alpha-2b in combination with a complex immunoglobulin preparation. The dynamics of the relief of individual viral diarrhea symptoms was assessed within 5 days after the patient was included in the study. Results: the analysis of the data revealed no significant differences in the efficiency of the investigated drugs, this fact suggests the equivalence of the produced therapeutic effect. The use of the preparation containing recombinant human interferon alpha-2b in combination with taurine, reduces the level of a drug load on the child’s organism without loss of the treatment efficiency.Key words: recombinant human interferon alpha-2b, taurine, an acute intestinal infection of viral etiology, treatment, children.

  6. Dutch Open Telescope: Status and Prospects

    NARCIS (Netherlands)

    Rutten, R.J.; Hammerschlag, R.H.; Bettonvil, F.C.M.

    1997-01-01

    The Dutch Open Telescope represents a new solar telescope concept. Being open rather than evacuated, it leads the way to large- aperture high resolution telescopes. It is now being installed on La Palma.

  7. 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.

  8. 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

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

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    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.

  10. Kinetics of Hepatitis B Virus Load During Haemodialysis Sessions and α-Interferon: A Prospective Study

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    Fabrizio Fabrizi

    2013-09-01

    Full Text Available Background: It has been reported a slow progression of hepatitis B in patients undergoing maintenance dialysis, and a role of dialysis session per se has been suggested. The aim of the present study is to evaluate the kinetics of the hepatitis B viral load (HBV DNA in serum during haemodialysis sessions using a highly sensitive technique; the role of interferon-α in lowering HBV viral load in such patients was also investigated. Methods: HBV DNA was determined in 24 HBsAg positive patients on maintenance hemodialysis immediately before and after a 4-hour hemodialysis session, the same measurements were repeated 48 and 72 hours later. HBV DNA quantitation was performed by a novel RealTime PCR assay. Serum IFN-α levels were tested in parallel in a subset of HD sessions (n=40 by ELISA. Results: 20 (83% HBsAg positive patients had detectable HBV DNA in serum. Positive status for HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in many patients after hemodialysis sessions 5.92 log10 IU/mL (95% CI, 5.34 to 6.28 log10 IU/mL vs. 4.79 log10 IU/mL (95% CI, 4.23 to 6.15 log10 IU/mL (P=0.02. A significant relationship between mean HBV DNA levels before dialysis and percentage reduction of HBV DNA during HD sessions occurred [F-test=5.41, rho (least squares=0.307]. Increase of serum IFN-α levels was found in a minority (3/40=7% of HD sessions. Conclusions: Hemodialysis procedure gives reduction of HBV load in HBsAg chronic carriers; no relationship with IFN-α activity during HD sessions was found. The kinetics of HBV viremia in HD procedures could explain the low viral load which is typically observed in these patients. Further studies to identify the mechanisms responsible for reduction of HBV viremia during HD procedures are under way.

  11. Prospects for the development of open innovation in project management

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    Sachuk S.N.

    2017-01-01

    Full Text Available from a management perspective, the organizational change process from closed to open innovations is one of actual problems in an inter-organizational cooperation, because companies need to introduce new organizational methods. In this context, the author proposes to consider project management under the model of open innovations. The article describes the author's approach in the study of project management in open innovation projects and their impact on traditional methods of project management.

  12. 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…

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

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    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.

  14. Dose-escalation of human anti-interferon-α receptor monoclonal antibody MEDI-546 in subjects with systemic sclerosis: a phase 1, multicenter, open label study.

    Science.gov (United States)

    Goldberg, Avram; Geppert, Thomas; Schiopu, Elena; Frech, Tracy; Hsu, Vivien; Simms, Robert W; Peng, Stanford L; Yao, Yihong; Elgeioushi, Nairouz; Chang, Linda; Wang, Bing; Yoo, Stephen

    2014-02-24

    Type I interferons (IFNs) are implicated in the pathogenesis of systemic sclerosis (SSc). MEDI-546 is an investigational human monoclonal antibody directed against the type I IFN receptor. This Phase 1 study evaluated the safety/tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of single and multiple intravenous doses of MEDI-546 in adults with SSc. Subjects (≥18 years) with SSc were enrolled in an open-label, dose-escalation study to receive single (0.1, 0.3, 1.0, 3.0, 10.0, or 20.0 mg/kg), or 4 weekly intravenous doses (0.3, 1.0, or 5.0 mg/kg/week) of MEDI-546. Subjects were followed for 12 weeks. Safety assessments included adverse events (AEs), laboratory results, and viral monitoring. Blood samples were collected from all subjects for determination of PK, presence of anti-drug antibodies (ADAs), and expression of type I IFN-inducible genes. Of 34 subjects (mean age 47.4 years), 32 completed treatment and 33 completed the study. Overall, 148 treatment-emergent AEs (TEAEs) were reported (68.9% mild, 27.7% moderate). TEAEs included one grade 1 infusion reaction (5.0 mg/kg/week multiple dose). Of 4 treatment-emergent serious AEs (skin ulcer, osteomyelitis, vertigo, and chronic myelogenous leukemia (CML)), only CML (1.0 mg/kg/week multiple dose) was considered possibly treatment-related. MEDI-546 exhibited non-linear PK at lower doses. ADAs were detected in 5 subjects; no apparent impact on PK was observed. Peak inhibition of the type I IFN signature in whole blood was achieved within 1 day and in skin after 7 days. The safety/tolerability, PK, and PD profiles observed in this study support further clinical development of MEDI-546. ClinicalTrials.gov NCT00930683.

  15. Intrahepatic expression of interferon alpha & interferon alpha ...

    African Journals Online (AJOL)

    kemrilib

    Alpha m-RNA while 30% only expressed Interferon Alpha Receptor m-RNA. Responders and non-responders to Interferon therapy ... expression of IFN Alpha Receptor mRNA. Regardless of the response to interferon, histological .... generation reverse hybridisation, line probe assay. (Inno-LiPA HCV II; Innogenetics, Ghent,.

  16. Patient adherence to and tolerability of self-administered interferon β-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study

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    Lugaresi Alessandra

    2012-03-01

    Full Text Available Abstract Background Achieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS. Methods BRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg, subcutaneously (sc, three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET for: physical examinations; diary card completion (baseline, Weeks 4, 8 only; neurological examinations (baseline, Week 12/ET only; MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only; Convenience Questionnaire (Week 12 only; Hospital Anxiety and Depression Scale (HADS; and Paced Auditory Serial Addition Task (PASAT; baseline only. Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device. Results Overall, 88.2% (105/119; intent-to-treat population of patients were adherent; 67.2% (80/119 administered all scheduled injections. Medical reasons accounted for 35.6% (31/87 of missed injections, forgetfulness for 20.6% (18/87. Adherence did not correlate with baseline Expanded Disability Status Scale (P = 0.821 or PASAT (P = 0.952 scores, or pre-study therapy (P = 0.303. No significant changes (baseline-Week 12 in mean HADS depression (P = 0.482 or anxiety (P = 0.156 scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly

  17. Functional outcomes after open versus arthroscopic Latarjet procedure: A prospective comparative study.

    Science.gov (United States)

    Nourissat, G; Neyton, L; Metais, P; Clavert, P; Villain, B; Haeni, D; Walch, G; Lafosse, L

    2016-12-01

    The Latarjet procedure provides effective stabilization of chronically unstable shoulders. Since this procedure is mainly performed in a young athletic population, the functional impact is significant. Published data does not shed light on the time needed to recover work-related or sports-related function. Performing this procedure arthroscopically may improve functional recovery. This led us to carry out a prospective, multicenter study to compare the functional recovery after arthroscopic versus open Latarjet procedure. Between June and November 2014, 184 patients were included in a prospective multicenter study: 85 in the open group and 99 in the arthroscopy group. The patients were evaluated preoperatively with the WOSI score. The early postoperative pain was evaluated on D3, D7 and D30. The WOSI score was determined postoperatively at 1, 3, 6 and 12 months of follow-up. The functional scores of the shoulder in both cohorts were identical overall preoperatively. In the immediate postoperative period, the arthroscopy group had statistically lower pain levels on D3 and D7. The postoperative WOSI was improved in both groups at 3 months, then continued to improve until it reached a plateau at 1 year. The WOSI score was better in the arthroscopy group at 3 months, but better in the open group at 6 months. This study found that a Latarjet procedure performed arthroscopically generates less immediately postoperative pain than when it is performed as an open procedure. The Latarjet procedure (whether open or arthroscopic) improves shoulder function, with normal function returning after 1 year. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Treatment of complete staghorn stones: a prospective randomized comparison of open surgery versus percutaneous nephrolithotomy.

    Science.gov (United States)

    Al-Kohlany, Khaled M; Shokeir, Ahmed A; Mosbah, Ahmed; Mohsen, Tarek; Shoma, Ahmed M; Eraky, Ibrahim; El-Kenawy, Mahmoud; El-Kappany, Hamdy A

    2005-02-01

    We studied the role of open surgery versus percutaneous nephrolithotomy (PCNL) in the treatment of complete staghorn stones in a prospective randomized manner. A total of 79 patients with 88 complete staghorn stones, defined as filling the entire collecting system or at least 80% of it, were prospectively randomized for PCNL (43) or open surgery (45). Intraoperative and postoperative morbidity, operative time, hospital stay, and stone clearance at discharge home and followup were compared for both methods. Patients with significant residuals in both groups were subjected to extracorporeal shock wave lithotripsy (Dornier Medical Systems, Inc., Marietta, Georgia) on an outpatient basis. Followup was completed for all cases with a mean duration +/- SD of 4.9 +/- 2.5 months (range 3 to 14). Renal function was evaluated by Tc-mercaptoacetyltriglycine renogram before and after treatment in both groups. Intraoperative complications in terms of bleeding requiring blood transfusion, and pleural, vascular or ureteral injuries were recorded in 7 patients (16.3%) in the PCNL and 17 (37.8%) in the open surgery groups, a difference of significant value (p work (2.5 +/- 0.8 vs 4.1 +/- 1 weeks, p hand both treatment groups were comparable in regard to stone-free rates at discharge home (49% vs 66%) and at followup (74% vs 82%). At followup renal function improved or remained stable in 91% and 86.7% in the PCNL and open surgery groups, respectively. PCNL is a valuable treatment option for complete staghorn stones with a stone-free rate approaching that of open surgery. Moreover, it has the advantages of lower morbidity, shorter operative time, shorter hospital stay and earlier return to work.

  19. Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model after Antibody Blockade of Type I Interferon (Open Access Publisher’s Version)

    Science.gov (United States)

    2017-01-09

    and Zika virus infections—an unprecedented epidemic wave of mosquito-borne viruses in the Pacific 2012–2014. Euro Surveill 19. 13. Campos GS...RESEARCH ARTICLE Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model after Antibody Blockade of Type I Interferon...joseph.w.golden.ctr@mail.mil (JWG) Abstract Animal models are needed to better understand the pathogenic mechanisms of Zika virus (ZIKV) and to

  20. 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

  1. Prospective randomized controlled trial to evaluate "fast-track" elective open infrarenal aneurysm repair.

    Science.gov (United States)

    Muehling, Bernd M; Halter, Gisela; Lang, Gunter; Schelzig, Hubert; Steffen, Peter; Wagner, Florian; Meierhenrich, Rainer; Sunder-Plassmann, Ludger; Orend, Karl-Heinz

    2008-05-01

    Fast-track programs have been introduced in many surgical fields to minimize postoperative morbidity and mortality. Morbidity after elective open infrarenal aneurysm repair is as high as 30%; mortality ranges up to 10%. In terms of open infrarenal aneurysm repair, no randomized controlled trials exist to introduce and evaluate such patient care programs. This study involved prospective randomization of 82 patients in a "traditional" and a "fast-track" treatment arm. Main differences consisted in preoperative bowel washout (none vs. 3 l cleaning solution) and analgesia (patient controlled analgesia vs. patient controlled epidural analgesia). Study endpoints were morbidity and mortality, need for postoperative mechanical ventilation, and length of stay (LOS) on intensive care unit (ICU). The need for assisted postoperative ventilation was significantly higher in the traditional group (33.3% vs. 5.4%; p = 0.011). Median LOS on ICU was shorter in the fast-track group, 41 vs. 20 h. The rate of postoperative medical complications was significantly lower in the fast-track group, 16.2% vs. 35.7% (p = 0.045). We introduced and evaluated an optimized patient care program for patients undergoing open infrarenal aortic aneurysm repair which showed a significant advantage for "fast-track" patients in terms of postoperative morbidity.

  2. Immune- and miRNA-response to recombinant interferon beta-1a: a biomarker evaluation study to guide the development of novel type I interferon- based therapies.

    Science.gov (United States)

    Coenen, Martin; Hinze, Annette Viktoria; Mengel, Martin; Fuhrmann, Christine; Lüdenbach, Bastian; Zimmermann, Julian; Dykstra, Verena; Fimmers, Rolf; Viviani, Roberto; Stingl, Julia; Holdenrieder, Stefan; Müller, Marcus; Hartmann, Gunther; Coch, Christoph

    2015-09-22

    The innate immune receptor RIG-I detects viral RNA within the cytosol of infected cells. Activation of RIG-I leads to the induction of antiviral cytokines, in particular type I interferon, the inhibition of a T(H)17 response as well as to the suppression of tumor growth. Therefore, RIG-I is a promising drug target for the treatment of cancer as well as multiple sclerosis. A specific ligand for RIG-I is currently in preclinical testing. The first-in-human trial will need to be carefully designed to avoid an overshooting cytokine response. Therefore, the ResI study was set up to analyze the human immune response to standard treatment with recombinant interferon-beta to establish biomarkers for safety and efficacy of the upcoming first-in-human trial investigating the RIG-I ligand. ResI is a single center, prospective, open label, non-randomized phase I clinical trial. Three different cohorts (20 healthy volunteers, 20 patients with RRMS and ongoing interferon-beta treatment and 10 patients starting on interferon-beta) will receive standard interferon-beta-1a therapy for nine days. The study will be conducted according to the principles of the german medicinal products act, ICH-GCP, and the Declaration of Helsinki on the phase I unit of the Institute of Clinical Chemistry and Clinical Pharmacology and in the Department of Neurology, both University Hospital Bonn. Interferon-beta-induced cytokine levels, surface marker on immune cells, mRNA- and miRNA-expression as well as psychometric response will be investigated as target variables. The ResI study will assess biomarkers in response to interferon-β treatment to guide the dose steps within the first-in-human trial with a newly developed RIG-I ligand. Thus, ResI is a biomarker study to enhance the safety of the clinical development of a first-in-class compound. The data can additionally be used for the development of other therapies based on type I interferon induction such as TLR ligands. Moreover, it will help to

  3. 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.

  4. Surgical complications of open nephrectomy in living related donors in Yemen: a prospective study.

    Science.gov (United States)

    Telha, Khaled Abdulla; Al Kataa, Mohamed Abdullah; Al-Kohlany, Khaled Mohamed; Al Badany, Tawfik Hassen; Alnono, Ibrahim Hussen

    2017-12-01

    Renal transplantation from living related donor is the best treatment option for chronic renal failure with experience for more than 50 years. However, this procedure may expose the health and even the life of otherwise normal individuals to risk. In this prospective study we described the surgical complications of open donor nephrectomies by Clavien grading system. Between May 2002 and December 2014, one hundred and seventy-two potentially healthy kidney donors were admitted to Althawrah General Hospital, Ibn-Sina Hospital and Military Hospital. The median age was 34 years (19-60 years) with male predominance in 64.5% of the cases. This prospective descriptive study reviews intra-, and post-operative surgical complications using Clavien grading system for surgical complications. The procedure was done via supracostal lumbotomy incision (above 12 th rib) in 112 cases (65.1%) and transcostal incision with resection of 11th rib in 60 cases (34.9%). Left kidney was taken in most of the cases (68%) while right kidney in the remaining 42% with an average warm ischemia time of 31 seconds (range, 22-34 seconds). Surgical complications by Clavien grading system were observed in 18.6% of the cases (32 cases). Grade 1 in 28 (16.4%); Grade 2 in 2 (1.2%) and Grade 3 in 2 cases (1.2%) were detected. There was no grade 4 or 5 cases in our series. Median postoperative hospital stay was 3 days (range: 2-4 days). We found that most of the complications of open living donor nephrectomy are of grade I and higher grade complications are negligible compared to the advantages for the recipients.

  5. Adjunctive use of repetitive transcranial magnetic stimulation in depressed adolescents: a prospective, open pilot study.

    Science.gov (United States)

    Wall, Christopher A; Croarkin, Paul E; Sim, Leslie A; Husain, Mustafa M; Janicak, Philip G; Kozel, F Andrew; Emslie, Graham J; Dowd, Sheila M; Sampson, Shirlene M

    2011-09-01

    Depression is often a serious and debilitating illness in adolescents. Unfortunately, a significant number of adolescents do not respond to antidepressant medications or psychotherapy. Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment intervention shown to benefit depression in adults. This study considered rTMS as an adjunctive treatment in adolescents with major depressive disorder. This prospective, open, multicenter trial of active adjunctive rTMS was conducted with 8 adolescents with DSM-IV-TR major depressive disorder (MDD) that had not responded sufficiently to 2 adequate antidepressant medication trials. All subjects were maintained on a stable dose of a selective serotonin reuptake inhibitor during the trial. Thirty daily rTMS treatments were given 5 days per week over 6 to 8 weeks. rTMS was applied to the left dorsolateral prefrontal cortex (120% of motor threshold; 10 Hz; 4-second trains; 26-second intertrain interval; 75 trains) for a total of 3,000 stimulations per treatment session. Seven of 8 adolescents completed all 30 treatments. rTMS was well tolerated, and no significant safety issues were identified. Suicidal ideation was present at baseline in 3 of the adolescents, and it improved during treatment. The primary outcome measure was the Children's Depression Rating Scale-Revised (CDRS-R); results improved significantly from baseline (mean [SD]) (65.9 [6.6]) to treatment 10 (50.9 [12]), P < .02. The CDRS-R scores continued to improve through the rTMS treatment series at treatment 20 (40.1 [14]), P < .01; treatment 30 (32.6 [7.3]), P < .0001; and at 6-month follow-up (32.7 [3.8]), P < .0001. This prospective open trial suggests that rTMS is a safe, feasible, and potentially effective adjunctive therapy for treatment-resistant MDD in adolescents. clinicaltrials.gov Identifier: NCT00587639. © Copyright 2011 Physicians Postgraduate Press, Inc.

  6. Prospective evaluation of laparoscopic colon resection versus open colon resection for adenocarcinoma. A multicenter study.

    Science.gov (United States)

    Franklin, M E; Rosenthal, D; Norem, R F

    1995-07-01

    Laparoscopic colon resection (LCR) has been performed in the United States sine 1990. This procedure has been accepted by many as a reasonable alternative for nonmalignant, colonic, surgical disease, but the laparoscopic approach remains controversial for curative treatment of carcinoma. In this paper, the results of a nonrandomized series of two large experiences of laparoscopic colon resections were performed and followed for 3 1/2 years in a prospective fashion against an equal number of patients who underwent open resection. The setting was several large metropolitan hospitals in San Antonio, Texas. Over 194 patients were involved in this study. Each patient once diagnosed with resectable colonic cancer was allowed to choose their own procedure, laparoscopic or open colon resection, either of which was performed by the authors. Factors considered include age, sex, body habitus, stage of cancer, margins of resection, numbers of lymph nodes retrieved, hospitalization time, and follow-up period. Observations at this time indicate the following: (1) LCR allows for resection comparable to the classical approach, (2) equal numbers of mesenteric lymph nodes can be retrieved, (3) adequacy of margins of resection can be accurately determined by colonoscopy during LCR, and (4) brief follow-up periods show comparable survival and disease-free intervals. It is the conclusion of the authors that with proper training LCR will come to be recognized as a safe, effective surgical option for treatment of selected patients with colon cancer.

  7. 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

  8. Transgender Day of Remembrance and a Prospective Student Open House: How One Student Inspired a School to Do Both

    Science.gov (United States)

    Fusarelli, Bonnie C.; Eaton, Lucy E.

    2011-01-01

    This case study explores the challenges a school leader faced when her commitment to diversity was tested by a scheduling conflict. The school principal approved a Transgender Day of Remembrance but then realized that it was scheduled for the same night as the school's Open House to recruit prospective students. The case study provides an…

  9. 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

  10. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Freedman, Mark S; Polman, Chris H

    2009-01-01

    with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon...... beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after....... No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and the favourable long-term safety...

  11. 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.

  12. 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.

  13. Interferential current is effective in palmar psoriaris: an open prospective trial.

    Science.gov (United States)

    Philipp, A; Wolf, G K; Rzany, B; Dertinger, H; Jung, E G

    2000-01-01

    Interferential current (IFC) has been shown to improve psoriasis in a small case series. So far no formal clinical trial had been conducted. As IFC is associated with slight prickling sensations a blinded study design was not feasible. Therefore, an open type prospective study was conducted with the assumption of 18% spontaneous remission rate. A response rate of 50% or less was judged as indicating no effect (hypothetical control), while 80% or more was considered as success (alternative hypothesis). In this "quasi-controlled" study 12 patients with therapy resistant palmar psoriasis received local treatment with IFC during a 12 week period. Treatment was performed at low current density in two daily sessions, each of 6 minutes duration. Erythema, scaling, induration, fissures and pustules were recorded in separate scores every 4 weeks. Response of a patient was judged positive when the total score of these criteria was reduced at least by two points at the end of treatment. After 12 weeks of treatment, 11 of 12 patients were cured or showed marked remission with the median overall score reduced by 4 points. An interim analysis was performed in order to decide whether the results had already reached significance (a < 0.05). The analysis revealed a statistically significant response rate of 90% (95% confidence interval 62-99%). These results are highly encouraging and should focus attention on this new therapy modality, which, in contrast to other treatments is not associated with side effects and discomfort.

  14. Biotechnology: interferon patent contested.

    Science.gov (United States)

    Earl, C; Beardsley, T

    Biogen, a biotechnology company based in Cambridge, Mass., and Geneva, Switzerland, has been notified by the European Patent Office that it will receive a product patent for its alpha interferon synthesized by recombinant DNA technology. Genentech, a San Francisco company which claims priority for producing mature interferon, is planning a vigorous appeal of the decision.

  15. [A prospective randomized controlled trial of laparoscopic repair versus open repair for perforated peptic ulcers].

    Science.gov (United States)

    Wang, Qiwei; Ge, Bujun; Huang, Qi

    2017-03-25

    To compared the clinical efficacy of laparoscopic repair (LR) versus open repair (OR) for perforated peptic ulcers. From January 2010 to June 2014, in Shanghai Tongji Hospital, 119 patients who were diagnosed as perforated peptic ulcers and planned to receive operation were prospectively enrolled. Patients were randomly divided into LR (58 patients) and OR(61 patients) group by computer. Intra-operative and postoperative parameters were compared between two groups. This study was registered as a randomized controlled trial by the China Clinical Trials Registry (registration No.ChiCTR-TRC-11001607). There was no significant difference in baseline data between two groups (all P>0.05). No significant differences of operation time, morbidity of postoperative complication, mortality, reoperation probability, decompression time, fluid diet recovery time and hospitalization cost were found between two groups (all P>0.05). As compared to OR group, LR group required less postoperative fentanyl [(0.74±0.33) mg vs. (1.04±0.39) mg, t=-4.519, P=0.000] and had shorter hospital stay [median 7(5 to 9) days vs. 8(7 to 10) days, U=-2.090, P=0.001]. In LR group, 3 patients(5.2%) had leakage in perforation site after surgery. One case received laparotomy on the second day after surgery for diffuse peritonitis. The other two received conservative treatment (total parenteral nutrition and enteral nutrition). There was no recurrence of perforation in OR group. One patient of each group died of multiple organ dysfunction syndrome (MODS) 22 days after surgery. LR may be preferable for treating perforated peptic ulcers than OR, however preventive measures during LR should be taken to avoid postopertive leak in perforation site.

  16. Laparoscopic versus open nephroureterectomy: perioperative and oncologic outcomes from a randomised prospective study.

    Science.gov (United States)

    Simone, Giuseppe; Papalia, Rocco; Guaglianone, Salvatore; Ferriero, Mariaconsiglia; Leonardo, Costantino; Forastiere, Ester; Gallucci, Michele

    2009-09-01

    Laparoscopic nephroureterectomy (LNU) is increasingly being used instead of open nephroureterectomy (ONU) for the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT), but the evidence of equal oncologic effectiveness is still lacking. To present perioperative and oncologic results from a prospective randomised study comparing ONU and LNU. Eighty patients with nonmetastatic UUT UC and without previous history of UC were enrolled. Of those, 40 patients (group A) randomly received ONU and 40 patients (group B) randomly received LNU. ONU was performed through a flank incision with a lower quadrant incision to allow excision of a bladder cuff. Transperitoneal LNU was performed with a four-trocar technique, and bladder cuff was detached with a 10-mm LigaSure device. Perioperative data were compared with the student t test. Bladder tumour-free survival (BTFS), metastasis-free survival (MFS), and cancer-specific survival (CSS) curves for both groups were compared with the log-rank test before and after stratifying patients for pT category and tumour grade. Operative times were comparable, while mean blood loss and mean time to discharge were significantly lower in group B (both p values ONU (p=0.039 and p=0.004, respectively, for pT3 tumours; p=0.078 and p=0.014, respectively, for high-grade tumours). The limitations of our study include the small sample size, the single-centre experience, the personal choice of laparoscopic technique, and not performing lymphadenectomies. Perioperative data and preliminary oncologic results were presented at 22nd Congress of the European Association of Urology, Berlin, Germany. In patients with organ-confined UUT UCs, LNU has the advantages of minimal invasiveness and oncologic outcomes comparable to those of ONU, while its effectiveness in patients with advanced stage diseases remains to be proven.

  17. 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.

  18. Efficacy of teriparatide in patients with hypoparathyroidism: A prospective, open-label study

    Directory of Open Access Journals (Sweden)

    Vimal Upreti

    2017-01-01

    Full Text Available Context: Conventional treatment of hypoparathyroidism with calcium, Vitamin D analogs, and thiazide diuretics is often suboptimal, and these patients have poor quality of life. Teriparatide (parathyroid hormone 1–34 [PTH (1–34], an amide of PTH, is widely available for the use in osteoporosis; however, its use in hypoparathyroidism is limited. Aims: The aim of this study is to evaluate the efficacy of PTH (1–34 in the treatment of patients with hypoparathyroidism. Settings and Design: This was a prospective, open-label interventional study in a tertiary care hospital of Indian Armed Forces. Subjects and Methods: All patients with hypoparathyroidism presented to the endocrinology outpatient department were included and were exhibited injection PTH (1–34 20 μg twice daily that was gradually reduced to 10 μg twice daily along with calcium, active Vitamin D (alfacalcidol, and hydrochlorothiazide. Oral calcium and alfacalcidol doses were also reduced to maintain serum calcium within normal range. The quality of life (QOL score was calculated using RAND 36 QOL questionnaire at baseline and termination of the study. Statistical Analysis Used: Paired t-test was used to calculate pre- and post-treatment variables. Results: Eight patients (two males were included in this study having mean age of 35.8 years. PTH (1–34 treatment led to the improvement in serum calcium (6.81–8.84 mg/dl, phosphorous (5.8–4.2 mg/dl, and 24 h urinary calcium excretion (416–203.6 mg. Parameters of QOL showed the improvement in overall QOL, physical performance, energy, and fatigue scores. No major adverse events were noted. Conclusions: Treatment of hypoparathyroidism with PTH (1–34 leads to improvement in calcium profile, reduction in hypercalciuria, and improvement in QOL, whereas it is safe and well tolerated.

  19. 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.

  20. 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.

  1. Does Zoledronate Prevent Femoral Head Collapse from Osteonecrosis? A Prospective, Randomized, Open-Label, Multicenter Study.

    Science.gov (United States)

    Lee, Young-Kyun; Ha, Yong-Chan; Cho, Yoon Je; Suh, Kuen Tak; Kim, Shin-Yoon; Won, Ye-Yeon; Min, Byung-Woo; Yoon, Taek Rim; Kim, Hee Joong; Koo, Kyung-Hoi

    2015-07-15

    Osteonecrosis of the femoral head frequently leads to collapse of the necrotic portion and subsequent degenerative joint disease of the hip, which is the most common diagnosis leading to total hip arthroplasty in young adults. Bisphosphonate therapy has been reported to potentially retard the collapse. We conducted a two-year prospective, randomized, open-label, multicenter study to determine whether zoledronate prevents the collapse and reduces the need for total hip arthroplasty. We randomly assigned patients who had Steinberg stage-I or II nontraumatic osteonecrosis of the femoral head with a necrotic area of ≥30% to either the zoledronate group or the control group. Patients in the zoledronate group received 5 mg of zoledronate intravenously per year for two years, while patients in the control group did not receive this medication. The primary efficacy outcome was the survival rate in terms of the occurrence of collapse (≥2 mm). The patients were observed for a minimum of two years after enrollment. A total of 110 patients (110 hips) underwent randomization; fifty-five patients were assigned to the zoledronate group and fifty-five, to the control group. During the two-year follow-up, twenty-nine femoral heads in the zoledronate group and twenty-two in the control group collapsed (p > 0.05). Nineteen hips in the zoledronate group and twenty in the control group underwent total hip arthroplasty (p > 0.05). Zoledronate for Steinberg stage-I or II osteonecrosis of the femoral head, with a medium to large necrotic area, did not prevent the collapse of the femoral head or reduce the need for total hip arthroplasty. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

  2. A prospective, open-label trial of clevidipine for controlled hypotension during posterior spinal fusion.

    Science.gov (United States)

    Kako, Hiromi; Gable, Andrew; Martin, David; Beebe, Allan; Thung, Arlyne; Samora, Walter; Klamar, Jan; Bhalla, Tarun; Tobias, Joseph D

    2015-01-01

    Controlled hypotension is one means to limit or avoid the need for allogeneic blood products. Clevidipine is a short-acting, intravenous calcium channel antagonist with a half-life of 1 to 3 minutes due to rapid metabolism by non-specific blood and tissue esterases. To date, there are no prospective evaluations with clevidipine in the pediatric population. We prospectively evaluated the dosing requirements, efficacy, and safety of clevidipine for ontrolled hypotension during spinal surgery for neuromuscular scoliosis in the pediatric population. Patients undergoing posterior spinal fusion for neuromuscular scoliosis were eligible for inclusion. The study was an open label, observational study. Maintenance anesthesia included desflurane titrated to maintain a bispectral index at 40 to 60 and a remifentanil infusion. Motor and somatosensory evoked potentials were monitored intraoperatively. When the mean arterial pressure (MAP) was ≥ 65 mmHg despite remifentanil at 0.3 mcg/kg/min, clevidipine was added to maintain the MAP at 55 to 65 mmHg. Clevidipine was initiated at 0.25 to 1 mcg/kg/min and titrated up in increments of 0.25 to 1 mcg/kg/min every 3 to 5 minutes to achieve the desired MAP. The study cohort included 45 patients. Fifteen patients (33.3%) did not require a clevidipine infusion to maintain the desired MAP range, leaving 30 patients including 13 males and 17 females for analysis. These patients ranged in age from 7.9 to 17.4 years (mean ± SD: 13.7 ± 2.2 years) and in weight from 18.9 to 78.1 kg (mean ± SD: 43.4 ± 14.2 kg). Intraoperatively, the clevidipine infusion was stopped in 6 patients as the surgeon expressed concerns regarding spinal cord perfusion and requested a higher MAP than the study protocol allowed. The data until that point were included for analysis. The target MAP was initially achieved at a mean time of 8.9 minutes. Sixteen of the 30 patients (53.3%) achieved the target MAP within 5 minutes. Heart rate (HR) increased from a

  3. Comparing the Open University Systems of China and India: Origins, Developments and Prospects

    Science.gov (United States)

    Perris, Kirk

    2015-01-01

    The national open universities of China and India are unique adaptations of the open university model that emanated from the UK. These institutions have expanded to become the largest universities in the world as measured by current enrollment of approximately four million each. This article comparatively analyzes how these open universities have…

  4. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. A. Minich

    2009-01-01

    Full Text Available Background: Both bacillus Calmette-Gue’rin (BCG and interferon-alpha (IFN-α are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.Subjects and methods: A total of 149 patients (mean age 63.2 years were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60 was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60 patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29 had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3% patients in the BCG group, 8 (13.3% patients in the BCG + IFN-αgroup and 18 (62.1% patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively. There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007. Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025. The respective rates ofmoderate

  5. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. A. Minich

    2014-07-01

    Full Text Available Background: Both bacillus Calmette-Gue’rin (BCG and interferon-alpha (IFN-α are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.Subjects and methods: A total of 149 patients (mean age 63.2 years were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60 was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60 patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29 had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3% patients in the BCG group, 8 (13.3% patients in the BCG + IFN-αgroup and 18 (62.1% patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively. There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007. Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025. The respective rates ofmoderate

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. The clinical utility of tuberculin skin test and interferon-γ release assay in the diagnosis of active tuberculosis among young adults: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Lee Sei Won

    2011-04-01

    Full Text Available Abstract Background The roles of the tuberculin skin test (TST and QuantiFERON®-TB Gold In-Tube assay (QFT-IT in the diagnosis of active tuberculosis (TB are not clear in young adults. We evaluated the diagnostic accuracy of the TST and QFT-IT in smear-negative TB among young adults with no underlying disease. Methods We prospectively enrolled 166 young participants 20-29 years of age with suspected active TB in a military hospital of South Korea. The TST and QFT-IT were performed for all participants. Results Of the 143 patients included in the analysis, active TB was diagnosed in 100 (69.9%. There were 141 male patients, none of whom had immunosuppressive disease. The sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of TST were 94% (95% CI, 87-98%, 88% (95% CI, 74-96%, 95% (95% CI, 88-98%, and 86% (95% CI, 72-94%, respectively. The sensitivity, specificity, PPV, and NPV of the QFT-IT were 93% (95% CI, 86-97%, 95% (95% CI, 81-99%, 98% (95% CI, 92-99%, and 84% (95% CI, 69-93%, respectively. No significant differences were found between the TST and QFT-IT in any statistic. Conclusions Both the TST and QFT-IT showed high sensitivity and specificity in differentiating active TB from other diseases. The diagnostic accuracy of these two tests did not differ significantly when applied to this clinical population of young, immunocompetent adults in whom neonatal BCG vaccination was common, there was no history of previous TB and in whom suspicion of TB was high. Trial registration ClinicalTrials.gov: NCT00982969

  11. A Prospective Comparative Study of Arthroscopic Versus Mini-Open Latarjet Procedure With a Minimum 2-Year Follow-up.

    Science.gov (United States)

    Marion, Blandine; Klouche, Shahnaz; Deranlot, Julien; Bauer, Thomas; Nourissat, Geoffroy; Hardy, Philippe

    2017-02-01

    To compare postoperative pain during the first postoperative week and the position of the coracoid bone block at the anterior aspect of the glenoid after the arthroscopic and the mini-open Latarjet procedure. The secondary purpose was to assess functional results and recurrence after at least 2 years of follow-up. This comparative prospective study included patients who underwent a Latarjet-Bristow procedure for anterior shoulder instability in 2012. The Latarjet procedure was performed by a mini-open approach (G1) in one center and by an arthroscopic approach (G2) in the other. The main evaluation criterion was average shoulder pain during the first postoperative week assessed by the patient on a standard 10-cm visual analog scale (0-10). Secondary criteria were consumption of analgesics during the first week, the position of the coracoid bone block on radiograph and computed tomography scan at the 3-month follow-up and clinical outcomes (Western Ontario Score Index and new surgery) after at least 2 years of follow-up. Fifty-eight patients were included, 22 G1 and 36 G2, 13 women and 45 men, mean age 26.9 ± 7.7 years. The mean follow-up was 29.8 ± 4.4 months. There was significantly less pain in the arthroscopic Latarjet group than in the mini-open group during the first postoperative week (2.5 ± 1.4 vs 1.2 ± 1.2, P = .002) with comparable consumption of analgesics (P > .05). The arthroscopic Latarjet procedure resulted in a more lateral coracoid bone block (P = .04) and a better equatorial position than the mini-open technique (P = .02). Three patients underwent revision surgery (1 recurrence [2.8%], 1 block fracture, 1 screw ablation) in the arthroscopic group, none in the mini-open group (P = .54). At the final follow-up, the Western Ontario Score Index score was good in all patients (G1: 78.5 ± 7.5% vs G2: 82.3 ± 7%, P = .03). This prospective comparative study showed that the arthroscopic Latarjet procedure was significantly less painful than

  12. Interferon Beta-1b Injection

    Science.gov (United States)

    Interferon beta-1b injection is used to reduce episodes of symptoms in patients with relapsing-remitting (course of disease ... problems with vision, speech, and bladder control). Interferon beta-1b is in a class of medications called ...

  13. 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 Epilepsy.

  14. Superstition predicts favorable weight change in an open-placebo trial: a prospective study.

    Science.gov (United States)

    Rekhviashvili, Nino; Gupta, Sumati

    2015-09-01

    Given the difficulty of losing weight via adhering to healthy lifestyle choices, this study sought to understand how a placebo may elicit favorable weight change. Specifically, we examined if superstition may be related to increased responsiveness to an open-placebo. In this pilot study of 25 undergraduate participants, it was hypothesized that individuals with higher levels of superstition may be more responsive to a 3-week open-placebo weight change trial. Participants were given once-daily saltine crackers to use as open-placebos for weight change in their preferred direction (gain or loss). The weight of each participant was measured before and after the 3-week open-placebo period. A Pearson's r correlation showed a significant positive relationship between superstition and placebo responsiveness, determined by weight gain or loss in the preferred direction, r (25) = 0.493, p placebo uses for weight management.

  15. 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;…

  16. Open-space preservation in the Netherlands : Planning, practice and prospects

    NARCIS (Netherlands)

    Koomen, Eric; Dekkers, Jasper; van Dijk, Terry

    Open-space preservation is a planner's issue that is constantly debated, in particular on the success of the implemented instruments. Assessments of policy effectiveness face many methodological problems that are briefly discussed here. We choose to analyse the contribution of Dutch policies to

  17. Open-space preservation in the Netherlands: Planning, practice and prospects

    NARCIS (Netherlands)

    Koomen, E.; Dekkers, J.; Dijk, van T.

    2008-01-01

    Open-space preservation is a planner's issue that is constantly debated, in particular on the success of the implemented instruments. Assessments of policy effectiveness face many methodological problems that are briefly discussed here. We choose to analyse the contribution of Dutch policies to

  18. A prospective randomized trial comparing traditional and fast-track patient care in elective open infrarenal aneurysm repair.

    Science.gov (United States)

    Muehling, Bernd; Schelzig, Hubert; Steffen, Peter; Meierhenrich, Rainer; Sunder-Plassmann, Ludger; Orend, Karl-Heinz

    2009-03-01

    Fast-track recovery programs have led to reduced patient morbidity and mortality after major surgery. In terms of elective open infrarenal aneurysm repair, no evidence is available about such programs. To address this issue, we have conducted a randomized prospective pilot study. The study involved prospective randomization of 101 patients with the indication for elective open aneurysm repair in a traditional and a fast-track treatment arm. The basic fast-track elements were no bowel preparation, reduced preoperative fasting, patient-controlled epidural analgesia (PCEA), enhanced postoperative feeding, and postoperative mobilization. Morbidity and mortality, need for postoperative mechanical ventilation, length of stay (LOS) in the intensive care unit (ICU) and total length of postoperative hospital stay were analyzed in terms of an intention to treat. Demographic data for the two groups were similar. In the fast-track group the need for postoperative ventilation was significantly lower (6.1% versus 32%; p = 0.002), the median LOS on ICU did not significantly differ (20 h versus 32 h; p = 0.183), full enteral feeding was achieved significantly earlier (5 versus 7 days; p < 0.0001), and the rate of postoperative medical complications-gastrointestinal, cardiac, pulmonary, renal, and infective-was significantly lower (16% versus 36%; p = 0.039). The postoperative hospital stay was significantly shorter in the fast-track group (10 days versus 11 days; p = 0.016); the mortality rate in both groups was 0%. An optimized patient care program in open infrarenal aortic aneurysm repair shows favorable results concerning need for postoperative assisted mechanical ventilation, time to full enteral feeding, and incidence of medical complications. Further ranomized multicentric trials are necessary to justify broad implementation (clinical trials. gov identifier NCT 00615888).

  19. Efficacy of sumatriptan nasal spray in recurrent migrainous headache: an open prospective study.

    Science.gov (United States)

    Carpay, J A; Linssen, W H J P; Koehler, P J J; Arends, L R; Tiedink, H G M

    2003-04-01

    To evaluate the effectiveness of sumatriptan 20 mg via nasal spray and 100-mg tablets in treating migrainous headache in patients without a concomitant migraine diagnosis. We prospectively investigated the efficacy of sumatriptan 20 mg via nasal spray and 100-mg tablets in patients with a history of at least 5 moderate to severe headache attacks lasting 2 to 72 hours that consistently did not meet the International Headache Society (IHS) criteria for migraine or episodic tension-type headache. Nineteen headache attacks classifiable as migrainous disorder without aura (IHS 1.7) were evaluated in 13 patients using 20-mg sumatriptan nasal spray within a 10-week period. A 2-point decrease in headache severity on a four-point scale was achieved in 74% (95% confidence interval [CI], 50% to 89%) of the attacks within 2 hours. The pain-free incidence (a reduction in headache severity from moderate or severe to none) was 37% (95% CI, 17% to 63%) after 2 hours. Ten patients completed the second part of the study, taking oral sumatriptan for 14 migrainous attacks: a 2-point decrease in headache severity was achieved in 38% (95% CI, 13% to 71%) of the attacks within 2 hours and in 77% (95% CI, 48% to 92%) within 4 hours. This is the first prospective study to show that intranasal or oral sumatriptan may be effective in patients experiencing moderate to severe headache attacks which consistently do not fulfill the IHS criteria for migraine or episodic tension-type headache.

  20. 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

  1. 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

  2. Norfloxacin as prophylaxis against urethral strictures following transurethral resection of the prostate: an open, prospective, randomized study.

    Science.gov (United States)

    Hammarsten, J; Lindqvist, K

    1993-11-01

    An open, prospective, randomized study was performed to investigate the effect of norfloxacin prophylaxis on stricture formation and operative outcome after transurethral resection of the prostate. After resection, the 359 patients studied were randomly divided into 2 groups: 1) those given norfloxacin as prophylaxis for 15 days following removal of the catheter (norfloxacin group) and 2) those given no antimicrobial prophylaxis during the same period (control group). Of the patients 94 were excluded. At followup 6 to 12 months postoperatively, the number of strictures in the anterior urethra was 2 of 135 in the norfloxacin group and 22 of 130 in the control group (p norfloxacin group, fewer patients in that group were dissatisfied with the operative outcome. The results suggest that norfloxacin provides effective prophylaxis against stricture formation after transurethral resection of the prostate.

  3. 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.

  4. 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 hospital stay of RAS approach (p 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.

  5. Randomized comparison of low-dose versus high-dose interferon-alfa in chronic myeloid leukemia: prospective collaboration of 3 joint trials by the MRC and HOVON groups

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke C.; Buck, Georgina; le Cessie, Saskia; Richards, Sue; Beverloo, H. Berna; Falkenburg, J. H. Frederik; Littlewood, Tim; Muus, Petra; Bareford, David; van der Lelie, Hans; Green, Anthony R.; Roozendaal, Klaas J.; Milne, Alison E.; Chapman, Claire S.; Shepherd, Patricia

    2004-01-01

    The optimal dose of interferon-alfa (IFN) for chronic myeloid leukemia (CML) is unknown. Retrospective analyses suggest that low doses are as effective as high doses, with less toxicity and fewer patients abandoning the drug. The Dutch Hemato-Oncology Association (HOVON) and British Medical Research

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

    Science.gov (United States)

    Gaia Collaboration; 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.; Biermann, M.; Evans, D. W.; Eyer, L.; Jansen, F.; Klioner, S. A.; Lammers, U.; Luri, X.; Mignard, F.; Panem, C.; Pourbaix, D.; Randich, S.; Sartoretti, P.; Siddiqui, H. I.; Soubiran, C.; Valette, V.; Walton, N. A.; Aerts, C.; Arenou, F.; Cropper, M.; Drimmel, R.; Høg, E.; Katz, D.; Lattanzi, M. G.; O'Mullane, W.; Grebel, E. K.; Holland, A. D.; Huc, C.; Passot, X.; Perryman, M.; Bramante, L.; Cacciari, C.; Castañeda, J.; Chaoul, L.; Cheek, N.; De Angeli, F.; Fabricius, C.; Guerra, R.; Hernández, J.; Jean-Antoine-Piccolo, A.; Masana, E.; Messineo, R.; Mowlavi, N.; Nienartowicz, K.; Ordóñez-Blanco, D.; Panuzzo, P.; Portell, J.; Richards, P. J.; Riello, M.; Seabroke, G. M.; Tanga, P.; Thévenin, F.; Torra, J.; Els, S. G.; Gracia-Abril, G.; Comoretto, G.; Garcia-Reinaldos, M.; Lock, T.; Mercier, E.; Altmann, M.; Andrae, R.; Astraatmadja, T. L.; Bellas-Velidis, I.; Benson, K.; Berthier, J.; Blomme, R.; Busso, G.; Carry, B.; Cellino, A.; Clementini, G.; Cowell, S.; Creevey, O.; Cuypers, J.; Davidson, M.; De Ridder, J.; de Torres, A.; Delchambre, L.; Dell'Oro, A.; Ducourant, C.; Frémat, Y.; García-Torres, M.; Gosset, E.; Halbwachs, J.-L.; Hambly, N. C.; Harrison, D. L.; Hauser, M.; Hestroffer, D.; Hodgkin, S. T.; Huckle, H. E.; Hutton, A.; Jasniewicz, G.; Jordan, S.; Kontizas, M.; Korn, A. J.; Lanzafame, A. C.; Manteiga, M.; Moitinho, A.; Muinonen, K.; Osinde, J.; Pancino, E.; Pauwels, T.; Petit, J.-M.; Recio-Blanco, A.; Robin, A. C.; Sarro, L. M.; Siopis, C.; Smith, M.; Smith, K. W.; Sozzetti, A.; Thuillot, W.; van Reeven, W.; Viala, Y.; Abbas, U.; Abreu Aramburu, A.; Accart, S.; Aguado, J. J.; Allan, P. M.; Allasia, W.; Altavilla, G.; Álvarez, M. A.; Alves, J.; Anderson, R. I.; Andrei, A. H.; Anglada Varela, E.; Antiche, E.; Antoja, T.; Antón, S.; Arcay, B.; Bach, N.; Baker, S. G.; Balaguer-Núñez, L.; Barache, C.; Barata, C.; Barbier, A.; Barblan, F.; Barrado y Navascués, D.; Barros, M.; Barstow, M. A.; Becciani, U.; Bellazzini, M.; Bello García, A.; Belokurov, V.; Bendjoya, P.; Berihuete, A.; Bianchi, L.; Bienaymé, O.; Billebaud, F.; Blagorodnova, N.; Blanco-Cuaresma, S.; Boch, T.; Bombrun, A.; Borrachero, R.; Bouquillon, S.; Bourda, G.; Bouy, H.; Bragaglia, A.; Breddels, M. A.; Brouillet, N.; Brüsemeister, T.; Bucciarelli, B.; Burgess, P.; Burgon, R.; Burlacu, A.; Busonero, D.; Buzzi, R.; Caffau, E.; Cambras, J.; Campbell, H.; Cancelliere, R.; Cantat-Gaudin, T.; Carlucci, T.; Carrasco, J. M.; Castellani, M.; Charlot, P.; Charnas, J.; Chiavassa, A.; Clotet, M.; Cocozza, G.; Collins, R. S.; Costigan, G.; Crifo, F.; Cross, N. J. G.; Crosta, M.; Crowley, C.; Dafonte, C.; Damerdji, Y.; Dapergolas, A.; David, P.; David, M.; De Cat, P.; de Felice, F.; de Laverny, P.; De Luise, F.; De March, R.; de Martino, D.; de Souza, R.; Debosscher, J.; del Pozo, E.; Delbo, M.; Delgado, A.; Delgado, H. E.; Di Matteo, P.; Diakite, S.; Distefano, E.; Dolding, C.; Dos Anjos, S.; Drazinos, P.; Durán, J.; Dzigan, Y.; Edvardsson, B.; Enke, H.; Evans, N. W.; Eynard Bontemps, G.; Fabre, C.; Fabrizio, M.; Faigler, S.; Falcão, A. J.; Farràs Casas, M.; Federici, L.; Fedorets, G.; Fernández-Hernández, J.; Fernique, P.; Fienga, A.; Figueras, F.; Filippi, F.; Findeisen, K.; Fonti, A.; Fouesneau, M.; Fraile, E.; Fraser, M.; Fuchs, J.; Gai, M.; Galleti, S.; Galluccio, L.; Garabato, D.; García-Sedano, F.; Garofalo, A.; Garralda, N.; Gavras, P.; Gerssen, J.; Geyer, R.; Gilmore, G.; Girona, S.; Giuffrida, G.; Gomes, M.; González-Marcos, A.; González-Núñez, J.; González-Vidal, J. J.; Granvik, M.; Guerrier, A.; Guillout, P.; Guiraud, J.; Gúrpide, A.; Gutiérrez-Sánchez, R.; Guy, L. P.; Haigron, R.; Hatzidimitriou, D.; Haywood, M.; Heiter, U.; Helmi, A.; Hobbs, D.; Hofmann, W.; Holl, B.; Holland, G.; Hunt, J. A. S.; Hypki, A.; Icardi, V.; Irwin, M.; Jevardat de Fombelle, G.; Jofré, P.; Jonker, P. G.; Jorissen, A.; Julbe, F.; Karampelas, A.; Kochoska, A.; Kohley, R.; Kolenberg, K.; Kontizas, E.; Koposov, S. E.; Kordopatis, G.; Koubsky, P.; Krone-Martins, A.; Kudryashova, M.; Kull, I.; Bachchan, R. K.; Lacoste-Seris, F.; Lanza, A. F.; Lavigne, J.-B.; Le Poncin-Lafitte, C.; Lebreton, Y.; Lebzelter, T.; Leccia, S.; Leclerc, N.; Lecoeur-Taibi, I.; Lemaitre, V.; Lenhardt, H.; Leroux, F.; Liao, S.; Licata, E.; Lindstrøm, H. E. P.; Lister, T. A.; Livanou, E.; Lobel, A.; Löffler, W.; López, M.; Lorenz, D.; MacDonald, I.; Magalhães Fernandes, T.; Managau, S.; Mann, R. G.; Mantelet, G.; Marchal, O.; Marchant, J. M.; Marconi, M.; Marinoni, S.; Marrese, P. M.; Marschalkó, G.; Marshall, D. J.; Martín-Fleitas, J. M.; Martino, M.; Mary, N.; Matijevič, G.; Mazeh, T.; McMillan, P. J.; Messina, S.; Michalik, D.; Millar, N. R.; Miranda, B. M. H.; Molina, D.; Molinaro, R.; Molinaro, M.; Molnár, L.; Moniez, M.; Montegriffo, P.; Mor, R.; Mora, A.; Morbidelli, R.; Morel, T.; Morgenthaler, S.; Morris, D.; Mulone, A. F.; Muraveva, T.; Musella, I.; Narbonne, J.; Nelemans, G.; Nicastro, L.; Noval, L.; Ordénovic, C.; Ordieres-Meré, J.; Osborne, P.; Pagani, C.; Pagano, I.; Pailler, F.; Palacin, H.; Palaversa, L.; Parsons, P.; Pecoraro, M.; Pedrosa, R.; Pentikäinen, H.; Pichon, B.; Piersimoni, A. M.; Pineau, F.-X.; Plachy, E.; Plum, G.; Poujoulet, E.; Prša, A.; Pulone, L.; Ragaini, S.; Rago, S.; Rambaux, N.; Ramos-Lerate, M.; Ranalli, P.; Rauw, G.; Read, A.; Regibo, S.; Reylé, C.; Ribeiro, R. A.; Rimoldini, L.; Ripepi, V.; Riva, A.; Rixon, G.; Roelens, M.; Romero-Gómez, M.; Rowell, N.; Royer, F.; Ruiz-Dern, L.; Sadowski, G.; Sagristà Sellés, T.; Sahlmann, J.; Salgado, J.; Salguero, E.; Sarasso, M.; Savietto, H.; Schultheis, M.; Sciacca, E.; Segol, M.; Segovia, J. C.; Segransan, D.; Shih, I.-C.; Smareglia, R.; Smart, R. L.; Solano, E.; Solitro, F.; Sordo, R.; Soria Nieto, S.; Souchay, J.; Spagna, A.; Spoto, F.; Stampa, U.; Steele, I. A.; Steidelmüller, H.; Stephenson, C. A.; Stoev, H.; Suess, F. F.; Süveges, M.; Surdej, J.; Szabados, L.; Szegedi-Elek, E.; Tapiador, D.; Taris, F.; Tauran, G.; Taylor, M. B.; Teixeira, R.; Terrett, D.; Tingley, B.; Trager, S. C.; Turon, C.; Ulla, A.; Utrilla, E.; Valentini, G.; van Elteren, A.; Van Hemelryck, E.; vanLeeuwen, M.; Varadi, M.; Vecchiato, A.; Veljanoski, J.; Via, T.; Vicente, D.; Vogt, S.; Voss, H.; Votruba, V.; Voutsinas, S.; Walmsley, G.; Weiler, M.; Weingrill, K.; Wevers, T.; Wyrzykowski, Ł.; Yoldas, A.; Žerjal, M.; Zucker, S.; Zurbach, C.; Zwitter, T.; Alecu, A.; Allen, M.; Allende Prieto, C.; Amorim, A.; Anglada-Escudé, G.; Arsenijevic, V.; Azaz, S.; Balm, P.; Beck, M.; Bernstein, H.-H.; Bigot, L.; Bijaoui, A.; Blasco, C.; Bonfigli, M.; Bono, G.; Boudreault, S.; Bressan, A.; Brown, S.; Brunet, P.-M.; Bunclark, P.; Buonanno, R.; Butkevich, A. G.; Carret, C.; Carrion, C.; Chemin, L.; Chéreau, F.; Corcione, L.; Darmigny, E.; de Boer, K. S.; de Teodoro, P.; de Zeeuw, P. T.; Delle Luche, C.; Domingues, C. D.; Dubath, P.; Fodor, F.; Frézouls, B.; Fries, A.; Fustes, D.; Fyfe, D.; Gallardo, E.; Gallegos, J.; Gardiol, D.; Gebran, M.; Gomboc, A.; Gómez, A.; Grux, E.; Gueguen, A.; Heyrovsky, A.; Hoar, J.; Iannicola, G.; Isasi Parache, Y.; Janotto, A.-M.; Joliet, E.; Jonckheere, A.; Keil, R.; Kim, D.-W.; Klagyivik, P.; Klar, J.; Knude, J.; Kochukhov, O.; Kolka, I.; Kos, J.; Kutka, A.; Lainey, V.; LeBouquin, D.; Liu, C.; Loreggia, D.; Makarov, V. V.; Marseille, M. G.; Martayan, C.; Martinez-Rubi, O.; Massart, B.; Meynadier, F.; Mignot, S.; Munari, U.; Nguyen, A.-T.; Nordlander, T.; O'Flaherty, K. S.; Ocvirk, P.; Olias Sanz, A.; Ortiz, P.; Osorio, J.; Oszkiewicz, D.; Ouzounis, A.; Palmer, M.; Park, P.; Pasquato, E.; Peltzer, C.; Peralta, J.; Péturaud, F.; Pieniluoma, T.; Pigozzi, E.; Poels, J.; Prat, G.; Prod'homme, T.; Raison, F.; Rebordao, J. M.; Risquez, D.; Rocca-Volmerange, B.; Rosen, S.; Ruiz-Fuertes, M. I.; Russo, F.; Sembay, S.; Serraller Vizcaino, I.; Short, A.; Siebert, A.; Silva, H.; Sinachopoulos, D.; Slezak, E.; Soffel, M.; Sosnowska, D.; Straižys, V.; ter Linden, M.; Terrell, D.; Theil, S.; Tiede, C.; Troisi, L.; Tsalmantza, P.; Tur, D.; Vaccari, M.; Vachier, F.; Valles, P.; Van Hamme, W.; Veltz, L.; Virtanen, J.; Wallut, J.-M.; Wichmann, R.; Wilkinson, M. I.; Ziaeepour, H.; Zschocke, S.

    2017-05-01

    Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims: We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods: Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results: Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions: The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs. Tables D.1 to D.19 are also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/601/A

  7. 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.

  8. 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.

  9. 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

  10. Prospective comparison of open vs. laparoscopic colon surgery for carcinoma. Five-year results.

    Science.gov (United States)

    Franklin, M E; Rosenthal, D; Abrego-Medina, D; Dorman, J P; Glass, J L; Norem, R; Diaz, A

    1996-10-01

    Laparoscopy for colonic diseases began in 1990 and has established a role in benign disease. Early observations and experiences demonstrated feasibility of laparoscopic surgery for a variety of colonic disease processes, but the applicability to colonic carcinoma was unclear. In 1990, we began a comparative study of open (OCR) vs. laparoscopic (LCR) approach to colon cancer. The study progressed 65 months, with 224 patients in OCR group and 191 patients in LCR group. Parameters studied are stage, location, length of specimen, number of lymph nodes resected, margins, postoperative course, wound complications, recurrence rates, and immediate and long-term survival. OCR were standardized by one group, and LCR were standardized by a second group. All patients undergoing LCR were given freedom to choose either OCR or LCR, and informed consent was obtained. Equal or greater lymph node retrieval, resections, and distal margins were evident with LCR. Benefits with LCR were shown with shorter hospitalization (5.7 vs. 9.7 days), less blood loss, less wound problems (1 vs. 14), and quicker return of bowel function. Survival, recurrence, and death rates were essentially the same. There were no trocar implants in the LCR group. After five years, this study shows that laparoscopy does no harm to the patient, offers comparable oncologic resections, and seems to be patient-friendly, with less pain, quicker return of bowel functions, shortened hospitalization, and quicker return to full activity.

  11. In-office, multisinus balloon dilation: 1-Year outcomes from a prospective, multicenter, open label trial.

    Science.gov (United States)

    Gould, James; Alexander, Ian; Tomkin, Edward; Brodner, David

    2014-01-01

    The objective of this prospective, multicenter study was to assess 1-year changes in sinonasal symptoms and health care use after office-based multisinus balloon dilation. Adults diagnosed with chronic or recurrent acute rhinosinusitis per the 2007 adult sinusitis guidelines were enrolled in this Institutional Review Board-approved study. Balloon dilation of the maxillary sinuses/ethmoid infundibula with or without frontal or sphenoid ostial dilation was performed in the physician's office under local anesthesia. Intraoperative procedure technical success and subject procedure tolerance were recorded. Efficacy was assessed using the patient-reported 20-item Sino-Nasal Outcome Test (SNOT-20) and Rhinosinusitis Symptom Inventory (RSI). Complications and revision surgeries were also recorded. A total of 313 ostial dilations were attempted and 307 were successfully completed (98.1%) in 81 subjects. Mean procedure tolerance was 2.8 ± 2.2 (0 = no pain; 10 = severe pain). Clinically meaningful and statistically significant (p < 0.0001) mean SNOT-20 symptom improvement was observed at 1 and 6 months and sustained through 1 year. The RSI treatment effect for all major rhinosinusitis symptoms was "large" and improvement in each was significant (p < 0.0001). Compared with the previous 1-year period, patients reported an average of 2.3 fewer acute sinus infections (p < 0.0001), 2.4 fewer antibiotic courses taken (p < 0.0001), and 3.0 fewer sinus-related physician visits (p < 0.0001) after balloon dilation. No serious device or procedure-related adverse events occurred. One subject (1.3%) underwent revision surgery. In-office, multisinus balloon dilation is safe, effective, and well tolerated. Patients reported significant reductions in both sinonasal symptoms and health care use after balloon dilation. Efficacy observed at 1 and 6 month follow-up was sustained through 1 year with a very low rate of revision surgery. This study was a part of the clinical trial NCT01612780

  12. 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…

  13. Interferon Alpha in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Timothy B. Niewold

    2010-01-01

    Full Text Available The pleiotropic cytokine interferon alpha is involved in multiple aspects of lupus etiology and pathogenesis. Interferon alpha is important under normal circumstances for antiviral responses and immune activation. However, heightened levels of serum interferon alpha and expression of interferon response genes are common in lupus patients. Lupus-associated autoantibodies can drive the production of interferon alpha and heightened levels of interferon interfere with immune regulation. Several genes in the pathways leading to interferon production or signaling are associated with risk for lupus. Clinical and cellular manifestations of excess interferon alpha in lupus combined with the genetic risk factors associated with interferon make this cytokine a rare bridge between genetic risk and phenotypic effects. Interferon alpha influences the clinical picture of lupus and may represent a therapeutic target. This paper provides an overview of the cellular, genetic, and clinical aspects of interferon alpha in lupus.

  14. 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.

  15. Extracorporeal shock wave therapy for the treatment of poststroke plantar-flexor muscles spasticity: a prospective open-label study.

    Science.gov (United States)

    Santamato, Andrea; Micello, Maria Francesca; Panza, Francesco; Fortunato, Francesca; Logroscino, Giancarlo; Picelli, Alessandro; Manganotti, Paolo; Smania, Nicola; Fiore, Pietro; Ranieri, Maurizio

    2014-01-01

    To assess the use of extracorporeal shock wave therapy (ESWT) for the treatment of equinus foot after stroke and to correlate the ESWT effect on spastic plantar-flexor muscles with echo intensity on the Heckmatt scale. The prospective open-label study examined 23 patients with poststroke lower limb spasticity. Adults with spastic equinus foot after stroke received one ESWT session on hypertonic plantar-flexor muscles. The effect on spasticity, degree of passive ankle dorsiflexion, and neurophysiological values were evaluated. Before treatment, participants underwent a sonography evaluation of calf muscles to identify echo intensity on the Heckmatt scale. Immediately after the session, ESWT induced a statistically significant reduction in muscle tone, increasing passive ankle dorsiflexion motion. At 30 days of follow-up, the effect persisted only in patients with echo intensity of spastic plantar-flexor muscles graded I, II, or III on the Heckmatt scale without any action related to spinal excitability. Mild adverse events were reported after the treatment but were resolved in a few days. ESWT is safe and efficacious for the treatment of poststroke plantar-flexor muscles spasticity, reducing muscle tone and improving passive ankle dorsiflexion motion. The effect was long lasting in subjects with echo intensity of calf muscles graded I, II, or III but was brief for echo intensity graded IV on the Heckmatt scale. The ESWT effect did not appear to be related to spinal excitability.

  16. 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.

  17. PTH(1-34) for Surgical Hypoparathyroidism: A Prospective, Open-Label Investigation of Efficacy and Quality of Life.

    Science.gov (United States)

    Santonati, Assunta; Palermo, Andrea; Maddaloni, Ernesto; Bosco, Daniela; Spada, Antonio; Grimaldi, Franco; Raggiunti, Bruno; Volpe, Raffaele; Manfrini, Silvia; Vescini, Fabio

    2015-09-01

    Conventional therapy for hypoparathyroidism consists of calcium and calcitriol, but sometimes normal serum calcium cannot be maintained, and/or this approach might lead to nephrocalcinosis, nephrolithiasis, or renal insufficiency. The objective of the study was to investigate the effects of 6 months of PTH(1-34) treatment in adult subjects with postoperative hypoparathyroidism and to evaluate quality-of-life changes. This was a 2-year prospective, open-label study. At baseline and after 6 months of PTH(1-34) treatment, calcium and vitamin D supplementation requirements, serum calcium, phosphate, creatinine, alkaline phosphatase, uric acid, and 24-hour urinary calcium excretion were evaluated. Quality of life was evaluated by the Rand 36-Item Short Form Health Survey covering eight domains of physical and mental health. This was an Italian multicentric study. Participants included 42 subjects with surgical hypoparathyroidism (90% females, age range 34-77 y). The intervention included a twice-daily PTH(1-34) 20 μg sc injection. The mean serum calcium levels significantly increased from baseline to 15 days (7.6 ± 0.6 vs 9.1 ± 0.9 mg/dL, P hypoparathyroidism, and it shows that PTH(1-34) may improve the mental and physical health in hypoparathyroid subjects.

  18. 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...

  19. Open fractures of the tibia treated by immediate intramedullary tibial nail insertion without reaming: a prospective study.

    Science.gov (United States)

    Kakar, S; Tornetta, P

    2007-03-01

    Does immediate tibial nail insertion without reaming as part of protocol-driven management provide a safe and effective treatment for open tibia fractures? Prospective cohort. Level 1 trauma center. A consecutive series of 161 patients with Gustilo grade I-IIIb open tibia fractures. Emergent incision and debridement of the wound with immediate tibial nail insertion without reaming, repeat incision and debridement, and soft-tissue coverage within 14 days. Time to union, number of secondary procedures performed to obtain union, implant failures, and the type and incidence of complications. One hundred and forty-three fractures were followed to union. Follow up averaged 2.2 years (0.6-5.5 years). Seventy-six fractures united in less than 6 months, 35 took between 6 and 9 months, and 32 took longer than 9 months. Twenty-five additional procedures were needed to obtain union in 16 of the delayed unions (12 nail exchanges, 4 bone grafts, 9 dynamizations). Complications included 3 patients with cellulitis, 1 superficial infection, 4 deep infections (1 grade I, 2 grade II, 1 grade IIIb), 3 loose screws, 2 broken screws, 5 malunions greater than 5 degrees, and 30 patients with decreased ankle motion when compared with the uninjured side. Not counting the ankle loss of motion, 18 complications occurred in 143 fractures (13%). Twenty-nine patients (20%) had complaints of minor knee pain and 30 (21%) had occasional fracture site pain after activity despite clinical and radiographic evidence of union. Eleven patients (8%) considered themselves completely disabled. Five patients were not treated by the standard protocol and are not included in the previously listed statistics; 3 were grade IIIB that did not have adequate coverage by 14 days, and 2 were grade II injuries that did not have a second debridement. Four of these 5 patients developed a complication. Protocol-driven management emphasizing meticulous soft-tissue management and the use of immediate tibial nailing without

  20. 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.

  1. 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....

  2. Prospective, randomized evaluation of endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome: an interim analysis.

    Science.gov (United States)

    Michelotti, Brett; Romanowsky, Diane; Hauck, Randy M

    2014-12-01

    Most randomized trials have shown similar results with endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR); however, there are studies suggesting less postoperative pain, faster improvement in grip and pinch strength, and earlier return to work with the endoscopic technique. The goal of this study was to prospectively examine subjective and functional outcomes, satisfaction, and complications after both ECTR and OCTR in the opposite hands of the same patient, serving as their own control. This was a prospective, randomized study in which patients underwent surgery for bilateral carpal tunnel syndrome. The first carpal tunnel release was performed on the most symptomatic hand-determined by the patient. Operative approach was randomly assigned and, approximately 1 month later, the alternative technique was performed on the contralateral side. Demographic data were obtained, and functional outcomes were recorded preoperatively and postoperatively, including pain score, 2-point discrimination, Semmes-Weinstein monofilament testing, thenar strength, and overall grip strength. The carpal tunnel syndrome-functional status score and carpal tunnel syndrome-symptom severity score were recorded before surgery and at 2, 4, 8, 12, and 24 weeks postoperatively. Overall satisfaction with each technique was recorded at the conclusion of the study. Currently, 25 subjects have completed final visit testing. There were no differences in pain score, 2-point discrimination, Semmes-Weinstein monofilament testing, thenar strength, or overall grip strength at any of the postoperative time points. Carpal tunnel syndrome-symptom severity score and carpal tunnel syndrome-functional status score were not significantly different between groups at any of the evaluations. Overall satisfaction, where patients recorded a number from 0 to 100, was significantly greater in the ECTR group (95.95 vs 91.60, P = 0.04). There were no complications with either technique. This

  3. 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.

  4. 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

  5. [Hernia recurrence long term follow-up after open procedures of abdominal wall plasty-prospective study including 142 patients].

    Science.gov (United States)

    Mureşan, Mircea; Mureşan, Simona; Bara, Tivadar; Neagoe, Radu; Sala, Daniela; Suciu, Bogdan

    2016-01-01

    The incisional hernia continues to be a frequent complication of laparotomies. The purpose of study is the analysis of hernia disease relapse after one year after different open plasties methods of the abdominal wall. A prospective longitudinal study was performed that included 142 patients. An analysis was performed on the individual data, the level of obesity, intra-surgical variations in intra-abdominal pressure, the intensity of post-surgical pain, the post-surgical complications, and the types of plasties of abdominal wall, simple and with polypropylene mesh. The analysis of studied group showed a general rate of relapse of 16.9%, and within the 4 procedures, 40.74% in the case of simple plasties, of 16.07% after the only plasties, 6.97% after the retro-muscular plasties, and 6.25% after the full substitution of parietal defect. On analysing the collected, hernia relapse was statistically significantly related to the level of obesity, variations in intra-abdominal pressure, post-surgical pain, and the type of procedure performed. Hernia is a frequent complication of laparotomies. Hernia relapse was more frequent in the case of simple plasties. Among the mesh procedures, the onlay plasty showed a higher rate of relapse and post-surgical complications. Hernia relapse was more frequent in the case of variations of intra-abdominal pressure, and with increased post-surgical pain. The use of an echography examination may increase the accuracy of the presence of hernia disease. Copyright © 2015 Academia Mexicana de Cirugía A.C. All rights reserved.

  6. 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.

  7. Arthroscopic Versus Open Latarjet in the Treatment of Recurrent Anterior Shoulder Dislocation With Marked Glenoid Bone Loss: A Prospective Comparative Study.

    Science.gov (United States)

    Zhu, Yiming; Jiang, Chunyan; Song, Guanyang

    2017-06-01

    Very few studies have compared open Latarjet versus arthroscopic Latarjet procedures. To compare the clinical and computed tomographic outcomes between open and arthroscopic Latarjet procedures. Cohort study; Level of evidence, 3. A prospective, comparative study was performed. The open Latarjet group included 44 patients, and the arthroscopic Latarjet group included 46 patients. All patients had more than 2 years of clinical follow-up (range of motion, American Shoulder and Elbow Surgeons [ASES] score, Constant-Murley score, and Rowe score). The position of the transferred coracoid, the screw orientation, and graft resorption were evaluated on computed tomography (CT) scan. The surgery time for the open group was significantly shorter than that for the arthroscopic group ( P = .003). No recurrent dislocation occurred in either group. The apprehension test was negative in all patients in both groups. At the final follow-up, no significant difference was detected between the open group and the arthroscopic group regarding any of the clinical outcome measurements. The transferred coracoid graft was level with the glenoid in all patients in both groups. The open group had better position in the superior-inferior direction compared with the arthroscopic group ( P Latarjet group showed notably less graft resorption compared with patients in the open Latarjet group.

  8. 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.

  9. Risk Factors for Motor Vehicle Collisions in Patients with Primary Open-Angle Glaucoma: A Multicenter Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Kenya Yuki

    Full Text Available To identify the incidence rate of motor vehicle collisions (MVCs in patients with no ocular pathology other than primary open-angle glaucoma (POAG and determine the putative risk factors for MVCs in this group of patients.We designed a prospective cohort study across three centers utilizing a consecutive sampling method to identify all patients with POAG between the ages of 40 and 80 years old. Patients with glaucoma were consecutively screened for eligibility. All study participants answered a questionnaire about motor vehicle collisions at baseline, and answered the questionnaire again every 12 months (± 1 month after baseline for three years. A binocular integrated visual field was calculated for each patient by merging a patient's monocular Humphrey Field Analyzer (HFA visual fields (VFs, using the 'best sensitivity' method. Patients with incident MVCs were defined as the "MVC+" group and patients without incident MVCs were defined as the "MVC-" group. Adjusted odds ratios for the incidence of MVCs were estimated with a logistic regression model.One hundred and ninety-one Japanese POAG patients were analyzed in this study. The age of the participants was 63.7 ± 10.2 [mean ± standard deviation]. A total of 28 participants experienced a MVC during the follow up period of three years (4.9% per year. Ten patients (5.2% experienced a MVC in the first year, 13 patients (6.8% in the second year, and 11 patients (5.8% in the third year (some patients experienced multiple MVCs over different years. Best corrected visual acuity in the worst eye was significantly worse in the MVC+ group (0.03 ± 0.01, mean ± standard deviation, LogMar compared with the MVC- group (0.01 ± 0.003, p = 0.01, and was the only variable identified as a significant predictor of future MVCs in the multiple logistic regression model [odds ratio: 1.2, 95% confidence interval (CI: 1.1 to 1.4].Deterioration in visual acuity in the worst eye is a risk factor for future MVCs in

  10. Discontinuation and restarting in patients on statin treatment: prospective open cohort study using a primary care database

    Science.gov (United States)

    Coupland, Carol; Brindle, Peter; Hippisley-Cox, Julia

    2016-01-01

    Objectives To estimate rates of discontinuation and restarting of statins, and to identify patient characteristics associated with either discontinuation or restarting. Design Prospective open cohort study. Setting 664 general practices contributing to the Clinical Practice Research Datalink in the United Kingdom. Data extracted in October 2014. Participants Incident statin users aged 25-84 years identified between January 2002 and September 2013. Patients with statin prescriptions divided into two groups: primary prevention and secondary prevention (those already diagnosed with cardiovascular disease). Patients with statin prescriptions in the 12 months before study entry were excluded. Main outcome measures Discontinuation of statin treatment (first 90 day gap after the estimated end date of a statin prescription), and restarting statin treatment for those who discontinued (defined as any subsequent prescription between discontinuation and study end). Results Of 431 023 patients prescribed statins as primary prevention with a median follow-up time of 137 weeks, 47% (n=204 622) discontinued treatment and 72% (n=147 305) of those who discontinued restarted. Of 139 314 patients prescribed statins as secondary prevention with median follow-up time of 182 weeks, 41% (n=57 791) discontinued treatment and 75% (43 211) of those who discontinued restarted. Younger patients (aged ≤50 years), older patients (≥75 years), women, and patients with chronic liver disease were more likely to discontinue statins and less likely to restart. However, patients in ethnic minority groups, current smokers, and patients with type 1 diabetes were more likely to discontinue treatment but then were more likely to restart, whereas patients with hypertension and type 2 diabetes were less likely to discontinue treatment and more likely to restart if they did discontinue. These results were mainly consistent in the primary prevention and secondary prevention groups

  11. Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: a prospective, open-label, randomised controlled trial.

    Science.gov (United States)

    Khalafallah, Alhossain A; Yan, Carl; Al-Badri, Raghad; Robinson, Ella; Kirkby, Brooke E; Ingram, Emily; Gray, Zara; Khelgi, Vinod; Robertson, Iain K; Kirkby, Brian P

    2016-09-01

    Despite increasing efforts in perioperative management, postoperative iron deficiency anaemia persists, and few data are available about the management of this condition. In this study, we aimed to determine whether giving postoperative intravenous iron (in the form of ferric carboxymaltose) improved iron stores, haemoglobin concentrations, and outcomes following surgery. We did a prospective, open-label, randomised, controlled study of patients at two centres (a general hospital and a private health-care centre) in Tasmania, Australia, undergoing elective surgery with functional iron deficiency anaemia (haemoglobin 70-120 g/L and ferritin ≤100 μg/L or iron saturation ≤20%), measured at day 1 postoperatively. Consecutive routine elective surgical patients who were having major orthopaedic surgery, abdominal, and genitourinary surgery, and other surgeries were recruited. Via computer-generated randomisation, patients were randomly assigned (1:1) to either a single dose of intravenous 1000 mg ferric carboxymaltose (intervention group) or standard care, consisting of observation (control group). The primary endpoints were changes in haemoglobin concentrations and iron stores at 4 weeks postoperatively, and the number of transfused units of blood required postoperatively until discharge. Analyses were done on an intention-to-treat basis. This trial is registered with the Australian New Zealand Clinical Trials Registry and the WHO International Clinical Trials Registry platform (number ACTRN12614001261606). Between Dec 17, 2014, and May 7, 2015, we recruited 201 eligible patients, assigning 103 to intravenous ferric carboxymaltose and 98 to standard care only. Baseline mean haemoglobin was 105·5 g/L (SD 13·8) in the standard care group versus 106·2 g/L (11·9) in the ferric carboxymaltose group, improving at 4 weeks to 121·5 g/L (SD 14·5) in the standard group and 130·1 g/L (11·3) in the ferric carboxymaltose group (mean difference of 7·84 g/L, 95% CI 3·79

  12. 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.

  13. Dermatomyositis and Type 1 Interferons

    Science.gov (United States)

    2010-01-01

    Dermatomyositis is a poorly understood multisystem disease predominantly affecting skin and muscle. This review focuses on the potential role of a group of related cytokines, the type 1 interferons, in the pathogenesis of dermatomyositis. Type 1 interferon–inducible transcripts and proteins are uniquely elevated in dermatomyositis muscle compared with all other muscle diseases studied to date. The endothelial cell tubuloreticular inclusions present in affected dermatomyositis muscle are biomarkers of type 1 interferon exposure. The cell-poor lichenoid reaction in skin with predominant involvement of the basal epidermal cell layer and its topologic equivalent in muscle, perifascicular atrophy, may be lesions that develop directly in response to type 1 interferon signaling. PMID:20425524

  14. Interferon Beta-1a Subcutaneous Injection

    Science.gov (United States)

    Interferon beta-1a subcutaneous injection is used to reduce episodes of symptoms and slow the development of disability in ... problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications called ...

  15. Interferon Beta-1a Intramuscular Injection

    Science.gov (United States)

    Interferon beta-1a intramuscular injection is used to reduce the number of episodes of symptoms and slow the development ... problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications called ...

  16. 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.

  17. Patient satisfaction following transition from the original to the new formulation of subcutaneous interferon beta-1a in relapsing multiple sclerosis: a randomized, two-arm, open-label, Phase IIIb study

    Directory of Open Access Journals (Sweden)

    William Camu

    2010-05-01

    Full Text Available William Camu1, Karim Hadjout2, Sabine Latour3, Dieter Pöhlau4, Said Masri51MS Clinic, CHU Gui de Chauliac, University of Montpellier I, Montpellier, France; 2Department of Neurology, Centre Hospitalier, Rodez, France; 3Merck Serono S.A. – Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany; 4Multiple Sclerosis Center, Kamillus-Klinik Asbach, Asbach, Germany; 5Praxis Masri, Berlin, GermanyObjective: To assess satisfaction with the serum-free formulation of subcutaneous (sc interferon (IFN beta-1a among patients with relapsing multiple sclerosis (MS.Methods: Patients with relapsing MS who had been receiving sc IFN beta-1a for at least 6 months, were transitioned to the new formulation, 44 μg three times weekly. Patients were randomized to preventative ibuprofen (400 mg 30–60 minutes prior to injection or ibuprofen as needed (PRN for 4 weeks. The primary endpoint was the ‘flu-like’ symptom (FLS domain score of the validated Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ.Results: Of the 117 patients enrolled, 109 (93.2% completed the study. Neither group’s MSTCQ FLS score showed a clinically meaningful change from baseline to week 4: mean ± SD changes were -1.1 ± 4.4 in the preventative ibuprofen group and 0.8 ± 3.6 in the ibuprofen PRN group. MSTCQ injection system satisfaction and global side-effect scores were unchanged; total and injection-site reaction scores improved moderately in both groups between baseline and week 4.Conclusions: Results showed continued or increased levels of satisfaction with the new formulation of sc IFN beta-1a. FLS occurring with the new formulation were generally mild and seldom sufficiently bothersome to require ibuprofen treatment.Keywords: multiple sclerosis, tolerability, ibuprofen, flu-like symptoms

  18. 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.

  19. A prospective study of closed and open reamed intramedullary nailing of 136 femoral shaft fractures in adults

    OpenAIRE

    Mohammad Gharehdaghi; Hasan Rahimi; Mahmoud Bahari; Javad Afzali

    2007-01-01

    BACKGROUND: Femoral shaft fractures are major causes of mortality and morbidity and are managed with intramedullary nailing (IMN). In this study we compared the results of open and closed nailing in femoral shaft fractures. Between 1993 and 2001 we managed 136 femoral shaft fractures by IMN (81 closed and 55 open nailings)
    METHODS: in 120 patients with mean age of 36.2 years. The mean time of follow up was two years. Radiolo...

  20. An ELISpot assay, measuringBorrelia burgdorferiB31-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

    2018-01-24

    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 immunospot (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 number of B. burgdorferi B31-specific IFN-γ secreting T-cells/2.5x10 5 PBMCs did not differ between active Lyme neuroborreliosis patients, treated Lyme neuroborreliosis patients and treated healthy individuals (6.0, interquartile range (IQR): 0.5 - 14.0; 4.5, IQR: 2.0 - 18.6; 7.4, IQR: 2.3 - 14.9; respectively) ( p 1.000); however, the median number of B. burgdorferi B31-specific IFN-γ secreting T-cells/2.5x10 5 PBMCs among untreated healthy individuals was lower (2.0, IQR: 0.5 - 3.9) ( p ≤0.016).We conclude that the Borrelia ELISpot, measuring the number of B. burgdorferi B31-specific INF-γ secreting T-cells/2.5x10 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.

  1. Effect of interferon treatment on glucose metabolism in children with chronic hepatitis B infection.

    Science.gov (United States)

    Kuloğlu, Zarife; Kansu, Aydan; Berberoğlu, Merih; Demirçeken, Fulya; Ocal, Gönül; Girgin, Nurten

    2004-03-01

    Interferon is known to have some effects on glucose metabolism, but this issue has not been investigated in children with chronic hepatitis B infection. The aim of this study was to investigate the impact of interferon on glucose metabolism and to investigate whether autoimmunity has a role in the pathogenesis. Fourteen patients (9 male, 6.3+/-2.7 years) with children with chronic hepatitis B infection were prospectively evaluated. They received interferon 10 MU/m2 for six months. Vral glucose tolerance test, fasting insulin and C-peptide, postprandial insulin and C-peptide, anti-GAD antibody, HOMA-IR and glucose/insulin ratio were measured before and after treatment. Before interferon, oral glucose tolerance test showed glucose intolerance in two patients (14.5%) and hypoglycemia in one patient (7.1%). One patient had hyperinsulinemia and insulin resistance (7.1%), and four patients had hypoinsulinemia and insulin hypersensitivity (28.5%). After interferon, oral glucose tolerance test was normal in 13 patients (92.8%). Abnormal oral glucose tolerance test persisted in the same patient, but no difference was found in insulin resistance. Hypoinsulinemia and insulin hypersensitivity were present in five patients (35.7%). DM related autoantibodies were negative in all patients before interferon; however, one patient, whose glucose metabolism was within normal limits, developed anti-GAD antibody after interferon. Children with children with chronic hepatitis B infection were shown to have hypoinsulinemia and insulin hypersensitivity. These children may have risk of progresssing to insuline dependent drabetes mellitus. We demonstrated that interferon did not seem to worsen glucose metabolism, but it had minimal positive impact on it. These results should be supported with other studies and interferon should be used carefully, especially in children with decreased beta cell reserve.

  2. A Prospective Longitudinal Study of U.S. Children Unable to Achieve Open-Set Speech Recognition 5 Years After Cochlear Implantation.

    Science.gov (United States)

    Barnard, Jennifer M; Fisher, Laurel M; Johnson, Karen C; Eisenberg, Laurie S; Wang, Nae-Yuh; Quittner, Alexandra L; Carson, Christine M; Niparko, John K

    2015-07-01

    To identify characteristics associated with the inability to progress to open-set speech recognition in children 5 years after cochlear implantation. Prospective, longitudinal, and multidimensional assessment of auditory development for 5 years. Six tertiary cochlear implant (CI) referral centers in the United States. Children with severe-to-profound hearing loss who underwent implantation before age 5 years enrolled in the Childhood Development after Cochlear Implantation study, categorized by level of speech recognition ability. Cochlear implantation before 5 years of age and annual assessment of emergent speech recognition skills. Progression to open-set speech recognition by 5 years after implantation. Less functional hearing before implantation, older age at onset of amplification, lower maternal sensitivity to communication needs, minority status, and complicated perinatal history were associated with the inability to obtain open-set speech recognition by 5 years. Characteristics of a subpopulation of children with CIs associated with an inability to achieve open-set speech recognition after 5 years of CI experience were investigated. These data distinguish pediatric CI recipients at risk for poor auditory development and highlight areas for future interventions to enhance support of early implantation.

  3. Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group.

    Science.gov (United States)

    Glue, P; Fang, J W; Rouzier-Panis, R; Raffanel, C; Sabo, R; Gupta, S K; Salfi, M; Jacobs, S

    2000-11-01

    The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.

  4. 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) (Pcannabis 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.

  5. The effect of time delay on infection in open long-bone fractures: a 5-year prospective audit from a district general hospital.

    Science.gov (United States)

    Spencer, Jonathan; Smith, Andrew; Woods, David

    2004-03-01

    To determine whether a time delay of greater than 6 h from injury to surgical debridement affected the infection rate in open long-bone fractures in a typical district general hospital in the UK. Prospective audit over 5 years. 142 open long-bone fractures in 130 patients were seen over a 5-year period between 1996 and 2001 in our hospital. 115 fractures in 103 patients were available for study. The data were collected prospectively in weekly audit meetings. Patients were followed until clinical or radiological union occurred or until a secondary procedure for non-union or infection was carried out. Surgical debridement was carried out in less than 6 h from injury in 60% of cases and in greater than 6 h from injury in 40% of cases. Infection rates were 10.1% and 10.8%, respectively. We could not demonstrate a significantly increased infection rate in patients in whom surgical debridement occurred greater than 6 h after injury.

  6. The Outcomes of Minimally Invasive versus Open Posterior Approach Spinal Fusion in Treatment of Lumbar Spondylolisthesis: The Current Evidence from Prospective Comparative Studies.

    Science.gov (United States)

    Wu, Ai-Min; Chen, Chun-Hui; Shen, Zhi-Hao; Feng, Zhen-Hua; Weng, Wan-Qing; Li, Shu-Min; Chi, Yong-Long; Yin, Li-Hui; Ni, Wen-Fei

    2017-01-01

    Purpose . To investigate the evidence of minimally invasive (MI) versus open (OP) posterior lumbar fusion in treatment of lumbar spondylolisthesis from current prospective literatures. Methods . The electronic literature database of Pubmed, Embase, and Cochrane library was searched at April 2016. The data of operative time, estimated blood loss and length of hospital stay, visual analog scale (VAS) of both lower back pain and leg pain, Oswestry disability index (ODI), SF-36 PCS (physical component scores) and SF-36 MCS (mental component scores), complications, fusion rate, and secondary surgery were extracted and analyzed by STATA 12.0 software. Results . Five nonrandom prospective comparative studies were included in this meta-analysis. The meta-analysis showed that the MI group had a significantly longer operative time than OP group, less blood loss, and shorter hospital stay. No significant difference was found in back pain, leg pain, ODI, SF-36 PCS, SF-36 MCS, complications, fusion rate, and secondary surgery between MI and OP groups. Conclusion . The prospective evidence suggested that MI posterior fusion for spondylolisthesis had less EBL and hospital stay than OP fusion; however it took more operative time. Both MI and OP fusion had similar results in pain and functional outcomes, complication, fusion rate, and secondary surgery.

  7. The Outcomes of Minimally Invasive versus Open Posterior Approach Spinal Fusion in Treatment of Lumbar Spondylolisthesis: The Current Evidence from Prospective Comparative Studies

    Directory of Open Access Journals (Sweden)

    Ai-Min Wu

    2017-01-01

    Full Text Available Purpose. To investigate the evidence of minimally invasive (MI versus open (OP posterior lumbar fusion in treatment of lumbar spondylolisthesis from current prospective literatures. Methods. The electronic literature database of Pubmed, Embase, and Cochrane library was searched at April 2016. The data of operative time, estimated blood loss and length of hospital stay, visual analog scale (VAS of both lower back pain and leg pain, Oswestry disability index (ODI, SF-36 PCS (physical component scores and SF-36 MCS (mental component scores, complications, fusion rate, and secondary surgery were extracted and analyzed by STATA 12.0 software. Results. Five nonrandom prospective comparative studies were included in this meta-analysis. The meta-analysis showed that the MI group had a significantly longer operative time than OP group, less blood loss, and shorter hospital stay. No significant difference was found in back pain, leg pain, ODI, SF-36 PCS, SF-36 MCS, complications, fusion rate, and secondary surgery between MI and OP groups. Conclusion. The prospective evidence suggested that MI posterior fusion for spondylolisthesis had less EBL and hospital stay than OP fusion; however it took more operative time. Both MI and OP fusion had similar results in pain and functional outcomes, complication, fusion rate, and secondary surgery.

  8. 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 trismus after oral cancer treatment. © 2014 Wiley Periodicals, Inc.

  9. 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.

  10. 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

  11. A prospective study of closed and open reamed intramedullary nailing of 136 femoral shaft fractures in adults

    Directory of Open Access Journals (Sweden)

    Mohammad Gharehdaghi

    2007-05-01

    Full Text Available BACKGROUND: Femoral shaft fractures are major causes of mortality and morbidity and are managed with intramedullary nailing (IMN. In this study we compared the results of open and closed nailing in femoral shaft fractures. Between 1993 and 2001 we managed 136 femoral shaft fractures by IMN (81 closed and 55 open nailings
    METHODS: in 120 patients with mean age of 36.2 years. The mean time of follow up was two years. Radiologic and clinical results were analyzed with SPSS software using student-t and Fisher test.
    RESULTS: 93.2% healed within six months. 2.9% required dynamization; total union rate was 96%. Full weight bearing was permitted between 5-16 weeks (mean of 10.62 weeks in the closed method, and 10-20 weeks (mean of 12.83 weeks in the open method (P<0.001. Complications included 4.41% nonunions, 2.9% shortening, 10.8% limited range of movement, 1.47% deep infection, and 6.6% malunion. Nonunion was observed in 2 cases in closed and in 4 patients in open method (P = 0.039. Closed series showed higher rate of malunion (P = 0.181, P = 0.221.
    CONCLUSIONS: In closed method attention should be paid to malalignment while locking the nail.

  12. 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

  13. 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

  14. Management of chronic hepatitis C treatment failures: role of consensus interferon

    Directory of Open Access Journals (Sweden)

    Stevan A Gonzalez

    2009-03-01

    Full Text Available Stevan A Gonzalez1, Emmet B Keeffe21Division of Hepatology, Baylor Regional Transplant Institute, Baylor All Saints Medical Center, Fort Worth and Baylor University Medical Center, Dallas, TX, USA; 2Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, CA, USAAbstract: A significant proportion of patients with chronic hepatitis C virus (HCV infection who undergo antiviral therapy have persistent or recurrent viremia and fail to achieve a sustained virologic response (SVR. Factors associated with treatment failure include HCV genotype 1 infection, high serum HCV RNA levels, and advanced fibrosis. Consensus interferon (CIFN is a synthetic type I interferon derived from a consensus sequence of the most common amino acids found in naturally occurring alpha interferon subtypes. Several prospective clinical studies have demonstrated that CIFN may be a treatment option in patients who have failed prior interferonbased therapy, including those who have failed combination therapy with standard interferon or peginterferon plus ribavirin. Daily CIFN in combination with ribavirin may be an effective regimen in this setting; however, optimal dose and treatment duration of CIFN therapy have not been well established. Patients who achieve viral suppression during prior interferon-based therapy and those who do not have advanced fibrosis have a greater likelihood of achieving a SVR with CIFN retreatment. Individualized therapy targeting specific patient groups will be an important consideration in the successful management of prior treatment failures. Additional prospective studies are required in order to identify optimal treatment strategies for the use of CIFN in these patients.Keywords: consensus interferon, hepatitis C, interferon, nonresponder, relapser

  15. A prospective, randomized study of intramedullary nails inserted with and without reaming for the treatment of open and closed fractures of the tibial shaft.

    Science.gov (United States)

    Finkemeier, C G; Schmidt, A H; Kyle, R F; Templeman, D C; Varecka, T F

    2000-01-01

    To determine if there are differences in healing, complications, or number of procedures required to obtain union among open and closed tibia fractures treated with intramedullary (IM) nails inserted with and without reaming. Prospective, surgeon-randomized comparative study. Level One trauma center. Ninety-four consecutive patients with unstable closed and open (excluding Gustilo Grade IIIB and IIIC) fractures of the tibial shaft treated with IM nail insertion between November 1, 1994, and June 30, 1997. Interlocked IM nail insertion with and without medullary canal reaming. Time to union, type and incidence of complications, and number of secondary procedures performed to obtain union. For open fractures, there were no significant differences in the time to union or number of additional procedures performed to obtain union in patients with reamed nail insertion compared with those without reamed insertion. A higher percentage of closed fractures were healed at four months after reamed nail insertion compared with unreamed insertion (p = 0.040), but there was not a difference at six and twelve months. More secondary procedures were needed to obtain union after unreamed nail insertion for the treatment of closed tibia fractures, but the difference was not statistically significant given the limited power of our study (p = 0.155). Broken screws were seen only in patients treated with smaller-diameter nails inserted without reaming, and the majority occurred in patients who were noncompliant with weight-bearing restrictions. There were no differences in rates of infection or compartment syndrome. Our findings support the use of reamed insertion of IM nails for the treatment of closed tibia fractures, which led to earlier time to union without increased complications. In addition, canal reaming did not increase the risk of complications in open tibia fractures.

  16. 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...

  17. Effects of palatal crib and bonded spurs in early treatment of anterior open bite: A prospective randomized clinical study.

    Science.gov (United States)

    Leite, Juliana S; Matiussi, Luciano B; Salem, Anne C; Provenzano, Maria G A; Ramos, Adilson L

    2016-09-01

    To evaluate the overbite correction of fixed palatal crib (FPC) and bonded lingual spur (BLS) in the early treatment of anterior open bite (AOB) in mixed dentition (primary outcome) as well as its influence on dental and skeletal cephalometric measurements (secondary outcome). The selected patients had AOB and a mean age of 8.23 years. They were divided into the following three groups by casting lots: control (n  =  13), palatal crib (n  =  13), and spur (n  =  13). Data from the lateral teleradiography was obtained at the beginning, at 6 months, and after 1 year. The cephalometric analysis was performed by Cef-X program, recording the values of SNA, SNB, ANB, SnG oGn, 1.PP, IMPA, nasolabial angle, overbite, and overjet. Intergroup and intragroup comparisons were obtained via one-way analysis of variance. The degree of AOB was similar at baseline (P > .05). At 6 months and then after 1 year all groups showed improvement in the overbite. However, only the crib and spur groups showed positive overbite. No cephalometric measurements changed significantly over the period analyzed. We conclude that the FPC and BLS are simple and effective for the treatment of anterior open bite, with the advantage given to the FPC.

  18. 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

  19. Interferon-free treatment for hepatitis C virus infection induces normalization of extrahepatic type I interferon signaling.

    Science.gov (United States)

    Sung, Pil Soo; Lee, Eun Byul; Park, Dong Jun; Lozada, Angelo; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

    2018-03-12

    Hepatitis C virus (HCV) replicates in the peripheral blood mononuclear cells (PBMCs), leading to the production of type I interferons (IFNs). It is well known that the gene expression profile of PBMC is similar to that of the liver. The present study explored the dynamic gene expression profile of PBMCs collected from HCV-infected patients undergoing direct-acting antiviral (DAA) therapy. A prospective cohort comprising 27 patients under DAA therapy was formed. Expression level of IFN-β and its downstream interferon-stimulated genes (ISGs) was measured in PBMCs before and after DAA treatment. Furthermore, immunoblotting was performed to identify the signaling molecules involved in the expression of ISGs. The pretreatment expression level of interferon-induced protein 44 (IFI44) and C-X-C motif chemokine ligand 10 (CXCL10) correlated with the pretreatment expression level of IFN-β. After DAA treatment, a significant decrease in the expression levels of IFN-β, IFI44, and CXCL10 was observed in the PBMCs. Furthermore, the pretreatment expression level of IFN-β and ISGs correlated with the level of signal transducer and activator of transcription 1 (STAT1) phosphorylation, and DAA treatment abrogated STAT1 phosphorylation. Pretreatment activation of IFN-β response is rapidly normalized after DAA treatment. The present study suggests that the decreased type I IFN response by the clearance of HCV might contribute to DAA-induced alleviation of extrahepatic manifestation of chronic HCV infection.

  20. Interferon prophylaxis of hepatic carcinoma.

    Science.gov (United States)

    Voiosu, R; Dimitriu, L; Dragomir, P; Eremia, L

    1999-01-01

    The present article reveals the importance of hepatic carcinoma among the other diseases in digestive oncology, and also the importance of a correct designation of these cases. Epidemiology and actual hypothesis on the mechanisms of oncogenesis are discussed. There are reviewed some studies in the literature concerning infection with hepatitis B virus, hepatitis C virus, coinfection (B and C viruses, B and D viruses), the role of interferon prophylaxis in such cases. Also there is present a statistics on chronic viral hepatits, cirrhosis of viral etiology and hepatic carcinoma, diagnosed in patients in "N.Gh.Lupu" Hospital, over two decades.

  1. 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.

  2. 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)

  3. Detection of Interferon Alpha Receptor 2 in Interferon Resistant HCV Patients.

    Science.gov (United States)

    Trali, Gulshan A; Naveed, Abdul Khaliq; Rasheed, Amir; Bashir, Qudsia; Khan, Rao Saad Ali; Majeed, Asifa; Razak, Suhail

    2014-05-01

    Hepatitis C virus infects more than 3% of the world's population and 4% of Pakistan's population. The virus multiplies in the host using novel methods, defending itself from the host's immune response, ultimately leading to liver cirrhosis and hepatocellular carcinoma. The approved therapy for the disease is interferon alpha combined with ribavirin. The disease is incurable, and often resistant, due to multiple viral and cellular factors. However, a strong host system can minimize the viral count to zero. This study was designed to detect the functional interferon alpha receptor 2 in liver biopsies of interferon resistant hepatitis C virus patients. Total messenger ribonucleic acid was isolated from the liver biopsies of the interferon resistant hepatitis C virus patients and subjected to complementary deoxyribonucleic acid synthesis. Primers specific to interferon alpha receptor 2 were designed and used in polymerase chain reaction to detect interferon alpha receptor 2. Interferon alpha receptor 2 was detected in 90% of interferon resistant hepatitis C virus patients. Lack of expression of functional Interferon Alpha Receptor 2 does not seem to be the major cause of interferon resistance in hepatitis C virus patients receiving standard interferon therapy.

  4. 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.

  5. Locking intramedullary nailing with and without reaming for open fractures of the tibial shaft. A prospective, randomized study.

    Science.gov (United States)

    Keating, J F; O'Brien, P J; Blachut, P A; Meek, R N; Broekhuyse, H M

    1997-03-01

    Ninety-one patients who had ninety-four open fractures of the tibial shaft were randomized into two treatment groups. Fifty fractures (nine type-I, eighteen type-II, sixteen type-IIIA, and seven type-IIIB fractures, according to the classification of Gustilo et al.) were treated with nailing after reaming, and forty-four fractures (five type-I, sixteen type-II, nineteen type-IIIA, and four type-IIIB fractures) were treated with nailing without reaming. The average diameter of the nail was 11.5 millimeters (range, nine to fourteen millimeters) in the group treated with reaming and 9.2 millimeters (range, eight to ten millimeters) in the group treated without reaming. Follow-up information was adequate for forty-five patients (forty-seven fractures) who had been managed with reaming and forty patients (forty-one fractures) who had been managed without reaming. No clinically important differences were found between the two groups with regard to the technical aspects of the procedure or the rate of early postoperative complications. The average time to union was thirty weeks (range, thirteen to seventy-two weeks) in the group treated with reaming and twenty-nine weeks (range, thirteen to fifty weeks) in the group treated without reaming. Four (9 per cent) of the fractures treated with reaming and five (12 per cent) of the fractures treated without reaming did not unite (p = 0.73). There were two infections in the group treated with reaming and one in the group treated without reaming. Significantly more screws broke in the group treated without reaming (twelve; 29 per cent) than in the group treated with reaming (four; 9 per cent) (p = 0.014). There was no difference between the two groups with regard to the frequency of broken nails (two nails that had been inserted after reaming broke, compared with one that had been inserted without reaming). The functional outcome, in terms of pain in the knee, range of motion, return to work, and recreational activity, did not

  6. 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

  7. 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

  8. Psychiatric side effects of interferon treatment.

    Science.gov (United States)

    Patten, Scott B

    2006-05-01

    Interferons are employed in the management of multiple sclerosis, hepatitis C and certain malignancies. Neuropsychiatric toxicity can interfere with the successful use of these drugs. This review was based on Medline literature searches, supplemented by bibliographical citations in identified papers. Information uncovered in the literature review was interpreted in light of related pharmacoepidemiological and psychiatric literature. Interferon-associated neurotoxicity does not adhere closely to standard psychiatric syndromal and diagnostic definitions. Delirium, depression, non-specific symptoms related to sickness behavior and, rarely, manic and psychotic syndromes are all potential adverse events during interferon treatment. For depression, the evidence of increased risk is stronger for interferon alpha than for interferon beta. The availability of preventive and treatment interventions suggest that neuropsychiatric toxicity can often be managed without needing to discontinue the treatment. Safety can be maximized by organization of health services in ways that enhance detection and management of neuropsychiatric problems, and which support access to basic and specialized mental health services.

  9. 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.

  10. 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.

  11. Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

    Science.gov (United States)

    Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

    2018-02-01

    The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

  12. A prospective randomized controlled trial of laparoscopic repair versus open repair for perforated peptic ulcers.

    Science.gov (United States)

    Ge, Bujun; Wu, Min; Chen, Qing; Chen, Quanning; Lin, Rui; Liu, Liming; Huang, Qi

    2016-02-01

    Although laparoscopic repair (LR) of perforated peptic ulcers (PPUs) has long been accepted, clinical evidence comparing LR versus open repair (OR) remains lacking. Consequently, this study compared the clinical outcomes and cost-effectiveness of LR versus OR. From January 2010 to June 2014, 119 patients with PPU were divided randomly into LR (58 patients) and OR (61 patients) groups that were comparable in age, sex, smoking and drinking history, symptom duration, comorbidity, American Society of Anesthesiologists grade, Boey score, and white blood cell count. The operative times for LR versus OR did not differ greatly (70 [interquartile range 60-90] vs 75 [60-90] minutes, respectively, P = .692), nor did postoperative complications. The LR group, however, required substantially less fentanyl than the OR group (0.74 ± 0.33 mg vs 1.04 ± 0.39 mg, P < .001). Moreover, the duration of hospital stay for the LR group was much shorter than those of the OR group (7 [5-9] vs 8 [7-10] days, respectively, P < .001). Although total hospital costs were similar (P = .465), the median intraoperative costs were greater for LR than for OR patients, at ¥6772 and ¥5626, respectively (P < .001). The median cost of ward stay tended to be ¥865 less in the LR group but was not statistically relevant. LR and conventional OR are comparable in terms of operative duration and complications. The obvious advantage of LR is the greatly decreased hospital stay and less postoperative pain, at similar total hospital costs. Therefore, LR may be preferable for treating PPU in selected patients. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  13. Pseudophakic Macular Edema in Primary Open-Angle Glaucoma: A Prospective Study Using Spectral-Domain Optical Coherence Tomography.

    Science.gov (United States)

    Lee, Kyoung Min; Lee, Eun Ji; Kim, Tae-Woo; Kim, Hyunjoong

    2017-07-01

    To determine the incidence of and risk factors for pseudophakic macular edema (PME) after uncomplicated cataract surgery in primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SDOCT). Cohort study. Macular retinal thickness was evaluated using SDOCT at 1 week before surgery and at 1, 3, 6, and 12 months postoperatively, in 70 POAG and 68 control eyes. Forty-three healthy subjects without impaired vision or cystoid PME were recruited separately as pilot samples to define significant PME. Significant PME was defined as an increase in the average thickness exceeding the mean + 3 standard deviations of the increase shown in the pilot samples. Significant PME (increase in the foveal 3-mm zone thickness of >19.5 μm) was observed in 31 (44%) eyes with POAG and in 14 (21%) control eyes (P = .003). The extent of PME was maximal at 3 months postoperatively and decreased gradually until 12 months. Regression tree analysis revealed that the risk of PME was the greatest in the POAG group using prostaglandin analogue (PGA) (odds ratio [OR] = 5.51), followed by POAG not using PGA (OR = 1.70), and control group (OR = 1.0). Risk factors for PME were younger age in all groups (OR = 1.07), systemic hypertension in PGA users (OR = 6.42), higher untreated IOP in PGA nonusers (OR = 1.09) and male sex (OR = 14.06) and diabetes mellitus (OR = 16.71) in the control group. The incidence of PME as observed by SDOCT was higher than previously reported after uncomplicated cataract surgery. Eyes with POAG were at greater risk for PME, which was mainly associated with perioperative PGA use. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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

  15. [A prospective trial comparing consecutive series of open retropubic and robot-assisted laparoscopic radical prostatectomy in a centre: Oncologic and functional outcomes].

    Science.gov (United States)

    Beauval, J-B; Roumiguié, M; Ouali, M; Doumerc, N; Thoulouzan, M; Mazerolles, C; Rischmann, P; Malavaud, B; Soulié, M

    2015-06-01

    Radical prostatectomy (RP) is an oncologic and functional challenge. Few series compare prospectively the two approaches, open retropubic (ORP) and laparoscopic robot-assisted RP (LRARP). The objective was to compare the oncological and functional results of ORP and LRARP. From January 2009 to March 2012, two practiced surgeons conducted 304 consecutive RP: respectively 129 ORP and 175 LRARP. Preoperative, perioperative and postoperative data (location and size of positive surgical margins [PSM]) were recorded prospectively and compared with oncological results (PSM, biochemical recurrence-free survival [BCR]) and functional outcomes (urinary and erectile) by self-validated questionnaires (USP, IIEF-15). The comparison was made by the Chi(2) test and Student t-test for qualitative and quantitative variables. The preoperative data 2 groups were comparable. MCP rate was 13.2% for the ORP and 20% for the LRARP (ns) and was 1.4% and 29.6% (ORP) versus 9.4% and 36.7% (LRARP) for pT2 and pT3 for respectively (P=0.078). BCR was the same in both groups (95.2% at 13.1 months). At 12 months, the results of continence showed no difference (P=0.49) and about erectile function, the EF-score was significantly higher in LRARP: 22 versus 17 for the ORP (P=0.03). Oncological results were comparable after ORP and LRARP. The recovery of continence was excellent regardless of the surgical technique, the recovery of erectile function a bit faster by LRARP. 3. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. 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 tre...

  17. Secondary hyperpigmentation during interferon alfa treatment for chronic hepatitis C virus infection.

    Science.gov (United States)

    Tsilika, Katerina; Tran, Albert; Trucchi, Régine; Pop, Sinziana; Anty, Rodolphe; Cardot-Leccia, Nathalie; Lacour, Jean-Philippe; Ortonne, Jean-Paul; Passeron, Thierry

    2013-06-01

    Interferon alfa remains the central treatment for chronic hepatitis C virus (HCV) infection. Cases of cutaneous and mucous hyperpigmentations during interferon alfa treatment have been reported, but they are considered rare adverse effects. To study the clinical presentation and frequency of hyperpigmentation in patients receiving interferon alfa treatment for chronic HCV infection. Prospective, descriptive clinical trial. Monocentric study performed in the Departments of Hepatology and Dermatology of the University Hospital of Nice, Nice, France. Consecutive patients treated with pegylated interferon alfa-2b and ribavirin for chronic HCV infection. Demographic data and medical history were noted. A systematic clinical and dermoscopic examination of skin, nails, and mucous membranes was performed, and skin biopsies were performed if needed. Of 77 patients who were included, 16 (21%) presented with hyperpigmentation. Hyperpigmentation of the oral mucous membrane, acquired longitudinal melononychia, and hyperpigmentation of the face were each observed in 7 patients (9%). All patients with hyperpigmentation of the skin had skin type III or IV and worked outside without sun protection. The intensity of pigmentation was reported to decrease progressively when interferon treatment was discontinued. Most patients with hyperpigmentation of the oral mucosa also had melanonychia. However, patients with hyperpigmentation of the skin did not have mucosal or nail involvement, suggesting 2 distinct mechanisms. Secondary hyperpigmentation during interferon alfa treatment occurs as an adverse event in 21% of patients, especially in those with dark skin types who have unprotected sun exposure. Physicians should be aware of the adverse effects of interferon treatment and advise patients in the use of sun protection, especially patients with darker skin types.

  18. Innate Interferons Regulate CNS Inflammation

    DEFF Research Database (Denmark)

    Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently......, there is no cure for MS, however a standard first-line therapy is recombinant interferon (IFN)-beta. IFN-beta belongs to the family of type I IFNs, which also include IFN-alpha. These engage to one common receptor, IFNAR. Type I IFNs can be induced by several innate immune receptors, including toll-like receptors...... mass homeostasis. Whether RANK-signaling is capable of inducing type I IFNs within the CNS has not yet been studied. Preliminary data from IFN-beta-luciferase reporter mice already show that RANK-signaling by intrathecally applied RANKL can induce CNS-endogenous IFN-beta. Experiments in IFN...

  19. The Sigma-trial protocol: a prospective double-blind multi-centre comparison of laparoscopic versus open elective sigmoid resection in patients with symptomatic diverticulitis

    Directory of Open Access Journals (Sweden)

    Lacy Antonio M

    2007-08-01

    Full Text Available Abstract Backround Diverticulosis is a common disease in the western society with an incidence of 33–66%. 10–25% of these patients will develop diverticulitis. In order to prevent a high-risk acute operation it is advised to perform elective sigmoid resection after two episodes of diverticulitis in the elderly patient or after one episode in the younger ( Method Indication for elective resection is one episode of diverticulitis in patients 50 years or in case of progressive abdominal complaints due to strictures caused by a previous episode of diverticulits. The diagnosis is confirmed by CT-scan, barium enema and/or coloscopy. It is required that the participating surgeons have performed at least 15 laparoscopic and open sigmoid resections. Open resection is performed by median laparotomy, laparoscopic resection is approached by 4 or 5 cannula. Sigmoid and colon which contain serosal changes or induration are removed and a tension free anastomosis is created. After completion of either surgical procedure an opaque dressing will be used, covering from 10 cm above the umbilicus to the pubic bone. Surgery details will be kept separate from the patient's notes. Primary endpoints are the postoperative morbidity and mortality. We divided morbidity in minor (e.g. wound infection, major (e.g. anastomotic leakage and late (e.g. incisional hernias complications, data will be collected during hospital stay and after six weeks and six months postoperative. Secondary endpoints are the operative and the postoperative recovery data. Operative data include duration of the operation, blood loss and conversion to laparotomy. Post operative recovery consists of return to normal diet, pain, analgesics, general health (SF-36 questionnaire and duration of hospital stay. Discussion The Sigma-trial is a prospective, multi-center, double-blind, randomized study to define the role of laparoscopic sigmoid resection in patients with symptomatic diverticulitis.

  20. Bipolar plasma enucleation of the prostate vs open prostatectomy in large benign prostatic hyperplasia cases - a medium term, prospective, randomized comparison.

    Science.gov (United States)

    Geavlete, Bogdan; Stanescu, Florin; Iacoboaie, Catalin; Geavlete, Petrisor

    2013-05-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: According to the EAU Guidelines 2012, large size benign prostatic hyperplasia (BPH) cases (>80 mL) continue to have open prostatectomy as the first line treatment alternative, despite the substantial peri-operative morbidity and extended catheterization and convalescence periods related to this undoubtedly invasive approach. During the past two decades, holmium laser enucleation of the prostate was constantly described as a successful choice for this category of patients. According to rather numerous studies, the technique displayed superior results in terms of surgical safety and postoperative recovery compared with the open procedure. On the other hand, the concept of electrosurgical enucleation of the prostate, using either a monopolar or bipolar cutting current, materialized into several technical applications that eventually failed to gain general acknowledgement as reliable alternatives to the BPH transurethral approach. While keeping in mind the already proved advantage of enucleating substantial quantities of BPH tissue, bipolar plasma enucleation of the prostate was introduced as a novel endoscopic approach in cases of large prostates. The present trial represents the first prospective, medium-term, randomized comparison to be published of this innovative technique with standard open prostatectomy. Basically, the premises for a viable alternative relied on the practical advantages provided by the 'button' electrode, mainly the large surface creating the conditions for a fast enucleation process, continuous vaporization and concomitant haemostasis. Eventually, it was concluded that the plasma enucleation procedure distinguished itself as a successful treatment option in large BPH patients, characterized by good surgical efficiency, significantly reduced complications, faster postoperative recovery, similar prostatic tissue ablation capabilities and satisfactory follow-up results compared with the

  1. 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...

  2. 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.

  3. 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

  4. PTH(1-34) for Surgical Hypoparathyroidism: A 2-Year Prospective, Open-Label Investigation of Efficacy and Quality of Life.

    Science.gov (United States)

    Palermo, Andrea; Santonati, Assunta; Tabacco, Gaia; Bosco, Daniela; Spada, Antonio; Pedone, Claudio; Raggiunti, Bruno; Doris, Tina; Maggi, Daria; Grimaldi, Franco; Manfrini, Silvia; Vescini, Fabio

    2018-01-01

    Daily parathyroid hormone (PTH) (1-34) administrations can reduce the required total daily dose of calcium and calcitriol and restore normocalcemia in refractory hypoparathyroidism. However, most PTH(1-34) trials have been conducted on small cohorts including subjects with hypoparathyroidism of various etiologies, and quality of life (QOL) was not investigated. To investigate the effects of 24-month PTH(1-34) treatment in a homogeneous cohort of adult subjects with postoperative hypoparathyroidism and to evaluate QOL changes. Prospective open-label study. Italian multicenter study. 42 subjects. Twice-daily PTH(1-34) 20 μg subcutaneous injection. Calcium and vitamin D supplementation requirements, serum calcium, phosphate, and urinary calcium excretion (3, 6, 12, 18, 24 months). At baseline and at 6 and 24 months, QOL was evaluated by the RAND 36-Item Short Form (SF-36) Health Survey, covering eight domains of physical and mental health. Mean serum calcium concentration significantly increased from baseline to 3 months (7.6 ± 0.6 vs 8.9 ± 1.1 mg/dL, P PTH(1-34) to treat adult patients with postsurgical hypoparathyroidism. PTH(1-34) may improve their mental and physical health. Copyright © 2017 Endocrine Society

  5. 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...

  6. Quality of life in treatment of mandibular fractures using closed reduction and maxillomandibular fixation in comparison with open reduction and internal fixation--a randomized prospective study.

    Science.gov (United States)

    Omeje, Kevin U; Rana, Majeed; Adebola, Adetokunbo R; Efunkoya, Akinwale A; Olasoji, Hector O; Purcz, Nicolai; Gellrich, Nils-Claudius; Rana, Madiha

    2014-12-01

    Treatment of mandibular fractures by open reduction and internal fixation (ORIF) is often assumed to be superior to treatment by close reduction and maxillomandibular fixation (MMF) because patients managed by ORIF seem to be rehabilitated earlier according to functional and social aspects. This assumption is often from surgeon's perspective, not taking into account patient's view point. This study highlights a comparative assessment between ORIF and MMF from the patients' perspective. Fifty six patients with mandibular fractures within the tooth bearing areas of the mandible were prospectively studied in a randomized controlled pattern for postoperative Quality of Life (QoL) after ORIF versus MMF. Both groups were analyzed preoperatively, at 1 day, 6 and 8 weeks regarding their QoL using the General Oral Health Assessment Index questionnaire (GOHAI). No significant statistical difference was found between the groups regarding overall QoL. Patients managed by MMF were more affected by psychosocial and physical domains whereas patients managed by ORIF were more affected by the pain domain. The results demonstrate that the treatment affects the psychosocial, physical and pain domain differentially. When both treatments are possible the patient's should be enlightened on the advantages and disadvantages of both treatment modalities to guide their choice of treatment. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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

  9. Inhibited interferon production after space flight

    Science.gov (United States)

    Sonnenfeld, G.; Gould, C. L.; Williams, J.; Mandel, A. D.

    1988-01-01

    Several studies have been performed in our laboratories indicating that interferon production may be impaired in rodents after space flight. Using an antiorthostatic suspension model that simulates some of the effects of microgravity seen during space flight, we have shown that interferon-alpha/beta production was inhibited. The inhibition was not due solely to the stress of suspension. The inhibited interferon production was transient, as suspended animals returned to normal caging recovered the ability to produce interferon. Antiorthostatic suspension of mice also resulted in a loss of resistance to infection with the diabetogenic strain of encephalomyocarditis virus, which correlated with the drop in interferon production. In rats flown in US Space Shuttle mission SL-3, interferon-gamma production was inhibited severely when spleen cells were challenged with concanavalin-A upon return to earth. In contrast, interleukin-3 production by these cells was normal. These results suggest that immune responses may be altered after antiorthostatic modeling or space flight, and the resistance to viral infections may be especially affected.

  10. Efficacy and safety of Everolimus in children with TSC - associated epilepsy – Pilot data from an open single-center prospective study

    Directory of Open Access Journals (Sweden)

    Sharon Samueli

    2016-11-01

    Full Text Available Abstract Background Epilepsy occurs in up to 90 % of all individuals with tuberous sclerosis complex (TSC. In 67 % disease onset is during childhood. In ≥ 50 % seizures are refractory to currently available treatment options. The mTOR-Inhibitor Everolimus (Votubia® was approved for the treatment of subependymal giant cell astrocytoma (SEGA and renal angiomyolipoma (AML in Europe in 2011. It’s anticonvulsive/antiepileptic properties are promising, but evidence is still limited. Study aim was to evaluate the efficacy and safety of Everolimus in children and adolescents with TSC-associated epilepsies. Methods Inclusion-criteria of this investigator-initiated, single-center, open, prospective study were: 1 the ascertained diagnosis of TSC; 2 age ≤ 18 years; 3 treatment indication for Votubia® according to the European Commission guidelines; 4 drug-resistant TSC-associated epilepsy, 5 prospective continuous follow-up for at least 6 months after treatment initiation and 6 informed consent to participate. Votubia® was orally administered once/day, starting with 4.5 mg/m2 and titrated to achieve blood trough concentrations between 5 and 15 ng/ml. Primary endpoint was the reduction in seizure frequency of ≥ 50 % compared to baseline. Results Fifteen patients (nine male with a median age of six (range; 1–18 years fulfilled the inclusion criteria. 26 % (4/15 had TSC1, 66 % (10/15 had TSC2 mutations. In one patient no mutation was found. Time of observation after treatment initiation was median 22 (range; 6–50 months. At last observation, 80 % (12/15 of the patients were responders, 58 % of them (7/12 were seizure free. The overall reduction in seizure frequency was 60 % in focal seizures, 80 % in generalized tonic clonic seizures and 87 % in drop attacks. The effect of Everolimus was seen already at low doses, early after treatment initiation. Loss of efficacy over time was not observed. Transient side effects were seen in 93

  11. Donepezil use in children and adolescents with tics and attention-deficit/hyperactivity disorder: an 18-week, single-center, dose-escalating, prospective, open-label study.

    Science.gov (United States)

    Cubo, Esther; Fernández Jaén, Alberto; Moreno, Celia; Anaya, Belén; González, Miguel; Kompoliti, Katie

    2008-01-01

    Striatal cholinergic dysfunction may be important in tics and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to determine the safety profile of donepezil and whether it improves chronic tics in young patients with comorbid ADHD. This 18-week (14 weeks of open treatment followed by a 4-week washout period), single-center, dose-escalating, prospective, open-label trial was conducted in patients aged 7 to 17 years with tics, including chronic motor or vocal tics and Tourette's syndrome, and ADHD. Patients were treated with once-daily oral donepezil doses of 2.5 mg for 2 weeks, 5 mg for the next 6 weeks, and 10 mg for the last 6 weeks, followed by a 4-week washout period. Patients were evaluated using the Children's Global Assessment Scale; the Yale Global Tic Severity Scale (YGTSS); the Revised Conners' Parent Rating Scale; the Symbol and Digit Wisconsin Card Sorting Test; the Stroop black/white, color, and interference tests; the Rey Complex Figure Test; and the Children's Yale-Brown Obsessive Compulsive Scale at 4 visits: baseline, week 8 (5-mg dose), week 14 (10-mg dose), and week 18 (washout). Seventeen males and 3 females (mean [SD] age, 11.3 [1.9] years [range, 8-14 years]; tic duration, 5.3 [1.9] years; ADHD duration, 6.5 [1.7] years) were included in this study. Tics were significantly reduced at the 10-mg (week-14) donepezil visit compared with the baseline and washout visits based on the total mean (SD) tic score of the YGTSS (18.6 [9.3] vs 12.2 [11.0]; P = 0.006). Fifty percent of patients withdrew and 65% experienced adverse events. These preliminary results suggest that donepezil significantly reduced tics in these children and adolescents with comorbid ADHD who completed the study. No significant improvement in the symptoms of comorbid ADHD was found with the use of donepezil 10 mg. Donepezil 5 and 10 mg were not well tolerated in these children and adolescents.

  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. 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.

  14. 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

  15. 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.

  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. Comparison of minimally invasive spine surgery using intraoperative computed tomography integrated navigation, fluoroscopy, and conventional open surgery for lumbar spondylolisthesis: a prospective registry-based cohort study.

    Science.gov (United States)

    Wu, Meng-Huang; Dubey, Navneet Kumar; Li, Yen-Yao; Lee, Ching-Yu; Cheng, Chin-Chang; Shi, Chung-Sheng; Huang, Tsung-Jen

    2017-08-01

    To date, the surgical approaches for the treatment of lumbar spondylolisthesis by transforaminal lumbar interbody fusion (TLIF) using minimally invasive spine surgery assisted with intraoperative computed tomography image-integrated navigation (MISS-iCT), fluoroscopy (MISS-FS), and conventional open surgery (OS) are debatable. This study compared TLIF using MISS-iCT, MISS-FS, and OS for treatment of one-level lumbar spondylolisthesis. This is a prospective, registry-based cohort study that compared surgical approaches for patients who underwent surgical treatment for one-level lumbar spondylolisthesis. One hundred twenty-four patients from January 2010 to March 2012 in a medical center were recruited. The outcome measures were clinical assessments, including Short-Form 12, visual analog scale (VAS), Oswestry Disability Index, Core Outcome Measurement Index, and patient satisfaction, and blood loss, hospital stay, operation time, postoperative pedicle screw accuracy, and superior-level facet violation. All surgeries were performed by two senior surgeons together. Ninety-nine patients (40M, 59F) who had at least 2 years' follow-up were divided into three groups according to the operation methods: MISS-iCT (N=24), MISS-FS (N=23), and OS (N=52) groups. Charts and surgical records along with postoperative CT images were assessed. MISS-iCT and MISS-FS demonstrated a significantly lowered blood loss and hospital stay compared with OS group (p2 mm) was found. However, a lower superior-level facet violation rate was observed in the MISS-iCT and OS groups (p=.049). MISS-iCT TLIF demonstrated reduced operation time, blood loss, superior-level facet violation, hospital stay, and improved functional outcomes compared with the MISS-FS and OS approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. An open-label prospective clinical study to assess the efficacy of increasing levocetirizine dose up to four times in chronic spontaneous urticaria not controlled with standard dose.

    Science.gov (United States)

    Sharma, Vinod Kumar; Gupta, Vishal; Pathak, Mona; Ramam, M

    2017-09-01

    The EAACI/GA 2 LEN/EDF/WAO recommendation of increasing antihistamines' dose up to four times in urticaria not adequately controlled with the standard dose is largely based on expert opinion. The objective of this study is to test the current urticaria guidelines of up-dosing antihistamines as second-line treatment. This was an open-label study conducted prospectively on 113 patients with chronic spontaneous urticaria. All patients were treated with sequentially increasing doses of levocetrizine (5 mg, 10 mg, 15 mg and 20 mg/day) every week till the patients became completely asymptomatic or dose of 20 mg/day reached. Urticaria Activity Score (UAS)-7, urticaria-related quality-of-life (CU-Q2oL) and patients' global assessment were used to assess treatment response. Twenty-one (18.58%) patients became asymptomatic with levocetirizine 5 mg/day, while 50 required higher doses of levocetirizine for complete control: 29/92 (31.52%), 6/63 (9.52%) and 15/57 (26.31%) with 10 mg, 15 mg and 20 mg/day, respectively. The percentage of patients experiencing >75% improvement increased with increasing doses of levocetirizine: 26.54%, 53.98%, 60.17% and 69.91% with 5 mg, 10 mg, 15 mg and 20 mg/day, respectively. Sequential up-dosing of levocetirizine produced a progressive improvement in both urticaria control (UAS-7) and quality-of-life (CU-Q2oL) without significantly increasing somnolence. Our results support the current recommendations of increasing antihistamines up to four times the standard dose in patients who fail the first-line treatment.

  19. An open-label, prospective clinical study to evaluate the efficacy and safety of TLPL/AY/01/2008 in the management of functional constipation

    Directory of Open Access Journals (Sweden)

    Renuka Munshi

    2011-01-01

    Full Text Available Functional constipation is one of the most common gastrointestinal symptoms across the globe. Its high prevalence rate, economic burden, and adverse implications on the quality of life make constipation a major public health issue. Though various treatment options are available for the management of constipation, evidence for their efficacy and safety are limited. An open-label, prospective, interventional, and exploratory clinical trial was carried out to evaluate the efficacy and safety of "TLPL/AY/01/2008" in 34 patients suffering from functional constipation. "TLPL/AY/01/2008" is an Ayurvedic proprietary polyherbal formulation in powder form, containing Isabgol husk, Senna extract, and Triphala extract. Administration of "TLPL/AY/01/2008" for 14 days showed a significant increase in mean weekly bowel movements from 10.19 ± 05.64 to 18.29 ± 05.72 (P<0.05. The mean average time spent on toilet for bowel evacuation reduced significantly from 11.02 ± 05.43 minutes (baseline value to 08.70 ± 04.72 minutes on day 14 (P<0.05. Mean stool form score assessed on Bristol stool form scale was improved from 02.97 ± 00.48 (baseline value to 04.61 ± 00.84 (P<0.05 on day 14. A significant improvement (P<0.05 was also noted in straining during defecation, sensation of incomplete evacuation, sensation of anorectal blockage, and other associated symptoms of functional constipation. The significant improvement in most of the above symptoms was endured for a post-treatment observatory period of one week. All the study patients showed an excellent tolerability to the study drug. These findings suggest that "TLPL/AY/01/2008" is an effective, safe, and non-habit-forming herbal laxative formulation for the management of constipation. Comparative clinical studies with larger sample size would be able to confirm the above findings.

  20. A multicenter prospective study of patients undergoing open ventral hernia repair with intraperitoneal positioning using the monofilament polyester composite ventral patch: interim results of the PANACEA study.

    Science.gov (United States)

    Berrevoet, Frederik; Doerhoff, Carl; Muysoms, Filip; Hopson, Steven; Muzi, Marco Gallinella; Nienhuijs, Simon; Kullman, Eric; Tollens, Tim; Schwartz, Mark R; LeBlanc, Karl; Velanovich, Vic; Jørgensen, Lars Nannestad

    2017-01-01

    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]). A single-arm, multicenter prospective study of 126 patients undergoing open ventral hernia repair with the PCO-VP was performed. Patient outcomes were assessed at discharge and at 10 days, 1, 6, 12, and 24 months postoperative. All patients had hernioplasty for umbilical (n = 110, 87.3%) or epigastric hernia (n = 16, 12.7%). Mean hernia diameter was 1.8 ± 0.8 cm. Mean operative time was 36.2 ±15.6 minutes, with a mean mesh positioning time of 8.1 ± 3.4 minutes. Surgeons reported satisfaction with mesh ease of use in 95% of surgeries. The cumulative hernia recurrence rate at 1 year was 2.8% (3/106). Numeric Rating Scale (NRS) pain scores showed improvement from 2.1 ± 2.0 at preoperative baseline to 0.5 ± 0.7 at 1 month postoperative ( P < 0.001), and this low pain level was maintained at 12 months postsurgery ( P < 0.001). The mean global Carolina's Comfort Scale ® (CCS) score improved postoperatively from 3.8 ± 6.2 at 1 month to 1.6 ± 3.5 at 6 months ( P < 0.001). One patient was unsatisfied with the procedure. This 1-year interim analysis using PCO-VP for primary umbilical and epigastric defects shows promising results in terms of mesh ease of use, postoperative pain, and patient satisfaction. Recurrence rate is low, but, as laparoscopic evaluation shows a need for patch repositioning in some cases, an accurate surgical technique remains of utmost importance.

  1. Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha.

    Science.gov (United States)

    Lotrich, Francis E; Ferrell, Robert E; Rabinovitz, Mordechai; Pollock, Bruce G

    2010-07-01

    Inflammatory cytokines may influence both labile anger and depression. Both psychiatric conditions can occur during interferon alfa-based treatments. Evidence also indicates a central nervous system role for tumor necrosis factor alpha (TNF-alpha), whose expression may be increased by interferon alfa. A polymorphism in the promoter region of TNF-alpha has been associated with various inflammatory illnesses. We therefore hypothesized that this TNF-alpha polymorphism would influence susceptibility to psychiatric symptoms during interferon alfa therapy. One hundred five patients with hepatitis C, initially without active major depression (major depressive disorder), were treated with interferon alfa and then prospectively monitored using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Beck Depression Inventory II, the Anger Irritability and Assault Questionnaire, and circulating TNF-alpha levels. The A-308G polymorphism (rs1800629) was determined using the 5'-nuclease assay. Repeated-measure mixed-effect analyses compared changes in symptoms over time. Beck Depression Inventory II score increased during interferon alfa therapy (F = 6.2; P depression incidence (chi = 0.0; P = 0.99) or increased Beck Depression Inventory II (F = 1.2; P = 0.31). Labile anger was not predicted by the serotonin transporter polymorphism (F = 0.8; P = 0.59). During treatment with an exogenous cytokine, vulnerability to worsening labile anger-distinct from major depression-is associated with genetic variability in TNF-alpha. This has implications both for patients being treated with interferon alfa and our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.

  2. 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

  3. 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.

  4. 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....

  5. 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

  6. Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study.

    Science.gov (United States)

    Pasquale, Louis R; Hyman, Leslie; Wiggs, Janey L; Rosner, Bernard A; Joshipura, Kaumudi; McEvoy, Mark; McPherson, Zachary E; Danias, John; Kang, Jae H

    2016-11-01

    Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. Prospective cohort study. Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. By using validated questions, we updated participants' status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; ≥ or <22 mmHg) or visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Multivariable relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated. Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95% CI, 1.06-1.97); in particular, a report within the past 2 years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95% CI, 1.07-3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes (P for heterogeneity ≥0.36), although associations were strongest in relation to the POAG subtypes with IOP <22 mmHg (MVRR, 1.93; 95% CI, 1.09-3.43) and early paracentral VF loss (MVRR, 2.27; 95% CI, 1.32-3.88). Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an

  7. Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis.

    Science.gov (United States)

    Uenishi, K; Tokiwa, M; Kato, S; Shiraki, M

    2018-03-01

    Intestinal fractional calcium absorption (FCA) was assessed before and after vitamin D3 treatment. Serum 1,25(OH) 2 D concentration was significantly increased by plain vitamin D3 and reduced by eldecalcitol. The 1α hydroxyl calcidiol and eldecalcitol treatments increased FCA, which may be induced through direct stimulation of vitamin D receptors in the intestine. To assess the effects of vitamin D3 compounds on intestinal FCA and calcium-regulating hormones in post-menopausal osteoporosis, a randomized open-label prospective study was conducted. Forty eligible patients were allocated randomly into four groups: eldecalcitol (ELD; 0.75 μg/day), 1α hydroxyl calcidiol (ALF; 1 μg/day), plain vitamin D3 (800 IU/day), and control. Before and after the 4-week treatment, intestinal FCA was estimated by using a double isotope method, and serum concentrations of calcium-regulating hormones and a bone turnover marker were measured. The baseline FCA value of the participants was 21.5 ± 7.9% (mean ± SD) and was significantly correlated with serum 1,25(OH) 2 D (calcitriol) concentration. After the treatment, the FCA significantly increased by 59.5% (95% CI, 41.6 to 77.4%) in the ELD group and by 45.9% (27.9 to 63.8%) in the ALF group, whereas no significant change in the plain vitamin D3 group was found. Unlike the baseline FCA, post-treatment FCA exhibited no significant correlation with serum calcitriol concentration. Parathyroid hormone levels were suppressed by ALF and plain vitamin D3 but were sustained in the ELD and control groups. Serum calcitriol tended to be suppressed by ELD, whereas plain vitamin D3 treatment increased both serum 25(OH)D and calcitriol concentrations. These findings suggest that oral administration of vitamin D3 analogues (ALF and ELD) stimulates FCA but plain vitamin D3 does not. Those effects of vitamin D3 compounds on FCA were independent of serum calcitriol concentration, suggesting that ALF and ELD may directly stimulate

  8. 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

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

    2016-10-01

    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. 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 variables before expansion. No significant differences were found between the EDO and the hyrax expander groups regarding skeletal changes. The EDO promoted significantly greater increases of intercanine width (difference, 3.63 mm) and smaller increases in canine buccal tipping than the conventional hyrax expander. No serious harm was observed other than transitory variable pressure sensations on the maxillary alveolar process in both groups. The EDO produced skeletal changes similar to the conventional hyrax expander. The differential expander is an adequate alternative to conventional rapid maxillary

  10. 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

  11. 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

  12. Efficacy and safety of flexibly dosed paliperidone palmitate in Chinese patients with acute schizophrenia: an open-label, single-arm, prospective, interventional study

    Directory of Open Access Journals (Sweden)

    Si TM

    2015-06-01

    Full Text Available Tianmei Si,1 Kerang Zhang,2 Jisheng Tang,3 Maosheng Fang,4 Keqing Li,5 Jianmin Zhuo,6 Yu Feng6 1Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Beijing, People’s Republic of China; 2Shanxi Medical University First Hospital, Shanxi, People’s Republic of China; 3Mental Health Center of Shandong Province, Shandong, People’s Republic of China; 4Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of China; 5Mental Health Center of Hebei Province, Hebei, People’s Republic of China; 6Janssen Research and Development, Beijing, People’s Republic of China Abstract: This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75–150 mg eq, deltoid/gluteal injection in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score ≥70, who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period. Primary efficacy endpoint was percentage of patients with ≥30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions–Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2% completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years. Total, 443/610 (72.6%, full analysis set patients achieved primary endpoint (mean [standard deviation] change from baseline: –30.9 [19.51]. All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5

  13. 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

  14. 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.

  15. Prospective, open-label, noncomparative study to assess cycle control, safety and acceptability of a new oral contraceptive containing gestodene 60 microg and ethinylestradiol 15 microg (Minesse).

    Science.gov (United States)

    Barbosa, Ione C; Filho, Carlos Isaia; Faggion, Dirceu; Baracat, Edmund Chada

    2006-01-01

    A prospective, open-label, noncomparative, multicenter study was carried out in 163 women aged 18-39 (mean 25+/-5 years), who used an ultra-low-dose oral contraceptive pill (OCP) containing gestodene (GTD) 60 mug/ethinylestradiol (EE) 15 mug for 6 months. The objective of the study was to evaluate the acceptability, safety, bleeding patterns and premenstrual symptomatology in these women. Patients used the OCP from Days 1-24, followed by a 4-day pill-free interval from Days 25-28 of the menstrual cycle. Physical and gynecological examinations were carried out at baseline and after 3 and 6 months, at which time blood pressure, weight, hemoglobin, hematocrit, SGOT, SGPT and urinalysis were also assessed. The Moos Menstrual Distress Questionnaire (MDQ) was completed on three consecutive days (Days 25-27 of the cycle) at baseline and at the end of the third and sixth cycles. Patients kept a menstrual diary throughout the study. A total of 146 women completed the study. Ten women discontinued because of adverse events and one undesired pregnancy occurred during treatment. No adverse metabolic effects were observed. The adverse event most frequently reported was breakthrough bleeding, which diminished, however, as the time of OC use increased. Cycle length and duration of bleeding decreased significantly with OC use (p<.01 and p<.05, respectively, after 6 months). Intensity of menstrual bleeding tended to decrease with OC use, but this difference was not statistically significant. Systolic and diastolic blood pressure were significantly lower after 6 months of OC use compared to baseline (p<.02). No alterations were recorded in body weight or laboratory evaluations. Statistically significant changes were found both in the total MDQ score and in several of the factors evaluated, and patients showed a statistically significant improvement in well-being with respect to premenstrual complaints and symptoms. This OC regimen is safe, well-accepted and well-tolerated, affects

  16. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

    Directory of Open Access Journals (Sweden)

    Hashimoto T

    2015-12-01

    Full Text Available Tasuku Hashimoto,1,2 Daiji Sakurai,1 Yasunori Oda,1 Tadashi Hasegawa,3 Nobuhisa Kanahara,4 Tsuyoshi Sasaki,3 Hideki Komatsu,3,5 Junpei Takahashi,1,5 Takahiro Oiwa,6 Yoshimoto Sekine,4,5 Hiroyuki Watanabe,1 Masaomi Iyo1,3 1Department of Psychiatry, Chiba University Graduate School of Medicine, 2Sodegaura Satsukidai Hospital, 3Department of Psychiatry, Chiba University Hospital, 4Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, 5Choshi Kokoro Clinic, 6Mobara Shinkeika Hospital, Chiba, Japan Background: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood.Methods: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs, moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines.Results: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10. Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031 and interleukin-8 (Z=-2.616; P=0.009 were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs. Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001 only in non-responders.Conclusion: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized

  17. Efficacy and Safety of Immunization With Pneumococcal Polysaccharide Vaccine in Children With Juvenile Idiopathic Arthritis: Preliminary Results of a Prospective Open-Label Study

    Directory of Open Access Journals (Sweden)

    Ekaterina I. Alexeeva

    2017-01-01

    Full Text Available Juvenile idiopathic arthritis (JIA is one of the most frequent and most disabling rheumatic diseases in children. Children with JIA receiving immunosuppressive and genetically engineered biologic drugs belong to the high-risk group for the development of bacterial and viral infections, including those administered by preventive vaccines.Objective: Our aim was to evaluate the efficacy and safety of 13-valent pneumococcal polysaccharide vaccine (PPV in children with JIA.Methods. In a prospective open-label comparative study, the efficacy of vaccination was determined by the level of specific anti-pneumococcal antibodies (anti-SPPIgG to Streptococcus pneumonia in the blood serum in patients with JIA. The safety of vaccination was assessed by determining a high-sensitivity C-reactive protein and S-100 protein as well as by the number of adverse events, by recording the number of infections of the upper respiratory tract and pneumonias, by the number of joints with active arthritis. Vaccination with 13-valent PPV was performed subcutaneously with one dose of 0.5 ml during therapy of the main disease with methotrexate or etanercept or 3 weeks before the appointment of methotrexate or etanercept. Patients were followed up for 1 year.Results. The study included 42 children with JIA: 21 with JIA in the active phase of the disease, 21 in remission of the disease. As a result of vaccination, the level of anti-pneumococcal antibodies (antiSPPIgG increased in the group of children with JIA in the active phase from 26.1 (14.3; 52.1 to 73.0 (52.5; 156.0 mg/l (p = 0.001, with JIA in remission — from 27.4 (18.2; 59.1 to 54.6 (35.3; 96.0 mg/l (p = 0.029. The concentration of the predictor of S-100 protein high activity after vaccination was not increased (p = 0.192. JIA aggravation episodes were not fixed in any patient. Serious adverse events were not observed during the trial.Conclusion. The vaccination of children with JIA with 13-valent PPV is highly

  18. Efficacy and safety of once-monthly injection of paliperidone palmitate in hospitalized Asian patients with acute exacerbated schizophrenia: an open-label, prospective, noncomparative study

    Directory of Open Access Journals (Sweden)

    Li HF

    2015-12-01

    Full Text Available HuaFang Li,1 Ibrahim Turkoz,2 Fan Zhang3 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Janssen Research & Development, LLC, Titusville, NJ, USA; 3Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Introduction: This single-group, open-label, prospective, noncomparative, multicenter, Phase IV study explored the efficacy and tolerability of paliperidone palmitate (PP in hospitalized patients with acute exacerbation of schizophrenia.Methods: Asian patients of either sex, between 18 and 65 years of age, diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition with acute exacerbations within the previous 4 weeks, were enrolled. Intramuscular PP was initiated at doses of 150 milligram equivalent (mg eq (day 1 and 100 mg eq (day 8, followed by a monthly maintenance dose between 75 mg eq and 150 mg eq (days 36 and 64. Primary efficacy endpoint was the change from baseline in the Positive and Negative Syndrome Scale (PANSS total score (last-observation-carried-forward at week 13.Results: Of the 212 enrolled patients, 152 (71.7% completed the 13-week treatment; withdrawal of consent (24 [11.3%] patients was the most common reason for study discontinuation. Mean (standard deviation PANSS total score from baseline (90.0 [17.41] improved significantly at day 4 (-6.1 [9.27]; 95% confidence interval: -7.38, -4.85; P<0.001 and week 13 endpoint (-23.9 [23.24]; 95% confidence interval: -27.10, -20.78; P<0.001. Similarly, the secondary endpoints (Clinical Global Impression-Severity, Physical and Social Performance, each PANSS subscale, and Marder factor scores improved significantly from baseline to week 13 endpoint (P<0.001 for all. At week 13, 112/210 (53.3% patients had a 40% improvement in the PANSS total score (responder rate, and 133/212 (62.7% patients were ready for hospital discharge. Overall, 139 (65

  19. A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial.

    Science.gov (United States)

    Ormiston, John A; Serruys, Patrick W; Regar, Evelyn; Dudek, Dariusz; Thuesen, Leif; Webster, Mark W I; Onuma, Yoshinobu; Garcia-Garcia, Hector M; McGreevy, Robert; Veldhof, Susan

    2008-03-15

    A fully bioabsorbable drug-eluting coronary stent that scaffolds the vessel wall when needed and then disappears once the acute recoil and constrictive remodelling processes have subsided has theoretical advantages. The bioasorbable everolimus-eluting stent (BVS) has a backbone of poly-L-lactic acid that provides the support and a coating of poly-D,L-lactic acid that contains and controls the release of the antiproliferative agent everolimus. We assessed the feasibility and safety of this BVS stent. In this prospective, open-label study we enrolled 30 patients who had either stable, unstable, or silent ischaemia and a single de-novo lesion that was suitable for treatment with a single 3.0 x 12 mm or 3.0 x 18 mm stent. Patients were enrolled from four academic hospitals in Auckland, Rotterdam, Krakow, and Skejby. The composite endpoint was cardiac death, myocardial infarction, and ischaemia-driven target lesion revascularisation. Angiographic endpoints were available for 26 patients and intravascular-ultrasound endpoints for 24 patients. Clinical endpoints were assessed in all 30 patients at 6 and 12 months. In a subset of 13 patients, optical coherence tomography was undertaken at baseline and follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00300131. Procedural success was 100% (30/30 patients), and device success 94% (29/31 attempts at implantation of the stent). At 1 year, the rate of major adverse cardiac events was 3.3%, with only one patient having a non-Q wave myocardial infarction and no target lesion revascularisations. No late stent thromboses were recorded. At 6-month follow-up, the angiographic in-stent late loss was 0.44 (0.35) mm and was mainly due to a mild reduction of the stent area (-11.8%) as measured by intravascular ultrasound. The neointimal area was small (0.30 [SD 0.44] mm2), with a minimal area obstruction of 5.5%. This study shows the feasibility of implantation of the bioabsorbable

  20. Interferon-α treatment in systemic mastocytosis

    DEFF Research Database (Denmark)

    Bjerrum, Ole Weis

    2011-01-01

    Patients with systemic mastocytosis are rare, constitute a heterogeneous clinical entity and some may not require treatment until long after diagnosis. However, most patients who present with disabling symptoms, organ involvement and fulfill B or C findings as outlined in the 2008 WHO...... 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-α, as mono- or combination therapy, in the treatment algorithm may only be definitely established...

  1. Interferon-α treatment in systemic mastocytosis

    DEFF Research Database (Denmark)

    Bjerrum, Ole Weis

    2011-01-01

    Patients with systemic mastocytosis are rare, constitute a heterogeneous clinical entity and some may not require treatment until long after diagnosis. However, most patients who present with disabling symptoms, organ involvement and fulfill B or C findings as outlined in the 2008 WHO...... 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...

  2. Le interferon mRNA from human fibroblasts.

    OpenAIRE

    Pang, R H; Hayes, T G; Vilcek, J

    1980-01-01

    Human F and Le interferon can be clearly distinguished on the basis of different antigenic properties and host range. After inoculation with Newcastle disease virus (NDV), GM-258 fibroblasts produced Le as well as F interferon; in contrast, only F interferon was detectable after stimulation with poly(I) . poly(C). Polyadenylylated mRNA isolated from fibroblasts induced with poly(I) . poly(C) or NDV was injected into Xenopus laevis oocytes and the interferon activities thus produced were analy...

  3. Ribavirin with or without alpha interferon for chronic hepatitis C

    DEFF Research Database (Denmark)

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

    2002-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy...

  4. Antiviral effects of interferon on a somatic cell hybrid between two Burkitt's lymphoma cell lines of different interferon sensitivities.

    OpenAIRE

    Lidin, B; Lamon, E W

    1982-01-01

    A somatic cell hybrid between two human Burkitt's lymphoma cell lines, Raji and Daudi, was infected with either Epstein-Barr virus or vesicular stomatitis virus after interferon treatment. Raji cells are resistant to the antiviral effects of exogenously added interferon, whereas Daudi cells are interferon sensitive. The Raji-Daudi hybrid showed an interferon sensitivity that was intermediary to that of the parental cells against both viruses.

  5. Neuropsychiatric Complications Associated with Interferon - Alpha ...

    African Journals Online (AJOL)

    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 ...

  6. Laboratory evaluation of commercial interferon preparations

    African Journals Online (AJOL)

    counter. The percentage inhibition of TCA precipitable counts was recorded at specific dilutions of the various interferon preparations. NKC stimulation assay. Mononuclear cells, obtained by Ficoll-Hypaque density gra- dient fractionation of peripheral blood donated by healthy volunteers, were used as the effector cells for ...

  7. [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

  8. Interferon modulation of c-myc expression in cloned Daudi cells: relationship to the phenotype of interferon resistance.

    Science.gov (United States)

    Dron, M; Modjtahedi, N; Brison, O; Tovey, M G

    1986-05-01

    Treatment of interferon-sensitive Daudi cell with electrophoretically pure human interferon alpha markedly reduced the level of c-myc mRNA, increased the level of class I histocompatibility antigen (HLA) mRNA, and did not affect the level of actin mRNA within the same cells. In contrast, the level of c-myc mRNA or HLA mRNA did not change significantly following interferon treatment in different clones of Daudi cells selected for resistance to the antiproliferative action of interferon. These cells possessed interferon receptors, however, and responded to interferon modulation of other genes, including 2',5' oligoisoadenylate synthetase (M. G. Tovey, M. Dron, K. E. Mogensen, B. Lebleu, N. Metchi, and J. Begon-Lours, Guymarho, J. Gen. Virol., 64:2649-2653, 1983; M. Dron, M. G. Tovey, and P. Eid, J. Gen. Virol., 66:787-795, 1985). A clone of interferon-resistant Daudi cells which had reverted to almost complete sensitivity to both the antiproliferative action of interferon and the interferon-enhanced expression of HLA mRNA remained refractory, however, to interferon modulation of c-myc expression, suggesting that a reduced level of c-myc mRNA may not be a prerequisite for inhibition of cell proliferation in interferon-treated cells. Our results do not exclude the possibility, however, that posttranscriptional modification(s) of c-myc expression may precede an inhibition of cell proliferation in interferon-treated cells.

  9. Throwing open the doors

    Energy Technology Data Exchange (ETDEWEB)

    Nadkarni, S.

    2000-03-01

    Expansion is on the cards, as the Indian government, in a surprise move, has thrown open the coal processing sector to foreign interests, and raised the ceiling in a few select areas, such as prospecting. 1 photo.

  10. 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.

  11. 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

  12. 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

  13. A multicenter prospective study of patients undergoing open ventral hernia repair with intraperitoneal positioning using themonofilament polyester composite ventral patch: interim results of the PANACEA study

    Directory of Open Access Journals (Sweden)

    Berrevoet F

    2017-05-01

    Full Text Available Frederik Berrevoet,1 Carl Doerhoff,2 Filip Muysoms,3 Steven Hopson,4 Marco Gallinella Muzi,5 Simon Nienhuijs,6 Eric Kullman,7 Tim Tollens,8 Mark R Schwartz,9 Karl LeBlanc,10 Vic Velanovich,11 Lars Nannestad Jørgensen12 1Department of General and Hepatopancreaticobiliary Surgery, Ghent University Hospital, Ghent, Belgium; 2General Surgery, Surgicare of Missouri, Jefferson City, MO, USA; 3Department of Surgery, AZ Maria Middelares Ghent, Ghent, Belgium; 4Bon Secours Hernia Center, Mary Immaculate Hospital, Newport News, VA, USA; 5University Hospital Tor Vergata, Rome, Italy; 6Catharina Hospital, Eindhoven, the Netherlands; 7Medicinskt Centrum Linköping, Linköping, Sweden; 8Imelda Hospital-General Surgery Imelda Hospital, Bonheiden, Belgium; 9Monmouth Medical Center, Long Branch, NJ, 10Our Lady of Lakes Regional Medical Center, Baton Rouge, LA, 11Tampa General Hospital, University of South Florida, Tampa, FL, USA; 12Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark 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 open ventral hernia repair with the PCO-VP was performed. Patient outcomes were assessed at discharge and at 10 days, 1, 6, 12, and 24 months postoperative.Results: All patients had hernioplasty for umbilical (n = 110, 87.3% or epigastric hernia (n = 16, 12.7%. Mean hernia diameter was 1.8 ± 0.8 cm. Mean operative time was 36.2 ±15.6 minutes, with a mean mesh positioning time of 8.1 ± 3.4 minutes. Surgeons reported satisfaction with mesh ease of use in 95% of surgeries. The cumulative hernia recurrence rate at 1 year was 2.8% (3/106. Numeric Rating Scale (NRS pain scores showed improvement from 2.1 ± 2.0 at preoperative baseline to 0.5 ± 0.7 at 1

  14. Interferon alpha for chronic hepatitis D.

    Science.gov (United States)

    Abbas, Zaigham; Khan, Muhammad Arsalan; Salih, Mohammad; Jafri, Wasim

    2011-12-07

    Hepatitis D virus is a small defective RNA virus that requires the presence of hepatitis B virus infection to infect a person. Hepatitis D is a difficult-to-treat infection. Several clinical trials have been published on the efficacy of interferon alpha for hepatitis D virus (HDV) infection. However, there are few randomised trials evaluating the effects of interferon alpha, and it is difficult to judge any benefit of this intervention from the individual trials. To evaluate the beneficial and harmful effects of interferon alpha for patients with chronic hepatitis D. We identified relevant for the review randomised clinical trials by electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until May 2011. We also checked the bibliographic references of identified randomised trials, textbooks, and review articles in order to find randomised trials not identified by the electronic searches. Randomised clinical trials evaluating interferon alpha versus placebo or no intervention for patients with chronic hepatitis D infection. Two authors assessed the trials and extracted data on mortality, virologic, biochemical, and histological response as well as adverse events at end of treatment and six months or more after completing treatment. The analyses were performed using the intention-to-treat principle including all randomised participants irrespective of follow-up. Drop-outs, withdrawals, and non-compliance were considered as treatment failures. Data were analysed with fixed- and random-effects models. Reported results were based on fixed-effect model except in cases where statistical significance varied between the two models. Six randomised trials fulfilled the inclusion criteria. Two hundred and one randomised participants (male = 174) were included. The risk of bias in all the included trials was high

  15. The effect of intact fibula on functional outcome of reamed intramedullary interlocking nail in open and closed isolated tibial shaft fractures: A prospective study.

    Science.gov (United States)

    Balaji, S Muthukumar; Chandra, P Madhu; Devadoss, Sathish; Devadoss, A

    2016-01-01

    Isolated tibial shaft (ITS) fracture with intact fibula is a common injury but records often fail to mention it. Our primary aim was to study the effect of the intact fibula in ITS fractures in closed and open injuries and that these fractures can unite without a primary fibulectomy. 56 patients who sustained an ITS fracture with an intact fibula who underwent closed or open reduction and reamed intramedullary interlocking nailing (IM IL nail) for closed and open fractures between August 2008 and April 2014 were included in this study. Four patients were lost to followup. One patient died due to causes not related to the surgery. At the time of final followup, 51 patients with 51 ITS fractures were available for the analysis. There were 33 closed and 18 open fractures. Patients were followed up at 4 weekly intervals until radiological signs of union were noted. They were assessed for functional outcome using the IOWA knee and ankle score systems at the time of final followup. The average time to union was 19.7 weeks. Closed fractures united in 17.7 weeks as compared to 23.5 weeks for open fractures (P fractures failed to unite (2 open). The functional outcome as per the knee score and ankle score evaluation system was 93.13 and 92.54, respectively. The knee scores were 93.81 and 91.8 for closed and open ITS fractures, respectively (P > 0.05). Similarly, the ankle scores were 94.96 and 88.1 for closed and open ITS fractures, respectively (P fracture with intact fibula is a common occurrence, and they can be treated safely with reamed IM nailing that provides good union rates and the excellent functional result even in open fractures.

  16. 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…

  17. 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 undergoin...

  18. 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

  19. Mini-Open Sinus Tarsi Approach with Percutaneous Screw Fixation of Displaced Calcaneal Fractures: A Prospective Computed Tomography-Based Study

    NARCIS (Netherlands)

    Nosewicz, Tomasz; Knupp, Markus; Barg, Alexej; Maas, Mario; Bolliger, Lilianna; Goslings, J. Carel; Hintermann, Beat

    2012-01-01

    Background: Open reduction and internal fixation (ORIF) of calcaneal fractures using an extended lateral approach results in soft tissue disruption and theoretically subtalar joint stiffness. A minimally invasive sinus tarsi approach for posterior facet exposure and percutaneous screw fixation of

  20. The effect of intact fibula on functional outcome of reamed intramedullary interlocking nail in open and closed isolated tibial shaft fractures: A prospective study

    Directory of Open Access Journals (Sweden)

    S Muthukumar Balaji

    2016-01-01

    Conclusion: ITS fracture with intact fibula is a common occurrence, and they can be treated safely with reamed IM nailing that provides good union rates and the excellent functional result even in open fractures.

  1. Severe Dermatomyositis Triggered by Interferon Beta-1a Therapy and Associated With Enhanced Type I Interferon Signaling

    Science.gov (United States)

    Somani, Ally-Khan; Swick, Alan R.; Cooper, Kevin D.; McCormick, Thomas S.

    2013-01-01

    Background Type I interferons (IFNs) are common therapeutics for several diseases, including viral infections and multiple sclerosis (MS). Although numerous studies have implicated type I INFs with the production of autoantibodies and the development of certain autoimmune disorders, interferon beta has not previously been described in association with dermatomyositis, to our knowledge. Previous microarray studies of muscle biopsy specimens from patients with dermatomyositis disclosed a type I IFN–induced gene expression profile. The central role of plasmacytoid dendritic cell precursors, together with increased type IIFN production, suggests a pivotal role for type I IFNs in dermatomyositis. We report a case of dermatomyositis exacerbated or induced by interferon beta therapy for MS and provide evidence that demonstrates enhanced type I IFN signaling in this patient. Observations We observed new-onset dermatomyositis in a 57-year-old patient treated with interferon beta for MS. His symptoms were exacerbated temporally by interferon beta injections. Immunohistochemical staining of skin biopsy specimens for myxovirus-resistance protein A (a surrogate marker for cutaneous type I IFN signaling) showed increased staining that correlated temporally with interferon beta treatment and subsequent disease activity. In vitro treatment with interferon beta of peripheral blood mononuclear cells isolated from our patient revealed enhanced type I IFN signaling assessed by interferon-induced gene expression profiles. Conclusions To our knowledge, this is the first description of dermatomyositis exacerbated or induced by interferon beta treatment. Our results demonstrate enhanced type I IFN signaling following interferon beta treatment in our patient with dermatomyositis. PMID:18936398

  2. Prospective randomized clinical trial of laparoscopic sleeve gastrectomy versus open Roux-en-Y gastric bypass for the management of patients with morbid obesity

    OpenAIRE

    Paluszkiewicz, Rafa?; Kalinowski, Piotr; Wr?blewski, Tadeusz; Bartoszewicz, Zbigniew; Bia?obrzeska-Paluszkiewicz, Janina; Ziarkiewicz-Wr?blewska, Bogna; Remiszewski, Piotr; Grodzicki, Mariusz; Krawczyk, Marek

    2012-01-01

    Introduction Roux-en-Y gastric bypass (RYGB) is considered the gold standard bariatric procedure with documented safety and effectiveness. Laparoscopic sleeve gastrectomy (LSG) is a newer procedure being done with increasing frequency. Randomized comparisons of LSG and other bariatric procedures are limited. We present the results of the first prospective randomized trial comparing LSG and RYGB in the Polish population. Aim To assess the efficacy and safety of LSG versus RYGB in the treatment...

  3. Antiviral effects of bovine interferons on bovine respiratory tract viruses.

    OpenAIRE

    Fulton, R W; Downing, M M; Cummins, J M

    1984-01-01

    The antiviral effects of bovine interferons on the replication of bovine respiratory tract viruses were studied. Bovine turbinate monolayer cultures were treated with bovine interferons and challenged with several bovine herpesvirus 1 strains, bovine viral diarrhea virus, parainfluenza type 3 virus, goat respiratory syncytial virus, bovine respiratory syncytial virus, bovine adenovirus type 7, or vesicular stomatitis virus. Treatment with bovine interferons reduced viral yield for each of the...

  4. Type I interferon pathway in adult and juvenile dermatomyositis

    Science.gov (United States)

    2011-01-01

    Gene expression profiling and protein studies of the type I interferon pathway have revealed important insights into the disease process in adult and juvenile dermatomyositis. The most prominent and consistent feature has been a characteristic whole blood gene signature indicating upregulation of the type I interferon pathway. Upregulation of the type I interferon protein signature has added additional markers of disease activity and insight into the pathogenesis of the disease. PMID:22192711

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

    NARCIS (Netherlands)

    M.P. Arts (Mark); W.C. Peul (Wilco); R. Brand (René); B.W. Koes (Bart); R.T.W.M. Thomeer (Raph)

    2006-01-01

    textabstractBackground: 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

  6. 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…

  7. 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

  8. 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...

  9. 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....... Mean operative time was 36.2 ±15.6 minutes, with a mean mesh positioning time of 8.1 ± 3.4 minutes. Surgeons reported satisfaction with mesh ease of use in 95% of surgeries. The cumulative hernia recurrence rate at 1 year was 2.8% (3/106). Numeric Rating Scale (NRS) pain scores showed improvement from...

  10. 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.

  11. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study

    OpenAIRE

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun; Bahk, Won-Myong

    2016-01-01

    Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was pri...

  12. Expansion of amphibian intronless interferons revises the paradigm for interferon evolution and functional diversity

    Science.gov (United States)

    Interferons (IFNs) are key cytokines identified in vertebrates, and evolutionary dominance of intronless IFN genes in amniotes is a signature event in IFN evolution. For the first time, we show that the emergence and expansion of intronless IFN genes is evident in amphibians, shown by 24-37 intronle...

  13. 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.

  14. 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......, and the capacity of CNS glial cells to produce and respond to Type I IFN. Differential signaling outcomes of IFN-α and IFN-β, which have been ascribed to differential affinity for IFNAR1 and IFNAR2, determine whether Type I IFN exert pathogenic or protective roles in the CNS. These points will be discussed...

  15. Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier

    OpenAIRE

    Lazear, Helen M.; Daniels, Brian P.; Pinto, Amelia K.; Huang, Albert C.; Vick, Sarah C.; Doyle, Sean E.; Gale, Michael; Klein, Robyn S.; Diamond, Michael S.

    2015-01-01

    Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even t...

  16. 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

  17. 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...

  18. 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)....

  19. Interferon-alpha in the treatment of multiple myeloma

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  20. Expression of human interferon gamma in Brassica napus seeds

    African Journals Online (AJOL)

    TUOYO

    2010-08-09

    Aug 9, 2010 ... express human therapeutic protein, interferon gamma (IFN_γ) in Brassica napus seeds. Kozak sequence was linked to the .... witness successful expression of the human interferon gamma in Brassica napus ..... Cytosolic factors block antibody binding to the C-terminal tail of the. KDEL receptor. Eur. J. Cell ...

  1. 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....

  2. Open-label prospective study of the safety and efficacy of glass-based yttrium 90 radioembolization for infiltrative hepatocellular carcinoma with portal vein thrombosis.

    Science.gov (United States)

    Kokabi, Nima; Camacho, Juan C; Xing, Minzhi; El-Rayes, Bassel F; Spivey, James R; Knechtle, Stuart J; Kim, Hyun S

    2015-07-01

    The safety and efficacy of yttrium 90 ((90) Y) therapy for unresectable infiltrative hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) requires further evaluation. A prospective, single-center safety and feasibility study recruited patients with unresectable (Barcelona Clinic Liver Cancer stage C) infiltrative HCC with PVT. Safety was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and time to progression (TTP) were measured from the first (90) Y therapy. Survival analysis was performed with Kaplan-Meier estimation. Prognostic factors were tested with a log-rank test and Cox proportional regression analysis. Overall, 45 patients were recruited, and 30 patients who met the study's inclusion criteria underwent glass-based (90) Y therapy. Four patients (13%) had transient hepatobiliary toxicity (grade ≥ 2). Ten patients (33%) had related emergency department visits, with 5 patients (17%) requiring short-term hospitalization. No radiation pneumonitis, gastrointestinal ulceration, or procedure-related mortality occurred. The median OS was 13 months (95% confidence interval, 4.4-22 months) with a TTP of 9 months (95% confidence interval, 6.2-13.1 months). Absence of ascites, an international normalized ratio 90) Y therapy appears to be a safe and viable therapy. © 2015 American Cancer Society.

  3. Therapeutic use of interferon-alpha for lymphomatoid papulosis.

    Science.gov (United States)

    Schmuth, M; Topar, G; Illersperger, B; Kowald, E; Fritsch, P O; Sepp, N T

    2000-10-01

    Lymphomatoid papulosis is a primary cutaneous, CD30 positive lymphoproliferative disorder with the potential to transform into systemic, malignant lymphoma. Therapeutic strategies for patients with lymphomatoid papulosis have been designed to prevent transformation but have proved to be either inefficacious or limited by side effects. The authors compared the clinical, histologic, and immunohistochemical features from a group of five patients receiving interferon-alpha (IFN-alpha) subcutaneously three times per week with the same features from a group of six patients receiving conventional therapy, including photochemotherapy, antibiotics, topical corticosteroids, or surgery, in an open trial. In the IFN-alpha group, four patients showed a complete remission, and one patient showed a partial remission within a time period of 6 weeks. Two patients developed disease recurrences after discontinuation of short term IFN-alpha therapy (5-7 months). Thereof, one patient went into stable remission after long term IFN-alpha therapy (17 months), and one patient remains in partial remission. In the control group, one patient went into spontaneous remission, two patients showed partial remission, of which one patient developed progressive disease at a later time point, whereas three patients have recurrent disease despite of treatment. The current results indicate that the treatment with IFN-alpha of patients with lymphomatoid papulosis alters the clinical course of the disease with fewer side effects than previous regimens; however, short term treatment does not induce stable remission. Therefore, prolonged treatment appears to be warranted for these patients.

  4. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

    DEFF Research Database (Denmark)

    Oji, Satoru; Nicolussi, Eva-Maria; Kaufmann, Nathalie

    2016-01-01

    ) 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......, 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...

  5. A Prospective, Randomized, Multicenter, Open-label Clinical Trial Comparing Intradiscal Biacuplasty to Conventional Medical Management for Discogenic Lumbar Back Pain.

    Science.gov (United States)

    Desai, Mehul J; Kapural, Leonardo; Petersohn, Jeffrey D; Vallejo, Ricardo; Menzies, Robert; Creamer, Michael; Gofeld, Michael

    2016-07-01

    This study was a prospective, randomized, crossover, multicenter trial for the evaluation of comparative effectiveness of intradiscal biacuplasty (IDB) versus conventional medical management (CMM) in the treatment of lumbar discogenic pain. The objective was to demonstrate the superiority of IDB over CMM in the treatment of discogenic pain with respect to the primary outcome measure. Current therapeutic options for the treatment of chronic low back pain of discogenic origin are limited. CMM is often unsatisfactory with regard to the treatment of discogenic pain. IDB offers a minimally invasive treatment that has been demonstrated to be superior to placebo in the past. A total of 63 subjects with lumbar discogenic pain diagnosed via provocation discography were randomized to IDB + CMM (n = 29) or CMM-alone (n = 34). At 6 months, patients in the CMM-alone group were eligible for crossover if desired. The primary outcome measure was the change in visual analog scale (VAS) from baseline to 6 months. Secondary outcome measures included treatment "responders," defined as the proportion of subjects with a 2-point or 30% decrease in VAS scores. Other secondary measures included changes from baseline to 6 months in (1) short form (SF) 36-physical functioning, (2) Oswestry Disability Index, (3) Beck Depression Inventory, (4) Patient Global Impression of Change, (5) EQ-5D VAS, and (6) back pain-related medication usage. In the IDB cohort, the mean VAS score reduction exceeded that in the CMM cohort (-2.4 vs. -0.56; P = 0.02), and the proportion of treatment responders was substantially greater (50% vs. 18%). Differences in secondary measures favored IDB. No differences in opioid utilization were noted between groups. Superior performance of IDB with respect to all study outcomes suggests that it is a more effective treatment for discogenic pain than CMM-alone. 2.

  6. 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.

  7. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial.

    Science.gov (United States)

    Simsarian, James P; Saunders, Carol; Smith, D Michelle

    2011-01-01

    Despite over 50 years of experience with adrenocorticotropic hormone (ACTH) as a treatment for acute exacerbations of multiple sclerosis, there have been no trials examining the options of the 2-3-week dosing regimen or intramuscular injection protocol used in the original trials. At our clinic, we performed a small, prospective, randomized pilot study to examine the efficacy and safety of, and patient satisfaction with, a short (five-day) self-administered ACTH dosing protocol for exacerbations of multiple sclerosis, and to compare the subcutaneous and intramuscular routes of administration. Patients for this study were recruited from an outpatient treatment clinic. Each patient self-administered natural ACTH gel 80 U/day by subcutaneous or intramuscular injection for five consecutive days and was evaluated at baseline and on days 7 and 14. Patient feedback was collected using the Patient Global Impression of Change (PGI-C, the primary efficacy measure), a patient global visual analog scale, the Expanded Disability Status Scale, a timed walk, the Nine-hole Peg Test, and the Clinical Global Impression of Change. Of the 20 enrolled patients (mean age 39.5 years), 19 completed the study. On day 14, 61.1% of patients (11 of 18 with day 14 scores) were treatment responders, and rated their condition as "very much improved" or "much improved" on the PGI-C. The intramuscular group had numerically more responders, but there was no significant difference in the proportion of responders between the intramuscular and subcutaneous groups at day 14 (P = 0.3). The intramuscular route of injection was associated with more injection site pain than the subcutaneous route. A shorter five-day course of intramuscular or subcutaneous ACTH gel may improve symptoms associated with acute exacerbations of multiple sclerosis. Larger studies with standard of care controls are needed to confirm whether this shorter course of intramuscular or subcutaneous ACTH gel is effective and could

  8. Open artery hypothesis: the impact of late recanalization of infarct related artery on myocardial perfusion. A prospective randomized study -preliminary data

    International Nuclear Information System (INIS)

    Soares, J. Jr.; Silva, J.C.; Izaki, M.; Giorgi, M.C. P.; Rochitte, C.E.; Oliveira, M.A.; Martinez-Filho, E.E.; Meneghetti, J.C.; Nicolau, J.C.

    2002-01-01

    Introduction: Clinical benefits of infarct related artery recanalization later than 12 hours after acute myocardial infarction (MI) still remain unclear. Aim: To investigate whether late recanalization of infarct related artery (IRA) would improve myocardial ischemia and viability at 6-month follow-up (FU). Methods: Eighteen patients (14 male, mean age 52.7 yr.) were studied between 12 hours and 14 days after the first episode of anterior myocardial infarction. All patients showed left anterior descending artery (LAD) occluded (TIMI 0/I) on the coronary angiography. Patients underwent myocardial perfusion scintigraphy with Thallium-201 (Tl-201) dipyridamol-redistribution and reinjection (Pre-angioplasty). Those patients without evidence of myocardial ischemia or significant viability on the LAD territory were randomized to either IRA recanalization by angioplasty (OPEN group- 9 pts) or no intervention (OCCLUDED group- 9 pts). Tl-201 myocardial scintigraphy was repeated 6 months later (Post-angioplasty). The regions of the LV included in the study were divided into 6 segments: anterior wall (3 segments), septal (2), and apical wall (1). The images were analyzed quantitatively by 2 observers and the segments were scored according to the degree of Tl-201 myocardial uptake into: 4 (no uptake), 3 (severe hypoperfusion), 2 (moderate hypoperfusion), 1 (mild uptake) and 0 (normal). Wilcoxon signed-rank tests based on the mean obtained of the score in the analyzed segments according to the phases (stress, redistribution and reinjection) were used to compare the groups. Results: The results obtained are presented in the table.There was no significant difference between groups at pre-angioplasty analysis, however there was a significant decrease of ischemia and improvement on myocardial perfusion at FU in the open group. Conclusion: Patients submitted to late recanalization of IRA had less ischemia in the infarcted segments and more viable myocardium at 6 months follow

  9. Interferons and viruses: signaling for supremacy.

    Science.gov (United States)

    Galligan, C L; Murooka, T T; Rahbar, R; Baig, E; Majchrzak-Kita, B; Fish, E N

    2006-01-01

    Interferon (IFN)-alpha and IFN-beta are critical mediators of host defense against microbial challenges, directly interfering with viral infection and influencing both the innate and adaptive immune responses. IFNs exert their effects in target cells through the activation of a cell-surface receptor, leading to a cascade of signaling events that determine transcriptional and translation regulation. Understanding the circuitry associated with IFN-mediated signal transduction that leads to a specific biological outcome has been a major focus of our laboratory. Through the efforts of graduate students, postdoctoral fellows, a skilled research technologist, and important collaborations with investigators elsewhere, we have provided some insights into the complexity of the IFN system-and the elegance and simplicity of how protein-protein interactions define biological function.

  10. [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.

  11. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study.

    Science.gov (United States)

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun; Bahk, Won-Myong

    2016-07-01

    The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, pblonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP. Blonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP.

  12. An open, prospective, randomized study comparing the immunogenicity and safety of two inactivated hepatitis A pediatric vaccines in toddlers, children and adolescents in China.

    Science.gov (United States)

    Li, Rong Cheng; Li, Yanping; Yi, Nong; Huang, Lirong; Wan, Zongju; Zhang, Yanping; Rasuli, Anvar

    2013-02-01

    Vaccines against hepatitis A provide long-lasting protection in both adults and children. The aim of this study was to demonstrate that the inactivated hepatitis A vaccine AVAXIM 80U Pediatric is safe and not inferior in terms of seroprotection rate to HAVRIX 720 vaccine 1 month after booster vaccination. An open, randomized, single-center trial was conducted in China in healthy antihepatitis A virus seronegative individuals from 12 months to 15 years of age. Participants were randomized in a 2:1 ratio to receive either AVAXIM 80U Pediatric or HAVRIX 720, followed by a booster vaccination, using the same vaccine 6 months afterward. A total of 720 individuals were included in the study, 480 in the AVAXIM 80U Pediatric group and 240 in the HAVRIX 720 group, and 686 individuals completed the full vaccination schedule. AVAXIM 80U Pediatric was statistically noninferior to HAVRIX 720 in terms of seroprotection rate for all individuals and in each of 3 age groups: toddlers (12-23 months), children (2-11 years) and adolescents (12-15 years). Antihepatitis A virus geometric mean titers were significantly higher with AVAXIM 80U Pediatric than with HAVRIX 720. Both inactivated hepatitis A vaccines were well-tolerated and had a similar incidence and type of adverse events. AVAXIM 80U Pediatric is safe and immunogenic, with a seroprotection rate that is not inferior to HAVRIX 720 in a pediatric population of healthy individuals.

  13. 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.

  14. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial

    Directory of Open Access Journals (Sweden)

    Simsarian JP

    2011-07-01

    Full Text Available James P Simsarian, Carol Saunders, D Michelle SmithNeurology Center of Fairfax Ltd, Fairfax, VA, USABackground: Despite over 50 years of experience with adrenocorticotropic hormone (ACTH as a treatment for acute exacerbations of multiple sclerosis, there have been no trials examining the options of the 2–3-week dosing regimen or intramuscular injection protocol used in the original trials. At our clinic, we performed a small, prospective, randomized pilot study to examine the efficacy and safety of, and patient satisfaction with, a short (five-day self-administered ACTH dosing protocol for exacerbations of multiple sclerosis, and to compare the subcutaneous and intramuscular routes of administration.Methods: Patients for this study were recruited from an outpatient treatment clinic. Each patient self-administered natural ACTH gel 80 U/day by subcutaneous or intramuscular injection for five consecutive days and was evaluated at baseline and on days 7 and 14. Patient feedback was collected using the Patient Global Impression of Change (PGI-C, the primary efficacy measure, a patient global visual analog scale, the Expanded Disability Status Scale, a timed walk, the Nine-hole Peg Test, and the Clinical Global Impression of Change.Results: Of the 20 enrolled patients (mean age 39.5 years, 19 completed the study. On day 14, 61.1% of patients (11 of 18 with day 14 scores were treatment responders, and rated their condition as "very much improved" or "much improved" on the PGI-C. The intramuscular group had numerically more responders, but there was no significant difference in the proportion of responders between the intramuscular and subcutaneous groups at day 14 (P = 0.3. The intramuscular route of injection was associated with more injection site pain than the subcutaneous route.Conclusion: A shorter five-day course of intramuscular or subcutaneous ACTH gel may improve symptoms associated with acute exacerbations of multiple sclerosis. Larger

  15. Prospective randomized clinical trial of laparoscopic sleeve gastrectomy versus open Roux-en-Y gastric bypass for the management of patients with morbid obesity.

    Science.gov (United States)

    Paluszkiewicz, Rafał; Kalinowski, Piotr; Wróblewski, Tadeusz; Bartoszewicz, Zbigniew; Białobrzeska-Paluszkiewicz, Janina; Ziarkiewicz-Wróblewska, Bogna; Remiszewski, Piotr; Grodzicki, Mariusz; Krawczyk, Marek

    2012-12-01

    Roux-en-Y gastric bypass (RYGB) is considered the gold standard bariatric procedure with documented safety and effectiveness. Laparoscopic sleeve gastrectomy (LSG) is a newer procedure being done with increasing frequency. Randomized comparisons of LSG and other bariatric procedures are limited. We present the results of the first prospective randomized trial comparing LSG and RYGB in the Polish population. To assess the efficacy and safety of LSG versus RYGB in the treatment of morbid obesity and obesity-related comorbidities. Seventy-two morbidly obese patients were randomized to RYGB (36 patients) or LSG (36 patients). Both groups were comparable regarding age, gender, body mass index (BMI) and comorbidities. The follow-up period was at least 12 months. Baseline and 6 and 12 month outcomes were analyzed including assessment of percent excess weight lost (%EWL), reduction in BMI, morbidity (minor, major, early and late complications), mortality, reoperations, comorbidities and nutritional deficiencies. There was no 30-day mortality and no significant difference in major complication rate (0% after RYGB and 8.3% after LSG, p > 0.05) or minor complication rate (16.6% after RYGB and 10.1% after LSG, p > 0.05). There were no early reoperations after RYGB and 2 after LSG (5.5%) (p > 0.05). Weight loss was significant after RYGB and LSG but there was no difference between both groups at 6 and 12 months of follow-up. At 12 months %EWL in RYGB and LSG groups reached 64.2% and 67.6% respectively (p > 0.05). There was no significant difference in the overall prevalence of comorbidities and nutritional deficiencies. Both LSG and RYGB produce significant weight loss at 6 and 12 months after surgery. The procedures are equally effective with regard to %EWL, reduction in BMI and amelioration of comorbidities at 6 and 12 months of follow-up. Laparoscopic sleeve gastrectomy and RYGB are comparably safe techniques with no significant differences in minor and major complication

  16. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients.

    Science.gov (United States)

    Arnaud, Laurent; Hervier, Baptiste; Néel, Antoine; Hamidou, Mohamed A; Kahn, Jean-Emmanuel; Wechsler, Bertrand; Pérez-Pastor, Gemma; Blomberg, Bjørn; Fuzibet, Jean-Gabriel; Dubourguet, François; Marinho, António; Magnette, Catherine; Noel, Violaine; Pavic, Michel; Casper, Jochen; Beucher, Anne-Bérangère; Costedoat-Chalumeau, Nathalie; Aaron, Laurent; Salvatierra, Juan; Graux, Carlos; Cacoub, Patrice; Delcey, Véronique; Dechant, Claudia; Bindi, Pascal; Herbaut, Christiane; Graziani, Giorgio; Amoura, Zahir; Haroche, Julien

    2011-03-10

    Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

  17. 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.

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

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    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.

  19. A Prospective, Nonrandomized, Open-Label Study of the Efficacy and Safety of OnabotulinumtoxinA in Adolescents with Primary Axillary Hyperhidrosis.

    Science.gov (United States)

    Glaser, Dee Anna; Pariser, David M; Hebert, Adelaide A; Landells, Ian; Somogyi, Chris; Weng, Emily; Brin, Mitchell F; Beddingfield, Frederick

    2015-01-01

    To evaluate the efficacy and safety of onabotulinumtoxinA in adolescents with primary axillary hyperhidrosis. This 52-week, multicenter, nonrandomized, open-label study was conducted in 141 adolescents ages 12 to 17 years with severe primary axillary hyperhidrosis. Patients could receive up to six treatments with onabotulinumtoxinA (50 U per axilla), with re-treatment occurring no sooner than 8 weeks after the prior treatment cycle and no later than 44 weeks after the initial treatment cycle. The primary efficacy measure was treatment response, based on self-assessed hyperhidrosis severity following the first two treatments using the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Other efficacy measures included spontaneous resting sweat production and health outcomes. Fifty-six (38.9%) participants underwent one treatment, 59 (41.0%) underwent two, 20 (13.9%) underwent three, 6 (4.2%) underwent four, and 3 (2.1%) underwent five. OnabotulinumtoxinA significantly improved HDSS scores and decreased sweat production compared with treatment cycle baselines. Seventy-nine patients (54.9%) responded to treatment based on HDSS criteria. From 56.6% to 72.3% of patients experienced a two-grade or more improvement at 4 and 8 weeks after each of the first two treatments. The majority (79.4%-93.2%) had a 75% or greater reduction in sweat production at week 4 (treatments 1-3). The median duration of effect for responders ranged from 134 to 152 days. Using quality of life measures, health outcomes improved markedly. Eight patients (5.6%) had mild or moderate treatment-related adverse events. No unexpected safety signals were observed in this study. Neutralizing antibodies to onabotulinumtoxinA did not develop. OnabotulinumtoxinA injections provided beneficial effects in adolescents with primary axillary hyperhidrosis. © 2015 The Authors. Pediatric Dermatology Published by Wiley Periodicals, Inc.

  20. 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.

  1. 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

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

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    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

  3. Effectiveness and tolerability of transdermal buprenorphine patches: a multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain.

    Science.gov (United States)

    Yoon, Do Heum; Bin, Seong-Il; Chan, Simon Kin-Cheong; Chung, Chun Kee; In, Yong; Kim, Hyoungmin; Lichauco, Juan Javier; Mok, Chi Chiu; Moon, Young-Wan; Ng, Tony Kwun-Tung; Penserga, Ester Gonzales; Shin, Dong Ah; You, Dora; Moon, Hanlim

    2017-08-04

    We examined the effectiveness and tolerability of transdermal buprenorphine (TDB) treatment in real-world setting in Asian patients with musculoskeletal pain. This was an open-label study conducted in Hong Kong, Korea, and the Philippines between June 2013 and April 2015. Eligible patients fulfilled the following criteria: 18 to 80 years of age; clinical diagnosis of osteoarthritis, rheumatoid arthritis, low back pain, or joint/muscle pain; chronic non-malignant pain of moderate to severe intensity (Box-Scale-11 [BS-11] pain score ≥ 4), not adequately controlled with non-opioid analgesics and requiring an opioid for adequate analgesia; and no prior history of opioid treatment. Patients started with a 5 μg/h buprenorphine patch and were titrated as necessary to a maximum of 40 μg/h over a 6-week period to achieve optimal pain control. Patients continued treatment with the titrated dose for 11 weeks. The primary efficacy endpoint was the change in BS-11 pain scores. Other endpoints included patients' sleep quality and quality of life as assessed by the 8-item Global Sleep Quality Assessment Scale (GSQA) questionnaire and the EuroQol Group 5-Dimension Self-Report Questionnaire-3 Level version (EQ-5D-3 L), respectively. Tolerability was assessed by collecting adverse events. A total of 114 eligible patients were included in the analysis. The mean BS-11 score at baseline was 6.2 (SD 1.6). Following initiation of TDB, there was a statistically significant improvement in BS-11 score from baseline to visit 3 (least squares [LS] mean change: -2.27 [95% CI -2.66 to -1.87]), which was maintained till the end of the study (visit 7) (LS mean change: -2.64 [95% -3.05 to -2.23]) (p < 0.0001 for both). The proportion of patients who rated sleep quality as 'good' increased from 14.0% at baseline to 26.9% at visit 6. By visit 6, the mean EQ VAS score increased by 7.7 units (SD 17.9). There were also significant improvements in patients' levels of functioning for all EQ

  4. Beta-interferon inhibits cell infection by Trypanosoma cruzi

    Science.gov (United States)

    Kierszenbaum, F.; Sonnenfeld, G.

    1984-01-01

    Beta interferon has been shown to inhibit the capacity of bloodstream forms of the flagellate Trypanosoma cruzi, the causative agent of Chagas' disease, to associate with and infect mouse peritoneal macrophages and rat heart myoblasts. The inhibitory effect was abrogated in the presence of specific antibodies to the interferon. Pretreatment of the parasites with interferon reduced their infectivity for untreated host cells, whereas pretreament of either type of host cell did not affect the interaction. The effect of interferon on the trypanosomes was reversible; the extent of the inhibitory effect was significantly reduced afer 20 min, and was undetectable after 60 min when macrophages were used as host cells. For the myoblasts, 60 min elapsed before the inhibitory effect began to subside and 120 min elapsed before it became insignificant or undetectable.

  5. Ocular changes due to systemic alpha-interferon therapy for hepatitis C Alterações oculares por uso sistêmico de alfa-interferon em pacientes com hepatite C

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    Liang Shih Jung

    2004-12-01

    Full Text Available PURPOSE: To describe ocular (specially fundoscopic changes due to systemic alpha-interferon (IFN therapy in patients with hepatitis C. This is a prospective, descriptive and observational (non-interventional study, and its results are preliminary. METHODS: Patients were selected with indication of alpha-interferon therapy for hepatitis C. They underwent ocular examinations before therapy and 1, 3, 6 and 12 months after starting the therapy. HIV patients and those who had a history of previous treatment with alpha-interferon were excluded from the study, but examined. RESULTS: Fifty-one patients were selected from November 1999 to June 2000. The male-to-female ratio was 1.55. The age average was 47 years. The best corrected visual acuity ranged from 20/15 to 20/40. Most of the symptomatic patients complained of foreign body sensation in the eyes, which became more tolerable with time. Complaints comprised flu-like symptoms, joint pain, depression, headache, and general weakness. Ocular findings related to alpha-interferon were: cotton wool spots (3 eyes and intraretinal hemorrhage (1 eye. One patient died during the study, due to another disease not related to hepatitis, and one patient refused to be examined. CONCLUSIONS: There are retinal vascular changes due to systemic alpha-interferon for hepatitis C. There are no studies in our country describing ocular changes in patients with hepatitis C on therapy with alpha-interferon. General physicians and specially gastroenterologists should pay special attention to this problem, and refer these patients to the ophthalmologist in order to determine and follow any lesion that may be related to the use of this drug.OBJETIVO: Avaliar alterações oculares (em especial lesões fundoscópicas em pacientes com hepatite C tratados com alfa-interferon (IFN. MÉTODOS: Estudo prospectivo, descritivo e observacional de pacientes com hepatite C do serviço de Gastroenterologia da UNIFESP com indicações de uso

  6. Treatment of Hepatitis C Infections with Interferon: A Historical Perspective

    Science.gov (United States)

    2010-01-01

    Treatment of Hepatitis C Infections with Interferon: A Historical Perspective Robert M. Friedman and Sara Contente Department of Pathology, Uniformed...sufficient quantities of it were available for treatment of hepatitis C virus (HCV) infections, Clinicians now have an excellent understanding of the basis...02 JUL 2010 2. REPORT TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Treatment of Hepatitis C Infections with Interferon

  7. Axonal interferon responses and alphaherpesvirus neuroinvasion

    Science.gov (United States)

    Song, Ren

    Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at a peripheral epithelial surface and continues into the peripheral nervous system (PNS) that innervates this tissue. Inflammatory responses are induced at the infected peripheral site prior to viral invasion of the PNS. PNS neurons are highly polarized cells with long axonal processes that connect to distant targets. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which include type I interferon (e.g. IFNbeta) and type II interferon (i.e. IFNgamma). IFNbeta can be produced by all types of cells, while IFNgamma is secreted by some specific types of immune cells. And both types of IFN induce antiviral responses in surrounding cells that express the IFN receptors. The fundamental question is how do PNS neurons respond to the inflammatory milieu experienced only by their axons. Axons must act as potential front-line barriers to prevent PNS infection and damage. Using compartmented cultures that physically separate neuron axons from cell bodies, I found that pretreating isolated axons with IFNbeta or IFNgamma significantly diminished the number of HSV-1 and PRV particles moving from axons to the cell bodies in an IFN receptor-dependent manner. Furthermore, I found the responses in axons are activated differentially by the two types of IFNs. The response to IFNbeta is a rapid, axon-only response, while the response to IFNgamma involves long distance signaling to the PNS cell body. For example, exposing axons to IFNbeta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFNgamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated IFNgamma-, but not IFNbeta-mediated antiviral effects. Proteomic analysis of IFNbeta- or IFNgamma-treated axons identified several differentially regulated proteins. Therefore

  8. Performance of an interferon-gamma release assay to diagnose latent tuberculosis infection during pregnancy.

    Science.gov (United States)

    Lighter-Fisher, Jennifer; Surette, Ann-Marie

    2012-06-01

    To evaluate an interferon (IFN)-gamma release assay in diagnosing latent tuberculosis infection in pregnant adolescents and women at risk for exposure to Mycobacterium tuberculosis. This was a prospective study of women and adolescents receiving health care at Bellevue Hospital Outpatient Clinics in New York City. Each patient was assessed for M tuberculosis risk factors, had a tuberculin skin test placed, and an IFN-gamma release assay performed. The concordance between the tuberculin skin test and the IFN-gamma release assay was calculated and the results analyzed according to the likelihood of exposure to M tuberculosis. Mean mitogen IFN-γ levels were used across groups to compare reliability between trimesters and assay performance in pregnant compared with nonpregnant females of childbearing age. A total of 140 pregnant and 140 nonpregnant females were enrolled in the study. The IFN-gamma release assay was highly specific, and IFN-gamma release assay positivity was associated with a greater likelihood of exposure to M tuberculosis. The overall agreement between the tuberculin skin test and IFN-gamma release assay results was 88% for all pregnant patients, corresponding to a κ of 0.452 (confidence interval 0.26-0.64). Interferon-γ release from the mitogen did not appear to have any temporal association with pregnancy trimester in cross-sectional or longitudinal studies. The IFN-gamma release assay performed equally well in pregnant and nonpregnant females. The IFN-gamma release assay performed equally well in each trimester of pregnancy with comparable results to nonpregnant females. Interferon-gamma release assays are much more specific, at least as sensitive, and may be a better predictor of disease progression than the tuberculin skin test. : II.

  9. Interferon Alpha Association with Neuromyelitis Optica

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    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.

  10. Evolution of vertebrate interferon inducible transmembrane proteins

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    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.

  11. 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.

  12. Hybrid (BDBB) interferon-alpha: preformulation studies.

    Science.gov (United States)

    Allen, J D; Bentley, D; Stringer, R A; Lowther, N

    1999-10-05

    A number of techniques, including RP-HPLC, HP-SEC and SDS-PAGE have been used in the delineation of degradative mechanisms of recombinant hybrid (BDBB) interferon-alpha (IFN-alpha) in the solution phase. Different degradation profiles are found according to medium pH. At pH 4.0 the major routes of degradation are via chemical transformation of the monomeric protein to a species which retains antiviral activity, and by self-proteolytic hydrolysis. At pH 7.6, methionine-oxidation is the major chemical degradative process. Protein aggregation is also a significant route of degradation at the higher pH. The results have assisted in a targeted preformulation screen of potentially stabilising excipients and possible parenteral solution dosage forms have been identified. Preliminary 'real-time' storage data confirm excellent chemical and physical stability of IFN-alpha in vehicles formulated at pH 7.6 or, especially, pH 4.0 under the proposed shelf conditions.

  13. 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.

  14. Evaluation of the EmbaGYN™ pelvic floor muscle stimulator in addition to Kegel exercises for the treatment of female stress urinary incontinence: a prospective, open-label, multicenter, single-arm study.

    Science.gov (United States)

    Eder, Scott Evan

    2014-01-01

    To assess the efficacy and safety of the EmbaGYN™ Pelvic Floor Exerciser, a battery-powered neuromuscular stimulation device with a vaginal, two-electrode stimulation probe in women with stress urinary incontinence. In this prospective, open-label, multicenter, single-arm study, patients with stress urinary incontinence (n = 83) underwent 12 weeks of treatment with EmbaGYN with Kegel exercises. At week 12, the mean number of incontinence episodes/day (primary end point) fell 56.2% (p = 0.152). A ≥50% decrease from baseline in incontinence episodes was seen in 65.3% of subjects (p = 0.006). The mean number of incontinence pads/day fell 57.1% (p = 0.001). Mean 24- and 1-h in-office urine loss declined 59.0% (p Kegel exercises resulted in significant reductions in urine loss, incontinence pad use and improved incontinence-related quality of life, but did not have a significant effect on incontinence episodes/day.

  15. 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%, Pserious adverse events were observed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  16. Open Chemistry: Realizing Open Data, Open Standards, and Open Source

    OpenAIRE

    Hanwell, Marcus; Harris, Chris; Lonie, David; Lutz, Kyle; Cole, David

    2012-01-01

    The Blue Obelisk has brought together the computational chemistry community and those who are passionate about Open Chemistry and realizing the promise of Open Data, Open Standards, and Open Software (ODOSOS); the three pillars the group promotes. We will present current work that has taken place over the past five years, which is inspired by these pillars, and present plans for future work.The group is actively engaged in multiple open source projects that rely on and promote open standards ...

  17. Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Hegen, H; Millonig, A; Bertolotto, A

    2014-01-01

    BACKGROUND: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6-18 months on therapy. OBJECTIVES: To investigate whether early binding antibody (BAb) titers or diffe......BACKGROUND: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6-18 months on therapy. OBJECTIVES: To investigate whether early binding antibody (BAb) titers...... or different IFN-b biomarkers predict NAb evolution. METHODS: We included patients with MS or clinically isolated syndrome (CIS) receiving de novo IFN-b treatment in this prospective European multicenter study. Blood samples were collected at baseline, before and after the first IFN-b administration, and again...... after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. RESULTS: We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment...

  18. 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.

  19. 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.

  20. The evolution of interferon-tau.

    Science.gov (United States)

    Ealy, Alan D; Wooldridge, Lydia K

    2017-11-01

    Thirty years ago, a novel type I interferon (IFN) was identified by molecular cloning of cDNA libraries constructed from RNA extracted from ovine and bovine pre-implantation embryos. This protein was eventually designated as IFN-tau (IFNT) to highlight its trophoblast-dependent expression. IFNT function is not immune related. Instead, it interacts with the maternal system to initiate the establishment and maintenance of pregnancy. This activity is indispensable for the continuation of pregnancy. Our review will describe how IFNT evolved from other type I IFNs to function in this new capacity. IFNT genes have only been identified in pecoran ruminants within the Artiodactyla order (e.g. cattle, sheep, goats, deer, antelope, giraffe). The ancestral IFNT gene emerged approximately 36 million years ago most likely from rearrangement and/or insertion events that combined an ancestral IFN-omega ( IFNW ) gene with a trophoblast-specifying promoter/enhancer. Since then, IFNT genes have duplicated, likely through conversion events, and mutations have allowed them to adapt to their new function in concert with the emergence of different species. Multiple IFNT polymorphisms have been identified in cattle, sheep and goats. These genes and gene alleles encode proteins that do not display identical antiviral, antiproliferative and antiluteolytic activities. The need for multiple IFNT genes, numerous alleles and distinct activities remains debatable, but the consensus is that this complexity in IFNT expression and biological activity must be needed to provide the best opportunity for pregnancy to be recognized by the maternal system so that gestation may continue. © 2017 Society for Reproduction and Fertility.

  1. 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...

  2. 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)

  3. DMPD: The interferon signaling network and transcription factor C/EBP-beta. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18163952 The interferon signaling network and transcription factor C/EBP-beta. Li H... The interferon signaling network and transcription factor C/EBP-beta. PubmedID 18163952 Title The interferon signaling network

  4. Comparative Pharmacokinetics, Tissue Distribution, Excretion of Recombinant Liver-Targeting Interferon with IFN α2b Administered Intramuscular in Rats.

    Science.gov (United States)

    Wang, Jie; Lu, Xuemei; Jin, Xiaobao; Zeng, Wenting; Zhu, Jiayong

    2015-01-01

    Interferon α2b (IFN α2b) is the first cytokine, which has been approved by FDA to treat chronic hepatitis B. However, it has no organ or tissue selectivity effect, and will be rapidly cleared out in the liver after the administration treatment. In our previous study, a novel liver-targeting fusion interferon (IFN-CSP) was constructed by recombining human IFN α2b with a CSP region I-plus peptide. The purpose of this study is to compare pharmacokinetics, tissue distribution, excretion of recombinant liver-targeting interferon IFN-CSP with IFN α2b following intramuscular administration in rats and estimate whether the fusion protein recombinant liver-targeting interferon has liver-targeting effect. Serum, tissue, urinary, fecal, and biliary concentrations of the drug were measured at various time points after administration using ELISA test. The pharmacokinetic character of IFN-CSP and IFNα2b was described using a non-compartmental model after a single intramuscular administration. Our results showed that there were no significant differences between these two drugs in pharmacokinetic and elimination. However, drug concentration of recombinant liver-targeting IFN was higher than IFN α2b in the liver after intramuscular administration in rats at different time points. It was increased in the spleen but not apparently, and decreased in the heart, lung and kidney. In conclusion, compared with traditional IFN α2b, the novel recombinant liver-targeting IFN will be more accumulated in the liver tissue. With this excellent property, IFN-CSP shows a great application prospect in clinical treatment, although further investigation is still needed.

  5. 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

  6. 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.

  7. Comparison of the Efficacy and Safety of Aripiprazole Versus Bupropion Augmentation in Patients With Major Depressive Disorder Unresponsive to Selective Serotonin Reuptake Inhibitors: A Randomized, Prospective, Open-Label Study.

    Science.gov (United States)

    Cheon, Eun-Jin; Lee, Kwang-Hun; Park, Young-Woo; Lee, Jong-Hun; Koo, Bon-Hoon; Lee, Seung-Jae; Sung, Hyung-Mo

    2017-04-01

    The purpose of this study was to compare the efficacy and safety of aripiprazole versus bupropion augmentation in patients with major depressive disorder (MDD) unresponsive to selective serotonin reuptake inhibitors (SSRIs). This is the first randomized, prospective, open-label, direct comparison study between aripiprazole and bupropion augmentation. Participants had at least moderately severe depressive symptoms after 4 weeks or more of SSRI treatment. A total of 103 patients were randomized to either aripiprazole (n = 56) or bupropion (n = 47) augmentation for 6 weeks. Concomitant use of psychotropic agents was prohibited. Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores were obtained at baseline and after 1, 2, 4, and 6 weeks of treatment. Overall, both treatments significantly improved depressive symptoms without causing serious adverse events. There were no significant differences in the Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, and Iowa Fatigue Scale scores, and response rates. However, significant differences in remission rates between the 2 groups were evident at week 6 (55.4% vs 34.0%, respectively; P = 0.031), favoring aripiprazole over bupropion. There were no significant differences in adverse sexual events, extrapyramidal symptoms, or akathisia between the 2 groups. The present study suggests that aripiprazole augmentation is at least comparable to bupropion augmentation in combination with SSRI in terms of efficacy and tolerability in patients with MDD. Both aripiprazole and bupropion could help reduce sexual dysfunction and fatigue in patients with MDD. Aripiprazole and bupropion may offer effective and safe augmentation strategies in patients with MDD who are unresponsive to SSRIs. Double-blinded trials are warranted to confirm the present findings.

  8. 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.

  9. 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.

    Science.gov (United States)

    Głuszko, Piotr; Stasiek, Małgorzata

    2016-01-01

    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). 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. 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 first observational study in Poland evaluating the effects of routine knee OA treatment with oral ASU. Only a small group of patients (13.2%) treated with ASU discontinued the study. The majority of patients adherent to the ASU treatment for 6 months showed gradual alleviation of joint pain, improvement in functional ability and a significant reduction in NSAIDs intake.

  10. 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.

  11. Open, Prospective, Multi-Center, Two-Part Study of Patient Preference with Monthly Ibandronate Therapy in Women with Postmenopausal Osteoporosis Switched From Daily or Weekly Alendronate or Risendronate-BONCURE: Results of Turkish Sub-Study

    Directory of Open Access Journals (Sweden)

    Nurten Eskiyurt

    2012-04-01

    Full Text Available Aim: BONCURE (Bonviva for Current Bisphosphonate Users Regional European Trial, aimed to evaluate patient preference with monthly ibandronate in women with postmenopausal osteoporosis who previously received daily or weekly alendronate or risendronate. Materials and Methods: This prospective, open-label study consisted of two sequential stages, Part A (screening and Part B (treatment. Patients enrolled into Part A completed the Candidate Identification Questionnaire (CIQ. In Part B, after completing the Osteoporosis Patient Satisfaction Questionnaire (OPSATQ, patients received monthly oral ibandronate 150 mg for 6 months. Following treatment, patients completed the OPSAT-Q and Preference Questionnaire. Results: A total of 223 patients (mean age, 63.7±9.51 years were enrolled in Part A from Turkey. Among them, 103 (46.2% answered “YES” to at least one CIQ question. The mean composite OPSAT-Q domain scores increased for convenience (mean change, 15.3±17.7 points, quality of life (10.4±20.4 points, overall satisfaction (11.9±22.7 points, and side effects (3.3±18.8 points. At month 6, 177 subjects (92.7% preferred once-monthly dosing schedule and 99.0% were compliant (≥80% with study treatment. Thirty (15.6% subjects experienced mild to moderate adverse events, mostly gastrointestinal. Conclusion: Postmenopausal women with osteoporosis prefer and are more satisfied and compliant with monthly dosing of ibandronate than daily or weekly bisphosphonate treatment. (Turkish Journal of Osteoporosis 2012;18:1-7

  12. An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder.

    Science.gov (United States)

    Zheng, Yi; Liang, Jian-Min; Gao, Hong-Yun; Yang, Zhi-Wei; Jia, Fu-Jun; Liang, Yue-Zhu; Fang, Fang; Li, Rong; Xie, Sheng-Nan; Zhuo, Jian-Min

    2015-11-20

    Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD. This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training. A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study. The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks. ClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Recruitment of Histone Deacetylase 3 to the Interferon-A Gene Promoters Attenuates Interferon Expression

    Science.gov (United States)

    Génin, Pierre; Lin, Rongtuan; Hiscott, John; Civas, Ahmet

    2012-01-01

    Background Induction of Type I Interferon (IFN) genes constitutes an essential step leading to innate immune responses during virus infection. Sendai virus (SeV) infection of B lymphoid Namalwa cells transiently induces the transcriptional expression of multiple IFN-A genes. Although transcriptional activation of IFN-A genes has been extensively studied, the mechanism responsible for the attenuation of their expression remains to be determined. Principal Findings In this study, we demonstrate that virus infection of Namalwa cells induces transient recruitment of HDAC3 (histone deacetylase 3) to IFN-A promoters. Analysis of chromatin-protein association by Chip-QPCR demonstrated that recruitment of interferon regulatory factor (IRF)3 and IRF7, as well as TBP correlated with enhanced histone H3K9 and H3K14 acetylation, whereas recruitment of HDAC3 correlated with inhibition of histone H3K9/K14 acetylation, removal of IRF7 and TATA-binding protein (TBP) from IFN-A promoters and inhibition of virus-induced IFN-A gene transcription. Additionally, HDAC3 overexpression reduced, and HDAC3 depletion by siRNA enhanced IFN-A gene expression. Furthermore, activation of IRF7 enhanced histone H3K9/K14 acetylation and IFN-A gene expression, whereas activation of both IRF7 and IRF3 led to recruitment of HDAC3 to the IFN-A gene promoters, resulting in impaired histone H3K9 acetylation and attenuation of IFN-A gene transcription. Conclusion Altogether these data indicate that reversal of histone H3K9/K14 acetylation by HDAC3 is required for attenuation of IFN-A gene transcription during viral infection. PMID:22685561

  19. 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....

  20. 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....

  1. Interferon free hepatitis C treatment regimens: the beginning of another era.

    Science.gov (United States)

    Poordad, Fred; Chee, Grace M

    2012-02-01

    Hepatitis C is a virus affecting millions worldwide and is a major health risk. With the potentially severe adverse event profile of the current backbone of therapy, interferon, there is an impetus to discover interferon free treatment regimens. With the development of new oral direct acting antivirals, interferon free regimens may be available in the next few years. This article discusses some of the preliminary data from interferon free studies.

  2. DMPD: Fifty years of interferon research: aiming at a moving target. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16979566 Fifty years of interferon research: aiming at a moving target. Vilcek J. I...mmunity. 2006 Sep;25(3):343-8. (.png) (.svg) (.html) (.csml) Show Fifty years of interferon research: aiming... at a moving target. PubmedID 16979566 Title Fifty years of interferon research: aiming at a moving target.

  3. 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

  4. 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 ...

  5. DMPD: Type I interferon receptors: biochemistry and biological functions. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502368 Type I interferon receptors: biochemistry and biological functions. de Wee...(.html) (.csml) Show Type I interferon receptors: biochemistry and biological functions. PubmedID 17502368 T...itle Type I interferon receptors: biochemistry and biological functions. Authors

  6. 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.

  7. Recombinant alpha-interferon as salvage therapy in multiple myeloma

    African Journals Online (AJOL)

    1989-08-05

    Aug 5, 1989 ... Ten patients with end-stage multiple myeloma refractory to conventional chemotherapy and hemibody irradiation received recombinant a-interferon as salvage therapy. The median duration of treatment was 8 weeks. One patient had an objective response and survived 8 months, whereas in the remaining ...

  8. Recombinant alpha-interferon as salvage therapy in multiple myeloma

    African Journals Online (AJOL)

    Ten patients with end-stage multiple myeloma refractory to conventional chemotherapy and hemibody irradiation received recombinant α-interferon as salvage therapy. The median duration of treatment was 8 weeks. One patient had an objective response and survived 8 months, whereas in the remaining 9 patients the ...

  9. Expression of recombinant interferon α-2a in tobacco chloroplasts ...

    African Journals Online (AJOL)

    Yomi

    2011-11-23

    Nov 23, 2011 ... Moreover, the interferon alpha-2a protein was purified by using Ni-NTA purification columns. The presence of a fragment of 20 kDa size on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and high performance liquid chromatography (HPLC) chromatogram confirms the expression ...

  10. 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.



  11. 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...

  12. Control of the interferon response in RNAi experiments

    Czech Academy of Sciences Publication Activity Database

    Nejepínská, Jana; Flemr, Matyáš; Svoboda, Petr

    2012-01-01

    Roč. 820, - (2012), s. 133-161 ISSN 1064-3745 R&D Projects: GA AV ČR IAA501110701; GA ČR GA204/09/0085 Grant - others:EMBO SDIG(DE) 1483 Institutional research plan: CEZ:AV0Z50520514 Keywords : RNAi * interferon * siRNA Subject RIV: EB - Genetics ; Molecular Biology

  13. 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 he...

  14. Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in mice

    DEFF Research Database (Denmark)

    Salem, Mohammad; Mony, Jyothi T; Lobner, Morten

    2011-01-01

    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. Inte...

  15. 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 ...

  16. Interferon-gamma confers resistance to experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Krakowski, M; Owens, T

    1996-01-01

    In experimental allergic encephalomyelitis (EAE), T cells infiltrate the central nervous system (CNS) and induce inflammation. These CD4+ T cells secrete interferon (IFN)-gamma, levels of which correlate with disease severity, and which is proposed to play a key role in disease induction. Many...

  17. Improved Refolding Efficacy of Recombinant Human Interferon α-2b ...

    African Journals Online (AJOL)

    Interferon α-2b via pH Modulation. Aziz Dashbolaghi1, Shohreh Khatami2, Sorush Sardari3, Reza Ahangari Cohan1 and Dariush Norouzian1*. 1Department of Pilot Biotechnology, 2Department of Biochemistry, 3Drug Design and Bioinformatics Unit, Medical Biotechnology. Department, Biotechnology Research Center, ...

  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. 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, ...

  20. 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…

  1. Long-term efficacy and safety of incobotulinumtoxinA and conventional treatment of poststroke arm spasticity: a prospective, non-interventional, open-label, parallel-group study.

    Science.gov (United States)

    Dressler, Dirk; Rychlik, Reinhard; Kreimendahl, Fabian; Schnur, Nicole; Lambert-Baumann, Judith

    2015-12-30

    To compare the efficacy and safety of incobotulinumtoxinA with conventional antispastic therapy for poststroke arm spasticity in routine clinical practice over a 1-year period. Prospective, non-interventional, open-label, parallel-group study. 47 centres in Germany. Patients with poststroke arm spasticity; 108 receiving incobotulinumtoxinA, 110 conventional therapy. Conventional antispastic treatment including oral antispastic medications, physiotherapy and occupational therapy or 3-monthly incobotulinumtoxinA injections plus conventional therapy if required. The main outcome measure was changes in muscle tone (Ashworth Scale) over the 1-year treatment period. Changes in functional disability (Disability Assessment Scale) and quality of life (Short-Form-12 Health Survey) were additionally assessed. Ratings for therapy outcome (Goal Attainment Scale), and efficacy and tolerability of treatment (Global Clinical Impression Scale) were also obtained. Muscle tone improved for all spasticity patterns with the Ashworth Scale responder rates between 63% and 86% (incobotulinumtoxinA) and 16-27% (conventional therapy). Median improvement in functional disability was -1.0 (incobotulinumtoxinA) and 0.0 (conventional measures) for all domains. Treatment goals were attained by 93% of incobotulinumtoxinA patients and 30% of patients under conventional therapy. Most physicians (93%) and patients (90%) rated efficacy as good or very good under incobotulinumtoxinA; the proportions were much lower under conventional therapy (36% and 37%). Tolerability under incobotulinumtoxinA was considered good or very good by 99% of physicians and patients (76% and 66%, respectively, under conventional therapy). Quality of life under incobotulinumtoxinA improved by 8.0 (physical score) and 10.8 (mental score) and by 0.8 and 5.7, respectively, under conventional therapy. IncobotulinumtoxinA combined with rehabilitation and oral medication produces a much more robust improvement in all aspects of

  2. The efficacy of continuous-flow cryo and cyclic compression therapy after hip fracture surgery on postoperative pain: design of a prospective, open-label, parallel, multicenter, randomized controlled, clinical trial.

    Science.gov (United States)

    Leegwater, Nick C; Nolte, Peter A; de Korte, Niels; Heetveld, Martin J; Kalisvaart, Kees J; Schönhuth, Casper P; Pijnenburg, Bas; Burger, Bart J; Ponsen, Kees-Jan; Bloemers, Frank W; Maier, Andrea B; van Royen, Barend J

    2016-04-08

    The number of hip fractures and resulting post-surgical outcome are a major public health concern and the incidence is expected to increase significantly. The acute recovery phase after hip fracture surgery in elder patients is often complicated by severe pain, high morphine consumption, perioperative blood loss with subsequent transfusion and delirium. Postoperative continuous-flow cryocompression therapy is suggested to minimize these complications and to attenuate the inflammatory reaction that the traumatic fracture and subsequent surgical trauma encompass. Based on a pilot study in patients undergoing total hip arthroplasty for osteoarthritis, it is anticipated that patients treated with continuous-flow cryocompression therapy will have less pain, less morphine consumption and lower decrease of postoperative hemoglobin levels. These factors are associated with a shorter hospital stay and better long-term (functional) outcome. One hundred and sixty patients with an intra or extracapsular hip fracture scheduled for internal fixation (intramedullary hip nail, dynamic hip screw or cannulated screws) or prosthesis surgery (total hip or hemiarthroplasty) will be included in this prospective, open-label, parallel, multicenter, randomized controlled, clinical superiority trial. Patients will be allocated to two treatment arms: group 'A' will be treated with continuous-flow cryocompression therapy and compared to group 'B' that will receive standard care. Routine use of drains and/or compressive bandages is allowed in both groups. The primary objective of this study is to compare acute pain the first 72 h postoperative, measured with numeric rating scale for pain. Secondary objectives are: (non-) morphine analgesic use; adjusted postoperative hemoglobin level; transfusion incidence; incidence, duration and severity of delirium and use of psychotropic medication; length of stay; location and duration of rehabilitation; functional outcome; short-term patient

  3. Does an Integrated Care Intervention for COPD Patients Have Long-Term Effects on Quality of Life and Patient Activation? A Prospective, Open, Controlled Single-Center Intervention Study.

    Directory of Open Access Journals (Sweden)

    Elena Titova

    Full Text Available Implementation of the COPD-Home integrated disease management (IDM intervention at discharge after hospitalizations for acute exacerbations of COPD (AECOPD led to reduced hospital utilization during the following 24 months compared to the year prior to study start.To analyze the impact of the COPD-Home IDM intervention on health related quality of life, symptoms of anxiety and depression, and the degree of patient activation during 24 months of follow-up and to assess the association between these outcomes.A single center, prospective, open, controlled clinical study. Changes in The St. George Respiratory Questionnaire (SGRQ, the Hospital anxiety (HADS-A and depression (HADS-D and the patient activation measure (PAM scores were compared between the patients in the integrated care group (ICG and the usual care group (UCG 6, 12 and 24 months after enrolment.The questionnaire response rate was 80-96%. There were no statistically significant differences in the change of the SGRQ scores between the groups during follow up. After 12 months of follow-up there was a trend towards a reduction in the mean HADS-A score in the ICG compared to the UCG. The HADS-D scores remained stable in the ICG compared with an increasing trend in the UCG. Clinically significant difference in the PAM score was achieved only in the ICG, 6.7 (CI95% 0.7 to 7.5 compared to 3.6 (CI95% -1.4 to 8.6 in the UCG. In a logistic regression model a higher HADS-D score and current smoking significantly increased the odds for a low PAM score.The COPD-Home IDM intervention did not result in any statistically significant changes in mean SGRQ, HADS-A, HADS- D or PAM scores during the 24 months of follow-up.The ID number for the study in the Clinical.Trials.gov registration system is 17417. ClinicalTrials.gov Identifier: NCT 00702078.

  4. 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

  5. Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial.

    Directory of Open Access Journals (Sweden)

    Kyung Won Park

    Full Text Available Studies investigating the impact of white matter hyperintensities (WMHs on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs.Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog from the baseline to the end of the study.Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46 during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70 and group 2 (-0.23±5.98 after the 24-week rivastigmine patch therapy (p = 0.378. The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037. The rates of adverse events (AEs (42.6 vs. 40.3% and discontinuation due to AEs (10.3% vs. 4.3% did not differ between the groups.Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs.ClinicalTrials.gov NCT01380288.

  6. Effect of flight in mission SL-3 on interferon-gamma production by rats

    Science.gov (United States)

    Gould, C. L.; Williams, J. A.; Mandel, A. D.; Sonnenfeld, G.

    1985-01-01

    Rats flown in Space Shuttle mission SL-3 were sacrificed after flight and spleens were removed. Cultures of spleen cells were challenged with the mitogen concanavalin-A to attempt to induce interferon-gamma. Most control, ground-based rats had spleen cells that produced moderate titers of interferon-gamma. Spleen cells from flown rats did not produce interferon-gamma in most cases, and one flown rat produced minimally detectable amounts of interferon. These data suggest that interferon-gamma production was inhibited in rats flown in mission SL-3 immediately upon return to earth.

  7. 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) =

  8. 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.

  9. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Song, Wuqi [The Heilongjiang Key Laboratory of Immunity and Infection, Heilongjiang (China); Department of Microbiology, Harbin Medical University (China); Kao, Wenping [The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Institutions (China); Department of Microbiology, Harbin Medical University (China); Zhai, Aixia [The Heilongjiang Key Laboratory of Immunity and Infection, Heilongjiang (China); Qian, Jun; Li, Yujun [The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Institutions (China); Zhang, Qingmeng [The Heilongjiang Key Laboratory of Immunity and Infection, Heilongjiang (China); Zhao, Hong; Hu, Yunlong; Li, Hui [Department of Microbiology, Harbin Medical University (China); Zhang, Fengmin, E-mail: fengminzhang@ems.hrbmu.edu.cn [The Heilongjiang Key Laboratory of Immunity and Infection, Heilongjiang (China); The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Institutions (China); Department of Microbiology, Harbin Medical University (China)

    2013-09-06

    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.

  11. Open Innovation

    OpenAIRE

    Gassmann, Oliver; Enkel, Ellen

    2006-01-01

    In the past 10 years, numerous interesting articles, book chapters, and books have been written on open innovation strategies in mainly large companies. While closed innovation models have resulted in important breakthrough innovations, many large companies have abandoned vertical integration strategies in recent years and have moved toward a combination of both closed and open innovation models that are used for reaching different sets of innovative goals. The definition of open innovation a...

  12. 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......), and potential solutions (e.g., EU funding programs) in the context of open innovation and innovation policy. With this background, the authors introduce select papers published in this Special Section of California Management Review that were originally presented at the second annual World Open Innovation...

  13. Open hardware for open science

    CERN Document Server

    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...

  14. Open Revolution.

    Directory of Open Access Journals (Sweden)

    Sean R Eddy

    2009-03-01

    Full Text Available Sean Eddy reviews "Opening Up Education," a collection of essays that explores how leaders in the "open education movement" intend to exploit digital communications technology, develop innovative and freely redistributable educational methods and resources, and improve education on a global level.

  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. Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report.

    Science.gov (United States)

    Zylberberg, H; Benhamou, Y; Lagneaux, J L; Landau, A; Chaix, M L; Fontaine, H; Bochet, M; Poynard, T; Katlama, C; Pialoux, G; Bréchot, C; Pol, S

    2000-11-01

    concentration decreased significantly after three and six months of ribavirin therapy (p= 0.0002 and p=0.0003, respectively) leading to withdrawal of therapy in one patient. These preliminary results show that: (1) despite in vitro interactions between ribavirin, zidovudine, and stavudine, significant variation in HIV replication does not usually occur in HCV-HIV coinfected patients receiving ribavirin and different antiretroviral regimens, including zidovudine and stavudine; (2) alpha interferon and ribavirin combination therapy induced primary and sustained virological responses in 28.5% and 14.3% of treated subjects (who were previous non-responders to interferon therapy), respectively; (3) anaemia is a frequent adverse event. Such results should be confirmed in larger prospective trials.

  17. 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.

  18. Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2005-02-01

    Full Text Available Abstract Background Recent studies have shown that gamma interferon (IFN-γ synergizes with the innate IFNs (IFN-α and IFN-β to inhibit herpes simplex virus type 1 (HSV-1 replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV replication. Results We have found that as with HSV-1, IFN-γ synergizes with the innate IFNs (IFN-α/β to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs with IFN-α, IFN-β or IFN-γ alone inhibited HCMV plaque formation by ~30 to 40-fold, treatment with IFN-α and IFN-γ or IFN-β and IFN-γ inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-α/β and IFN-γ was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE genes (IE1 and IE2 revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-α/β and IFN-γ (~5-11-fold as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence. Conclusion These findings suggest that IFN-α/β and IFN-γ synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-γ produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-05-01

    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 /sup 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.

  20. 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

  1. 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

  2. Acute pericarditis due to pegylated interferon alpha therapy for chronic HCV hepatitis - Case report

    Science.gov (United States)

    2011-01-01

    Background Cardio toxicity due to interferon therapy was reported only in small case series or case reports. The most frequent cardiac adverse effects related to interferon are arrhythmias and ischemic manifestations. The cardiomyopathy and pericarditis are rare but can be life threatening. The predisposing factors for interferon cardio toxicity were described only for ischemic manifestations and arrhythmias. Case presentation The authors report a case of pericarditis due to alpha interferon therapy for chronic hepatitis C, in a young woman without previous cardiac pathology. The clinical manifestations started during the 7-th month of interferon treatment. The cessation of interferon was necessary. After interferon discontinuation the patient recovered, with complete resolution of pericarditis. The patient scored 9 points on the Naranjo ADR probability scale, indicating a very probable association between pericarditis and interferon administration. Conclusion If a patient receiving interferon therapy complains of chest pain of sudden onset, a cardiac ultrasound should be performed in order to rule out pericarditis. We point out the possibility of an infrequent but severe adverse effect of interferon therapy. PMID:21453456

  3. Open Source and Open Standards

    NARCIS (Netherlands)

    Koper, Rob

    2006-01-01

    Publication reference: Koper, R. (2008). Open Source and Open Standards. In J. M. Spector, M. Merrill, J. van Merriënboer & M. P. Driscol (Eds.), Handbook of Research on Educational Communications and Technology (3rd ed., pp. 355-368). New York: Routledge.

  4. 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.

  5. Interferon regulatory factor 8 regulates bone metabolism by suppressing osteoclastogenesis

    OpenAIRE

    Zhao, Baohong; Takami, Masamichi; Yamada, Atsushi; Wang, Xiaogu; Koga, Takako; Hu, Xiaoyu; Tamura, Tomohiko; Ozato, Keiko; Choi, Yongwon; Ivashkiv, Lionel B.; Takayanagi, Hiroshi; Kamijo, Ryutaro

    2009-01-01

    Bone metabolism results from a balance between osteoclast-driven bone resorption and osteoblast-mediated bone formation. Diseases such as periodontitis and rheumatoid arthritis are characterized by increased bone destruction due to enhanced osteoclastogenesis1,2. Here we report that interferon regulatory factor 8 (IRF8), a transcription factor expressed in immune cells, is a key regulatory molecule for osteoclastogenesis. IRF8 expression in osteoclast precursors was downregulated during the i...

  6. Interferons and Alphavirus Pathogenesis: Implications for Developing Medical Countermeasures

    Science.gov (United States)

    2005-12-01

    ines qui interferent avec la croissance d’un virus. Depuis cette d~couverte, on a trouv6 plusieurs sortes d’INF que lPon a classifid en trois types...Defence Research and Recherche et developpement Development Canada pour la defense Canada DEFENCE •DFFENSE a Interferons and Alphavirus Pathogenesis...majestd la reine, reprdsentde par le ministre de la DMfense nationale, 2005 Abstract Our immune system can launch a quick defence against a large

  7. 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

    patients with an increased expression of interferon-β-inducible genes in peripheral blood mononuclear cells and interferon-β-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-β-treated multiple sclerosis patients had...... increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro, neutralization of interleukin-10 and monocyte depletion increased CD4+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4+ T-cell reactivity to myelin basic......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...

  8. 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.

  9. 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....

  10. 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....... Other biomarkers such as interferon-gamma-induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections. OBJECTIVES: To describe IP-10 concentrations and their association to TST and INF-gamma responses in children recently exposed to adults with smear-positive TB in Brazil...... and Nepal. METHODS:: Two surveys using the same design were undertaken to describe TST, INF-gamma, and IP-10 responses in 146 children in Nepal and 113 children in Brazil. RESULTS: The concordance of TST and QuantiFERON-TB gold in-tube (QFT-IT) was high (kappa 0.73 in Brazil and 0.80 in Nepal). IP-10...

  11. 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)

  12. 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.

  13. HIV-1, interferon and the interferon regulatory factor system: an interplay between induction, antiviral responses and viral evasion.

    Science.gov (United States)

    Marsili, Giulia; Remoli, Anna Lisa; Sgarbanti, Marco; Perrotti, Edvige; Fragale, Alessandra; Battistini, Angela

    2012-01-01

    Thirty years after the first isolation of the etiological agent of AIDS, the virus HIV-1 is still a major threat worldwide with millions of individuals currently infected. Although current combination therapies allow viral replication to be controlled, HIV-1 is not eradicated and persists in drug- and immune system-insensitive reservoirs and a cure is still lacking. Pathogens such as HIV-1 that cause chronic infections are able to adapt to the host in a manner that ensures long term residence and survival, via the evolution of numerous mechanisms that evade various aspects of the innate and adaptive immune response. One such mechanism is targeted to members of the interferon (IFN) regulatory factor (IRF) family of proteins. These transcription factors regulate a variety of biological processes including interferon induction, immune cell activation and downstream pattern recognition receptors (PRRs). HIV-1 renders IRFs harmless and hijacks them to its own advantage in order to facilitate its replication and evasion of immune responses. Type I interferon (IFN), the canonical antiviral innate response, can be induced in both acute and chronic HIV-1 infection in vivo, but in the majority of individuals this initial response is not protective and can contribute to disease progression. Type I IFN expression is largely inhibited in T cells and macrophages in order to successfully establish productive infection, whereas sustained IFN production by plasmacytoid dendritic cells is considered an important source of chronic immune activation, a hallmark to AIDS progression. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

    Science.gov (United States)

    Borges, T J; O'Malley, J T; Wo, L; Murakami, N; Smith, B; Azzi, J; Tripathi, S; Lane, J D; Bueno, E M; Clark, R A; Tullius, S G; Chandraker, A; Lian, C G; Murphy, G F; Strom, T B; Pomahac, B; Najafian, N; Riella, L V

    2016-07-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. 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.

  16. Implications of prognostic variables in the assessment of autoimmunity in hepatitis C patients receiving interferon therapy

    OpenAIRE

    Arooj, Mahwish; Malik, Arif; Basit, Abdul; Husain Qazi, Mahmood; Asif, Muhammad; Sarwar Jamal, Mohammad; Mostafa Mahmoud, Maged; Choudhry, Hani; Natesan Pushparaj, Peter; Rasool, Mahmood

    2016-01-01

    Systematic administration of interferon-alpha (INF-alpha) is considered as the backbone of HCV therapy since 1991. Interferon (IFN) therapy can cause vasculitis, glomerulonephritis, cryoglobulinemia and certain other autoimmune diseases such as sialoadentitis, lichen planus and thyroiditis. Related to the factors of interferons, extensively studied gland is thyroid gland. A strong association was observed between thyroid disease and HCV patient when they were exposed to IFN therapy. Vitamin D...

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

    OpenAIRE

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

    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...

  18. 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...

  19. Conditions required for induction of interferon by rotaviruses and for their sensitivity to its action

    International Nuclear Information System (INIS)

    McKimm-Breschkin, J.L.; Holmes, I.H.

    1982-01-01

    Our investigations of interferon induction by rotaviruses showed that only when cells were pretreated with interferon, i.e., primed, could infectious rotaviruses induce significant quantities of interferon. As little as 0.5 U of interferon provided sufficient priming for this induction. UV-irradiated rotaviruses induced significant levels of interferon, and priming only marginally enhanced the yields. Neither heat-inactivated virus nor serum-neutralized virus was able to induce interferon, even when cells were primed. When cells were treated with purified virus double-stranded RNA in the presence of DEAE-dextran to facilitate uptake, interferon was induced, although priming did not enhance yields. These results strongly implicate the viral double-stranded RNA as the effector for interferon induction. The insensitivity of rotaviruses to interferon in vitro was also studied. Results suggested that this lack of sensitivity was not due to any inherent resistance of the virus to the antiviral proteins, but rather to lack of activation of cellular enzymes exhibiting antiviral activity

  20. 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%, Pnutritional support were even more pronounced after 48 weeks. Preventive nutritional support markedly ameliorates decreases of paid labour productivity, physical exercise and performance status during PEG-interferon-containing treatment for chronic hepatitis C. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. 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…

  2. Interferons beta have vasoconstrictive and procoagulant effects: a woman who developed livedo reticularis and Raynaud phenomenon in association with interferon beta treatment for multiple sclerosis.

    Science.gov (United States)

    Rot, Uroš; Ledinek, Alenka Horvat

    2013-12-01

    A 31-year-old woman with MS developed livedo reticularis and secondary Raynaud phenomenon 2.5 years after introduction of interferon beta-1b. The symptoms disappeared after withdrawal of the drug. Livedo reticularis and Raynaud phenomenon as well as pulmonary arterial hypertension, venous sinus thrombosis, pulmonary embolism and renal thrombotic microangiopathy have all been described in association with interferon beta therapy. These complications strongly suggest that type I interferons have vasoconstrictive and procoagulant effects with potentially serious systemic complications. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. 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 cal...

  4. opened capsule

    African Journals Online (AJOL)

    The accuracy of the off-label opened capsule dosing method for stavudine is acceptable. There is no need to instruct caregivers to include sediment in the aliquot given to the infant. However, studies that confirm adequate bioavailability and efficacy are needed. In addition, it is important to avoid supplying generic capsules ...

  5. Opening Address

    Science.gov (United States)

    Garbers, C. F.

    1987-09-01

    Ladies and gentlemen, it is indeed a great privilege and pleasure for me to present the opening address at this, the 17th International Congress on High Speed Photograpy and Photonics. Before turning to the business of the Congress, I would like to briefly introduce you to South Africa: its scientific past and its research challenges for the future.

  6. 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...

  7. Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia.

    Science.gov (United States)

    Holcombe, David J; Lee, Graham A

    2006-10-01

    To evaluate topical interferon alfa-2b (IFN-alpha2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). Prospective, noncomparative, interventional consecutive case series. Ten patients with recalcitrant OSSN were treated with topical IFN-alpha2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow-up of six months. Eight of 10 patients achieved clinical resolution from topical IFN-alpha2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). Topical IFN-alpha2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision.

  8. Novel interferon-gamma assays for diagnosing tuberculosis in young children in India

    Science.gov (United States)

    Shaikh, N.; Gupte, A.; Dharmshale, S.; Pokkali, S.; Thakar, M.; Upadhye, V. J.; Ordonez, A. A.; Kinikar, A.; Gupte, N.; Mave, V.; Kagal, A.; Gupta, A.; Lalvani, A.; Paranjpe, R.; Bharadwaj, R.; Jain, S. K.

    2017-01-01

    SUMMARY SETTING The tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used as supportive evidence to diagnose active tuberculosis (TB). Novel IGRAs could improve diagnosis, but data are lacking in young children. DESIGN Children (age ≤ 5 years) with suspected TB were prospectively screened at a tertiary hospital in Pune, India; the children underwent TST, and standard (early secretory antigenic target 6 and culture filtrate protein 10) and enhanced (five additional novel antigens) enzyme-linked immunospot (ELISpot) assays. RESULTS Of 313 children (median age 30 months) enrolled, 92% had received bacille Calmette-Guérin vaccination, 53% were malnourished and 9% were coinfected with the human immunodeficiency virus (HIV); 48 (15%) had TB, 128 (41%) did not, and TB could not be ruled out in 137 (44%). The sensitivity of enhanced (45%) and standard (42%) ELISpot assays for diagnosing TB was better than that of TST (20%) (P ≤ 0.03); however, enhanced ELISpot was not more sensitive than the standard ELISpot assay (P= 0.50). The specificity of enhanced ELISpot, standard ELISpot and TST was respectively 82% (95%CI 74–89), 88% (95%CI 81–94) and 98% (95%CI 93–100). Rv3879c and Rv3615c, previously reported to be promising antigens, failed to improve the diagnostic performance of the ELISpot assay. CONCLUSION The TST and the standard and novel ELISpot assays performed poorly in diagnosing active TB among young children in India. PMID:28284256

  9. 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…

  10. [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.

  11. 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)

  12. Stratification by interferon-γ release assay level predicts risk of incident TB.

    Science.gov (United States)

    Winje, Brita Askeland; White, Richard; Syre, Heidi; Skutlaberg, Dag Harald; Oftung, Fredrik; Mengshoel, Anne Torunn; Blix, Hege Salvesen; Brantsæter, Arne Broch; Holter, Ellen Kristine; Handal, Nina; Simonsen, Gunnar Skov; Afset, Jan Egil; Bakken Kran, Anne Marte

    2018-04-05

    Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to 4.00 IU/mL, respectively, compared with negative tests (TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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...... is rejected, abandoned, or fails. Finally, we consider how OI can be better linked to prior theoretical research, including topics such as absorptive capacity, user innovation, resources, dynamic capabilities, business models, and the definition of the firm....

  18. 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)

  19. 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.

  20. 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

  1. Opening education.

    Science.gov (United States)

    Smith, Marshall S

    2009-01-02

    Spurred by the publication of Massachusetts Institute of Technology OpenCourseWare in 2002, the open educational resources (OER) movement, which has rapidly expanded and captured the imagination and energy of millions of creators and users throughout the world, now faces many opportunities and substantial challenges as it moves to become an integral part of the world's educational environment. The confluence of the Web and a spirit of sharing intellectual property have fueled a worldwide movement to make knowledge and education materials open to all for use. OER are content (courses, books, lesson plans, articles, etc.), tools (virtual laboratories, simulations, and games), and software that support learning and educational practice. OER are free on the Web, and most have licenses that allow copyright holders to retain ownership while providing specified rights for use in original and modified forms. At the least, OER have helped to level the distribution of knowledge across the world. A second promise of OER is to help transform educational practices. This article explores the history of and promises and challenges for OER.

  2. 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.

  3. A Double Blind Study Comparing Virucare and Inter-feron as ...

    African Journals Online (AJOL)

    Objective: To present the results of a comparative double blind study between. Virucare and Interferon to evaluate their efficacy, safety and tolerability in treating Hepatitis C Virus and its complications. Keywords: Hepatitis C, polymerase chain reaction, interferon. Egypt. J. Hum. Genet Vol. 9 (1) 2008: pp. 71-84 ...

  4. Guideline for the use of beta-interferons in patients with multiple ...

    African Journals Online (AJOL)

    Aim. To determine guidelines for use of beta-interferons in South African patients with multiple sclerosis. Method. Review of existing international protocols. Opinions of South African neurologists who have an interest in multiple sclerosis. Conclusions. The main indication for interferon use is the relapsing and remitting form ...

  5. Chemokine receptor expression on B cells and effect of interferon-beta in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Roed, Hanne; Sellebjerg, Finn

    2002-01-01

    We investigated the B-cell expression of chemokine receptors CXCR3, CXCR5 and CCR5 in the blood and cerebrospinal fluid (CSF) from patients in relapse of multiple sclerosis (MS) and in neurological controls. Chemokine receptor expression was also studied in interferon-beta-treated patients with r......, and chemokine receptor expression was not affected by interferon-beta treatment....

  6. 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 ...

  7. 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

  8. 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...varik P, Sauer I, Schaljo B. Immunobiology. 2007;212(9-10):895-901. Epub 2007 Nov 8. (.png) (.svg) (.html) (.csml) Show Molecular... mechanisms of the anti-inflammatory functions of interferons. PubmedID 18086388 Title Molecular

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

    African Journals Online (AJOL)

    Kaposi's sarcoma in homosexual men. Ann Imem Med 1982; 96: 693-700. 8. Einhom S, Blomgren H, Strander H. Interferon and spontaneous cytotoxiciry in man: enhancement of spontaneous cytotoxiciry in patients receiving human leukocyOc interferon. J Cancer 1980; 26: 419-428. 9. Lorzova E, Savary CA, Queseda JR, ...

  10. Pyoderma gangrenosum in a patient with cryoglobulinemia and hepatitis C successfully treated with interferon alfa.

    Science.gov (United States)

    Smith, J B; Shenefelt, P D; Soto, O; Valeriano, J

    1996-05-01

    We describe a patient with long-standing pyoderma gangrenosum unresponsive to therapy. The patient had concomitant cryoglobulinemia and hepatitis C. When the hepatitis C was treated with interferon alfa-2a his pyoderma gangrenosum resolved. Whether this was from the interferon alfa or spontaneous resolution is not known.

  11. Interferon gamma-induced protein-10 concentrations in children with previous tuberculosis infections and disease

    NARCIS (Netherlands)

    Bihari, Smiti; Cavalcanti, Nara; Correia, Jailson B.; Alves, Gerlane; Souza, Edvaldo; Brabin, Bernard J.; Cuevas, Luis E.

    2012-01-01

    Interferon gamma-induced protein-10 is a diagnostic test for tuberculosis infection. There is no information on its concentrations over time. Interferon gamma-induced protein-10 was evaluated in 72 children formerly treated or in former contact with tuberculosis using Quantiferon Gold in-tube. Cases

  12. 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

  13. 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.

  14. Signal transduction by interferon-α through arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Hannigan, G.E.; Williams, B.R.G.

    1991-01-01

    Molecular mechanisms that mediate signal transduction by growth inhibitory cytokines are poorly understood. Type 1 (α and β) interferons (IFNs) are potent growth inhibitory cytokines whose biological activities depend on induced changes in gene expression. IFN-α induced the transient activation of phospholipase A 2 in 3T3 fibroblasts and rapid hydrolysis of [ 3 H]arachidonic acid (AA) from prelabeled phospholipid pools. The phospholipase inhibitor, bromophenacyl bromide (BPB), specifically blocked IFN-induced binding of nuclear factors to a conserved, IFN-regulated enhancer element, the interferon-stimulated response element (ISRE). BPB also caused a dose-dependent inhibition of IFN-α-induced ISRE-dependent transcription in transient transfection assays. Specific inhibition of AA oxygenation by eicosatetraynoic acid prevented IFN-α induction of factor binding to the ISRE. Treatment of intact cells with inhibitors of fatty acid cyclooxygenase or lipoxygenase enzymes resulted in amplification of IFN-α-induced ISRE binding and gene expression. Thus, IFN-α receptor-coupled AA hydrolysis may function in activation of latent transcription factors by IFN-α and provides a system for studying the role of AA metabolism in transduction of growth inhibitory signals

  15. 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.

  16. Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

    Science.gov (United States)

    Trott, Josephine F; Kim, Jeffrey; Abu Aboud, Omran; Wettersten, Hiromi; Stewart, Benjamin; Berryhill, Grace; Uzal, Francisco; Hovey, Russell C; Chen, Ching-Hsien; Anderson, Katie; Graef, Ashley; Sarver, Aaron L; Modiano, Jaime F; Weiss, Robert H

    2016-10-11

    Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC.

  17. 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.

  18. 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.

  19. Effect of interferon on the development of Trypanosoma cruzi in tissue culture "Vero" cells

    Directory of Open Access Journals (Sweden)

    R. R. Golgher

    1980-01-01

    Full Text Available Results are presented on the effects of interferon on the intracellular stages of T. cruzi in tissue culture "Vero" cells. Interferon was obtained by infecting monolayers of human amniotic cells with inactivated Newcastle disease virus. Interferon has not affected the cell infection by T. cruzi culture infective stages and neither has it prevented the transformation of amastigote into trypomastigote stages.Interferon obtido através da infecção de células amnióticas humanas por vírus inativado da doença de Newcastle foi incapaz de influir sobre a infectividade de formas de cultura do T. cruzi para células "Vero" de cultura de tecido. A transformação amastigota-tripomastigota também não foi afetada pelo interferon.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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 ...

  5. 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)

  6. Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier.

    Science.gov (United States)

    Lazear, Helen M; Daniels, Brian P; Pinto, Amelia K; Huang, Albert C; Vick, Sarah C; Doyle, Sean E; Gale, Michael; Klein, Robyn S; Diamond, Michael S

    2015-04-22

    Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1(-/-) mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1(-/-) mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1(-/-) mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis- and signal transducer and activator of transcription 1 (STAT1)-independent manner. Our data establish an indirect antiviral function of interferon-λ in which noncanonical signaling through IFNLR1 tightens the blood-brain barrier and restricts viral neuroinvasion and pathogenesis. Copyright © 2015, American Association for the Advancement of Science.

  7. 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

  8. 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 cel...b 2007 Aug 16. (.png) (.svg) (.html) (.csml) Show The role of the interferon regulatory factor (IRF) family ...e interferon regulatory factor (IRF) family in dendritic celldevelopment and function. Authors Gabriele L, O

  9. 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

  10. Efficacy and safety of a herbal mixture (Viron® tablets in the treatment of patients with chronic hepatitis C virus infection: a prospective, randomized, open-label, proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Shawkat H

    2015-02-01

    Full Text Available Hisham Shawkat,1 Mostafa Yakoot,2 Tarek Shawkat,1,3 Sherine Helmy4 1KEMET Clinic, Cairo, Egypt; 2Green Clinic and Research Center, Alexandria, Egypt; 3Internal Medicine Department, Cape Canaveral Hospital, Cocoa Beach, FL, USA; 4Pharco Corporation, Alexandria, Egypt Background: Development of an optimal interferon-free regimen for chronic hepatitis C virus infection is believed to require the combination of different drug classes to provide good antiviral efficacy, clinical and quality of life benefits, as well as a high barrier to resistance. Viron® is a new herbal drug in film-coated tablet form, and is based on a mixture of herbs with known hepatoprotective and antiviral properties. We conducted this study to explore the safety and the potential clinical and quality of life benefits of this product in patients with chronic hepatitis C infection.Methods: Eighty-two consecutive patients presenting to our outpatient clinics as already-known or newly-diagnosed cases of chronic hepatitis C virus (HCV infection, were entered into the study and randomized to three groups to receive escalating doses of Viron for 6 months. Virological, clinical, and enzyme responses, as well as quality of life index scores for chronic liver disease were compared between the groups.Results: Of the 20 patients treated with the highest dose of Viron (three tablets twice daily, two (10% had a complete virological response at the end of treatment (ETR and two (10% had a partial ETR, defined as a decrease in viral load of at least 2-log10 at the end of 6 months of treatment, whereas patients treated with the medium dose (two tablets twice daily and the lowest dose (one tablet twice daily showed a significantly lower ETR (P=0.043. Alanine aminotransferase levels and scores on the Chronic Liver Disease Questionnaire improved to a significantly greater extent in the highest dose group (P=0.007 and P=0.021, respectively. No serious adverse effects attributable to the herbal

  11. 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

  12. 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.

  13. 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.)

  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. 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.

  16. 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.

  17. 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.

  18. Postoperative C-reactive protein concentration and clinical outcome: comparison of open cystectomy to robot-assisted laparoscopic cystectomy with extracorporeal or intracorporeal urinary diversion in a prospective study.

    Science.gov (United States)

    Kingo, Pernille Skjold; Nørregaard, Rikke; Borre, Michael; Jensen, Jørgen Bjerggaard

    2017-10-01

    This study aimed to compare clinical outcome and postoperative systemic inflammatory response using C-reactive protein (CRP) levels, to quantify the degree of tissue injury in open mini-laparotomy cystectomy (OMC) versus robot-assisted laparoscopic cystectomy with extracorporeal (RALC-EUD) or intracorporeal urinary diversion (RALC-IUD). From September 2012 to September 2015, 309 patients diagnosed with bladder cancer underwent radical cystectomy with urinary diversion. Of these, 175 patients were eligible for the study and underwent OMC (n = 125), RALC-EUD (n = 12) or RALC-IUD (n = 38). Blood samples were obtained preoperatively and postoperatively on days 1-7. Clinical and perioperative parameters, including demographics, comorbidity, tumour stage and postoperative outcomes, were collected from medical records. Age, American Society of Anesthesiologists score and Charlson score were significantly higher in OMC than in the robotic groups (p = 0.020, 0.012 and 0.008, respectively). Other demographic data showed no significant group differences. Estimated blood loss and blood transfusion volume were higher in OMC (p OMC and RALC-EUD (p OMC CRP levels were higher than RALC-EUD. In this study, robotic techniques seem less traumatic overall than open surgery, as OMC had higher postoperative CRP levels than RALC-EUD. The higher CRP levels in RALC-IUD may be more reflective of the urinary diversion technique than the true tissue trauma.

  19. 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.

  20. Interferon in resistance to bacterial and protozoan infections

    Science.gov (United States)

    Sonnenfeld, Gerald; Gould, Cheryl L.; Kierszenbaum, Felipe; Degee, Antonie L. W.; Mansfield, John M.

    1986-01-01

    The effects of genetic differences in mouse strains on the modulation of protozoan infections by interferon (IFN) were investigated. In one set of experiments, three different strains of mice were injected with T. cruzi, and their sera were assayed at five time intervals for IFN titer. A greater quantity of IFN was produced by mouse strains that were susceptible to T. cruzi infection than by the more resistant strain. In another set of experiments, spleen cell cultures from inbred strains of mice were challenged with an antigen made from T.b. rhodesiense. The cells from mice resistant to infection, produced greater amounts of IFN-gamma than did cells from the susceptible mice. In a third set of experiments, it was found that mice injected with T.b. rhodesiense before being infected with a diabetogenic virus (EMC-D) were resistant to the effects of the virus and did not produce virus-specific antibody.

  1. [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.

  2. Type I Interferon in Chronic Virus Infection and Cancer.

    Science.gov (United States)

    Snell, Laura M; McGaha, Tracy L; Brooks, David G

    2017-08-01

    Type I interferons (IFN-Is) are emerging as key drivers of inflammation and immunosuppression in chronic infection. Control of these infections requires IFN-I signaling; however, prolonged IFN-I signaling can lead to immune dysfunction. IFN-Is are also emerging as double-edged swords in cancer, providing necessary inflammatory signals, while initiating feedback suppression in both immune and cancer cells. Here, we review the proinflammatory and suppressive mechanisms potentiated by IFN-Is during chronic virus infections and discuss the similar, newly emerging dichotomy in cancer. We then discuss how this understanding is leading to new therapeutic concepts and immunotherapy combinations. We propose that, by modulating the immune response at its foundation, it may be possible to widely reshape immunity to control these chronic diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Endometriosis and Type I Interferon & Characterization of a Mammalian Flippase

    DEFF Research Database (Denmark)

    Vestergaard, Anna Lindeløv

    2010-01-01

    Endometriosis and Type I Interferon   Endometriosis is a painful chronic disease in which endometrium-like lesions are located ectopically, frequently in the pelvic cavity but also in more distant sites. The pathogenesis of endometriosis is unclear and involves complex hormonal, genetic......) and in eutopic endometrium (Eu) and ectopic endometriosis lesions (Ec) of women with endometriosis. The four genes BST2, COL16A1, ISG20 and HOXB2 appeared significantly differentially regulated between the groups. However, after a thorough investigation of appropriate reference genes for normalization......, validation by qRT-PCR confirmed only that ISG20 and HOXB2 were significantly downregulated in the Ec group compared with the Eu and C groups. BST2 and COL16A1, as well as the highly IFN-stimulated genes ISG12A and 6-16, displayed merely insignificant variation between the groups. Endometriosis displays...

  4. 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.)

  5. Lepromatous leprosy treated with recombinant interferon gamma: cutaneous histologic changes.

    Science.gov (United States)

    Bottasso, O; Besuschio, S; Merlin, V; Morini, J C; Bernabo, J; Falcoff, R; Falcoff, E

    1992-11-01

    We report on the histologic changes occurring in single cutaneous lesions, from six active lepromatous patients, 1 week following the administration of three daily intradermal injections, 35 micrograms each, of recombinant interferon gamma (rIFN-gamma). Except for a strong induration at the injection site, rIFN-gamma produced no adverse systemic reactions and was able to promote a remarkable influx of T-lymphocytes, mononuclear phagocytes with large nuclei, nonvacuolated cytoplasm, and reduced lysozyme reactivity. Furthermore, despite no clear-cut reduction of mycobacterial dermal burden, bacilli showed a clear increase in the granular appearance. Present findings provide a basis for further elucidation of rIFN-gamma as an additional tool for leprosy treatment.

  6. Immune activation in multiple sclerosis and interferon-beta therapy

    DEFF Research Database (Denmark)

    Krakauer, Martin

    2007-01-01

    -lymphocytes produce proinflammatory cytokines, which induce pathogenic effector cells. Recently, another Th subset relevant to MS has been identified. This is termed Th17 and is partly induced by IL-23. T-cells respond to chemotactic cytokines, termed chemokines, in order to migrate towards sites...... 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...

  7. 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.

  8. 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...... analyzed in 109 patients with relapsing-remitting MS treated with IFN-beta who were followed clinically for 1 year. Cellular CCR5 expression was measured by flow cytometry. RESULTS: Patients with MS had a higher percentage of CCR5-positive monocytes than healthy controls. Increased monocyte expression...... of CCR5 correlated weakly with an increased short-term relapse risk but there was no relationship between CCR5 Delta32 allele and CCR5 promoter polymorphism genotypes and relapse risk. CONCLUSIONS: The results do not support a major role of CCR5 in the pathogenesis of relapses in MS patients treated...

  9. Increased sensitivity to interferon-alpha in psoriatic T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Lovato, Paola; Skov, Lone

    2005-01-01

    Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important...... disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers...... and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT...

  10. 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

  11. Interferon-alpha induced depressive-like behavior in rats

    DEFF Research Database (Denmark)

    Fischer, C. W.; Liebenberg, N.; Elfving, B.

    2013-01-01

    Background: A subpopulation of individuals with major depressive disorder (MDD) show increased levels of peripheral inflammatory biomarkers, indicating an association of MDD with a chronically activated immune system. Administration of the immune stimulating cytokine, interferon-alpha (IFN-(alpha...... of an inflammation-induced model of depression will be pivotal for our understanding of the underlying pathophysiological immune mechanisms in MDD and may lead to the design of better and more effective treatment options in the near future....... to link inflammation and depression, such as increased levels of the neurotoxic tryptophan metabolite, quinolinic acid (QUIN), and decreased brain-derived neurotrophic factor (BDNF), a protein that plays an important role in survival, differentiation and growth of neurons. The successful development...

  12. 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.

  13. 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.

  14. 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...

  15. Generalized lichen nitidus with involvement of the palms following interferon alpha treatment.

    Science.gov (United States)

    Scheler, Marina; Proelss, Julia; Bräuninger, Wolfgang; Bieber, Thomas; Wenzel, Joerg

    2007-01-01

    Lichen nitidus is an uncommon dermatosis of unknown etiology. Here we present the case of a generalized lichen nitidus with involvement of the palms in a patient with hepatitis C after systemic treatment with interferon alpha and ribavirin. Furthermore in our patient we could show a strong lesional expression of MxA, a protein specifically induced by type I interferon. It is tempting to speculate that interferon alpha may be involved in the pathogenesis of lichen nitidus. Copyright 2007 S. Karger AG, Basel.

  16. 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.

  17. The effects of high dose interferon-β1a on plasma microparticles: Correlation with MRI parameters

    Directory of Open Access Journals (Sweden)

    Ganta Chaitanya V

    2011-05-01

    Full Text Available Abstract Objectives We previously reported a correlation between levels of microparticles carrying CD31 (PMP CD31+ and disease activity in MS. However, the effects of long term (12 month treatment with high dose, high frequency interferon-β1a (Rebif™ on plasma levels of PMPCD31+, PMPCD146+, and PMPCD54+ and MRI measures of disease activity have not yet been assessed. Methods During this prospective 1-year study, we used flow cytometry to measure changes in plasma microparticles (PMP bearing CD31 (PMPCD31+, CD146 (PMPCD146+, and CD54/ICAM-1 (PMPCD54+ in 16 consecutive patients with relapsing-remitting MS (RRMS before and after 3, 6, and 12 months of subcutaneous therapy with interferon-beta1a (44 micrograms, 3X weekly. At each visit, clinical exams and expanded disability status scale (EDSS scores were recorded. Results Plasma levels of PMPCD31+, and PMPCD54+ were significantly reduced by treatment with IFN-β1a. PMPCD146+ appeared to decrease only at 3 months and did not persist at 6 and 12 months (p = 0.0511. In addition, the decrease in plasma levels of PMPCD31+ and PMPCD54+ levels at 12 months were associated with a significant decrease in the number and volume of contrast enhancing T1-weigthed lesions. Conclusion Our data suggest that serial measurement of plasma microparticles (PMP, particularly in the initial stages of MS (when neuro-inflammatory cascades are more intense, may serve as reliable and reproducible surrogate markers of response to IFN-β1a therapy for MS. In addition, the progressive decline in plasma levels of PMPCD31+ and PMPCD54+ further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells during pathogenesis of MS.

  18. A novel member of the interferon receptor family complements functionality of the murine interferon gamma receptor in human cells.

    Science.gov (United States)

    Hemmi, S; Böhni, R; Stark, G; Di Marco, F; Aguet, M

    1994-03-11

    Expression of the human interferon gamma receptor (IFN-gamma R) in mouse cells is not sufficient to confer biological responsiveness to human IFN-gamma and vice versa. An additional species-specific component is required for signal transduction. We identified this cofactor by expression cloning in simian COS cells stably transfected with the nonfunctional murine IFN-gamma R and a IFN-gamma-inducible reporter construct encoding the human Tac antigen (interleukin-2 receptor alpha chain, CD25). A cDNA clone was obtained that, upon stable transfection, rendered human HEp-2 cells expressing the murine IFN-gamma R fully responsive to murine IFN-gamma. This cDNA encodes a novel 332 amino acid type I transmembrane protein that belongs to the IFN receptor family and that we designate IFN-gamma R beta chain.

  19. 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

  20. 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.

  1. Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review.

    Science.gov (United States)

    Machado, Myrela O; Oriolo, Giovanni; Bortolato, Beatrice; Köhler, Cristiano A; Maes, Michael; Solmi, Marco; Grande, Iria; Martín-Santos, Rocío; Vieta, Eduard; Carvalho, André F

    2017-02-01

    A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment. A diagnosis of MDE had to be established by means of a standardized diagnostic interview at baseline and endpoint. Eight unique references met inclusion criteria. A total of 826 participants with HCV (37.3% females, mean age 46.7 years) were included in this systematic review. The overall MDE incidence rate was 34.8%, with follow-up ranging between 4 and 48 weeks. The methodological quality varied across selected studies. It was observed that Interleukin-6, salivary cortisol, arachidonic acid / eicosapentaenoicacid plus docosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression. A meta-analysis could not be performed due to the diverse biological mechanisms investigated and the lack of replicated evidence. This systematic review indicates that several potential mechanisms may be implicated in the onset of a MDE following IFN-α-based immunotherapy for chronic HCV. However, replicated evidence is lacking and therefore the mechanisms involved in IFN-α-induced depression in humans remain unclear. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Challenges in the development of an immunochromatographic interferon-gamma test for diagnosis of pleural tuberculosis.

    Directory of Open Access Journals (Sweden)

    Claudia M Denkinger

    Full Text Available Existing diagnostic tests for pleural tuberculosis (TB have inadequate accuracy and/or turnaround time. Interferon-gamma (IFNg has been identified in many studies as a biomarker for pleural TB. Our objective was to develop a lateral flow, immunochromatographic test (ICT based on this biomarker and to evaluate the test in a clinical cohort. Because IFNg is commonly present in non-TB pleural effusions in low amounts, a diagnostic IFNg-threshold was first defined with an enzyme-linked immunosorbent assay (ELISA for IFNg in samples from 38 patients with a confirmed clinical diagnosis (cut-off of 300 pg/ml; 94% sensitivity and 93% specificity. The ICT was then designed; however, its achievable limit of detection (5000 pg/ml was over 10-fold higher than that of the ELISA. After several iterations in development, the prototype ICT assay for IFNg had a sensitivity of 69% (95% confidence interval (CI: 50-83 and a specificity of 94% (95% CI: 81-99% compared to ELISA on frozen samples. Evaluation of the prototype in a prospective clinical cohort (72 patients on fresh pleural fluid samples, in comparison to a composite reference standard (including histopathological and microbiologic test results, showed that the prototype had 65% sensitivity (95% CI: 44-83 and 89% specificity (95% CI: 74-97. Discordant results were observed in 15% of samples if testing was repeated after one freezing and thawing step. Inter-rater variability was limited (3%; 1 out of 32. In conclusion, despite an iterative development and optimization process, the performance of the IFNg ICT remained lower than what could be expected from the published literature on IFNg as a biomarker in pleural fluid. Further improvements in the limit of detection of an ICT for IFNg, and possibly combination of IFNg with other biomarkers such as adenosine deaminase, are necessary for such a test to be of value in the evaluation of pleural tuberculosis.

  3. Opening address

    International Nuclear Information System (INIS)

    Henrich, E.W.

    2005-01-01

    Full text: It is an honour for me to make this opening address on behalf of the European Commission which has cooperated with the International Atomic Energy Agency in organizing this Conference, and in particular on behalf of Hans Forsstroem from the Directorate-General, Research, who will arrive only later this week. Protection of the environment is, and will continue to be, an important consideration in the development and application of soundly based radiation protection standards. Current standards rest largely on the premise that, in protecting man, the environment is afforded an adequate level of protection. While this premise is broadly accepted by the radiation protection profession, it has come under increasing challenge in recent years. This challenge has not arisen because of any observable damage to the environment while operating within current standards. Rather, it has different origins including: - The robustness of the premise that protection of man affords protection of the environment, in particular the extent to which it is based on value judgements as opposed to rigorous scientific argument; - The more explicit inclusion of protection of the environment into national legislation on radiation protection and the need to demonstrate compliance; - A desire to achieve greater comparability between radiation and other pollutants. These trends were recognized by the Commission in the late 1990s and, as a result, the topic of protection of the environment was included as an important element of the European Union's 5th Research Framework Programme. Community support has been given to the FASSET project about which we will hear much during this Conference. This multinational project is providing much of the scientific basis underpinning and informing ongoing discussions on the development of a system of protection for the environment. Much, however, remains to be done to establish a well conceived and practicable system for protection of the environment

  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. [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.

  6. 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

  7. 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.

  8. Inhibition of type I interferon induction and signalling by mosquito-borne flaviviruses.

    Science.gov (United States)

    Cumberworth, Stephanie L; Clark, Jordan J; Kohl, Alain; Donald, Claire L

    2017-05-01

    The Flavivirus genus (Flaviviridae family) contains a number of important human pathogens, including dengue and Zika viruses, which have the potential to cause severe disease. In order to efficiently establish a productive infection in mammalian cells, flaviviruses have developed key strategies to counteract host immune defences, including the type I interferon response. They employ different mechanisms to control interferon signal transduction and effector pathways, and key research generated over the past couple of decades has uncovered new insights into their abilities to actively decrease interferon antiviral activity. Given the lack of antivirals or prophylactic treatments for many flaviviral infections, it is important to fully understand how these viruses affect cellular processes to influence pathogenesis and disease outcome. This review will discuss the strategies mosquito-borne flaviviruses have evolved to antagonise type I interferon mediated immune responses. © 2017 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

  9. 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.

  10. [Antiviral activity of recombinant interferon-alpha-2b in combination with certain antioxidant].

    Science.gov (United States)

    Vasil'ev, A N; Deriabin, P G; Galegov, G A

    2011-01-01

    In vitro activity of interferon-alpha-2b in combination with various antioxidants against the influenza virus and Herpes simplex was studied. The standard strains and a clinical strain of Herpes simplex isolated from a patient with resistance to acyclovir were used. The in vitro studie showed that antioxidants, such as alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes simplex variants. They protected up to 100% of the cell monolayer from the virus cytopathic effect. The taurin solutions had no antiviral activity irrespective of the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic effect: the antiviral activity of interferon increased several times. The antiinfluenza activity of interferon-a-2b in the presence of various concentrations of taurin did not change.

  11. 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.

  12. 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....... Conclusion 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...

  13. Role of interferon-γ and cytotoxic T lymphocytes in intraocular tumor rejection.

    Science.gov (United States)

    Ligocki, Ann J; Brown, Joseph R; Niederkorn, Jerry Y

    2016-05-01

    The eye is normally an immunosuppressive environment. This condition is better known as immune privilege and protects the eye from immune-mediated inflammation of tissues that cannot regenerate. However, immune privilege creates a dilemma for the eye when intraocular neoplasms arise. In some cases, immune privilege is suspended, resulting in the immune rejection of intraocular tumors. This study employed a mouse model in which interferon-γ-dependent intraocular tumor rejection occurs. We tested the hypothesis that this rejection requires interferon-γ for the generation and functional capacity of cytotoxic T lymphocyte-mediated rejection of intraocular tumors. Tumors grew progressively in the eyes of interferon-γ knockout mice, even though the mice generated tumor-specific cytotoxic T lymphocyte responses in the periphery. However, interferon-γ knockout mice rejected tumors that were introduced into extraocular sites. Subcutaneous tumor immunization before intraocular challenge led to tumor rejection and preservation of the eye in wild-type mice. By contrast, tumors grew progressively in the eyes of interferon-γ knockout mice despite their ability to generate peripheral tumor-specific cytotoxic T lymphocytes as well as the capacity of CD8(+) T cells to enter the eye as shown by the presence of CD8 and perforin message and CD3(+)CD8(+) leukocytes within the tumor-bearing eye. We found that cytotoxic T lymphocytes generated in wild-type mice and adoptively transferred into interferon-γ knockout mice mediated the rejection of intraocular tumors in interferon-γ knockout hosts. The results indicate that interferon-γ is critical for the initial priming and differentiation of cytotoxic T lymphocytes residing in the periphery to produce the most effect antitumor function within the eye. © Society for Leukocyte Biology.

  14. The Role of the Interferon-Gamma-Jak/STAT Pathway in Rheumatoid Arthritis

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-16-1-0537 TITLE: The Role of the Interferon-Gamma-Jak/STAT Pathway in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Stanley...Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Role of the Interferon-Gamma-Jak/STAT Pathway in Rheumatoid Arthritis 5b...subsets that likely counteracts IL-2 regulator activity and contribute to the pathogenesis of RA. 15. SUBJECT TERMS Rheumatoid arthritis ; Autoimmunity; T

  15. 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 ...

  16. Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon

    DEFF Research Database (Denmark)

    Bouwhuis, Marna G; Suciu, Stefan; Collette, Sandra

    2009-01-01

    BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treat......BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation...

  17. Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses

    DEFF Research Database (Denmark)

    Hamming, Ole Jensen; Terczynska-Dyla, Ewa; Vieyres, Gabrielle

    2013-01-01

    to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion....... Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection...

  18. 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

  19. Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection

    DEFF Research Database (Denmark)

    Stylianou, E; Aukrust, P; Bendtzen, K

    2000-01-01

    Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-alpha, IFN-gamma, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV...... seemed not to involve enhanced lymphocyte apoptosis. Our findings suggest a pathogenic role of IFN-alpha in HIV infection, which may be a potential target for immunomodulating therapy in combination with HAART....

  20. 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.

  1. 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

  2. Interferon beta-1b-induced postmenopausal bleeding in a patient with multiple sclerosis.

    Science.gov (United States)

    Perlman, B; Heller, D; Cracchiolo, B

    2016-12-01

    Postmenopausal bleeding must always be evaluated to rule out endometrial carcinoma, although there are many benign etiologies. There have been rare reports of premenopausal bleeding with interferon beta-1b, used to treat multiple sclerosis, but no prior reports in postmenopausal women. Literature searches were performed using PubMed and Medline for articles with content related to premenopausal and postmenopausal bleeding while taking interferon beta-1b. The searches were restricted to the English language. Search terms included interferon beta-1b and/or uterine hemorrhage and/or vaginal bleeding and/or postmenopausal and/or menopause. The literature review found no related articles for postmenopausal bleeding while taking interferon beta-1b. We present a case of a patient with postmenopausal bleeding attributed to elevation of serum estradiol in association with interferon beta-1b therapy. It is important for patients and providers to be aware of the association between postmenopausal bleeding with the use of interferon beta-1b therapy which could be due to elevated serum estradiol levels.

  3. Interferon induces up-regulation of Spi-1/PU.1 in human leukemia K562 cells.

    Science.gov (United States)

    Gutiérrez, P; Delgado, M D; Richard, C; Moreau-Gachelin, F; León, J

    1997-11-26

    The human K562 cell line is derived from a chronic myelogenous leukemia in blastic crisis. Treatment of K562 cells with interferons alpha, beta or gamma resulted in inhibition of cell proliferation. Spi-1/PU.1 is a transcription factor of the Ets family which is required for normal hematopoyesis. We have found that spi-1 mRNA and protein as well as Spi-1-DNA binding activity increase after exposure of K562 cells to interferons. The increase in spi-1 expression ranged from 4- to 8-fold with the different interferons. K562 cells can be differentiated in vitro towards erythroid cells or monocyte-macrophage cells. Interestingly, the regulation of spi-1 by interferon-alpha depended on the differentiated phenotype of K562 cells: interferon-alpha failed to induce spi-1 in erythroid differentiated cells, whereas it induced spi-1 in monocyte-macrophage differentiated cells. The results suggest a role for Spi-1 in the cytostatic response to interferons.

  4. 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

  5. Studies of human Interferon α, β and γ activities on different cell cultures against rubella virus

    International Nuclear Information System (INIS)

    Ahmad, A.M.

    2006-01-01

    Human interferon (IFN) has complex effects but probably the main antiviral action is to reduce the translation of viral mRNA.IFNs induce the antiviral state of the cell when they bind to specific receptor.In our study, should that at least two functional IFN receptors on human cells.IFN α and β bind to one type of receptor where as IFN γ bind to another.Natural cell culture (HAC) which was used in the present study containing both receptors to IFN α, β and γ while MRC-5 which treated with some chemicals to be diploid cells lost receptors IFN γ.HeLa cells on the other hand which is malignant cells lost both receptors on the other hand all types of interferon are non toxic at concentration up to 1000 unit/ml to all types of tissue culture involved in this study while all types of interferon inhibit rubella virus growth at concentration of (2.5 unit/ml) and by use of therapeutic index (TI) which is the ratio of the dose of interferon which is just toxic to the dose which is just effective.If this index is one or less it is not possible to use in man, if this index larger than the margin of study is great.The (TI) of interferon against rubella virus was more than 500, therefore interferon if used in such concentration ( around 5 unit/ml) in human have no side effect

  6. 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

  7. Interferon beta-1a-induced depression and suicidal ideation in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lana-Peixoto Marco Aurélio

    2002-01-01

    Full Text Available Depression and suicide have been reported in association with multiple sclerosis (MS. Some studies show that interferon beta may increase the depression rate. We report a case of depression and suicidal ideation in coincidence with the start of increased doses of interferon beta-1a and their complete reversal following the drug withdrawal. The patient was a 21-year-old man with MS and no past history of affective disorders who was given interferon beta-1a in the dose of 11 mug three times per week. As a new relapse occurred the dose of interferon beta-1a was increased to 22 mug three times a week. The patient then observed increased worry, irritability and a sense of discouragement as well as recurring suicidal thoughts. His mood was rapidly restored following interferon beta-1a withdrawal. This case suggests that patients with MS may develop depression and suicidal thoughts when treated with high doses of interferon beta-1a.

  8. 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.

  9. 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…

  10. Effects of 6-month eicosapentaenoic acid treatment on postprandial hyperglycemia, hyperlipidemia, insulin secretion ability, and concomitant endothelial dysfunction among newly-diagnosed impaired glucose metabolism patients with coronary artery disease. An open label, single blinded, prospective randomized controlled trial.

    Science.gov (United States)

    Sawada, Takahiro; Tsubata, Hideo; Hashimoto, Naoko; Takabe, Michinori; Miyata, Taishi; Aoki, Kosuke; Yamashita, Soichiro; Oishi, Shogo; Osue, Tsuyoshi; Yokoi, Kiminobu; Tsukishiro, Yasue; Onishi, Tetsuari; Shimane, Akira; Taniguchi, Yasuyo; Yasaka, Yoshinori; Ohara, Takeshi; Kawai, Hiroya; Yokoyama, Mitsuhiro

    2016-08-26

    recovery of concomitant endothelial dysfunction in newly diagnosed IGM patients with CAD. Clinical Trial Registration UMIN Registry number: UMIN000011265 ( https://www.upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013200&language=E ).

  11. Involvement of gamma interferon in antibody enhancement by adjuvants.

    Science.gov (United States)

    Odean, M J; Frane, C M; Van derVieren, M; Tomai, M A; Johnson, A G

    1990-02-01

    In a previous study the adjuvant action of a monophosphoryl lipid A, a nontoxic derivative of endotoxic lipopolysaccharide (LPS), was found to be negated by a monoclonal anti-gamma interferon (anti-IFN-gamma) antibody. The present investigation centered on three other adjuvants of diverse microbial origins, testing for their capacity to affect the release of IFN-gamma as an explanation for their antibody-enhancing action. The adjuvant action of each of the three, a wild-type LPS, synthetic poly(A)-poly(U) complexes, and a synthetic muramyl dipeptide, n-acetylmuramyl-L-alanyl-D-glutaminyl-n-butyl ester (murabutide), was transferable by adjuvant-stimulated T cells to normal spleen cells on coculture. Supernatant fluids from these T cells contained increased levels of IFN-gamma. Addition of a monoclonal anti-IFN-gamma antibody to adjuvant-stimulated spleen cell cultures reduced the adjuvant action by approximately one-half. Removal of natural killer cells from spleen cell populations prior to culture with antigen had no effect on the enhancement induced by LPS and monophosphoryl lipid A. It was concluded that the enhancement induced by the adjuvants LPS, poly(A)-poly(U), and murabutide is mediated in part by their action on T cells resulting in release of IFN-gamma suggesting activation of a common transmembrane signal.

  12. Interferon-Gamma Promotes Infection of Astrocytes by Trypanosoma cruzi

    Science.gov (United States)

    Silva, Rafael Rodrigues; Mariante, Rafael M.; Silva, Andrea Alice; dos Santos, Ana Luiza Barbosa; Roffê, Ester; Santiago, Helton; Gazzinelli, Ricardo Tostes; Lannes-Vieira, Joseli

    2015-01-01

    The inflammatory cytokine interferon-gamma (IFNγ) is crucial for immunity against intracellular pathogens such as the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (CD). IFNγ is a pleiotropic cytokine which regulates activation of immune and non-immune cells; however, the effect of IFNγ in the central nervous system (CNS) and astrocytes during CD is unknown. Here we show that parasite persists in the CNS of C3H/He mice chronically infected with the Colombian T. cruzi strain despite the increased expression of IFNγ mRNA. Furthermore, most of the T. cruzi-bearing cells were astrocytes located near IFNγ+ cells. Surprisingly, in vitro experiments revealed that pretreatment with IFNγ promoted the infection of astrocytes by T. cruzi increasing uptake and proliferation of intracellular forms, despite inducing increased production of nitric oxide (NO). Importantly, the effect of IFNγ on T. cruzi uptake and growth is completely blocked by the anti-tumor necrosis factor (TNF) antibody Infliximab and partially blocked by the inhibitor of nitric oxide synthesis L-NAME. These data support that IFNγ fuels astrocyte infection by T. cruzi and critically implicate IFNγ-stimulated T. cruzi-infected astrocytes as sources of TNF and NO, which may contribute to parasite persistence and CNS pathology in CD. PMID:25695249

  13. 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.

  14. Interferon-gamma promotes infection of astrocytes by Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Rafael Rodrigues Silva

    Full Text Available The inflammatory cytokine interferon-gamma (IFNγ is crucial for immunity against intracellular pathogens such as the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (CD. IFNγ is a pleiotropic cytokine which regulates activation of immune and non-immune cells; however, the effect of IFNγ in the central nervous system (CNS and astrocytes during CD is unknown. Here we show that parasite persists in the CNS of C3H/He mice chronically infected with the Colombian T. cruzi strain despite the increased expression of IFNγ mRNA. Furthermore, most of the T. cruzi-bearing cells were astrocytes located near IFNγ+ cells. Surprisingly, in vitro experiments revealed that pretreatment with IFNγ promoted the infection of astrocytes by T. cruzi increasing uptake and proliferation of intracellular forms, despite inducing increased production of nitric oxide (NO. Importantly, the effect of IFNγ on T. cruzi uptake and growth is completely blocked by the anti-tumor necrosis factor (TNF antibody Infliximab and partially blocked by the inhibitor of nitric oxide synthesis L-NAME. These data support that IFNγ fuels astrocyte infection by T. cruzi and critically implicate IFNγ-stimulated T. cruzi-infected astrocytes as sources of TNF and NO, which may contribute to parasite persistence and CNS pathology in CD.

  15. Influence of recombinant bovine gamma interferon on neutrophil function

    Energy Technology Data Exchange (ETDEWEB)

    Steinbeck, M.J.

    1987-01-01

    To determine the role of cytokines in enhancing neutrophil function, peripheral blood neutrophils from healthy cattle were preincubated with recombinant bovine gamma interferon (rboIFN-gamma). Pretreatment of neutrophils with rboIFN-gamma activated neutrophils to have enhanced antibody-dependent (ADCC) and -independent (AINC) cytotoxicity and impaired random migration. Neutrophil ingestion, superoxide anion production, and iodination activity were not consistently affected by rboIFN-gamma pretreatment. In order to better understand the activation process, the molecular events involved in the enhancement of neutrophil cytotoxicity and the inhibition random migration were investigated. Both RNA and protein syntheses by neutrophils were required for the enhancement of AINC activity and the inhibition of random migration, but were not required for the enhancement of ADCC by rboIFN-gamma. Specifically, rbo-IFN-gamma treatment of neutrophils enhanced the expression of two major proteins of molecular mass 60,000 and 94,000 as determined by SDS-polyacrylamide, linear-gradient gel electrophoresis and /sup 35/S-fluorography.

  16. The Unresolved Role of Interferon-λ in Asthma Bronchiale

    Directory of Open Access Journals (Sweden)

    Nina Sopel

    2017-08-01

    Full Text Available Asthma bronchiale is a disease of the airways with increasing incidence, that often begins during infancy. So far, therapeutic options are mainly symptomatic and thus there is an increasing need for better treatment and/or prevention strategies. Human rhinoviruses (HRVs are a major cause of asthma exacerbations and might cause acute wheezing associated with local production of pro-inflammatory mediators resulting in neutrophilic inflammatory response. Viral infections induce a characteristic activation of immune response, e.g., TLR3, 4, 7, 8, 9 in the endosome and their downstream targets, especially MyD88. Moreover, other cytoplasmic pattern recognition molecules (PRMs like RIG1 and MDA5 play important roles in the activation of interferons (IFNs of all types. Depending on the stimulation of the different PRMs, the levels of the IFNs induced might differ. Recent studies focused on Type I IFNs in samples from control and asthma patients. However, the administration of type I IFN-α was accompanied by side-effects, thus this possible therapy was abandoned. Type III IFN-λ acts more specifically, as fewer cells express the IFN-λ receptor chain 1. In addition, it has been shown that asthmatic mice treated with recombinant or adenoviral expressed IFN-λ2 (IL–28A showed an amelioration of symptoms, indicating that treatment with IFN-λ might be beneficial for asthmatic patients.

  17. Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

    Directory of Open Access Journals (Sweden)

    Sanghyun Lee

    2017-06-01

    Full Text Available 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.

  18. 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.

  19. 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.

  20. 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.

  1. Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis.

    Science.gov (United States)

    Zhao, Baohong; Takami, Masamichi; Yamada, Atsushi; Wang, Xiaogu; Koga, Takako; Hu, Xiaoyu; Tamura, Tomohiko; Ozato, Keiko; Choi, Yongwon; Ivashkiv, Lionel B; Takayanagi, Hiroshi; Kamijo, Ryutaro

    2009-09-01

    Bone metabolism results from a balance between osteoclast-driven bone resorption and osteoblast-mediated bone formation. Diseases such as periodontitis and rheumatoid arthritis are characterized by increased bone destruction due to enhanced osteoclastogenesis. Here we report that interferon regulatory factor-8 (IRF-8), a transcription factor expressed in immune cells, is a key regulatory molecule for osteoclastogenesis. IRF-8 expression in osteoclast precursors was downregulated during the initial phase of osteoclast differentiation induced by receptor activator of nuclear factor-kappaB ligand (RANKL), which is encoded by the Tnfsf11 gene. Mice deficient in Irf8 showed severe osteoporosis, owing to increased numbers of osteoclasts, and also showed enhanced bone destruction after lipopolysaccharide (LPS) administration. Irf8-/- osteoclast precursors underwent increased osteoclastogenesis in response to RANKL and tumor necrosis factor-alpha (TNF-alpha). IRF-8 suppressed osteoclastogenesis by inhibiting the function and expression of nuclear factor of activated T cells c1 (NFATc1). Our results show that IRF-8 inhibits osteoclast formation under physiological and pathological conditions and suggest a model where downregulation of inhibitory factors such as IRF-8 contributes to RANKL-mediated osteoclastogenesis.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. 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.

  9. Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C

    Science.gov (United States)

    Ishiguro, Haruya; Abe, Hiroshi; Seki, Nobuyoshi; Sugita, Tomonori; Aida, Yuta; Itagaki, Munenori; Sutoh, Satoshi; Shimada, Noritomo; Furihata, Tomomi; Tsubota, Akihito; Aizawa, Yoshio

    2015-01-01

    AIM: To evaluate interferon-λ3 (IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin (Peg-IFNα/RBV) therapy for genotype 2 (G2) chronic hepatitis C. METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were treated with response-guided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV sub-genotype 2a or 2b. RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b. CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients. PMID:25852275

  10. 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.

  11. 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

  12. Codominant Role of Interferon-γ– and Interleukin-17–Producing T Cells During Rejection in Full Facial Transplant Recipients

    Science.gov (United States)

    Borges, T. J.; O’Malley, J. T.; Wo, L.; Murakami, N.; Smith, B.; Azzi, J.; Tripathi, S.; Lane, J. D.; Bueno, E. M.; Clark, R. A.; Tullius, S. G.; Chandraker, A.; Lian, C. G.; Murphy, G. F.; Strom, T. B.; Pomahac, B.; Najafian, N.; Riella, L. V.

    2016-01-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean followup of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-c/interleukin-17–producing cells in peripheral blood and in the allograft’s skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17–mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development. PMID:26749226

  13. Validity of aspartate aminotransferase to platelet ratio index as predictor of early viral response in patients with hepatitis C treated by interferon-based therapy.

    Science.gov (United States)

    Samiullah, Shaikh; Bikharam, Devrajai; Musarat, Kalhoro

    2012-10-01

    To observe any change in value of aspartate aminotransferase to platelet ratio index from the baseline and to compare it with the Hepatitis C virus ribonucleic acid at 12 weeks after the start of interferon-based treatment in patients with Hepatitis C. The prospective study, conducted at the Department of Medicine, Liaquat University of Medical and Health Sciences Hospital, Jamshoro, Pakistan, from September 2009 to March 2010, included 158 consecutive, chronic patients of Hepatitis C with grade > or = 2 fibrosis on liver biopsy, or having aspartate aminotransferase/Platelet ratio index of > 1. The aspartate aminotransferase to platelet ratio index was determined as aspartate aminotransferase level (upper normal limit)/platelets counts (10(9)/L) x 100. Eligible patients were assigned to receive thrice weekly subcutaneous injection of 3MIU standard interferon > or = -2b and weight-base dosage of ribavirin. The early virological response was defined as undetectable Hepatitis C virus ribonucleic acid test at week 12 of the study. APRI virus ribonucleic acid after 12 weeks of treatment was non-detectable (early viral response achieved) in 72 (80%) patients. A strong relation was found between aspartate aminotransferase to platelet ratio index and Negative polymerase chain reaction with early virological response as only 2 (4.5%) patients with negative polymerase chain reaction at 12 weeks had aspartate aminotransferase to platelet ratio index > 1 (p = 0.001). APRI can act as a predictor of early viral response in patients with Hepatits C.

  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. Effects of Interferon β-1a and Interferon β-1b Monotherapies on Selected Serum Cytokines and Nitrite Levels in Patients with Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Stępień, Adam; Chalimoniuk, Ma?gorzata; Lubina-Dąbrowska, Natalia

    2013-01-01

    Interferon (IFN)β treatment is a mainstay of relapsing-remitting multiple sclerosis (RRMS) immunotherapy. Its efficacy is supposedly a consequence of impaired trafficking of inflammatory cells into the central nervous system and modification of the proinflammatory/antiinflammatory cytokine balance...

  16. Interferon lambda genotype and low serum LDL cholesterol levels in patients with chronic hepatitis C infection

    Science.gov (United States)

    Li, Josephine H.; Lao, Xiang Qian; Tillmann, Hans L.; Rowell, Jennifer; Patel, Keyur; Thompson, Alexander; Suchindran, Sunil; Muir, Andrew J.; Guyton, John R.; Gardner, Stephen D.; McHutchison, John G.; McCarthy, Jeanette J.

    2010-01-01

    Background Recently, genetic polymorphisms occurring in the interferon lambda gene region were associated with response to interferon-based treatment of hepatitis C infection. Both infection with the hepatitis C virus and interferon therapy are associated with decreased serum cholesterol and high cholesterol has been associated with increased likelihood to respond to interferon. We sought to determine if the interferon lambda gene variant was also associated with serum lipid levels in chronic hepatitis C patients. We compared genotypes of the rs12979860 polymorphism, located proximal to the IL28 gene, with serum lipid and apolipoprotein levels in 746 subjects with chronic HCV infection, not currently undergoing treatment, using multivariable analysis of variance. Results Levels of total cholesterol (p=6.0×10-4), apolipoprotein B (p=1.3×10-6) and low density lipoprotein (LDL) cholesterol (p=8.9×10-10) were significantly higher in subjects carrying the rs12979860 CC ‘responder’ genotype compared to those with the CT or TT genotype. Levels of triglycerides (p=0.03), apolipoprotein A-I (p=0.06) and apolipoprotein E (p=0.01) were slightly lower in the rs12979860 CC genotype group, while levels of high density lipoprotein cholesterol (p=0.78) and apolipoprotein C-III (p=0.74) did not vary by rs12979860 genotype. Conclusions Our results suggest that low levels of LDL cholesterol in chronic hepatitis C patients may be a marker of host endogenous interferon response to hepatitis C and that subjects with the rs12979860 CC ‘responder’ genotype may have a lower endogenous interferon response to the virus. PMID:20235331

  17. Prospective Primary School Teachers' Perceptions on Boiling and Freezing

    Science.gov (United States)

    Senocak, Erdal

    2009-01-01

    The aim of this study was to investigate the perceptions of prospective primary school teachers on the physical state of water during the processes of boiling and freezing. There were three stages in the investigation: First, open-ended questions concerning the boiling and freezing of water were given to two groups of prospective primary school…

  18. Interferon: ten stories in one. A short review of some of the highlights in the history of an almost quinquagenarian.

    Science.gov (United States)

    De Clercq, E

    2005-01-01

    This short review article on some pertinent observations in the unfolding story of interferon is dedicated to Professor Ilona Béládi on the occasion of her 80th birthday. This by no means covers the whole story on interferon. It just highlights some of the more striking findings made with interferon (or its inducers) over a time span of almost 50 years since its original discovery (in 1957) by Isaacs and Lindenmann. These observations concern (i) the induction of interferon by synthetic polyanions such as polyacrylic acid and polymethacrylic acid; (ii) the prolonged antiviral activity shown by polyacrylic acid in vivo; (iii) the interferon-inducing ability of double-stranded RNAs such as poly(I) x poly(C) and (iv) mismatched derivatives thereof (i.e. ampligen); (v) the cloning and expression of interferon-beta, and (vi) its usefulness in the treatment of multiple sclerosis; (vii) the potential of (pegylated) interferon-alpha in the treatment of hepatitis C and (viii) the therapy/prophylaxis of SARS; (ix) the efficacy of interferon (inducers) in the experimental treatment of flavivirus encephalitis and enterovirus myocarditis; and, finally, (x) the role of interferon in the activity shown by S-adenosylhomocysteine inhibitors such as 3-deazaneplanocin A against experimental Ebola virus infections in mice.

  19. From Open Source to Open Collaboration

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Open source is the right to modify, not the right to contribute. Are external contributions absent from your project? Have you ever thought about what is it like to be a new contributor on your project? I challenge you to transform your project from Open Source to an Open Collaboration.

  20. Open Geospatial Education

    Directory of Open Access Journals (Sweden)

    Mariana Belgiu

    2015-04-01

    Full Text Available The advances in open data, free and open source software solutions and open access to research publications have influenced the emergence of open educational resources (OER initiatives. These initiatives permit access to openly licensed learning resources including courses, webinars, training materials and textbooks. Thereby, an increasing number of users has the opportunity to broaden their knowledge and gain new skills. The goal of this paper is to evaluate open education initiatives in the geospatial domain and its synergies with open spatial data and software movements. The paper is focusing on the Massive Open Online Course (MOOCs movement. The advantages and challenges of open geospatial education will be thoroughly discussed.

  1. Open access, open education resources and open data in Uganda.

    Science.gov (United States)

    Salvo, Ivana Di; Mwoka, Meggie; Kwaga, Teddy; Rukundo, Priscilla Aceng; Ernest, Dennis Ssesanga; Osaheni, Louis Aikoriogie; John, Kasibante; Shafik, Kasirye; de Sousa, Agostinho Moreira

    2015-01-01

    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 Uganda which encompasses the scientific community, librarians, academia, researchers and students. The IFMSA students held the workshop with the support of: Consortium for Uganda University Libraries (CUUL), The Right to Research Coalition, Electronic Information for Libraries (EIFL), Makerere University, International Health Sciences University (IHSU), Pan African Medical Journal (PAMJ) and the Centre for Health Human Rights and Development (CEHURD). All these organizations are based or have offices in Kampala. The event culminated in a meeting with the Science and Technology Committee of Parliament of Uganda in order to receive the support of the Ugandan Members of Parliament and to make a concrete change for Open Access in the country.

  2. Beryllium, an adjuvant that promotes gamma interferon production.

    Science.gov (United States)

    Lee, J Y; Atochina, O; King, B; Taylor, L; Elloso, M; Scott, P; Rossman, M D

    2000-07-01

    Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.

  3. Interferon-γ-induced protein 10 in Dengue Virus infection.

    Science.gov (United States)

    Fallahi, P; Elia, G

    2016-01-01

    Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Interferons (IFNs), and IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ-induced protein 10 (IP-10), CXCL9/MIG and CXCL11/I-TAC, and their common receptor chemokine (C-X-C motif) receptor (CXCR)3 are induced by DENV infection; however it has been shown that the latter two could not compensate for the absence of IP-10. This paper reviews studies about DENV and IP-10. Evidences show the importance of IP-10 induction during DENV infection, in macrophages, lymphocytes, hepatic cells, denritic cells, in skin and in the brain. Furthermore it has been shown that chemokines IP-10, I-TAC and their receptor CXCR3 are involved in severity of dengue; in fact, pulmonary effusion or ascites, painful hepatomegaly or aspartate aminotransferase increase, are correlated with IP-10 levels. It has been also demonstrated that IP-10 was more elevated in subjects who subsequently developed dengue hemorrhagic fever or dengue shock syndrome. It has been also shown that IP-10 has a direct action in control of dengue viral replication. Furthermore IP-10 circulating levels may be used to discriminate dengue fever from other febbrile diseases. This is of particular importance in certain situations, for example to discriminate occupationally acquired dengue, in patients with febbrile disorders coming from endemic countries. These studies suggested that these chemokines can be used as potential biomarkers for differential diagnosis and the disease progression, while others can be used to control dengue viral replication, thus representing a viable targets for drug therapy.

  4. Recurrence of depressive disorders after interferon-induced depression.

    Science.gov (United States)

    Chiu, W-C; Su, Y-P; Su, K-P; Chen, P-C

    2017-02-07

    Interferon alpha (IFN-α)-treated patients commonly develop depression during the therapy period. Although most IFN-α-induced depressive disorders achieve remission after IFN-α therapy, no studies have examined the long-term mood effects of IFN-α treatment. We conducted a 12-year population-based cohort study of hepatitis C virus (HCV)-infected patients who were older than 20 years and had received IFN-α therapy. The sample was obtained from the Taiwan National Health Insurance Research Database. The cohort included patients with and without IFN-α-induced depression, matched randomly by age, sex and depression history, at a ratio of 1:10. The follow-up started after the last administration of IFN-α and was designed to determine the incidence of recurrent depressive disorder after IFN-α therapy. A total of 156 subjects were identified as having IFN-α-induced depression and achieving full remission after IFN-α therapy. The overall incidence of recurrent depressive disorders among patients with and without IFN-α-induced depression was 56.8 (95% confidence interval (CI), 42.4-76.1) and 4.1 (95% CI, 2.9-5.8) cases, respectively, per 100 000 person-years, Pdepressive disorder were 13.5 (95% CI, 9.9-18.3) in the IFN-α-treated cohort and 22.2 (95% CI, 11.2-44.2) in the matched cohort for IFN-α-induced depression patients after adjusting for age, sex, income, urbanization and comorbid diseases. IFN-α-induced depression was associated with a high risk of recurrent depression. It was not a transient disease and might be considered an episode of depressive disorder. Continuation therapy might be considered, and further research is needed.

  5. Antagonism of type I interferon responses by new world hantaviruses.

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    Levine, Jessica R; Prescott, Joseph; Brown, Kyle S; Best, Sonja M; Ebihara, Hideki; Feldmann, Heinz

    2010-11-01

    Evasion of interferon (IFN)-mediated antiviral signaling is a common defense strategy for pathogenic RNA viruses. To date, research on IFN antagonism by hantaviruses is limited and has focused on only a subset of the numerous recognized hantavirus species. The host IFN response has two phases, an initiation phase, resulting in the induction of alpha/beta IFN (IFN-α/β), and an amplification phase, whereby IFN-α/β signals through the Jak/STAT pathway, resulting in the establishment of the cellular antiviral state. We examined interactions between these critical host responses and the New World hantaviruses. We observed delayed cellular responses in both Andes virus (ANDV)- and Sin Nombre virus (SNV)-infected A549 and Huh7-TLR3 cells. We found that IFN-β induction is inhibited by coexpression of ANDV nucleocapsid protein (NP) and glycoprotein precursor (GPC) and is robustly inhibited by SNV GPC alone. Downstream amplification by Jak/STAT signaling is also inhibited by SNV GPC and by either NP or GPC of ANDV. Therefore, ANDV- and SNV-encoded proteins have the potential for inhibiting both IFN-β induction and signaling, with SNV exhibiting the more potent antagonism ability. Herein we identify ANDV NP, a previously unrecognized inhibitor of Jak/STAT signaling, and show that IFN antagonism by ANDV relies on expression of both the glycoproteins and NP, whereas the glycoproteins appear to be sufficient for antagonism by SNV. These data suggest that IFN antagonism strategies by hantaviruses are quite variable, even between species with similar disease phenotypes, and may help to better elucidate species-specific pathogenesis.

  6. Immunomodulatory intervention with Gamma interferon in mice with sepsis.

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    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.

  7. Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas

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    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

  8. 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.

  9. Innate immune interferon responses to human immunodeficiency virus-1 infection.

    Science.gov (United States)

    Hughes, Rose; Towers, Greg; Noursadeghi, Mahdad

    2012-07-01

    Type I interferon (IFN) responses represent the canonical host innate immune response to viruses, which serves to upregulate expression of antiviral restriction factors and augment adaptive immune defences. There is clear evidence for type I IFN activity in both acute and chronic HIV-1 infection in vivo, and plasmacytoid dendritic cells have been identified as one important source for these responses, through innate immune detection of viral RNA by Toll-like receptor 7. In addition, new insights into the molecular mechanisms that trigger induction of type I IFNs suggest innate immune receptors for viral DNA may also mediate these responses. It is widely recognised that HIV-1 restriction factors share the characteristic of IFN-inducible expression, and that the virus has evolved to counteract these antiviral mechanisms. However, in some target cells, such as macrophages, IFN can still effectively restrict virus. In this context, HIV-1 shows the ability to evade innate immune recognition and thereby avoid induction of type I IFN in order to successfully establish productive infection. The relative importance of evasion of innate immune detection and evasion of IFN-inducible restriction in the natural history of HIV-1 infection is not known, and the data suggest that type I IFN responses may play a role in both viral control and in the immunopathogenesis of progressive disease. Further study of the relationship between HIV-1 infection and type I IFN responses is required to unravel these issues and inform the development of novel therapeutics or vaccine strategies. Copyright © 2012 John Wiley & Sons, Ltd.

  10. [Hepatitis C, interferon a and depression: main physiopathologic hypothesis].

    Science.gov (United States)

    Vignau, J; Karila, L; Costisella, O; Canva, V

    2005-01-01

    Imputability of thymic disorders caused by IFNalpha during the chronic Hepatitis C treatment -- hepatitis C and depression -- the infection by the hepatitis C virus (HCV) is a major public health concern since it affects 1.2% in the French population. Eighty percent of those contaminated by HCV keep bearing the virus chronically although they remain asymptomatic during many years. HCV infection is associated with psychiatric symptoms like depression. Together with other factors (eg the severity of hepatic condition), depression may induce significant impairment in quality of life. Conversely, some psychiatric conditions may increase the risk of HCV infection. In drug-addicted subjects using intravenous route, HCV contamination rate ranges from 74 to 100%. Compared with general population, a higher HCV contamination rate has also been noticed in some other subgroups of subjects (patients with alcohol abuse or dependence, with alcohol-induced hepatic disease and psychiatric inpatients). However, no valid explanation to this phenomenon has been established. Interferon alpha and depression - Interferons are a variety of cytokines naturally produced by human tissues and have also been synthesized for therapeutic purposes (treatment of a variety of cancers and viral infections). Many psychobehavioural symptoms are observed under IFNalpha treatment. Among them, mood disorders are known to occur early after entry into treatment and to be within the reach of preventive measures. The reported frequency of depression during IFNalpha treatment ranges from 0 to 37%. This variation reflects either methodological biases (eg differences in psychiatric assessment) or the heterogeneity of the population of patients accepted in therapeutic protocols. Note that the adjunction of ribavirine to IFNalpha in therapeutic protocols has not brought any changes in the depression frequency. The causal relationship between IFNalpha administration and the occurrence of mood disorders has been

  11. 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

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    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.

  12. Inhibitory effect of a triterpenoid compound, with or without alpha interferon, on hepatitis C virus infection.

    Science.gov (United States)

    Watanabe, Takako; Sakamoto, Naoya; Nakagawa, Mina; Kakinuma, Sei; Itsui, Yasuhiro; Nishimura-Sakurai, Yuki; Ueyama, Mayumi; Funaoka, Yusuke; Kitazume, Akiko; Nitta, Sayuri; Kiyohashi, Kei; Murakawa, Miyako; Azuma, Seishin; Tsuchiya, Kiichiro; Oooka, Shinya; Watanabe, Mamoru

    2011-06-01

    A lack of patient response to alpha interferon (α-IFN) plus ribavirin (RBV) treatment is a major problem in eliminating hepatitis C virus (HCV). We screened chemical libraries for compounds that enhanced cellular responses to α-IFN and identified a triterpenoid, toosendanin (TSN). Here, we studied the effects and mechanisms of action of TSN on HCV replication and its effect on α-IFN signaling. We treated HCV genotype 1b replicon-expressing cells and HCV-J6/JFH-infected cells with TSN, with or without α-IFN, and the level of HCV replication was quantified. To study the effects of TSN on α-IFN signaling, we detected components of the interferon-stimulated gene factor 3 (ISGF3), phosphorylated signal transducer and activator of transcription 1 (STAT1), and STAT2 by Western blotting analysis; expression levels of mRNA of interferon regulatory factor 9 using real-time reverse transcription-PCR (RT-PCR); and interferon-stimulated response element reporter activity and measured the expression levels of interferon-inducible genes for 2',5'-oligoadenylate synthetase, MxA, protein kinase R, and p56 using real-time RT-PCR. TSN alone specifically inhibited expression of the HCV replicon (50% effective concentration = 20.6 nM, 50% cytotoxic concentration > 3 μM, selectivity index > 146). Pretreatment with TSN prior to α-IFN treatment was more effective in suppressing HCV replication than treatment with either drug alone. Although TSN alone did not activate the α-IFN pathway, it significantly enhanced the α-IFN-induced increase of phosphorylated STATs, interferon-stimulated response element activation, and interferon-stimulated gene expression. TSN significantly increased baseline expression of interferon regulatory factor 9, a component of interferon-stimulated gene factor 3. Antiviral effects of treatment with α-IFN can be enhanced by pretreatment with TSN. Its mechanisms of action could potentially be important to identify novel molecular targets to treat HCV

  13. Impact of DaTscan SPECT imaging on clinical management, diagnosis, confidence of diagnosis, quality of life, health resource use and safety in patients with clinically uncertain parkinsonian syndromes: a prospective 1-year follow-up of an open-label controlled study.

    Science.gov (United States)

    Kupsch, Andreas R; Bajaj, Nin; Weiland, Frederick; Tartaglione, Antonio; Klutmann, Susanne; Buitendyk, Melanie; Sherwin, Paul; Tate, Ann; Grachev, Igor D

    2012-06-01

    This study assessed the impact of DaTscan on clinical management, diagnosis, confidence of diagnosis (CoD), quality of life (QoL), health resource use (HRU) and safety during a 1-year follow-up in patients with clinically uncertain parkinsonian syndromes (CUPS). A total of 19 university hospital centres in Europe and the USA participated in this open-label, single-dose, prospective, clinical trial in patients with CUPS who were randomised to a DaTscan imaging group or to a no-imaging (control) group. The proportion of patients with changes in clinical management, diagnosis, CoD, QoL and HRU from baseline through 1 year post-DaTscan was compared between groups. There were 273 patients randomised (135 DaTscan, 138 control). Significantly more patients in the DaTscan imaging group had at least one change in their actual clinical management after 12 weeks (p=0.002) and after 1 year (pmanagement, diagnosis and CoD in patients with CUPS. DaTscan is safe and well tolerated, and is a useful adjunct to differentiate a diagnosis of CUPS. Trial registration number http://ClinicalTrials.gov Identifier: NCT00382967.

  14. SERUM PROLACTIN IN MELANOMA PATIENTS WITH INTERFERON ALPHA2B TREATMENT.

    Science.gov (United States)

    Ene, Corina-Daniela; Nicolae, Ilinca

    2015-01-01

    The authors' interest was focused on prolactin status in patients with melanocytic lesions and on changes induced by interferon treatment in melanoma patients. The study lasted 5 years and included 128 melanoma patients, 48 dysplastic nevi patients and 48 healthy volunteers. Sixty melanoma cases were selected after surgical removal of tumor and divided into 2 groups: 30 patients with 10 MUmp(-1) interferon alpha2b treatment, three times a week, one year and 30 patients without interferon treatment. Prolactin assessment was made at inclusion in the study, after surgical removal of tumor, when patients started the treatment, after 1, 6, 12 months of treatment and 6 months after treatment end. In melanoma patients, high values of prolactin (10.55 ± 5.94 ng/ml) were detected when compared with dysplastic nevi group (5.94 ± 2.87 ng/ml) and control group (5.74 ± 3.66 ng.ml). Prolactin levels decreased after surgical removal of melanoma, significantly increased during interferon treatment and returned to baseline few months after the immunomodulatory treatment. The treatment with interferon alpha2b stimulated reversible and non-cumulative prolactin production. Evaluating prolactin in melanoma patients could become necessary in the future, both for finding a possible pituitary disorder, but also for a new pharmacological intervention.

  15. Recessive genetic deregulation abrogates c-myc suppression by interferon and is implicated in oncogenesis

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    Kimchi, A.; Resnitzky, D.; Ber, R.; Gat, G.

    1988-07-01

    Previously the authors demonstrated that many hematopoietic tumor cells are resistant to the inhibitory effects that interferon exerts on c-myc mRNA expression without losing other receptor-mediated intracellular responses. They report here that this partial resistance was overridden in two independent stable somatic cell hybrids prepared by fusion between sensitive and resistant cells. The c-myc mRNA transcribed from the active allele of the resistant parent cell was reduced by interferon within the context of the cell hybrid. It was therefore concluded that changes in the cis-acting sequences of c-myc were not involved in this type of relaxed regulation and that resistance resulted rather from inactivation or loss of postreceptor elements which operate in trans. The growth-stimulating effect that this genetic deregulation might have on cells was tested in experimental systems of cell differentiation in which an autocrine interferon is produced. For that purpose the authors isolated variant clones of M1 myeloid cells which were partially resistant to alpha and beta interferons and tested their growth behaviour during in vitro-induced differentiation. The resistant clones displayed higher proliferative activity on days 2 and 3 of differentiation than did the sensitive clones, which stopped proliferating. The loss of c-myc responses to the self-produced interferon disrupted the normal cessation of growth during differentiation and therefore might lead cells along the pathway of neoplasia.

  16. Aggressive giant cell granuloma of the jaws treated with interferon alpha: a report of two cases.

    Science.gov (United States)

    O'Connell, J E; Kearns, G J

    2013-06-01

    Giant cell granulomas (GCGs) are benign tumours of the jaws of unknown aetiology. Aggressive lesions are difficult to manage and demonstrate a tendency to recur after surgical curettage. In the early 1980s, interferon alpha-2a was found to inhibit angiogenesis through a series of laboratory experiments and was subsequently used to treat a child with pulmonary haemangiomatosis. It has been hypothesised that GCGs are proliferative vascular lesions and would, therefor, be expected to respond to antiangiogenic therapy. The purpose of this study is to report a treatment protocol consisting of enucleation, followed by subcutaneous interferon alpha. Patients with a biopsy-confirmed giant cell lesion satisfying criteria for "aggressive" giant cell tumours were included. All lesions were enucleated, and the patients commenced interferon alpha-2a (3,000,000 units/m(2)) 48-72 h post-operatively. Two patients satisfied the criteria for aggressive giant cell lesions. All tumours were enucleated. There were no post-operative complications, and all patients tolerated the interferon therapy well. To date, there has been no evidence of tumour recurrence. The follow-up periods were 144 and 81 months, respectively. Antiangiogenic therapy, in combination with curettage, has proven to be a useful strategy for the management of these tumours. The use of interferon alpha-2a, following enucleation of these lesions, resulted in complete remission of all lesions, and decreased operative morbidity compared with conventional treatment.

  17. Cutaneous Sarcoidosis: An Uncommon Side Effect of Pegylated Interferon and Ribavirin Use for Chronic Hepatitis C

    Science.gov (United States)

    Martins, Elson Vidal; Gaburri, Ana Karla; Gaburri, Debora; Sementilli, Angelo

    2009-01-01

    The treatment of chronic hepatitis C (CHC) has evolved in the past 15 years and combination of pegylated interferon plus ribavirin is its current standard therapy. However, several side effects are commonly observed and frequently lead to transient or definitive interruption of treatment. Although sarcoidosis in its systemic or cutaneous form is a very rare side effect in such circumstances, some cases have been reported even with conventional interferon. This brief review of the literature and description of a case of sarcoidosis occurring in a tattoo and a scar patient's face, during treatment with pegylated interferon alpha-2b plus ribavirin, is an educative report directed in special to dermatologists. The lesion improved after drug interruption and recurred after retreatment with pegylated interferon alpha-2a. We conclude that this side effect must call the attention of doctors to seek for the diagnosis and therapy as soon as possible in such circumstances. No differences were noticed neither with alpha-2a nor alpha-2b pegylated interferon employment. PMID:21103255

  18. Pulmonary abnormalities caused by interferon with or without herbal drug. CT and radiographic findings

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    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.)

  19. 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

    2018-02-13

    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.

  20. Onset of Celiac Disease after Treatment of Chronic Hepatitis C with Interferon Based Triple Therapy

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    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.