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Sample records for comparator epoetin alfa

  1. Epoetin Alfa Injection

    Science.gov (United States)

    Epoetin alfa injection is used to treat anemia (a lower than normal number of red blood cells) in people with chronic ... working over a period of time). Epoetin alfa injection is also used to treat anemia caused by ...

  2. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial

    National Research Council Canada - National Science Library

    Carrera, Fernando; Lok, Charmaine E; de Francisco, Angel; Locatelli, Francesco; Mann, Johannes F E; Canaud, Bernard; Kerr, Peter G; Macdougall, Iain C; Besarab, Anatole; Villa, Giuseppe; Kazes, Isabelle; Van Vlem, Bruno; Jolly, Shivinder; Beyer, Ulrich; Dougherty, Frank C

    2010-01-01

    .... We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly...

  3. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial.

    Science.gov (United States)

    Carrera, Fernando; Lok, Charmaine E; de Francisco, Angel; Locatelli, Francesco; Mann, Johannes F E; Canaud, Bernard; Kerr, Peter G; Macdougall, Iain C; Besarab, Anatole; Villa, Giuseppe; Kazes, Isabelle; Van Vlem, Bruno; Jolly, Shivinder; Beyer, Ulrich; Dougherty, Frank C

    2010-12-01

    Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly. Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50-53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953. Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups. Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa.

  4. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial

    OpenAIRE

    Carrera, Fernando; Charmaine E. Lok; de Francisco, Angel; Locatelli, Francesco; Mann, Johannes F.E.; Canaud, Bernard; Kerr, Peter G.; Macdougall, Iain C.; Besarab, Anatole; Villa, Giuseppe; Kazes, Isabelle; Van Vlem, Bruno; Jolly, Shivinder; Beyer, Ulrich; Dougherty, Frank C.

    2010-01-01

    Background. Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly. Methods. Haemodialysis patients (n = 490)...

  5. Epoetin alfa and beta differ in their erythropoietin isoform compositions and biological properties.

    Science.gov (United States)

    Storring, P L; Tiplady, R J; Gaines Das, R E; Stenning, B E; Lamikanra, A; Rafferty, B; Lee, J

    1998-01-01

    Epoetin alfa and beta are the two forms of recombinant DNA-derived erythropoietin (rEPO), both synthesized in Chinese hamster ovary cells, which are used for the treatment of erythropoietin (EPO)-responsive anaemias. Several batches of each of these rEPOs were compared for differences in their EPO isoform compositions by isoelectric focusing (IEF) and in a range of lectin-binding assays, and for differences in their EPO activities by in-vivo and in-vitro mouse bioassays and by immunoassay. Epoetin beta was found to differ from epoetin alfa in containing: (a) a greater proportion of more basic isoforms, (b) a greater proportion of EPO binding to Erythrina cristagalli agglutinin (which binds N-glycans with nonsialylated outer Gal beta1-4GlcNAc moieties), and (c) isoforms with higher in-vivo:in-vitro bioactivity ratios. Epoetin beta also contained slightly more than epoetin alfa of EPO binding to Lycopersicon esculentum agglutinin (which binds N-glycans containing repeating Gal beta1-4GlcNAc sequences), to the leucoagglutinin of Phaseolus vulgaris (which binds tetraantennary and 2,6-branched triantennary N-glycans) and to Agaricus bisporus agglutinin (which binds Gal beta1-3GalNAc containing O-glycans). No differences were found between the two rEPOs in their binding to a further five lectins. The differences between the isoform composition of epoetin alfa and beta, and the smaller inter-batch differences appear to be due to differences in glycosylation. The higher murine in-vivo:in-vitro bioactivity ratio of epoetin beta compared to epoetin alfa could not be explained in terms of differences in their degrees of sialylation, but was consistent with differences in their pharmacokinetics and pharmacodynamics observed in human subjects. There have been no reports that epoetin alfa differs from epoetin beta in its clinical efficacy, but the differences between epoetin alfa and beta in some analytical systems suggest that there might be a need for separate international

  6. Epoetin alfa ja namaluva nefrotoksicnosta inducirana so cisplatin kaj staorci

    Directory of Open Access Journals (Sweden)

    Dimce Zafirov

    2006-06-01

    Full Text Available Klinickata efikasnost na cisplatin kako antitumorski lek e nesomnena, no dozno-limitiracki faktor za negova upotreba pretstavuva izrazitata nefrotoksicnost. Najnovite istrazuvawa pokazuvaat deka epoetin alfa moze da ima znacajna uloga ne samo vo terapiski celi za korekcija na razni vidovi na anemii, tuku istiot moze da bide efikasen i kako nevroprotektiv, hepatoprotektiv, kardioprotektiv i osobeno znacajno kako nefroprotektiv kaj nefrotoksicnost inducirana od preparati na baza na platina. Glavna cel na ovaa studija bese da se utvrdi efektot na epoetin alfa vo prevencijata na nefrotoksicnost eksperimentalno inducirana so dolgotrajna administracija na cisplatin vo doza od 2 mg/kg/t.t./nedela vo tek na 8 nedeli, kaj Wistar staorci. Dobienite rezultati od ovaa studija pokazuvaat deka epoetin alfa signifikantno gi ublazuva funkcionalnite bubrezni poremetuvawa inducirani so dolgotrajna administracija na cisplatin, ja podobruva opstata sostojba i go namaluva mortalitetot kaj ispituvanite zivotni.

  7. Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

    Science.gov (United States)

    Provenzano, Robert; Besarab, Anatole; Wright, Steven; Dua, Sohan; Zeig, Steven; Nguyen, Peter; Poole, Lona; Saikali, Khalil G; Saha, Gopal; Hemmerich, Stefan; Szczech, Lynda; Yu, K H Peony; Neff, Thomas B

    2016-06-01

    Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (Proxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed

  8. Economic evaluation of weekly epoetin alfa versus biweekly darbepoetin alfa for chemotherapy-induced anaemia: evidence from a 16-week randomised trial.

    Science.gov (United States)

    Reed, Shelby D; Radeva, Jasmina I; Daniel, Davey B; Mody, Samir H; Forlenza, Jamie B; McKenzie, R Scott; Schulman, Kevin A

    2006-01-01

    A 16-week, open-label, multicentre, randomised trial of weekly epoetin alfa 40 000 units versus biweekly darbepoetin alfa 200microg among 358 patients with solid-tumour cancers and chemotherapy-induced anaemia demonstrated superior haematological outcomes with epoetin alfa. We sought to compare resource use, costs and clinical outcomes between treatment groups and report the results using a cost-consequences framework. Pre-specified methods were used to assign costs (US dollars, year 2004-5 values) to medical resources and patient time using a societal perspective. Costs for inpatient care, outpatient care and physician services were based on US Medicare reimbursement rates. Indirect costs assigned to patient time spent receiving study medication were based on the mean hourly wage in the US. In the base-case analysis, the average wholesale price was used to assign costs to medications. Clinical outcomes included all haemoglobin levels and transfusions recorded throughout the trial. Sensitivity analyses were performed to evaluate the impact of different costing methods, cost sources, perspectives and methods to assign haemoglobin values following a blood transfusion. Over a mean follow-up duration of 11.8 weeks, the average cost of study medications and their administration was the single largest component of total costs and was similar between groups (epoetin alfa 5979 US dollars and darbepoetin alfa 5935 US dollars, difference 44 US dollars; 95% CI -590, 692). There were no significant differences in the proportions of patients hospitalised (epoetin alfa 24.6%, darbepoetin alfa 22.0%; p = 0.57). Patients randomised to epoetin alfa experienced more inpatient days, on average, than patients randomised to darbepoetin alfa (2.6 vs 1.6, 95% CI for the difference, 0.07, 2.27). However, with regard to transfusions, patients in the epoetin alfa arm required fewer units of blood than patients in the darbepoetin alfa arm (0.46 vs 0.88, 95% CI for the difference -0.77, -0

  9. Impact of illegal trade on the quality of epoetin alfa in Thailand.

    Science.gov (United States)

    Fotiou, Fotis; Aravind, Suresh; Wang, Ping-Ping; Nerapusee, Osot

    2009-02-01

    Reports from the World Health Organization have suggested that counterfeit medicines pose a serious problem in developing countries. An investigation of anti-erythropoietin antibody-mediated pure red cell aplasia in Thailand found evidence of drug smuggling, which may have serious safety implications. This study assessed the authenticity and quality of epoetin alfa samples in Thailand. Samples of epoetin alfa-prefilled syringes were collected from the pharmacies at 2 major hospitals (62 samples), 8 retail pharmacies (41 samples), and Thai authorities (30 samples confiscated from smugglers at 2 airports, and 6 samples from a condominium used by smugglers). These samples were tested against the European Union Pharmacopeia specifications for aggregate content in epoetins of packaging components (eg, batch number, expiration date, appearance, letter size), and company's confidential features (eg, nature of the ink, type and quality of the paper, other covered features) were also investigated. The main outcome measures were protein aggregate content, determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting; and isoform distribution, assessed by isoelectric focusing and Western blotting. Epoetin alfa samples obtained from the company's cold-chain and authorized distribution channels met all quality standards, as did all epoetin alfa samples obtained from the hospital pharmacies. However, evidence showed that some samples were being smuggled or sold illegally through certain unauthorized retail pharmacies. The epoetin alfa samples obtained from both airports and the condominium were stored improperly at room temperature. Aggregate levels exceeded the specification of packaging were found to be authentic. This investigation found evidence that some epoetin alfa samples were smuggled into Thailand without proper cold chain, contained high levels of protein aggregates, and were sold illegally through certain retail pharmacies. The Thai

  10. Rituximab therapy for pure red cell aplasia due to anti-epoetin antibodies in a woman treated with epoetin-alfa: a case report.

    Science.gov (United States)

    Behler, Caroline M; Terrault, Norah A; Etzell, Joan E; Damon, Lloyd E

    2009-07-06

    Pure red cell aplasia due to anti-epoetin antibodies is a known complication of epoetin therapy for anemia due to chronic kidney disease. This disease has not previously been well described in the setting of therapy for chronic hepatitis C virus infection. While treatment for pure red cell aplasia due to anti-epoetin antibodies is usually with immunosuppressive therapy such as calcineurin inhibition, the safety of this treatment in chronic hepatitis C virus infection is unknown. To date, little has been published on the efficacy of rituximab on pure red cell aplasia due to anti-epoetin antibodies. This report describes a 65-year-old Asian-American woman who developed pure red cell aplasia from high titer neutralizing anti-epoetin antibodies after epoetin-alfa therapy during ribavirin and peg-interferon treatment for chronic hepatitis C virus infection. We describe the outcome of her treatment with rituximab. The reticulocyte count increased, and anti-epoetin antibody titer decreased with a loss of neutralizing activity in vitro, leading to a reduction in blood transfusions, and eventual resolution of anemia, without reactivation of hepatitis C virus. The diagnosis of pure red cell aplasia from anti-epoetin antibodies should be considered in patients undergoing therapy for chronic hepatitis C virus infection who develop severe anemia after administration of erythropoietin or darbepoetin. Though it is currently an off-label indication, rituximab is a therapeutic option for patients with pure red cell aplasia due to anti-epoetin antibodies.

  11. Switch from epoetin to darbepoetin alfa in hemodialysis: dose equivalence and hemoglobin stability

    Directory of Open Access Journals (Sweden)

    Arrieta J

    2014-10-01

    Full Text Available Javier Arrieta,1 Iñigo Moina,1 José Molina,2 Isabel Gallardo,3 María Luisa Muñiz,4 Carmen Robledo,5 Oscar García,5 Fernando Vidaur,6 Rosa Inés Muñoz,3 Izaskun Iribar,7 Román Aguirre,7 Antonio Maza8 1Hospital de Basurto, Bilbao, 2Hospital de Donostia, Donostia-San Sebastián, 3Hospital de Galdakao-Usansolo, Galdakao, 4Hospital de Cruces, Baracaldo, 5Hospital de Santiago, Vitoria-Gasteiz, 6Policlínica de Guipúzcoa, Donostia-San Sebastián, 7Hemobesa Clinica Virgen Blanca, Bilbao, 8Dialbilbo, Bilbao, Spain Aim: The objective of the study reported here was to describe dose equivalence and hemoglobin (Hb stability in a cohort of unselected hemodialysis patients who were switched simultaneously from epoetin alfa to darbepoetin alfa. Methods: This was a multicenter, observational, retrospective study in patients aged $18 years who switched from intravenous (IV epoetin alfa to IV darbepoetin alfa in October 2007 (Month 0 and continued on hemodialysis for at least 24 months. The dose was adjusted to maintain Hb within 1.0 g/dL of baseline. Results: We included 125 patients (59.7% male, mean [standard deviation (SD] age 70.4 [13.4] years. No significant changes were observed in Hb levels (mean [SD] 11.9 [1.3] g/dL, 12.0 [1.5], 12.0 [1.5], and 12.0 [1.7] at Months −12, 0, 12 and 24, respectively, P=0.409. After conversion, the erythropoiesis-stimulating agent (ESA dose decreased significantly (P<0.0001, with an annual mean of 174.7 (88.7 international units (IU/kg/week for epoetin versus 95.7 (43.4 (first year and 91.4 (42.7 IU/kg/week (second year for darbepoetin (65% and 64% reduction, respectively. The ESA resistance index decreased from 15.1 (8.5 IU/kg/week/g/dL with epoetin to 8.1 (3.9 (first year and 7.9 (4.0 (second year with darbepoetin (P<0.0001. The conversion rate was 354:1 in patients requiring high (>200 IU/kg/week doses of epoetin and 291:1 in patients requiring low doses. Conclusion: In patients on hemodialysis receiving ESAs

  12. Rituximab therapy for pure red cell aplasia due to anti-epoetin antibodies in a woman treated with epoetin-alfa: a case report

    Directory of Open Access Journals (Sweden)

    Behler Caroline M

    2009-07-01

    Full Text Available Abstract Introduction Pure red cell aplasia due to anti-epoetin antibodies is a known complication of epoetin therapy for anemia due to chronic kidney disease. This disease has not previously been well described in the setting of therapy for chronic hepatitis C virus infection. While treatment for pure red cell aplasia due to anti-epoetin antibodies is usually with immunosuppressive therapy such as calcineurin inhibition, the safety of this treatment in chronic hepatitis C virus infection is unknown. To date, little has been published on the efficacy of rituximab on pure red cell aplasia due to anti-epoetin antibodies. Case presentation This report describes a 65-year-old Asian-American woman who developed pure red cell aplasia from high titer neutralizing anti-epoetin antibodies after epoetin-alfa therapy during ribavirin and peg-interferon treatment for chronic hepatitis C virus infection. We describe the outcome of her treatment with rituximab. The reticulocyte count increased, and anti-epoetin antibody titer decreased with a loss of neutralizing activity in vitro, leading to a reduction in blood transfusions, and eventual resolution of anemia, without reactivation of hepatitis C virus. Conclusion The diagnosis of pure red cell aplasia from anti-epoetin antibodies should be considered in patients undergoing therapy for chronic hepatitis C virus infection who develop severe anemia after administration of erythropoietin or darbepoetin. Though it is currently an off-label indication, rituximab is a therapeutic option for patients with pure red cell aplasia due to anti-epoetin antibodies.

  13. Efficacy and safety analysis of epoetin alfa in patients with small-cell lung cancer: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Grote, Thomas; Yeilding, Allen L; Castillo, Rene; Butler, Dean; Fishkin, Ellioth; Henry, David H; DeLeo, Michael; Fink, Kenneth; Sullivan, Daniel J

    2005-12-20

    This randomized, double-blind, placebo-controlled trial (N93-004) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer (SCLC). Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy. Survival was assessed for 3 years. The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles. The trial was terminated prematurely after 224 of a projected 400 patients were accrued. Baseline characteristics were similar between groups. Epoetin alfa and placebo patients (n = 109 and n = 115, respectively) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL, respectively. Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles (72% and 67%, respectively; 95% CI of difference, -6% to 18%) and after completion of chemotherapy (60% and 56%, respectively; 95% CI of difference, -9% to 17%). Epoetin alfa and placebo groups had similar median overall survival (10.5 and 10.4 months, respectively) and overall mortality (91.7% and 87.8%, respectively; hazard ratio, 1.172; 95% CI, 0.887 to 1.549; P = .264). Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients, but decreased substantially in placebo patients. Fewer epoetin alfa patients than placebo patients required transfusion. These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival. However, the early trial closure makes these conclusions preliminary.

  14. Epoetin alfa increases hemoglobin levels and improves quality of life in anemic geriatric cancer patients receiving chemotherapy.

    Science.gov (United States)

    Aapro, Matti S; Dale, David C; Blasi, Michael; Sarokhan, Brenda; Ahmed, Fawzia; Woodman, Richard C

    2006-12-01

    To evaluate epoetin alfa (EPO) treatment of anemia in geriatric cancer patients receiving chemotherapy, a retrospective subgroup analysis was conducted of anemic cancer patients > or =65 years of age from three 16-week community-based studies of thrice-weekly (TIW) or once-weekly (QW) EPO for chemotherapy-related anemia (CRA). Analyses were conducted on the overall geriatric population (> or =65 years) and by age subgroup (65-74, 75-84, and > or =85 years), and compared with younger patients (geriatric patients were compared with 3,467 younger patients. From baseline to final measurement, EPO therapy significantly increased Hb by 2.0 g/dl in patients > or =65 years and 1.9 g/dl in patients quality of life (QOL), measured by the 100-mm Linear Analog Assessment Scale (LASA). In younger patients, mean LASA changes were significantly greater than those in geriatric patients (Pgeriatric age subgroups or between TIW and QW regimens for Hb change or QOL improvement. Overall hematopoietic response rate to EPO was 65.4% for patients > or =65 years and 64.7% for patients geriatric patients receiving EPO for CRA responded comparably to younger patients <65 years and should be treated similarly.

  15. Epoetin alfa improves anemia and anemia-related, patient-reported outcomes in patients with breast cancer receiving myelotoxic chemotherapy: Results of a european, multicenter, randomized, controlled trial

    NARCIS (Netherlands)

    P. Pronzato (Paolo); E. Cortesi (Enrico); C.C.D. van der Rijt (Carin); A. Bols (Alain); J.A. Moreno-Nogueira (José); C.F. de Oliveira; P. Barrett-Lee (Peter); P.J. Ostler (Peter); R. Rosso (Ricardo)

    2010-01-01

    textabstractPurpose. To evaluate the effects of epoetin alfa on patient- reported outcomes (PROs) in patients with breast cancer receiving myelotoxic chemotherapy. Materials and Methods. Women with hemoglobin concentrations ≤12.0 g/dl and an Eastern Cooperative Oncology Group performance status

  16. Epoetin alfa 40000 U once weekly and intravenous iron supply in solid tumor patients: early increase of hemoglobin level during chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lalle, M.; Antimi, M. [Ospedale S. Eugenio, Rome (Italy). Unita operativa complessa di oncologia medica; Pistillucci, G.; D' Aprile, M. [Ospedale S. Maria Goretti, Latina (Italy). Unita operativa complessa di oncologia medica

    2005-06-15

    The objective of this observational study was the early evaluation of the impact, a week after the first administration of epoetin alfa 40000 U once weekly and i.v. dose of 62.5 mg sodium ferric gluconate for seven days in improving hemoglobin levels in cancer patients affected by mild/moderate or severe anemia during chemotherapy. Twenty patients affected by solid tumors who received epoetin alfa 40000 U once weekly and daily i.v. sodium ferric gluconate for one week were evaluated: 90% of the patients showed hemoglobin increase, with a median level of hemoglobin increase of 0.73 g/L from baseline, and 50% of them showing a hemoglobin increase > 1 gr/L. The treatment was well tolerated and no adverse event was observed. The early increase of hemoglobin level from baseline is interesting and suggestive for the possibility of achieving an adequate hemoglobin level with a short-term treatment. It is still necessary to further explore the real need of iron supplementation to maintain adequate erythropoiesis prior and during epoetin therapy.

  17. Potential cost saving of Epoetin alfa in elective hip or knee surgery due to reduction in blood transfusions and their side effects: a discrete-event simulation model.

    Directory of Open Access Journals (Sweden)

    Jörg Tomeczkowski

    Full Text Available OBJECTIVES: Transfusion of allogeneic blood is still common in orthopedic surgery. This analysis evaluates from the perspective of a German hospital the potential cost savings of Epoetin alfa (EPO compared to predonated autologous blood transfusions or to a nobloodconservationstrategy (allogeneic blood transfusion strategyduring elective hip and knee replacement surgery. METHODS: Individual patients (N = 50,000 were simulated based on data from controlled trials, the German DRG institute (InEK and various publications and entered into a stochastic model (Monte-Carlo of three treatment arms: EPO, preoperative autologous donation and nobloodconservationstrategy. All three strategies lead to a different risk for an allogeneic blood transfusion. The model focused on the costs and events of the three different procedures. The costs were obtained from clinical trial databases, the German DRG system, patient records and medical publications: transfusion (allogeneic red blood cells: €320/unit and autologous red blood cells: €250/unit, pneumonia treatment (€5,000, and length of stay (€300/day. Probabilistic sensitivity analyses were performed to determine which factors had an influence on the model's clinical and cost outcomes. RESULTS: At acquisition costs of €200/40,000 IU EPO is cost saving compared to autologous blood donation, and cost-effective compared to a nobloodconservationstrategy. The results were most sensitive to the cost of EPO, blood units and hospital days. CONCLUSIONS: EPO might become an attractive blood conservation strategy for anemic patients at reasonable costs due to the reduction in allogeneic blood transfusions, in the modeled incidence of transfusion-associated pneumonia andthe prolongedlength of stay.

  18. Increased injection pain with darbepoetin-alpha compared to epoetin-beta in paediatric dialysis patients.

    Science.gov (United States)

    Schmitt, Claus Peter; Nau, Barbara; Brummer, Christiane; Rosenkranz, Joachim; Schaefer, Franz

    2006-12-01

    Darbepoetin-alpha is applicable at longer injection intervals. Our early experience in children on peritoneal dialysis suggested increased injection pain compared to epoetin-beta, possibly due to technical differences or patient anxiety. To verify a possible difference in the painfulness of the injected fluids per se, we performed a prospective, randomized, double-blind trial in 13 paediatric end-stage renal disease patients. They received three injections of equivalent doses of darbepoetin-alpha or epoetin-beta in 0.6 ml saline, using neutral syringes and 27G needles, at 4 week intervals. Pain perception was recorded immediately and after 30 min on a visual analogue scale (VAS, 0 = no pain, 10 = maximal pain; complemented by 5 faces for young children). The patients perceived more intense immediate injection pain with darbepoetin-alpha than with epoetin-beta (5.4 +/- 1 vs 2.3 +/- 0.6, P or =4 VAS points) with darbepoetin-alpha. After 30 min, the injection site was largely painless with both drugs. No significant local reactions occurred with either medication (0.3 +/- 0.1 vs 0.3 +/- 0.1 on a 5-score scale). Subcutaneous injections of darbepoetin-alpha are more painful than those of epoetin-beta in the majority of paediatric patients. The observed difference in painfulness is related to the nature of the injected compounds and may limit the subcutaneous applicability of darbepoetin-alpha in children.

  19. Alfa

    OpenAIRE

    Louis, A.; Despois, J.

    2013-01-01

    On confond habituellement sous le nom de ḥalfa (alfa) deux plantes assez voisines : l’alfa véritable (stipa tenacissima) dont la feuille se replie en demi-gaine et l’épi rappelle un peu celui de l’orge, et le lygée ou sparte « fol alpha» (lygeum spartum), aux dimensions plus réduites, à l’allure plus raide; encore que les gens du Sud tunisien désignent le premier par geddīm et le lygée par ḥalfa. Le premier habite les zones montagneuses et les hauts plateaux ; on le désigne en Tunisie sous le...

  20. Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients

    DEFF Research Database (Denmark)

    Mann, J; Kessler, M; Villa, Giulio Palludan

    2007-01-01

    AIM: Darbepoetin alfa has a longer half-life than epoetin-(EPO) alfa or beta, allowing administration at less frequent intervals for the treatment of renal anemia. The aim of the present analysis was to evaluate the efficacy and tolerability of an every-2-week (Q2W) schedule of darbepoetin alfa...

  1. Comparative study of lignins isolated from Alfa grass (Stipa tenacissima L.).

    Science.gov (United States)

    Nadji, H; Diouf, P N; Benaboura, A; Bedard, Y; Riedl, B; Stevanovic, T

    2009-07-01

    Soda lignin, dioxane lignin and milled lignin were isolated from Alfa grass (Stipatenacissima L.). The physico-chemical characterization of three different lignins: one industrial lignin precipitated from soda spent liquor and two lignin preparations isolated under laboratory conditions from Alfa grass (also know as Esparto grass) was performed. The structures of lignins were studied by three non-destructive (FT-IR, solid state (13)C NMR and UV/visible spectroscopy) and two destructive (nitrobenzene oxidation and thermogravimetric analysis) methods. Elemental analysis and the methoxyl content determination were performed in order to determine the C(9) formulae for the studied lignins. The total antioxidant capacity of the studied lignins has been determined and compared to commercial antioxidants commonly used in thermoplastic industry.

  2. The Use of Epoetin-α in Revision Knee Arthroplasty

    Directory of Open Access Journals (Sweden)

    Lawrence A. Delasotta

    2012-01-01

    Full Text Available Introduction. To evaluate the efficacy of epoetin-α prior to revision total knee arthroplasty, we hypothesized that epoetin-α will reduce blood transfusion. Methods. Eighty-one patients were compared in this retrospective review; twenty-eight patients received our dosing regimen. All patients were mildly anemic. Epoetin-α to control (1 : 2 patient matching occurred so that one of two attending surgeons, gender, BMI, complexity of surgery, ASA score, and age were similar between groups. The clinical triggers for blood transfusion during or after the procedure were determined based on peri- and postoperative hemoglobin levels, ASA score, and/or clinical symptoms consistent with anemia. Blood salvage was not used. Results. Blood transfusion and length of stay were lower in the study group. None of the patients who received epoetin-α underwent transfusion. Hemoglobin increased from 11.97 to 13.8, preoperatively. Hemoglobin at day of surgery and time of discharge were higher. Gender, BMI, ASA score, total and hidden blood losses, calculated blood loss, preop PLT, PT, PTT, and INR were similar between groups. One Epogen patient had an uncomplicated DVT (3.6%. Conclusions. Epoetin-α may have a role in the mildly anemic revision knee patient. It may also decrease patient length of stay allowing for earlier readiness to resume normal activities and/or meet short-term milestones. A randomized study to evaluate the direct and indirect costs of such a treatment methodology in the mildly anemic revision patient may be warranted.

  3. Cost effectiveness of epoetin-alpha to augment preoperative autologous blood donation in elective cardiac surgery.

    Science.gov (United States)

    Coyle, D; Lee, K M; Fergusson, D A; Laupacis, A

    2000-08-01

    The objective of this study was to assess the cost effectiveness of using epoetin-alpha (erythropoietin) to augment preoperative autologous donation (PAD) of blood prior to elective cardiac surgery. We designed a decision-analytic model incorporating the risk of receiving allogeneic blood, the costs of blood products, the likelihood of developing transfusion-related diseases, the costs of transfusion-related diseases and their impact on life expectancy, and the effect of epoetin-alpha on the probability of transfusion. The efficacy of epoetin-alpha was derived from data from a meta-analysis of published randomised trials comparing the use of epoetin-alpha to augment PAD with the use of PAD alone. Estimates for the other parameters were obtained by a systematic review of the literature. The use of epoetin-alpha reduced the proportion of patients receiving allogeneic transfusions by 60% (from 31.6 to 12.7%). However, this led to only a modest benefit of 0.000035 life years gained per patient and an incremental cost per life year gained of $Can44.6 million (1998 Canadian dollars). A detailed sensitivity analysis confirmed that the cost-effectiveness ratio was larger than that which is generally considered acceptable. Our study indicates that the use of epoetin-alpha to reduce perioperative allogeneic transfusions in cardiac surgery is not cost effective.

  4. Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

    Directory of Open Access Journals (Sweden)

    Davis-Ajami ML

    2014-04-01

    Full Text Available Mary Lynn Davis-Ajami,1 Jun Wu,2 Katherine Downton,3 Emilie Ludeman,3 Virginia Noxon4 1Organizational Systems and Adult Health, University of Maryland School of Nursing, Baltimore, MD, USA; 2South Carolina College of Pharmacy, University of South Carolina, Greenville, SC, USA; 3Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA; 4Department of Clinical Pharmacy and Outcomes Science, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA Abstract: Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L. This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility. Keywords: biosimilar, chronic kidney disease, epoetin alfa, erythropoiesis, renal anemia, Retacrit®

  5. Análise comparativa do controle interno no contas a receber e a pagar nas empresas Beta Ltda e Alfa Ltda = A comparative internal control analysis of receivable and payable accounts in Beta and Alfa Ltd Companies

    Directory of Open Access Journals (Sweden)

    Cleyton de Oliveira Ritta

    2010-07-01

    Full Text Available A necessidade constante de um excelente desempenho empresarial leva à busca da qualidade e confiabilidade da informação para o auxílio na tomada de decisão. Neste contexto, a auditoria contábil tem um papel importante na análise das práticas administrativas adotadas pelas entidades. Desse modo, o objetivo deste artigo é comparar a estruturação dos controles internos no contas a receber e a pagar nas empresas Beta Ltda, a qual não contrata serviços de auditoria externa, e Alfa Ltda, que os contrata. Este estudo caracteriza-se como de caso comparativo de caráter descritivo por meio de questionário e entrevista. Os resultados apontam que a empresa Alfa Ltda tem melhores níveis de controle interno e, consequentemente, está menos exposta a erros e fraudes. Desse modo, entende-se que os seviços de auditoria atuam como um instrumento de auxílio para minimização dos riscos operacionais e servem de alerta aos gestores quanto à eficiência das transações. Contudo, percebe-se que a qualidade dos controles internos nas organizações depende diretamente da utilização de procedimentos de monitoramento.The constant need for excellent business performance triggers the quest for information quality and reliability to help in decision making. Considering this context, accounting auditing plays an important role in the analysis of administrative practices adopted by entities. Thus, the objective of this article is to compare the structure of the internal controls for receivable and payable accounts in Beta Ltd companies, which do not contract external auditing services, and Alfa Ltd, which does. This study is a descriptive comparative case study, carried out through questionnaire and interview. The results have showed that Alfa Ltd has better internal control levels and consequently is less exposed to errors and fraud. This way, auditing services are seen as auxiliary instruments to minimize operational risks and serve to alert

  6. A cost-effectiveness evaluation comparing originator follitropin alfa to the biosimilar for the treatment of infertility

    Directory of Open Access Journals (Sweden)

    Gizzo S

    2016-12-01

    Full Text Available Salvatore Gizzo,1 Juan A Garcia-Velasco,2 Franca Heiman,3 Claudio Ripellino,3 Klaus Bühler4 1Department of Woman and Child Health, University of Padua, Padua, Italy; 2Department of Obstetrics and Gynecology, Rey Juan Carlos University Madrid, Madrid, Spain; 3IMS Health Information Solutions Italy Srl, Milan, Italy; 4Centre for Gynaecology, Endocrinology, and Reproductive Medicine, Ulm and Stuttgart, Germany Objectives: To perform a cost-effectiveness evaluation comparing the originator follitropin alfa (Gonal-f® to the biosimilar (Bemfola® in the Italian and Spanish contexts, with an assessment of the German and UK backgrounds. Methods: Starting from the study by Rettenbacher et al, a cost-effectiveness model was developed in the Italian and Spanish contexts. Clinical data on subjects, doses of gonadotropin, pregnancies, live-born children, and ovarian hyperstimulation syndrome were used to feed the model. Costs related to drugs, hospitalizations, specialist visits, and examinations were retrieved from Italian and Spanish tariffs. Gonadotropin acquisition costs for Germany and the UK were also taken into account to expand the economical assessment to the other countries. The evaluation was done based on the National Health Service perspective. Sensitivity analyses, both univariate and probabilistic, as long as scenario analyses, tested the robustness of the model. Results: Originator follicle-stimulating hormone (FSH costs were €3,663 and €6,387 in Italy and Spain, respectively, whereas biosimilar FSH costs were €3,483 and €6,342. The efficacy was found to be 0.52 for the originator and 0.47 for the biosimilar. The average cost per live birth was estimated to be €7,044 and €12,283 for the originator FSH and €7,411 and €13,494 for the biosimilar for Italy and Spain, respectively. Furthermore, the originator FSH generated an incremental cost-effectiveness ratio of €3,600 for Italy and €900 for Spain compared to the

  7. Comparing effects of Beractant and Poractant alfa in decreasing mortality rate due to respiratory distress syndrome in premature infants

    Directory of Open Access Journals (Sweden)

    Saeidi R

    2011-02-01

    Full Text Available "nBackground: Exogenous natural and synthetic surfactants is a rescue treatment for respiratory distress syndrome (RDS. The goals of the study were to compare the clinical response and side-effects of two frequently used surfactants, poractant alfa (Curosurf and beractant (Survanta, for the treatment of respiratory distress syndrome in preterm infants."n "nMethods: This clinical trial study was performed during a two-year period in the Neonatal Intensive Care Unit of Ghaem Hospital in Mashhad, Iran. Sample size calculated by a 95% confidence and power of 80, included 104 premature neonates, 74 in survanta and 30 in curosurf groups. The level of statistical significance was considered to be < 0.05."n "nResults: There were no statistically significant differences between the infants treated by survanta or cursurf groups regarding their mean gestational age (30.58 Vs. 29.00 weeks and birth weight (1388 Vs. 1330 g, (p=0.3 There were also no significant differences between the two groups regarding incidences of broncho- pulmonary dysplasia (BPD (40.5% Vs. 40%, intraventricular hemorrhage (IVH grades III/IV (13.5% Vs. 13.3%, pneumothorax (both 20%, patent ductus arteriosus (PDA (28/3% Vs. 20% or death (28% Vs. 26.6% on the 28th day postpartum."n "nConclusion: This study showed that survanta and curosurf had similar therapeutic effects in the treatment of neonatal respiratory distress syndrome.

  8. Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

    Directory of Open Access Journals (Sweden)

    Paulo D. Picon

    2014-08-01

    Full Text Available OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation. METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36 or the biosimilar epoetin formulation (n = 38 in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89 in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA. The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy and safety.

  9. Secondary analysis of the CHOIR trial epoetin-α dose and achieved hemoglobin outcomes

    OpenAIRE

    Szczech, Lynda A.; Barnhart, Huiman X; Inrig, Jula K.; Reddan, Donal N.; Sapp, Shelly; Califf, Robert M.; Patel, Uptal D.; Singh, Ajay K.

    2008-01-01

    Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets. We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials. In the 4 month analysis, significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm ...

  10. Drotrecogin alfa Eli Lilly

    NARCIS (Netherlands)

    de Jonge, E.

    2002-01-01

    Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant developed and launched by Eli Lilly & Co for the treatment of sepsis [333781], [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris for drotrecogin alfa in June 2001. This trade name had been

  11. Nadir Hemoglobin Levels after Discontinuation of Epoetin in Hemodialysis Patients

    OpenAIRE

    Calvo, Jose A.; Miskulin, Dana C.; Meyer, Klemens B.; Weiner, Daniel E.

    2010-01-01

    Background and objectives: In hemodialysis patients, both hemoglobin variability and targeting normalization of hemoglobin may have adverse consequences. There are few data on epoetin management in patients achieving high hemoglobin levels.

  12. ALFA Detector Control System

    CERN Document Server

    Oleiro Seabra, Luis Filipe; The ATLAS collaboration

    2015-01-01

    ALFA (Absolute Luminosity For ATLAS) is one of the sub-detectors of ATLAS/LHC. The ALFA system is composed by two stations installed in the LHC tunnel 240 m away from each side of the ATLAS interaction point. Each station has a vacuum and ventilation system, movement control and all the required electronic for signal processing. The Detector Control System (DCS) provides control and monitoring of several components and ensures the safe operation of the detector contributing to good Data Quality. This paper describes the ALFA DCS system including a detector overview, operation aspects and hardware control through a SCADA system, WinCC OA.

  13. ALFA Detector Control System

    CERN Document Server

    Oleiro Seabra, Luis Filipe; The ATLAS collaboration

    2015-01-01

    ALFA (Absolute Luminosity For ATLAS) is one of the sub-detectors of ATLAS (A Toroidal LHC Apparatus). The ALFA system is composed by four stations installed in the LHC tunnel 240 m away from the ATLAS interaction point. Each station has a vacuum and ventilation system, movement control and all the required electronics for signal processing. The Detector Control System (DCS) provides control and monitoring of several components and ensures the safe operation of the detector contributing to good Data Quality. This paper describes the ALFA DCS system including a detector overview, operation aspects and hardware control through a SCADA system, WinCC OA.

  14. Dgroup: DG00177 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG00177 Chemical ... DGroup Erythropoietin ... D03231 ... Epoetin alfa (USAN/INN); Epoetin alfa (genetica...l recombination) (JP17) ... D03232 ... Epoetin beta (USAN/INN); Epoetin beta (genetical recombina...tion) (JP17) ... D04032 ... Epoetin delta (USAN) D09737 ... Epoetin kappa (INN); Epoetin kappa (genetical recombina...tion) (Epoetin alfa biosimilar 1) (JAN) ... D09998 ... Epoetin beta pegol (genetical ...recombination) (JAN) ... D10000 ... Epoetin epsilon (INN); Epoetin epsilon (genetical recombination) (JAN) D1084

  15. Interferon Alfa-2b Injection

    Science.gov (United States)

    Interferon alfa-2b injection is used to treat a number of conditions.Interferon alfa-2b injection is used alone or in combination ... Hodgkin's lymphoma (NHL; a slow-growing blood cancer). Interferon alfa-2b is in a class of medications called ...

  16. Comparison of peginterferon alfa-2a and alfa-2b for treatment of patients with chronic hepatitis C: a retrospective study using the Japanese Interferon Database.

    Science.gov (United States)

    Sato, Izumi; Shimbo, Takuro; Kawasaki, Yohei; Masaki, Naohiko

    2015-01-01

    We aimed to compare the rates of sustained virologic response (SVR) achieved with peginterferon (PEG-IFN) alfa-2a and alfa-2b in combination with ribavinin (RBV) for chronic hepatitis C, using a large database of hepatitis cases to improve the generalizability of these results. We identified patients with chronic hepatitis C who were treated with PEG-IFN alfa-2a or alfa-2b and RBV, from the Japanese Interferon Database, between December 2009 and April 2013. This database contains the medical records of IFN treatment collected from 36 prefectures in Japan. Multivariable logistic regression analysis was used to compare SVR rates obtained with PEG-IFN alfa-2a and alfa-2b, in combination with RBV. A total of 16,349 patients were recorded in the Japanese Interferon Database. After application of the exclusion criteria, 12,706 patients (3,578 [1,710 males, 1,868 females] on PEG-IFN alfa-2a; and 9,128 [4,652 males, 4,476 females] on PEG-IFN alfa-2b) were included in this analysis. The SVR rate in the PEG-IFN alfa-2b group was 62.0%, as compared with a rate of 55.1% in the PEG-IFN alfa-2a group (crude odds ratio =1.31; 95% confidence interval [CI]: 1.23 to 1.44). There was no significant difference in the adjusted SVR rates between the two groups (adjusted odds ratio =0.96; 95% CI: 0.88 to 1.05). Similar proportions of adverse events were observed in the two groups, with the exception of thrombocytopenia, retinopathy, and anemia. There was no significant difference in the SVR rates and safety profile between chronic hepatitis C patients treated with the PEG-IFN alfa-2a and alfa-2b.

  17. Elosulfase alfa: first global approval.

    Science.gov (United States)

    Sanford, Mark; Lo, Jin Han

    2014-04-01

    Elosulfase alfa (Vimizim™) is a recombinant form of N-acetylgalactosamine-6-sulfatase (GALNS) that was developed by BioMarin Pharmaceutical Inc. as an enzyme replacement therapy for patients with mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome. Patients with MPS IVA have a GALNS deficiency, which results in serious musculoskeletal, cardiorespiratory and other system disturbances. Elosulfase alfa was approved by the US FDA on 14 February 2014 for the treatment of MPS IVA. The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has recently recommended that elosulfase alfa be approved for use in the EU in the same indication. Within the last year, the manufacturer has also filed applications for approval for the use of elosulfase alfa in MPS IVA in Brazil, Australia, Canada and Mexico. This article summarizes the milestones in the development of elosulfase alfa leading to its first global approval in MPS IVA.

  18. Methods in ALFA Alignment

    CERN Document Server

    Melendez, Jordan

    2014-01-01

    This note presents two model-independent methods for use in the alignment of the ALFA forward detectors. Using a Monte Carlo simulated LHC run at \\beta = 90m and \\sqrt{s} = 7 TeV, the Kinematic Peak alignment method is utilized to reconstruct the Mandelstam momentum transfer variable t for single-diractive protons. The Hot Spot method uses fluctuations in the hitmap density to pinpoint particular regions in the detector that could signal a misalignment. Another method uses an error function fit to find the detector edge. With this information, the vertical alignment can be determined.

  19. The use of growth factors to manage the hematologic side effects of PEG-interferon alfa and ribavirin.

    Science.gov (United States)

    Collantes, Rochelle S; Younossi, Zobair M

    2005-01-01

    Hematologic side effects (anemia, neutropenia, and thrombocytopenia) of combination therapy with pegylated (PEG)-interferon alfa and ribavirin are commonly encountered during antiviral therapy for chronic hepatitis C (HCV). An important consequence of these side effects is dose modification of PEG-interferon alfa, ribavirin, or both. Dose modification (including discontinuation) diminishes the efficacy of optimal treatment regimen for HCV and may have a negative impact on sustained virologic response. Additionally, fatigue associated with anemia may impair patients' quality of life. The clinical implications of neutropenia or thrombocytopenia are less clear than for anemia; nevertheless, severe infection and bleeding are uncommon. Dose adjustments effectively treat these hematologic side effects, but the resulting suboptimal dosing and potential impact on virologic response are major concerns. Recent attempts to maximize adherence to the optimal treatment regimen have used hematopoietic growth factors rather than dose adjustment to treat side effects. Research on growth factor support has focused on anemia and neutropenia. Epoetin alfa and darbepoetin alfa are erythropoietic growth factors that effectively increase hemoglobin while maintaining the optimal ribavirin dose and improving patients' quality of life. Preliminary work suggests that filgrastim, granulocyte colony stimulating factors, may be an effective treatment of interferon-induced neutropenia. Although this early work shows tremendous promise for managing hematologic side effects of combination therapy for HCV, and potentially enhancing adherence, further research is needed to clarify the efficacy, safety, and cost-effectiveness of growth factors in the management of patients with chronic HCV.

  20. Cost-effectiveness and cost-utility of the treatment of chronic hepatitis B with peginterferon alfa-2a, interferon alfa, and lamivudine in Lithuania.

    Science.gov (United States)

    Vanagas, Giedrius; Padaiga, Zilvinas; Mickevičienė, Aušra

    2010-01-01

    Chronic hepatitis B infection is an important health care problem worldwide. According to the World Health Organization, 10% to 15% of population is infected with hepatitis B virus. Nearly 100 new cases of acute hepatitis B are annually registered in Lithuania, but official statistics covers only 8-25% of all disease incidence. The aim of this study was to evaluate the cost-effectiveness of the treatment of chronic hepatitis B with peginterferon alfa-2a and compare it to treatment with interferon alfa and lamivudine in Lithuania. A Markov model was used to evaluate long-term cost-effectiveness of the treatment with peginterferon alfa-2a and to compare it with treatment with interferon alfa and lamivudine. Peginterferon alfa-2a was administered by subcutaneous injections at a dosage of 180 μg every week for 48 weeks; interferon alfa, 6 million IU three times a week for 24 weeks; and lamivudine, 100 mg per day from 48 weeks to 5 years for HBeAg-positive chronic hepatitis B and 100 mg per day up to 5 years in HBeAg-negative chronic hepatitis B. Treatment with peginterferon alfa-2a gained 1.179 life years as compared to 0.658 life years gained with treatment with interferon alfa; incremental costs per incremental life-year gained (LYG) were 51,256.92 Lt (14,845.03 €). Treatment with peginterferon alfa-2a gained 0.545 quality-adjusted life-years (QALYs) with incremental costs per incremental QALY of 48,980.08 Lt (14,185.61 €). Treatment with peginterferon alfa-2a had twice higher cost-effectiveness than treatment with interferon alfa: 50,4167.00 Lt (146,016.85 €) vs. 954,020.08 Lt (276,303.31 €), respectively. Costs for a complete response were also twice lower. Treatment with peginterferon alfa-2a gained 0.757 incremental LYG more compared to lamivudine (48-week course). Comparing incremental cost-effectiveness using peginterferon alfa-2a for treatment, incremental costs per incremental LYG were 41,993.67 Lt (12,162.21 €); additionally there was a gain of 0

  1. Cost-utility analysis of Ruconest® (conestat alfa) compared to Berinert® P (human C1 esterase inhibitor) in the treatment of acute, life-threatening angioedema attacks in patients with hereditary angioedema

    Science.gov (United States)

    Holko, Przemysław; Paszulewicz, Anna

    2013-01-01

    Introduction Administration of human C1 esterase inhibitor (Berinert® P) from target import is the most widespread treatment strategy for patients with hereditary angioedema (HAE). However, a therapeutic health program including Ruconest® (conestat alfa) could shorten a patient's expectancy for a life-saving treatment. Aim To evaluate the cost-utility of Ruconest® (conestat alfa) financed from public funds within the newly introduced therapeutic health program compared with Berinert® P (human C1 esterase inhibitor) in the treatment of acute angioedema attacks in adults with HAE. Material and methods The cost-utility analysis from the Polish healthcare payer's perspective was performed for 1 year (2012). The costs and health outcomes were simulated for three pairs of eligible HAE patient groups (active treatment and corresponding placebo). The incremental costs of each intervention compared with placebo were listed together (direct or indirect comparisons between options were impossible due to limited clinical data available). Results The incremental cost-utility ratios (ICURs) for the evaluated interventions compared with placebo were as follows: EUR 15,226 per QALY (Ruconest®) and EUR 27,786 per QALY (Berinert® P). The probability of cost-utility (ICUR < EUR 24,279 per QALY) assessed for Ruconest® administered in the case of acute angioedema attack was 61% and 41% for Berinert® P. Conclusions The administration of Ruconest® in acute life-threatening angioedema attacks is economically justified from the Polish healthcare payer's perspective, results in lower costs and is characterized by higher cost-utility probability compared with Berinert® P. PMID:24278067

  2. ALFA beam halo

    CERN Document Server

    Komarek, Tomas

    2014-01-01

    This note serves as a final report about CERN Summer Student Programme 2014 project. The beam halo is an undesired phenomenon for physics analyses on particle accelerators. It surrounds the beam core and constitutes an important part of background for signal measurements on some detectors, eg. in the forward region. In this study, the data from the ALFA detector were used, specifically from the run 191373 ($\\beta^*=90\\unit{m}$) and the run 213268 ($\\beta^*=1\\unit{km}$). Using the ROOT framework, a software for beam halo events selection was created and beam halo properties were examined. In the run 213268, excessive beam halo is suspected to be the reason for multiple beam scrapings that occurred. A kinematic reconstruction of beam halo particles is attempted in order to understand beam halo properties in the interaction point. Some further simulations are employed to find constraints for beam halo particles in order to survive in the accelerator for a longer time/many revolutions. This work represents a st...

  3. Estado vegetativo-alfa persistente

    Directory of Open Access Journals (Sweden)

    R. Oliveira-Souza

    1989-06-01

    Full Text Available Após revisão sumária dos conceitos de «coma» e «coma-alfa», relatamos o caso de uma paciente com doença de Pick provável que, nos estágios terminais da doença, permaneceu várias semanas em estado vegetativo com EEG de vigília normal e reativo à fotoestimulação. Enfatizamos (a algumas das implicações do aspecto dos olhos nesses pacintes, (b a importância de distinguir a atividade alfa do ritmo alfa verdadeiro e (c sugerimos que a categoria «coma-alfa» inclua apenas aqueles com afecções do tegmento da junção pontomesencefálica, de qualquer natureza, reservando a designação «estado vegetativo-alfa» persistente para os que se encontrem em estado vegetativo e exibam EEG em virgília idêntico ao normal.

  4. A randomized phase II trial of azacitidine +/− epoetin-β in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents

    Science.gov (United States)

    Thépot, Sylvain; Ben Abdelali, Raouf; Chevret, Sylvie; Renneville, Aline; Beyne-Rauzy, Odile; Prébet, Thomas; Park, Sophie; Stamatoullas, Aspasia; Guerci-Bresler, Agnes; Cheze, Stéphane; Tertian, Gérard; Choufi, Bachra; Legros, Laurence; Bastié, Jean Noel; Delaunay, Jacques; Chaury, Marie Pierre; Sanhes, Laurence; Wattel, Eric; Dreyfus, Francois; Vey, Norbert; Chermat, Fatiha; Preudhomme, Claude; Fenaux, Pierre; Gardin, Claude

    2016-01-01

    The efficacy of azacitidine in patients with anemia and with lower-risk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-β. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one “epigenetic mutation” and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352). PMID:27229713

  5. Comparison of peginterferon alfa-2a and alfa-2b for treatment of patients with chronic hepatitis C:a retrospective study using the Japanese Interferon Database

    Directory of Open Access Journals (Sweden)

    Sato I

    2014-12-01

    Full Text Available Izumi Sato,1 Takuro Shimbo,2 Yohei Kawasaki,3 Naohiko Masaki41Department of Clinical Study and Informatics, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan; 2Ohta Nishinouchi Hospital, Fukushima, Japan; 3Department of Mathematics, Tokyo University of Science, Tokyo, Japan; 4The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, JapanPurpose: We aimed to compare the rates of sustained virologic response (SVR achieved with peginterferon (PEG-IFN alfa-2a and alfa-2b in combination with ribavinin (RBV for chronic hepatitis C, using a large database of hepatitis cases to improve the generalizability of these results.Methods: We identified patients with chronic hepatitis C who were treated with PEG-IFN alfa-2a or alfa-2b and RBV, from the Japanese Interferon Database, between December 2009 and April 2013. This database contains the medical records of IFN treatment collected from 36 prefectures in Japan. Multivariable logistic regression analysis was used to compare SVR rates obtained with PEG-IFN alfa-2a and alfa-2b, in combination with RBV. Results: A total of 16,349 patients were recorded in the Japanese Interferon Database. After application of the exclusion criteria, 12,706 patients (3,578 [1,710 males, 1,868 females] on PEG-IFN alfa-2a; and 9,128 [4,652 males, 4,476 females] on PEG-IFN alfa-2b were included in this analysis. The SVR rate in the PEG-IFN alfa-2b group was 62.0%, as compared with a rate of 55.1% in the PEG-IFN alfa-2a group (crude odds ratio =1.31; 95% confidence interval [CI]: 1.23 to 1.44. There was no significant difference in the adjusted SVR rates between the two groups (adjusted odds ratio =0.96; 95% CI: 0.88 to 1.05. Similar proportions of adverse events were observed in the two groups, with the exception of thrombocytopenia, retinopathy, and anemia.Conclusion: There was no significant difference in the SVR rates and safety profile

  6. Insect Pheromone-Alfa Chemistry.pptx

    OpenAIRE

    Keller, Tylor

    2017-01-01

    Pheromones are substances produced as messengers that affect the behavior of other insects, animals and members of the same species. Alfa Chemistry offers a wide range of different insect pheromones that respond to control pests effectively and respectfully with the environment. Visit http://www.alfa-chemistry.com/products/insect-pheromone-5.htm for more.

  7. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    Science.gov (United States)

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  8. Drug: D03231 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03231 Drug Epoetin alfa (genetical recombination) (JP16); Epoetin alfa (USAN/INN);...gents affecting metabolism 39 Other agents affecting metabolism 399 Miscellaneous 3999 Others D03231 Epoetin alfa (genetica...S B03X OTHER ANTIANEMIC PREPARATIONS B03XA Other antianemic preparations B03XA01 Erythropoietin D03231 Epoetin alfa (genetica...Products/Modifiers/Volume Expanders Blood Formation Modifiers Epoetin alfa D03231 Epoetin alfa (genetical re...eceptor [HSA:2057] [KO:K05079] Erythropoietin [ATC:B03XA01] D03231 Epoetin alfa (genetical recombination) (J

  9. Turoctocog alfa: an evidence-based review of its potential in the treatment of hemophilia A

    Directory of Open Access Journals (Sweden)

    Takedani H

    2015-03-01

    Full Text Available Hideyuki Takedani, Jun Hirose Department of Joint Surgery, Research Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, Japan Abstract: Turoctocog alfa is the first B-domain-truncated third generation recombinant coagulation factor VIII (FVIII product. Nonclinical in vitro and animal model studies have demonstrated that turoctocog alfa has similar functional potency and hemostatic efficacy as comparator FVIII products. With respect to discrepancies in the level of FVIII concentrate in plasma of current FVIII products on comparing measurement results between one-stage clot and chromogenic assays, there was no difference in the in vitro turoctocog alfa study; however, measured FVIII concentrate in field study was higher with the chromogenic assay (1.08 IU/mL than with one-stage assay (0.83 IU/mL. Two published clinical studies on previously treated patients (PTPs and clinical pharmacokinetics have described that the pharmacokinetic parameters are similar, and the safety and efficacy for prevention and treatment for bleeding are also similar to those of standard half-life FVIII products. Three clinical trials are ongoing to assess the long-term safety and efficacy of turoctocog alfa for PTPs and previously untreated patients. Those data will be published in the near future, and it will be possible to use turoctocog alfa for all hemophilia patients. However, studies will be needed to confirm the turoctocog alfa profile, such as the stability of dissolved turoctocog alfa over 24 hours at room temperature and post-marketing clinical research aimed at meeting Europe Medicines Agency post-marketing safety and efficacy requirements in PTPs. It is recommended to wait before using turoctocog alfa for previously untreated patients and major surgery until further data have been collected and published. Keywords: hemophilia A, B-domain-truncated, third generation factor VIII product, previous untreated patients, chromogenic assay

  10. Drug: D09737 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09737 Drug Epoetin kappa (genetical recombination) (Epoetin alfa biosimilar 1) (JA...ts affecting metabolism 39 Other agents affecting metabolism 399 Miscellaneous 3999 Others D09737 Epoetin kappa (genetical...opoietin D09737 Epoetin kappa (genetical recombination) (Epoetin alfa biosimilar 1) (JAN); Epoetin kappa (IN...etin [ATC:B03XA01] D09737 Epoetin kappa (genetical recombination) (Epoetin alfa biosimilar 1) (JAN); Epoetin...tors Erythropoietin [ATC:B03XA01] D09737 Epoetin kappa (genetical recombination)

  11. CMV seropositivity determines epoetin dose and hemoglobin levels in patients with CKD

    NARCIS (Netherlands)

    M.G.H. Betjes (Michiel); W. Weimar (Willem); N.H.R. Litjens (Nicolle)

    2009-01-01

    textabstractCytomegalovirus (CMV)-seropositive patients with ESRD may have more CD4+T cells lacking the co-stimulatory molecule CD28 (CD4+CD28null) than CMV-seronegative patients. Increased numbers of CD28null T cells associates with epoetin nonresponsiveness in patients with ESRD, but whether

  12. Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.

    Science.gov (United States)

    Capuron, Lucile; Pagnoni, Giuseppe; Drake, Daniel F; Woolwine, Bobbi J; Spivey, James R; Crowe, Ronald J; Votaw, John R; Goodman, Mark M; Miller, Andrew H

    2012-10-01

    Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function. To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior. Cross-sectional and longitudinal studies. Outpatient research unit and neuroimaging facilities at Emory University, Atlanta, Georgia. Medically stable adults with chronic hepatitis C virus (HCV) infection eligible for interferon alfa treatment. Neural activity in the ventral striatum during a hedonic reward task as measured by functional magnetic resonance imaging, uptake and turnover of radiolabeled fluorodopa F 18 (18F-dopa) in caudate and putamen using positron emission tomography, and interferon alfa-induced depression, anhedonia, fatigue, and neurotoxicity. Patients with HCV receiving interferon alfa for 4 to 6 weeks (n = 14) exhibited significantly reduced bilateral activation of the ventral striatum in the win vs lose condition of a gambling task compared with patients with HCV awaiting interferon alfa treatment (n = 14). Reduced activation of the ventral striatum was, in turn, significantly correlated with anhedonia, depression, and fatigue. In a separate longitudinal study, patients with HCV treated with interferon alfa for 4 to 6 weeks (n = 12) exhibited significantly increased 18F-dopa uptake and decreased 18F-dopa turnover in caudate and putamen and in the same ventral striatal regions identified in the functional magnetic resonance imaging study. Baseline and percentage change in 18F-dopa uptake and turnover were correlated with behavioral alterations, including depression, fatigue, and neurotoxicity, during interferon alfa administration. These data replicate and extend findings that inflammatory stimuli

  13. 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 interferon alfa and our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.

  14. ALFA detector before LHC Run 2

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00188264; The ATLAS collaboration

    2016-01-01

    The operation experience with ATLAS ALFA detectors in the LHC environment during the Run1 period has shown significant beam-induced heating. Subsequent comprehensive studies revealed that heating effects could be disastrous in the case of the larger beam intensities foreseen for higher luminosities in the LHC Run2. During the first LHC long shutdown (LS1) all ALFA detectors have been removed from the LHC tunnel and their covers - Roman Pots - underwent a geometry upgrade to minimize the impedance losses. It will be shown that this modification together with a system improving the internal heat transfer and an air cooling system, significantly shifted the temperatures of ALFA detectors away from the critical limits throughout the LHC Run2. Also ALFA trigger system was considerably upgraded to keep measured data safely inside the Run2 ATLAS latency budget and to minimize dead time. The needed hardware changes of the trigger system are also described

  15. ALFA detector upgrade before LHC Run 2

    CERN Document Server

    Vorobel, Vit; The ATLAS collaboration

    2016-01-01

    The operation experience with ATLAS ALFA detectors in the LHC environment during the Run1 period has shown significant beam-induced heating. Subsequent comprehensive studies revealed that heating effects could be disastrous in the case of the larger beam intensities foreseen for higher luminosities in the LHC Run2. During the first LHC long shutdown (LS1) all ALFA detectors have been removed from the LHC tunnel and their covers - Roman Pots - underwent a geometry upgrade to minimize the impedance losses. It will be shown that this modification together with a system improving the internal heat transfer and an air cooling system, significantly shifted the temperatures of ALFA detectors away from the critical limits throughout the LHC Run2. Also ALFA trigger system was considerably upgraded to keep measured data safely inside the Run2 ATLAS latency budget and to minimize dead time. The needed hardware changes of the trigger system will be presented in the second part of the talk.

  16. "Alfa" i "Võmpel" bez maski / Andrei Sharov

    Index Scriptorium Estoniae

    Sharov, Andrei

    2004-01-01

    Venemaa FSB keskuse, mille koosseisu kuuluvad ka eriüksused Alfa ja Võmpel, töötajad osalevad terroristide neutraliseerimise ja pantvangide vabastamise erioperatsioonides. Intervjuu keskuse staabi uue juhiga

  17. Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment

    Directory of Open Access Journals (Sweden)

    Agostinetto Rita

    2009-05-01

    Full Text Available Abstract Background Gonadotrophins are routinely administered in assisted reproductive technology (ART treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa and recombinant human luteinizing hormone (r-hLH; lutropin alfa can be administered individually or in a fixed combination. The ability to vary the FSH to LH dose ratio in a single injection without compromising the bioactivity of either gonadotrophin or generating losses of active principle is important for physicians and patients alike. Methods This study investigated whether follitropin alfa (GONAL-f (R, as lyophilized powder for reconstitution or solution from the GONAL-f (R (filled-by-mass [FbM] Prefilled Pen, could be used to reconstitute Pergoveris TM (follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder. In Ratio Groups 1 and 2, the r-hFSH:r-hLH ratio was 3:1; in Ratio Groups 3 and 4, the ratios of r-hFSH:r-hLH were 5:1 and 8:1, respectively. The protein content and bioactivity of each mixed solution were evaluated. The r-hFSH and r-hLH content was determined using reverse-phase high performance liquid chromatography. The biological activity of r-hFSH and r-hLH was assessed using the Steelman-Pohley and Van Hell in vivo bioassays in rats, respectively. Results Follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder could be successfully mixed with follitropin alfa 75 IU FbM solution that was either reconstituted from lyophilized powder or injected directly from the prefilled pen to create solutions with ratios of r-hFSH and r-hLH from 3:1 to 8:1. The measured content of r-hFSH and r-hLH corresponded favourably with the target protein content in Ratio Groups 1–4. The in vivo target and measured bioactivity of r-hFSH and r-hLH were also closely matched in all Ratio Groups. Conclusion Follitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder to

  18. 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....

  19. Interferon-alfa treatment of facial infantile haemangiomas

    DEFF Research Database (Denmark)

    Fledelius, Hans C.; Illum, N.; Jensen, H.

    2001-01-01

    ophthalmology, haemangiomas of the face, infancy, Interferon alfa, eye at risk, amblyopia, induced refractive change, ultrasound imaging......ophthalmology, haemangiomas of the face, infancy, Interferon alfa, eye at risk, amblyopia, induced refractive change, ultrasound imaging...

  20. Implementation of Trigger Tiles for ALFA Simulation

    CERN Document Server

    Rehaag, Thomas Joseph

    2017-01-01

    The Absolute Luminosity For ATLAS (ALFA) experiment was designed to accurately measure the luminosity of the intersecting proton beams at the ATLAS interaction point [1]. However, the ALFA experiment has shifted its primary purpose from luminosity measurement to elastic and inelastic proton collisions. This change was the result of difficulty in fitting parameters in the region governed by Coulomb scattering. The operational principle for luminosity measurement with ALFA relied on detecting elastic proton collisions, so the detector is suited to its role in proton collision measurements. The ALFA detector consists of several sensitive components, including the main detector (MD), overlap detectors (ODs) and trigger tiles. A diagram of the ALFA detector is shown in Figure 1. The main detector is composed of layers of 0.5 × 0.5 mm2 cross section scintillating fibres with an active area of 0.48 × 0.48 mm2, which are directed diagonally across the detector with 64 fibres in each layer. The 20 total layers ar...

  1. A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment.

    Science.gov (United States)

    Wilson, J; Yao, G L; Raftery, J; Bohlius, J; Brunskill, S; Sandercock, J; Bayliss, S; Moss, P; Stanworth, S; Hyde, C

    2007-04-01

    To assess the effectiveness and cost-effectiveness of epoetin alpha, epoetin beta and darbepoetin alpha (referred to collectively in this report as epo) in anaemia associated with cancer, especially that attributable to cancer treatment. Electronic databases were searched from 2000 (1996 in the case of darbepoetin alpha) to September 2004. Using a recently published Cochrane review as the starting point, a systematic review of recent randomised controlled trials (RCTs) comparing epo with best standard was conducted. Inclusion, quality assessment and data abstraction were undertaken in duplicate. Where possible, meta-analysis was employed. The economic assessment consisted of a systematic review of past economic evaluations, an assessment of economic models submitted by the manufacturers of the three epo agents and development of a new individual sampling model (the Birmingham epo model). In total 46 RCTs were included within this systematic review, 27 of which had been included in the Cochrane systematic review. All 46 trials compared epo plus supportive care for anaemia (including transfusions), with supportive care for anaemia (including transfusions), alone. Haematological response (defined as an improvement by 2 g/dl(-1)) had a relative risk of 3.4 [95% confidence interval (CI) 3.0 to 3.8, 22 RCTs] with a response rate for epo of 53%. The trial duration was most commonly 16-20 weeks. There was little statistical heterogeneity in the estimate of haematological response, and there were no important differences between the subgroups examined. Haemoglobin (Hb) change showed a weighted mean difference of 1.63 g/dl(-1) (95% CI 1.46 to 1.80) in favour of epo. Treatment with erythropoietin in patients with cancer-induced anaemia reduces the number of patients who receive a red blood cell transfusion (RBCT) by an estimated 18%. Health-related quality of life (HRQoL) data were analysed using vote counting and qualitative assessment and a positive effect was observed in

  2. OPPORTUNITIES OF DORNASE ALFA IN PEDIATRICS

    Directory of Open Access Journals (Sweden)

    O.I. Simonova

    2011-01-01

    Full Text Available Early treatment with Pulmozyme (dornase alfa and its prolonged use in combination with basis therapy results in decrease of exacerbation rate, prolongation of remission of bronchopulmonary process with normal ventilation functions of lungs and gives patients with cystic fibrosis an opportunity to live an active life. The drug is effective as a conservative treatment of chronic sinusitis polyposis; it’s frequent complication of cystic fibrosis. Dornase alfa has 3 clinical effects: strong mucolytic, anti-inflammatory and antibacterial effect. That is the reason for the treatment of other chronic bronchopulmonary diseases with this drug. Efficacy of dornase alpha depends on rough maintenance of the terms of drug use.Key words: children, dornase alfa, cystic fibrosis, chronic bronchopulmonary diseases, chronic rhinosinusitis, nasal polyposis, nebulizer therapy.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (4: 145–152

  3. Epoetin beta for the treatment of chemotherapy-induced anemia: an update

    Directory of Open Access Journals (Sweden)

    Galli L

    2015-03-01

    Full Text Available Luca Galli,1 Clara Ricci,2 Colin Gerard Egan2 1Oncology Unit 2, University Hospital of Pisa, Pisa, Italy; 2Primula Multimedia SRL, Pisa, Italy Abstract: Epoetin beta belongs to the class of erythropoiesis-stimulating agents (ESAs that are currently available to treat anemic patients receiving chemotherapy. Chemotherapy-induced anemia affects a high percentage of cancer patients and, due to its negative effects on disease outcome and the patient’s quality of life, should be treated when first diagnosed. Initial trials with ESAs have shown efficacy in improving quality of life and reducing the need for blood transfusions in patients with chemotherapy-induced anemia. However, recent meta-analyses have provided conflicting data on the impact of ESAs on survival and tumor progression. Here we provide an overview of these recent data and review the role of epoetin beta in the treatment of chemotherapy-induced anemia over the past 20 years. Keywords: epoetin beta, erythropoietin, chemotherapy, cancer, anemia, treatment

  4. Effects of MAPP Compatibilization and Acetylation Treatment Followed by Hydrothermal Aging on Polypropylene Alfa Fiber Composites

    Directory of Open Access Journals (Sweden)

    Noura Hamour

    2015-01-01

    Full Text Available This work investigates the effect of hydrothermal aging on the properties of polypropylene/alfa fiber composites. Hydrothermal aging was induced in an environmental testing chamber at 65°C and 75% relative humidity (RH over a 1000 h period. At the beginning (t=0 h, the results showed that Young’s moduli of the untreated alfa fibers and the acetylation-treated fibers increased by 21% and 36%, respectively, compared with the virgin polypropylene (PP. Additionally, Young’s moduli decreased by 7% for the compatibilized composites composed of maleic anhydride grafted polypropylene (MAPP. After 1000 h of aging, Young’s moduli decreased by 36% for untreated alfa fibers and 29% for the acetylation-treated alfa fibers and the compatibilized composites. Significant degradation was observed in the untreated alfa fiber samples. The Fourier transformed infrared (FTIR allows us to distinguish the characteristic absorption bands of the main chemical functions present in the composite material before and after aging. The thermal properties showed that the thermal stability and the degree of crystallinity of the composites decreased after hydrothermal aging; this result was corroborated by the dynamical mechanical analysis (DMA results.

  5. Nebulised dornase alfa versus placebo or hypertonic saline in adult critically ill patients

    DEFF Research Database (Denmark)

    Claudius, Casper; Perner, Anders; Møller, Morten Hylander

    2015-01-01

    BACKGROUND: Nebulised dornase alfa is used off-label in critically ill patients. We aimed to assess the benefits and harms of nebulised dornase alfa versus placebo, no prophylaxis, or hypertonic saline on patient-important outcome measures in adult critically ill patients. METHODS: We performed...... a systematic review with meta-analysis and trial sequential analysis (TSA) using the Cochrane Collaboration methodology. Eligible trials were randomised clinical trials comparing nebulised dornase alfa with placebo, no prophylaxis, or hypertonic saline. The predefined outcome measures were all-cause mortality...... of the primary estimate was assessed by TSA. RESULTS: Two trials (n = 63) were included; both were judged to have high risk of bias. There was no statistically significant difference in mortality (random effects model RR (95 % CI) 0.73 (0.09-5.77); P = 0.24; I (2) = 30 %). TSA could not be conducted because less...

  6. Velaglucerase alfa for the management of type 1 Gaucher disease.

    Science.gov (United States)

    Morris, Jennifer L

    2012-02-01

    with complete clinical datasets at 57 months identified achievement and maintenance of therapeutic goals set by the International Collaborative Gaucher Group for anemia, platelet counts, hepatosplenomegaly, and bone mineral density. Thirty-eight patients enrolled in an open-label, therapy-switch trial who received velaglucerase alfa at doses consistent with current doses of imiglucerase maintained hemoglobin (-0.101 g/dL [95% CI, -0.272 to 0.07]) and platelet counts (7.04% [95% CI, 0.54% to 13.53%]) at 53 weeks after therapy change. Phase III data evaluating 2 dosing regimens of velaglucerase alfa 60 and 45 U/kg intravenously every other week reported significant improvements in most measured clinical parameters at 12 months: hemoglobin concentrations (60 U/kg, 2.429 [0.324] g/dL [P Safety was reported in 3 identified studies and in data reported from the early access program: 3 peer-reviewed publications, 3 studies reported in clinical trial registries, and 1 abstract publication. Patients experienced a minimal number of adverse effects, and most reactions were mild to moderate in severity; 1 patient developed an anaphylactoid reaction and was discontinued from the trial. Antibody formation has been described with velaglucerase alfa but when compared with that of imiglucerase, seroconversion is less frequent (1% and 23%, respectively). Dosing regimens, from 30 to 60 U/kg intravenously every other week, have been assessed. Currently, the manufacturer recommends 60 U/kg intravenously every other week; however, further studies and evaluation of current study dosing regimens are needed to determine if there is a lower effective dose. Although a minimal amount of data are available for this relatively new biological agent, velaglucerase alfa reportedly is effective in the achievement and maintenance of therapeutic goals in type 1 GD in both treatment-naive and patients previously treated with imiglucerase. This agent has been reasonably well tolerated in clinical trials

  7. A risk model for severe anemia to select cancer patients for primary prophylaxis with epoetin alpha: a prospective randomized controlled trial of the ELYPSE study group.

    Science.gov (United States)

    Ray-Coquard, I; Dussart, S; Goillot, C; Mayeur, D; Debourdeau, P; Ghesquieres, H; Bachelot, T; Le Cesne, A; Anglaret, B; Agostini, C; Guastalla, J-P; Lancry, L; Biron, P; Desseigne, F; Blay, J-Y

    2009-06-01

    Epoetin (EPO) administration reduces the need for transfusion. Identifying patients at high risk of anemia requiring red blood cell (RBC) transfusion is needed. This multicentric phase III trial tested epoetin alpha (EPOalpha) administration according to our risk model on the basis of three clinical parameters: hemoglobin (Hb) 1. Patients >or=18 years with chemotherapy-treated solid or hematologic tumors were randomized to 150 UI/kg/TIW s.c. EPOalpha (arm 1) or no EPOalpha (arm 2) and stratified on Hb level at day 0, lymphocyte count, and PS. The primary end point was transfusion rate; secondary end points included overall survival (OS), safety, and quality of life. From September 2000 to January 2005, 218 patients (median age 64 years, 42.7% males) with principally breast cancer, sarcoma, or lung carcinoma were included. In total, 93% patients had PS >1 and 35% had compared with two factors (8.3 months) (P < 0.001). No difference in toxicity (47% versus 41%) or thrombovascular events (4.5% versus 3.7%) was observed. Patients at high risk for RBC transfusion according to the ELYPSE model could be given prophylactic EPO with significantly reduced RBC transfusions and no significant impact on side-effects, progression-free survival, and OS.

  8. Thyrotoxicosis with pegylated interferon alfa-2b.

    Science.gov (United States)

    Lowndes, Sarah A; Asher, Ruth; Middleton, Mark R

    2010-11-01

    Despite adequate surgery, a diagnosis of stage III melanoma carries a high risk of relapse, and hence mortality. Interferon alfa is the only treatment that has currently been shown to alter the natural history of the disease, delaying relapse-free survival, particularly in patients with micrometastatic disease. There is also recent evidence of a prognostic advantage conferred by the development of autoimmune conditions in patients receiving adjuvant interferon therapy. We present the case of a 27-year-old woman with stage IIIa melanoma who was entered into the European Organisation for the Research and Treatment of Cancer 18991 trial of 5-year adjuvant treatment with pegylated interferon (peginterferon) alfa-2b. The patient developed thyrotoxicosis 3 months after commencing treatment, which required treatment with propylthiouracil. The degree of thyrotoxicosis corresponded closely to the dose of peginterferon alfa-2b given. However, in this patient, the hyperthyroidism resolved spontaneously after 4 years when peginterferon treatment was still ongoing. Seven years following the initial diagnosis, the patient has not had disease relapse. Hyperthyroidism is less common than hypothyroidism as a consequence of interferon therapy, and this case is atypical in that it resolved spontaneously during interferon therapy but is in accordance with the recent evidence of a positive association between interferon-associated autoimmunity and prognosis.

  9. Evaluation of the absolute bioavailability of pegylated interferon alfa-2a after subcutaneous administration to healthy male volunteers: an open-label, randomized, parallel-group study.

    Science.gov (United States)

    Brennan, Barbara J; Xu, Zhi-Xin; Grippo, Joseph F

    2012-09-01

    Interferon (IFN)-based therapy is the recommended treatment for hepatitis C virus. Because pegylated IFN (PEG-IFN) alfa-2a is administered subcutaneously, it is of interest to determine the proportion of the dose that is absorbed from the subcutaneous (SC) tissue and ultimately reaches systemic circulation. The goal of this study was to characterize the absolute bioavailability of PEG-IFN alfa-2a (40 kDa) after SC dosing (180 μg) and to evaluate the pharmacokinetics of PEG-IFN alfa-2a after intravenous (IV) and SC administration. In this parallel-group study, 18 participants were given a single IV dose of PEG-IFN alfa-2a 90 μg and 18 participants received PEG-IFN alfa-2a 180 μg SC. Serum concentrations of PEG-IFN alfa-2a were measured predose and serially until 312 hours after the first dose. Pharmacokinetic parameters (CL/F, volume of distribution, C(max), and T(max)) were estimated using noncompartmental methods. Bioavailability was calculated by using the following formula: (AUC(SC)/AUC(IV)) · (dose(IV)/dose(SC)). Eighteen healthy males received IV PEG-IFN alfa-2a, and an additional 18 healthy males received SC PEG-IFN alfa-2a. Subjects in each group had comparable mean weight, height, and body mass index. After IV administration of PEG-IFN alfa-2a (90 μg), there was a slow decline in serum concentration, the mean rate of systemic clearance was low at 126 mL/h, and the estimated mean volume of distribution at steady state was 9 L. After SC administration of PEG-IFN alfa-2a 180 μg, absorption was sustained, with mean T(max) occurring 102 hours after administration. The mean absolute bioavailability was 84%. A higher rate of influenza-like symptoms was observed after IV administration, along with decreased neutrophil counts, compared with subjects who underwent SC dosing. Approximately 84% of a SC-administered dose of PEG-IFN alfa-2a reached the systemic circulation in these male healthy volunteers. The slow absorption, restricted distribution, and slow

  10. Stock footage ATLAS-ALFA experiment September 2016

    CERN Multimedia

    2016-01-01

    Stock footage of the ATLAS- ALFA subdetector in the LHC tunnel at IP1 taken during the LHC technical shut-down in September 2016. The ATLAS/ALFA experiment and studies the elastic scattering of protons, which are not observable in normal operation runs. In the elastic scattering process, the two protons survive their encounter intact and only change directions by exchanging momentum.

  11. Interview with Dr Ghassan K Abou-Alfa.

    Science.gov (United States)

    Abou-Alfa, G K

    2016-11-01

    Ghassan K Abou-Alfa joined the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York back in 2001. Dr Abou-Alfa specializes in the treatment of gastrointestinal malignancies. Dr Abou-Alfa received his medical degree from the American University of Beirut, Lebanon, and completed his post-doctoral training at Yale University School of Medicine. His research is dedicated to finding novel therapies and improving the effectiveness of the current therapies for hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer, while continuing to understand the basic mechanisms of the diseases and its therapy. Dr Abou-Alfa has invested several years in helping develop multi-tyrosine kinases and more immune-modulator therapies. Dr Abou-Alfa has many publications in the field. He led on many occasions international teams of investigators. Dr Abou-Alfa serves as the chair of the National Cancer Institute (NCI) Task Force for Hepatobiliary Cancers and the chair of the AIDS Malignancy Consortium (AMC) Non-AIDS Defining Malignancies (NADC) Liver/GI Task Force. Dr Abou-Alfa also co-chairs the hepatobiliary cancers subgroup of the Alliance cooperative group, and is a cadre member of both the gastrointestinal cancers and pharmacogenomics and population pharmacology committees. Dr Abou-Alfa who has lectured worldwide on the subject on gastrointestinal malignancies, is also a strong advocate for raising awareness and support for improving the outcome of patients with this disease, and enhancing oncologic education worldwide.

  12. Drotrecogin alfa (activated in severe sepsis: a systematic review and new cost-effectiveness analysis

    Directory of Open Access Journals (Sweden)

    Brophy James M

    2007-06-01

    Full Text Available Abstract Background Activated drotrecogin alfa (human activated protein C, rhAPC, is produced by recombinant DNA technology, and purports to improve clinical outcomes by counteracting the inflammatory and thrombotic consequences of severe sepsis. Controversy exists around the clinical benefits of this drug and an updated economic study that considers this variability is needed. Methods A systematic literature review was performed using Medline, Embase and the International Network of Agencies for Health Technology Assessment (INAHTA databases to determine efficacy, safety and previous economic studies. Our economic model was populated with systematic estimates of these parameters and with population life tables for longer term survival information. Monte Carlo simulations were used to estimate the incremental cost-effectiveness ratios (ICERs and variance for the decision analytic models. Results Two randomized clinical trials (RCTS of drotrecogin alfa in adults with severe sepsis and 8 previous economic studies were identified. Although associated with statistical heterogeneity, a pooled analysis of the RCTs did not show a statistically significant 28-day mortality benefit for drotrecogin alfa compared to placebo either for all patients (RR: 0.93, 95% CI: 0.69, 1.26 or those at highest risk as measured by APACHE II ≥ 25 (RR: 0.90, 95% CI: 0.54, 1.49. Our economic analysis based on the totality of the available clinical evidence suggests that the cost-effectiveness of drotrecogin alfa is uncertain ( Conclusion The evidence supporting the clinical and economic attractiveness of drotrecogin alfa is not conclusive and further research appears to be indicated.

  13. Pegylated interferon alfa and ribavirin for children with chronic hepatitis C.

    Science.gov (United States)

    Rosen, Irit; Kori, Michal; Eshach Adiv, Orly; Yerushalmi, Baruch; Zion, Nataly; Shaoul, Ron

    2013-02-21

    To study current treatment options for pediatric hepatitis C infection and their associated success rates. We retrospectively reviewed charts of thirty children who had been treated with combination therapy of pegylated interferon alfa plus ribavirin for chronic hepatitis C infection. Patients had been treated with ribavirin (15 mg/kg per day) and either pegylated interferon alfa 2a (180 mg/m(2) once weekly) or pegylated interferon alfa 2b (1.5 mg/kg once weekly). Patients' follow-up included subjective assessment of complaints, physical examination including weight and height, as well as laboratory evaluations for viral load [before treatment, at 12 wk, and 6 mo following treatment completion, as determined by sustained viral response (SVR)], complete blood count, liver enzymes, alkaline phosphatase, bilirubin, renal function tests, and thyroid function tests. For patients not achieving a two log decrease in viral load at treatment week 12, treatment was discontinued and the patient was considered a treatment non-responder. Thirty children aged 3-18 years were included in the study. Twenty patients (11 males, 9 females) received pegylated interferon alfa 2b and ten patients (6 males, 4 females) received pegylated interferon alfa 2a. Twenty-three patients were infected with genotype 1, six patients were infected with genotype 3, and one patient was infected with genotype 2. Twenty patients (67%) achieved SVR. Treatment success rates were 90% with pegylated interferon alfa 2a vs 55% with pegylated interferon alfa 2b. Although a trend was noted for improved outcomes in the group receiving pegylated interferon alfa 2a, there were no statistically significant outcome differences between the two treatment groups (P = 0.1). Treatment success was 56.5% for patients infected with genotype 1 virus, compared to 100% for patients infected with other genotypes (P = 0.064). There was no difference in treatment response between males and females. A cut-off age of twelve years

  14. Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B

    DEFF Research Database (Denmark)

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

    2005-01-01

    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....

  15. Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B

    DEFF Research Database (Denmark)

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

    2002-01-01

    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....

  16. Pegylated interferons Lambda-1a and alfa-2a display different gene induction and cytokine and chemokine release profiles in whole blood, human hepatocytes and peripheral blood mononuclear cells.

    Science.gov (United States)

    Freeman, J; Baglino, S; Friborg, J; Kraft, Z; Gray, T; Hill, M; McPhee, F; Hillson, J; Lopez-Talavera, J C; Wind-Rotolo, M

    2014-06-01

    Pegylated interferon-lambda-1a (Lambda), a type III interferon (IFN) in clinical development for the treatment of chronic HCV infection, has shown comparable efficacy and an improved safety profile to a regimen based on pegylated IFN alfa-2a (alfa). To establish a mechanistic context for this improved profile, we investigated the ex vivo effects of Lambda and alfa on cytokine and chemokine release, and on expression of IFN-stimulated genes (ISGs) in primary human hepatocytes and peripheral blood mononuclear cells (PBMCs) from healthy subjects. Our findings were further compared with changes observed in blood analysed from HCV-infected patients treated with Lambda or alfa in clinical studies. mRNA transcript and protein expression of the IFN-λ-limiting receptor subunit was lower compared with IFN-α receptor subunits in all cell types. Upon stimulation, alfa and Lambda induced ISG expression in hepatocytes and PBMCs, although in PBMCs Lambda-induced ISG expression was modest. Furthermore, alfa and Lambda induced release of cytokines and chemokines from hepatocytes and PBMCs, although differences in their kinetics of induction were observed. In HCV-infected patients, alfa treatment induced ISG expression in whole blood after single and repeat dosing. Lambda treatment induced modest ISG expression after single dosing and showed no induction after repeat dosing. Alfa and Lambda treatment increased IP-10, iTAC, IL-6, MCP-1 and MIP-1β levels in serum, with alfa inducing higher levels of all mediators compared with Lambda. Overall, ex vivo and in vivo induction profiles reported in this analysis strongly correlate with clinical observations of fewer related adverse events for Lambda vs those typically associated with alfa. © 2014 John Wiley & Sons Ltd.

  17. Mecanismos de cloración de alfa-aminoácidos y de fragmentación de (N-X)-alfa-aminoácidos

    OpenAIRE

    Canle, Moisés

    2011-01-01

    [Resumen] SE HAN ESTUDIADO LOS PROCESOS DE CLORACION DE ALFA-AMINOACIDOS Y DE FRAGMENTACION DE (N-X)-ALFA-AMINOACIDOS EN MEDIO ACUOSO.LA CLORACION DE ALFA-AMINOACIDOS TIENE LUGAR POR TRANSFERENCIA DIRECTA DE CLORO DESDE EL OXIGENO DEL ACIDO HIPOCLOROSO AL NITROGENO DEL GRUPO AMINO LIBRE DEL ALFA-AMINOACIDO, ESTANDO EL PROCESO CONTROLADO QUIMICAMENTE Y TRANSCURRIENDO A TRAVES DE UN ESTADO DE TRANSICION CICLICO O ABIERTO SEGUN SEA EL ALFA-AMINOACIDO.LA FRAGMENTACION DE (N-X)-ALFA-AMINOA...

  18. Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Devos, Michel; Humaidan, Peter

    2013-01-01

    OBJECTIVE: To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH antagonist protocol. DESIGN: Retrospective pilot study. SETTING: University-based tertiary care center. PATIENT(S): Poor ovarian responders fulfilling the Bologna criteria...... developed by European Society for Human Reproduction and Embryology Consensus Group. INTERVENTION(S): Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Endocrinologic profile and ongoing pregnancy rates. RESULT(S): Among 43 women treated...... compared with a cohort of patients treated during 2011 with the standard protocol for poor responders in our center (short agonist-hMG) (7% vs. 6.3%). CONCLUSION(S): Treatment of poor ovarian responders, as described by the Bologna criteria, with corifollitropin alfa in a GnRH antagonist protocol results...

  19. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial.

    Science.gov (United States)

    Gore, Martin E; Griffin, Clare L; Hancock, Barry; Patel, Poulam M; Pyle, Lynda; Aitchison, Michael; James, Nicholas; Oliver, Roderick T D; Mardiak, Jozef; Hussain, Tahera; Sylvester, Richard; Parmar, Mahesh K B; Royston, Patrick; Mulders, Peter F A

    2010-02-20

    In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a. RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965. 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37.2 months (24.8-52.3). Median overall survival was 18.8 months (17.0-23.2) for patients receiving interferon alfa-2a versus 18.6 months (16.5-20.6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1.05 [95% CI 0.90-1.21], p=0.55; absolute difference 0.3% (-5.1 to 5.6) at 1 year and 2.7% (-8.2 to 2.9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment. Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial. UK Medical Research Council. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. Epoetin therapy and hemoglobin level variability in nondialysis patients with chronic kidney disease.

    Science.gov (United States)

    Minutolo, Roberto; Chiodini, Paolo; Cianciaruso, Bruno; Pota, Andrea; Bellizzi, Vincenzo; Avino, Deborah; Mascia, Sara; Laurino, Simona; Bertino, Valerio; Conte, Giuseppe; De Nicola, Luca

    2009-03-01

    Intrapatient variability of hemoglobin (Hb) is a newly proposed determinant of adverse outcome in chronic kidney disease (CKD). We evaluated whether intensity of epoetin therapy affects Hb variability and renal survival in nondialysis CKD. We calculated the individual therapeutic index (TI) for epoetin (EPO; difference between rates of visits that required EPO dosage change and those with effective EPO change) from 1198 visits during the first year of EPO in 137 patients. Renal death was registered in the subsequent 18.1 mo. Analysis was made by TI tertile (lower, middle, and higher; i.e., from more to less intensive therapy). Main features and visit number were similar in tertiles. Lower Hb response to first EPO dosage was an independent predictor of higher TI (P = 0.002). The area under the curve for Hb (11.56 +/- 0.87, 11.46 +/- 1.20, and 10.95 +/- 1.48 g/dl per yr; P = 0.040) decreased from lower to higher tertile. Hb variability increased in parallel, as shown by the reduction of time with Hb at target (time in target, from 9.2 +/- 2.0 to 3.0 +/- 2.2 mo; P < 0.0001) and the wider values of within-patient Hb standard deviation (from 0.70 to 0.96; P = 0.005) and Hb fluctuations across target (P < 0.0001). In Cox analyses (hazard ratio [95% confidence interval]), risk for renal death was increased in the middle and higher tertiles (2.79 [1.36 to 5.73] and 2.94 [1.40 to 6.20]) and reduced by longer time in target (0.90 [0.83 to 0.98]). Lack of adjustment of EPO worsens Hb variability in CKD. Hb variability may be associated with renal survival, but further studies are needed to explore the association versus causal relationship.

  1. Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b.

    Science.gov (United States)

    Flisiak, Robert; Kawazoe, Seiji; Znoyko, Olga; Assy, Nimer; Gadano, Adrian; Kao, Jia-Horng; Lee, Kwan-Sik; Zwirtes, Ricardo; Portsmouth, Simon; Dong, Yuping; Xu, Dong; Kumada, Hiromitsu; Srinivasan, Subasree

    2016-11-01

    The study objective was to compare the efficacy and safety of peginterferon lambda-1a combined with ribavirin/daclatasvir (Lambda/RBV/DCV), versus peginterferon alfa-2a combined with ribavirin/telaprevir (Alfa/RBV/TVR), in patients chronically infected with hepatitis C virus (HCV), genotype 1b. This was a prospective, randomized, open-label, phase 3 study (NCT01718158) in adults (aged ≥18 years) who were treatment naïve or prior relapsers to peginterferon alfa/ribavirin therapy. The primary endpoint was sustained virologic response at post-treatment follow-up week 12 (SVR12). Patients were randomized in a 2:1 ratio to receive 24 weeks of Lambda/RBV/DCV or response-guided 24 or 48 weeks of Alfa/RBV/TVR. Overall, 440 patients were treated (294 with Lambda/RBV/DCV; 146 with Alfa/RBV/TVR). The proportion of patients achieving SVR12 was 88.8% in the Lambda/RBV/DCV arm and 70.5% in the Alfa/RBV/TVR arm (difference between arms: 18.3%; 95% confidence interval: 9.9-25.7; P < 0.0001). Patients in the Lambda/RBV/DCV group had fewer rash-related adverse events (AEs), cytopenic abnormalities, flu-like symptoms, serious AEs, and discontinuations due to AEs, but more liver abnormalities than those in the Alfa/RBV/TVR group. In conclusion, treatment with Lambda/RBV/DCV led to higher SVR12 rates and a more favorable safety profile than Alfa/RBV/TVR in patients with chronic HCV, genotype 1b infection.

  2. Biosimilar Retacrit® (epoetin zeta in the treatment of chemotherapy-induced symptomatic anemia in hematology and oncology in Germany (ORHEO – non-interventional study

    Directory of Open Access Journals (Sweden)

    Losem C

    2017-02-01

    Full Text Available Christoph Losem,1 Michael Koenigsmann,2 Christine Rudolph3 1Praxis für Hämatologie und Onkologie, Neuss, 2Onkologisches Ambulanzzentrum, Marienstr, Hannover, 3Hospira Germany, A Pfizer Company, München, Germany Background: Symptomatic anemia is a frequent and severe complication of chemotherapy that is commonly treated with erythropoiesis-stimulating agents. The primary objective of this study was to assess the change in hemoglobin levels in patients with chemotherapy-induced anemia (CIA following treatment with biosimilar Retacrit® (epoetin zeta. Secondary objectives included changes in hematologic parameters and tolerability. Methods: This was a non-interventional, multicenter, long-term observational study that is part of an ongoing surveillance program for epoetin zeta. Adult patients (N=291 with solid tumors, malignant lymphomas or multiple myeloma, and chemotherapy-induced symptomatic anemia, who were eligible for treatment with biosimilar epoetin zeta, were enrolled. Patients were evaluated at enrollment, 3 months, and 6 months. Results: Evaluable patients had lymphoma or myeloma (n=30 or solid tumors (n=260. At 3 months, patients with lymphoma and myeloma showed the greatest increase in mean (SD hemoglobin from 9.2 (0.9 to 11.0 (1.8 g/dL, whereas patients with breast cancer showed the smallest increase from 10.0 (1.0 to 11.1 (1.2 g/dL. At 6 months, the greatest mean increase occurred in patients with lymphoma or myeloma from 11.0 (1.8 to 11.7 (2.3 g/dL, and the smallest in patients with other solid tumors from 10.9 (1.4 to 11.1 (1.5 g/dL. Patient evaluation of epoetin zeta therapy was positive, as most patients expressed satisfaction with epoetin zeta treatment during the study, compliance with treatment was high, and most indicated their willingness to be retreated if necessary. Epoetin zeta was also well tolerated; overall, in 25 patients (8.6%, there were 31 adverse events. Conclusion: Despite variability among different disease

  3. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa

    NARCIS (Netherlands)

    Olivennes, F.; Trew, G.; Borini, A.; Broekmans, F.|info:eu-repo/dai/nl/145488594; Arriagada, P.; Warne, D. W.; Howles, C. M.

    2015-01-01

    In this randomized, controlled, open-label, phase IV study, ovarian response after a follitropin alfa starting dose determined by the CONSORT calculator was compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years) eligible for assisted reproductive techniques were recruited

  4. JSC “ALFA-BANK” marketing policy. problems and perspectives

    OpenAIRE

    Kirillov, A.; Kuznetcova, E.; Martirosian, M.

    2013-01-01

    The article is devoted to the results of JSC “Alfa-Bank” consumers’ segmentation and the following complex marketing research. The article suggests the ways of the bank’s marketing policy improvement.

  5. Treatment of anemia with darbepoetin alfa in systolic heart failure

    DEFF Research Database (Denmark)

    Swedberg, Karl; Young, James B; Anand, Inder S

    2013-01-01

    Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia.......Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia....

  6. Responses to peginterferon alfa-2a vs alfa-2b plus ribavirin in a Mexican population with chronic hepatitis C.

    Science.gov (United States)

    Sandoval-Ramirez, Jorge Luis; Mata-Marín, José Antonio; Huerta García, Gloria; Gaytán-Martínez, Jesús Enrique

    2015-03-15

    The WHO estimates that 180 million people are chronically infected with hepatitis C virus (HCV) throughout the world. Despite the emergence of new therapies, the combination of pegylated interferon and ribavirin remains the accepted standard of care in low-income countries, including Mexico. Two types of peginterferon are available (peginterferon alfa-2a and peginterferon alfa-2b), and both are recommended for the treatment of HCV, although there is controversy over which treatment option is most effective. This was a retrospective cohort study at a infectious disease center in Mexico City. Patients were included if they had received peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin. Age, sex, body mass index, AST platelet ratio index, HCV RNA viral load, levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, and hemoglobin, and platelet and leukocyte counts of the subjects were assessed before treatment and at weeks 4, 12, 24, 48, and 6 months post treatment. Eighty-seven patients met the inclusion criteria. A sustained virological response (SVR) occurred in 33 (38%) of them, 11 (33%) given peginterferon alfa-2a and 22 (67%) given peginterferon alfa-2b (p = 0.17). Seventeen patients (20%) relapsed, 7 (41%) of those given peginterferon alfa-2a and 10 (59%) of those given peginterferon alfa-2b (p = 0.76); 27 (31%) patients were non-responders (p = 0.09). The rates of anemia, thrombocytopenia, and leukopenia were similar in both groups. Similar SVR rates and frequencies of adverse events were observed. Either type of interferon can be used to treat HCV infection in the Mexican population.

  7. Preparation And Properties Of Bionanocomposite Films Reinforced With Nanocellulose Isolated From Moroccan Alfa Fibres

    Directory of Open Access Journals (Sweden)

    Youssef Benyoussif

    2015-09-01

    Full Text Available Nanocellulose (NC were extracted from the Moroccan Alfa plant (Stipa tenacissima L. and characterised. These Alfa cellulosic nanoparticles were used as reinforcing phase to prepare bionanocomposite films using carboxymethyl cellulose as matrix. These films were obtained by the casting/evaporation method. The crystallinity of NC was analysed by X-ray diffraction, the dimension of NC by atomic force microscopy, molecular interactions due to incorporation of NC in carboxymethyl cellulose (CMC matrix were supported by Fourier transforms infrared (FTIR spectroscopy. The properties of the ensuing bionanocomposite films were investigated using tensile tests, water vapour permeability (WVP study and thermogravimetric analysis. With the progress of purification treatment of cellulose, the crystallinity is improved compared to the untreated fibres; this can be explained by the disappearance of the amorphous areas in cellulose chain of the plant. Consequently, the tensile modulus and tensile strength of CMC film increased by 60 and 47%, respectively, in the bionanocomposite films with 10 wt% of NC, and decrease by 8.6% for WVP with the same content of NC. The NC obtained from the Moroccan Alfa fibres can be used as a reinforcing agent for the preparation of bionanocomposites, and they have a high potential for the development of completely biodegradable food packaging materials.

  8. Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods.

    Science.gov (United States)

    Serag, Ahmed; Blesa, Manuel; Moore, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Wilkinson, A G; Macnaught, Gillian; Semple, Scott I; Boardman, James P

    2016-03-24

    Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases 'uniformly' distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.

  9. Health-related quality of life in patients with high-risk melanoma randomised in the Nordic phase 3 trial with adjuvant intermediate-dose interferon alfa-2b

    DEFF Research Database (Denmark)

    Brandberg, Y; Aamdal, S; Bastholt, Lars

    2012-01-01

    To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN).......To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN)....

  10. Albinterferon alfa-2b, a novel fusion protein of human albumin and human interferon alfa-2b, for chronic hepatitis C.

    Science.gov (United States)

    Rustgi, Vinod K

    2009-04-01

    New treatment options for chronic hepatitis C (CHC) that offer improved efficacy, tolerability, and convenience compared with weekly interferon alfa (IFNalpha)-based regimens are needed. Longer-acting IFNalpha formulations with reduced dosing requirements and improved tolerability have been a focus of drug development efforts. The objective of this report is to review the characteristics, pharmacokinetics, pharmacodynamics, and clinical and virologic outcomes reported in studies of albinterferon alfa-2b (alb-IFN), a novel fusion protein of human albumin and human IFNalpha-2b. This review was based on all published data regarding alb-IFN to date. An unlimited PubMed database search was conducted using the keywords 'albuferon,' 'albinterferon,' and 'albumin AND interferon.' Albinterferon alfa-2b has been developed for the treatment of CHC. This agent exhibits a prolonged half-life and duration of antiviral activity that indicate potential suitability for dosing intervals of 2-4 weeks. Phase 2 trials in prior IFN nonresponders and IFN-naïve patients with genotype 1 or 2/3 CHC have shown antiviral activity and acceptable safety/tolerability of alb-IFN 900-1500 microg every 2 weeks and 1200-1500 microg every 4 weeks. Based on the phase 2 data, alb-IFN 900 microg and 1200 microg every 2 weeks were selected for two ongoing phase 3 trials in IFN-naïve patients with genotype 1 and 2/3 CHC. Albinterferon alfa-2b exhibits high antiviral activity, and appears to offer safety/tolerability comparable to the current standard of care, and health-related quality-of-life benefits in patients with CHC. Its ability to maintain drug concentrations above the 90% effective concentration over prolonged dosing intervals suggests that it may be an ideal partner for combination therapy with direct antiviral agents in CHC. The results of the phase 3 trials are eagerly anticipated as they should greatly clarify the future role of alb-IFN in the treatment of CHC.

  11. The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight®), in patients with hemophilia A.

    Science.gov (United States)

    Jiménez-Yuste, V; Lejniece, S; Klamroth, R; Suzuki, T; Santagostino, E; Karim, F A; Saugstrup, T; Møss, J

    2015-03-01

    Turoctocog alfa (NovoEight(®)) is a human recombinant coagulation factor VIII (rFVIII) for the treatment of patients with hemophilia A. To evaluate the pharmacokinetics of turoctocog alfa in all age groups across clinical trials. Data from previously treated patients with severe hemophilia A (FVIII activity level of ≤ 1%) with no history of FVIII inhibitors, in a non-bleeding state, were included. The pharmacokinetics were assessed following a wash-out period and a subsequent single intravenous 50 IU kg(-1) dose of turoctocog alfa. Blood was sampled during a 48-h period postdose. Standard pharmacokinetic (PK) parameters were estimated on the basis of plasma FVIII activity vs. time (PK profiles) with non-compartmental methods. Furthermore, a population PK analysis was conducted. Data from 76 patients (aged 1-60 years) enrolled globally across six clinical trials were included, totaling 105 turoctocog alfa PK profiles. Single-dose PK results 3-6 months after the first dose of turoctocog alfa were comparable with the results obtained after the first dose. Similar PK characteristics were shown for different lots and strengths of the drug product. Overall, area under the plasma concentration (activity) curve from administration to infinity (AUC) and t1(/2) tended to increase with increasing age, with lower AUC and shorter t(1/2) being seen in children than in adolescents and adults. The PK profiles of turoctocog alfa and other commercially available plasma-derived FVIII and rFVIII products were similar in all age groups. The PK characteristics of turoctocog alfa have been thoroughly studied, and shown to be consistent over time, reproducible between different lots and strengths of drug product, and similar to those observed for other FVIII products. © 2014 International Society on Thrombosis and Haemostasis.

  12. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

    Science.gov (United States)

    Solal-Celigny, P; Lepage, E; Brousse, N; Reyes, F; Haioun, C; Leporrier, M; Peuchmaur, M; Bosly, A; Parlier, Y; Brice, P

    1993-11-25

    Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin's lymphoma. In 1986, we designed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin's lymphoma. The trial involved 242 patients with advanced low-grade follicular non-Hodgkin's lymphoma selected on the basis of clinical, radiographic, and biologic criteria. All patients were treated with a regimen consisting of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP), given monthly for six cycles and then every two months for one year. After randomization, 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months. The remaining 119 patients received chemotherapy alone. As compared with the patients treated with CHVP only, the patients treated with CHVP plus interferon alfa had a higher overall rate of response (85 percent vs. 69 percent, P = 0.006), a longer median event-free survival (34 months vs. 19 months, P < 0.001), and a higher rate of survival at 3 years (86 percent vs. 69 percent, P = 0.02). Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone. There were no treatment-related deaths. Interferon alfa had to be stopped because of toxic effects (fatigue and hepatitis) in 13 patients (11 percent). The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response, event-free survival, and overall survival in patients with advanced follicular non-Hodgkin's lymphoma, without serious toxicity, although some patients were unable to tolerate the side effects.

  13. Reveglucosidase alfa (BMN 701), an IGF2-Tagged rhAcid α-Glucosidase, Improves Respiratory Functional Parameters in a Murine Model of Pompe Disease.

    Science.gov (United States)

    Peng, Jeffrey; Dalton, Jill; Butt, Mark; Tracy, Kristin; Kennedy, Derek; Haroldsen, Peter; Cahayag, Rhea; Zoog, Stephen; O'Neill, Charles A; Tsuruda, Laurie S

    2017-02-01

    Pompe disease is a rare neuromuscular disorder caused by an acid α-glucosidase (GAA) deficiency resulting in glycogen accumulation in muscle, leading to myopathy and respiratory weakness. Reveglucosidase alfa (BMN 701) is an insulin-like growth factor 2-tagged recombinant human acid GAA (rhGAA) that enhances rhGAA cellular uptake via a glycosylation-independent insulin-like growth factor 2 binding region of the cation-independent mannose-6-phosphate receptor (CI-MPR). The studies presented here evaluated the effects of Reveglucosidase alfa treatment on glycogen clearance in muscle relative to rhGAA, as well as changes in respiratory function and glycogen clearance in respiratory-related tissue in a Pompe mouse model (GAAtm1Rabn/J). In a comparison of glycogen clearance in muscle with Reveglucosidase alfa and rhGAA, Reveglucosidase alfa was more effective than rhGAA with 2.8-4.7 lower EC50 values, probably owing to increased cellular uptake. The effect of weekly intravenous administration of Reveglucosidase alfa on respiratory function was monitored in Pompe and wild-type mice using whole body plethysmography. Over 12 weeks of 20-mg/kg Reveglucosidase alfa treatment in Pompe mice, peak inspiratory flow (PIF) and peak expiratory flow (PEF) stabilized with no compensation in respiratory rate and inspiratory time during hypercapnic and recovery conditions compared with vehicle-treated Pompe mice. Dose-related decreases in glycogen levels in both ambulatory and respiratory muscles generally correlated to changes in respiratory function. Improvement of murine PIF and PEF were similar in magnitude to increases in maximal inspiratory and expiratory pressure observed clinically in late onset Pompe patients treated with Reveglucosidase alfa (Byrne et al., manuscript in preparation). Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

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

    Science.gov (United States)

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

    2009-05-01

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

  15. Associations among epoetin therapy, inflammation, nutritional status, and mortality in patients on hemodialysis.

    Science.gov (United States)

    Honda, Hirokazu; Kimata, Naoki; Wakai, Kenji; Akizawa, Tadao

    2014-09-01

    Inflammation contributes to hemopoiesis by lowering responses to epoetin (EPO) and to an increase in the mortality of patients on hemodialysis. However, nutritional status might alter associations among inflammation, EPO responsiveness, and the risk of mortality. We assessed the effect of inflammation on mortality according to nutritional status among EPO responses in a cohort of prevalent hemodialysis patients. The observational cohort study analyzed data from the Japanese Dialysis Registry (2005-2006; n = 36,956; mean follow-up 11.5 months). Patients were categorized into tertiles of the EPO responsiveness index (ERI; the weekly weight-adjusted EPO dose [IU/kg/week] divided by hemoglobin [g/dL]) and an EPO-free group. Body mass index (BMI) and C-reactive protein (CRP) levels were measured. Bimodal peaks indicated associations between CRP and BMI in each group. Hazard ratio (HR) curves of CRP for mortality according to BMI in the upper ERI tertile, particularly among those with diabetes mellitus (DM), were reverse J-shaped. However, HR curves in the other groups were increased below a threshold BMI of 21 kg/m(2). These associations were confirmed in propensity score-matched populations. Risk of CRP for death is apparently changed by BMI in hemodialysis patients with a lower EPO response, especially in those with DM. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  16. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Annelies De Beuf

    2010-01-01

    Full Text Available Erythropoietin (EPO exerts (renal tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs from oxidative stress and if so which pathways are involved. EPO (epoetin delta could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1, aquaporin-1 (AQP-1, and B-cell CLL/lymphoma 2 (Bcl-2 have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM, dipeptidyl peptidase IV (DPPIV, and cytoglobin (Cygb to play a role in this process.

  17. Safety and antiviral activity of albinterferon alfa-2b in prior interferon nonresponders with chronic hepatitis C.

    Science.gov (United States)

    Nelson, David R; Rustgi, Vinod; Balan, Vijayan; Sulkowski, Mark S; Davis, Gary L; Muir, Andrew J; Lambiase, Louis R; Dickson, Rolland C; Weisner, Russell H; Fiscella, Michele; Cronin, Patrick W; Pulkstenis, Erik; McHutchison, John G; Subramanian, G Mani

    2009-02-01

    Pegylated interferon alfa-2a/2b is used in combination with ribavirin to treat patients with chronic hepatitis C (CHC), although many do not achieve a sustained virologic response (SVR). Albinterferon alfa-2b, a recombinant protein consisting of interferon alfa-2b fused to human albumin, may increase drug exposure. This phase 2 study evaluated the safety/efficacy of albinterferon in CHC patients who had not responded to interferon-based regimens. A total of 115 patients were assigned to 5 groups given 1200 microg albinterferon every 4 weeks or 900, 1200, 1500, or 1800 microg every 2 weeks, plus oral ribavirin, for 48 weeks. The primary efficacy end point was achievement of an SVR after 24 weeks. Treatment was extended to 72 weeks for 6 slow responders who were negative for hepatitis C virus RNA after 24 weeks. The types of adverse events were similar across groups; the overall discontinuation rate as a result of adverse events was 10.4%. Reductions in absolute neutrophil counts were less frequent in the every 4 weeks group and comparable among the every 2 weeks groups. The overall SVR rate was 17% (11% for previous nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection). An SVR occurred in 3 of 6 slow responders by 72 weeks. The greatest reductions in hepatitis C virus RNA in nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection were observed in the 1800-microg group. In patients with CHC who did not respond to interferon-based regimens, higher doses of albinterferon had significant early antiviral activity and a low incidence of adverse events, with the types of adverse events similar to those observed with interferon.

  18. Changes in in vivo confocal microscopic findings of ocular surface squamous neoplasia during treatment with topical interferon alfa-2b.

    Science.gov (United States)

    Zarei-Ghanavati, Mehran; Mousavi, Ebrahim; Nabavi, Amin; Latifi, Golshan; Mehrjardi, Hadi Z; Mohebbi, Masoomeh; Ghassemi, Hamed; Mirzaie, Farrin; Zare, Mohammad Ali

    2018-01-03

    To evaluate in vivo confocal microscopy (IVCM) findings of ocular surface squamous neoplasia (OSSN) during treatment with topical interferon alfa-2b (IFN alfa-2b). In this prospective interventional case series, 20 eyes from 20 patients with OSSN were treated with topical IFN alfa-2b 3 million IU/mL four times a day. Treatment was continued for 2 or 3 months after clinical resolution. IVCM was done at baseline, on a monthly basis, and at the end of treatment. Confocal images were evaluated in conjunction with clinical findings during treatment. Limbal dendritic cell (DC) density within the involved areas was calculated manually in confocal images. Topical therapy resulted in clinical resolution of neoplasia in 80% of eyes. Main features of OSSN on IVCM were hyper-reflectivity of epithelium, demarcation line between neoplastic and normal epithelium, and pleomorphic cells. These findings became less prominent in response to IFN alfa-2b therapy. However, some degree of residual epithelial hyper-reflectivity could be detected in 9 (56.2%) subjects who responded to therapy at time of treatment cessation. Limbal DCs density within involved areas was significantly increased at month 1 follow-up compared to baseline only in responders (P alfa-2b than non-responders (208.6 ± 53.5 vs. 153.1 ± 48.2 cell/mm 2 , respectively; P = .08) at month 1 follow-up. IVCM is proposed as an adjunctive tool for monitoring OSSN during topical treatment. IVCM documents epithelial cell response as well as limbal DC density increase during topical IFN therapy. Copyright © 2018. Published by Elsevier Inc.

  19. Hashimoto encephalopathy with pegylated interferon alfa-2b and ribavirin.

    Science.gov (United States)

    Deutsch, Melanie; Koskinas, John; Tzannos, Konstatinos; Vassilopoulos, Dimitrios; Mailis, Antonis; Tolis, George; Hadziyannis, Stephanos

    2005-10-01

    To report an instance of Hashimoto encephalopathy probably resulting from pegylated interferon alfa-2b and ribavirin. A 36-year-old woman with a 10-year history of autoimmune thyroiditis presented with symptoms and signs consistent with Hashimoto encephalopathy during therapy with pegylated interferon alfa-2b and ribavirin for chronic hepatitis C. Hashimoto encephalopathy is a rare autoimmune condition that occurs in patients with Hashimoto thyroiditis and high titers of antithyroid antibodies. It is characterized by a variety of nonspecific neuropsychiatric symptoms, increased cerebrospinal fluid protein level, and abnormal brain imaging and electroencephalogram. Prompt response to corticosteroids is observed in most cases. As of August 29, 2005, this is the first report of such an association. An objective causality assessment revealed that the Hashimoto encephalopathy was probably caused by the patient's medications. Hashimoto encephalopathy may rarely be triggered by interferon alfa therapy in susceptible patients.

  20. 90 m β* Optics for ATLAS/ALFA

    CERN Document Server

    Cavalier, S; Burkhardt, H; Grafstrom, P

    2011-01-01

    We describe a high β∗ optics developed for the ATLAS detector at the LHC interaction point IP1. Roman Pots have been installed 240 m left and right of IP1 to allow to measure the absolute luminosity and the total elastic cross section for ATLAS with ALFA (Absolute Luminosity for ATLAS). Ultimately, it is planned to perform these measurements at a very high β∗ of 2625 m. Here we describe a new, intermediate β∗ = 90 m optics, which has been optimized for compatibility with the present LHC running conditions. We describe the main features and the expected performance of this optics for ALFA.

  1. Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure

    NARCIS (Netherlands)

    Swedberg, Karl; Young, James B.; Anand, Inder S.; Cheng, Sunfa; Desai, Akshay S.; Diaz, Rafael; Maggioni, Aldo P.; McMurray, John J. V.; O'Connor, Christopher; Pfeffer, Marc A.; Solomon, Scott D.; Sun, Yan; Tendera, Michal; van Veldhuisen, Dirk J.

    2013-01-01

    BACKGROUND Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. METHODS In this randomized, double-blind

  2. Virologic responses and tolerance of peginterferon alfa plus ribavirin ...

    African Journals Online (AJOL)

    Date of Acceptance: 17-Aug-2015. Introduction. Chronic hepatitis C virus (HCV) infection has caused heavy social and economic burden worldwide over the past. Virologic responses and tolerance of peginterferon alfa plus ribavirin treatment for patients with chronic hepatitis C virus infection in different age categories. Z ...

  3. Physics prospects with the ALFA and AFP detectors

    CERN Document Server

    Hamal, Petr; The ATLAS collaboration

    2013-01-01

    The ATLAS ALFA and AFP detectors - the experimental challenge of measuring forward protons at the LHC. We will describe the experimental challenge presented by the measurement of the forward protons at the LHC. The ATLAS ALFA and AFP projects involve the deployment of detectors capable of detecting protons that emerge intact from the interaction with very small scattering angles. In the case of the ALFA detector, located at ±240m from the ATLAS interaction point, this measurement has to be performed using special high \\beta* beam optics. The detector chosen for the task is a nearly edgeless scintillating fibre tracker capable of making measurements at very low t – below 10-3 GeV2 – in the Nuclear Coulomb interference region. In order to reach these very small t-values we need to deploy the detector very near to the beam line utilizing Roman Pots. The main purpose of the ALFA detector is to measure the total p-p cross-section, a fundamental quantity in hadronic physics of importance to particle and to cos...

  4. Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.

    Science.gov (United States)

    Kishnani, Priya S; Rush, Eric T; Arundel, Paul; Bishop, Nick; Dahir, Kathryn; Fraser, William; Harmatz, Paul; Linglart, Agnès; Munns, Craig F; Nunes, Mark E; Saal, Howard M; Seefried, Lothar; Ozono, Keiichi

    2017-09-01

    Hypophosphatasia (HPP) is a rare, inherited, systemic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The disease is associated with a broad range of signs, symptoms, and complications, including impaired skeletal mineralization, altered calcium and phosphate metabolism, recurrent fractures, pain, respiratory problems, impaired growth and mobility, premature tooth loss, developmental delay, and seizures. Asfotase alfa is a human, recombinant enzyme replacement therapy that is approved in many countries for the treatment of patients with HPP. To address the unmet need for guidance in the monitoring of patients receiving asfotase alfa, an international panel of physicians with experience in diagnosing and managing HPP convened in May 2016 to discuss treatment monitoring parameters. The panel discussions focused on recommendations for assessing and monitoring patients after the decision to treat with asfotase alfa had been made and did not include recommendations for whom to treat. Based on the consensus of panel members, this review provides guidance on the monitoring of patients with HPP during treatment with asfotase alfa, including recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment. Recommended assessments are based on patient age and include regular monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life. Because of the systemic presentation of HPP, a coordinated, multidisciplinary, team-based, patient-focused approach is recommended in the management of patients receiving asfotase alfa. Monitoring of efficacy and safety outcomes must be tailored to the individual patient, depending on medical history, clinical manifestations, availability of resources in the clinical

  5. Macroscale production of crystalline interferon alfa-2b in microgravity on STS-52

    Science.gov (United States)

    Nagabhushan, Tattanahalli L.; Reichert, Paul; Long, Marianna M.; DeLucas, Lawrence J.; Bugg, Charles E.

    1995-01-01

    Macroscale crystallization of zinc interferon alfa-2b was achieved on STS-52 in October 1992 in the Protein Crystallization Facility. Conditions for crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alfa-2b in high yield and under cleanroom conditions. As a control for the STS-52 mission, a ground experiment was run simultaneously and in the same configuration as the flight experiment. Greater than 95% of the available protein crystallized in both the ground and flight experiments. Using a battery of physical, biochemical and biological characterization assays, demonstrated that sample processing, polysulfone bottle confinement and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Space grown crystals have remained a stable free flowing suspension for over 2 years. Based on these results, further experiments are envisioned to investigate macroscale crystallization of biologically active macromolecules in microgravity.

  6. A randomized, open-label, multicenter study evaluating the efficacy of peginterferon alfa-2a versus interferon alfa-2a, in combination with ribavirin, in naïve and relapsed chronic hepatitis C patients.

    Science.gov (United States)

    Nevens, F; Van Vlierberghe, H; D'Heygere, E; Delwaide, J; Adler, M; Henrion, J; Lenaerts, A; Hendlisz, A; Michielsen, P; Bastens, B; Brenard, R; Laureys, A

    2010-01-01

    A large multicenter trial to compare the efficacy of peginterferon alfa-2a with interferon alfa-2a, in combination with ribavirin, in chronic hepatitis C patients. Efficacy data for prior relapsers are reported because treatment recommendations for this patient population are not well defined. This study was a multicenter, prospective, randomized clinical trial. The primary efficacy endpoint was sustained virologic response in naive patients (n = 348) and relapsers (n = 95). Sustained virologic response rates were similar in naïve patients and relapsers, both for non-pegylated and pegylated interferon (respectively 27 and 26% and 54 and 43%). Pegylated interferon given for 48 weeks did not improved the relapse rate: 15.9 and 27.3% for non-pegylated and 16.7 and 30.4% for pegylated interferon, naïve vs relapsers respectively. Stepwise logistic regression analysis revealed a significant association between slow response (detectable HCV RNA at week 12 and undetectable at week 24) and relapse in patients with an end-of-treatment response (55% versus 13% respectively; p = 0.02; odds ratio = 6.07). This trial confirms the value of using peginterferon alfa-2a in both naïve and relapsed patients and provides support for a more tailored approach to treatment for relapsers and particulary for patients with a slow viral response.

  7. Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa

    Energy Technology Data Exchange (ETDEWEB)

    Vander Woude, D.L.; Wagner, P.D.; Shu, S.; Chang, A.E. (Univ. of Michigan, Ann Arbor (USA))

    1991-03-01

    Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer.

  8. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa

    Directory of Open Access Journals (Sweden)

    Ma Weimin

    2011-01-01

    Full Text Available Abstract In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-α, the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR and in 28 non-responder(NR to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-α therapy.

  9. Reversing factor Xa inhibitors – clinical utility of andexanet alfa

    Directory of Open Access Journals (Sweden)

    Kaatz S

    2017-09-01

    Full Text Available Scott Kaatz,1 Hardik Bhansali,1 Joseph Gibbs,2 Robert Lavender,3 Charles E Mahan,4 David G Paje5 1Division of Hospital Medicine, 2Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, 3Division of General Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 4University of New Mexico, Presbyterian Healthcare Services, Albuquerque, NM, 5Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA Abstract: Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs. Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications. Andexanet alfa is a FXa decoy designed to reverse all anticoagulants that act through this part of the coagulation cascade including anti-FXa DOACs, such as apixaban, edoxaban and rivaroxaban, and indirect FXa inhibitors such as low-molecular-weight heparins. This narrative reviews the development of andexanet alfa and explores its basic science, pharmacokinetics/pharmacodynamics, animal models, and human studies. Keywords: factor Xa, DOAC, andexanet alfa, reversal, rivaroxaban, apixaban

  10. Upgrade of ATLAS-ALFA for Run2

    CERN Document Server

    Jakobsen, Sune; The ATLAS collaboration

    2016-01-01

    Early experience with the operation of the ALFA detectors in the LHC environment has shown significant beam-induced heating. Comprehensive studies on the effects of heating with a spare detector module have furthermore revealed that heating effects could be disastrous in the case of the larger beam intensities foreseen for higher luminosity. A temporary solution was implemented and kept the detectors below the critical temperature in 2012. In LS1 all ALFA stations have been removed from LHC and are undergoing an upgrade of the geometry of Roman Pots to minimize the impedance losses. When the stations were re-installed ~4 m distance was added between them to gain level arm in the angular measurement between the stations. The updated geometry of the Roman Pot, together with a system to improve the internal heat transfer and an air cooling system, is expected to keep the temperatures of ALFA detectors below critical limits throughout the LHC Run2 and first results from the performance in 2016 will be presented. ...

  11. Physics prospects with the ALFA and AFP detectors

    CERN Document Server

    Hamal, P; The ATLAS collaboration

    2013-01-01

    We will describe the experimental challenge presented by the measurement of the forward protons at the LHC. The ATLAS ALFA and AFP projects involve the deployment of detectors capable of detecting protons that emerge intact from the interaction with very small scattering angles. In the case of the ALFA detector, located at $\\pm${240}~m from the ATLAS interaction point, this measurement has to be performed using special high $\\beta^*$ beam optics. The detector chosen for the task is a nearly edgeless scintillating fibre tracker capable of making measurements at very low $t$ - below $10^{-3} \\text{GeV}^2$ - in the Nuclear Coulomb interference region. In order to reach these very small $t$ values we need to deploy the detector very near to the beam line utilizing Roman Pots. The main purpose of the ALFA detector is to measure the total p-p cross-section, a fundamental quantity in hadronic physics of importance to particle and to cosmic ray physicists and to provide absolute measurement of luminosity which includ...

  12. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease

    DEFF Research Database (Denmark)

    Pfeffer, Marc A; Burdmann, Emmanuel A; Chen, Chao-Yin

    2009-01-01

    BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately...... tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin...... assigned to darbepoetin alfa and 496 patients assigned to placebo (Pchronic kidney disease...

  13. Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders.

    Science.gov (United States)

    Humaidan, P; Chin, W; Rogoff, D; D'Hooghe, T; Longobardi, S; Hubbard, J; Schertz, J

    2017-03-01

    How does the efficacy and safety of a fixed-ratio combination of recombinant human FSH plus recombinant human LH (follitropin alfa plus lutropin alfa; r-hFSH/r-hLH) compare with that of r-hFSH monotherapy for controlled ovarian stimulation (COS) in patients with poor ovarian response (POR)? The primary and secondary efficacy endpoints were comparable between treatment groups and the safety profile of both treatment regimens was favourable. Although meta-analyses of clinical trials have suggested some beneficial effect on reproductive outcomes with r-hLH supplementation in patients with POR, the definitions of POR were heterogeneous and limit the comparability across studies. Phase III, single-blind, active-comparator, randomized, parallel-group clinical trial. Patients were followed for a single ART cycle. A total of 939 women were randomized (1:1) to receive either r-hFSH/r-hLH or r-hFSH. Randomization, stratified by study site and participant age, was conducted via an interactive voice response system. Women classified as having POR, based on criteria incorporating the ESHRE Bologna criteria, were down-regulated with a long GnRH agonist protocol and following successful down-regulation were randomized (1:1) to COS with r-hFSH/r-hLH or r-hFSH alone. The primary efficacy endpoint was the number of oocytes retrieved following COS. Safety endpoints included the incidence of adverse events, including ovarian hyperstimulation syndrome (OHSS). Post hoc analyses investigated safety outcomes and correlations between live birth and baseline characteristics (age and number of oocytes retrieved in previous ART treatment cycles or serum anti-Müllerian hormone (AMH)). The significance of the treatment effect was tested by generalized linear models (Poisson regression for counts and logistic regression for binary endpoints) adjusting for age and country. Of 949 subjects achieving down-regulation, 939 were randomized to r-hFSH/r-hLH (n = 477) or r-hFSH (n = 462) and received

  14. Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers.

    Science.gov (United States)

    Costa, Marisa Boff; Picon, Paulo Dornelles; Sander, Guilherme Becker; Cuni, Hugo Nodarse; Silva, Carmen Valenzuela; Meireles, Rolando Páez; Góes, Ana Carolina Magalhães Andrade; Batoreu, Nadia Maria; Maia, Maria de Lourdes de Sousa; Albuquerque, Elizabeth Maciel; Matos, Denise Cristina de Souza; Saura, Pedro Lopez

    2018-01-04

    Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 μg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (T max : 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(-1) [p = 0.0153]; t 1/2 : 192 vs. 108 h [p = 0.0218]). BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 ). This trial was retrospectively registered in June 2013.

  15. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study.

    Science.gov (United States)

    Hézode, Christophe; Hirschfield, Gideon M; Ghesquiere, Wayne; Sievert, William; Rodriguez-Torres, Maribel; Shafran, Stephen D; Thuluvath, Paul J; Tatum, Harvey A; Waked, Imam; Esmat, Gamal; Lawitz, Eric J; Rustgi, Vinod K; Pol, Stanislas; Weis, Nina; Pockros, Paul J; Bourlière, Marc; Serfaty, Lawrence; Vierling, John M; Fried, Michael W; Weiland, Ola; Brunetto, Maurizia R; Everson, Gregory T; Zeuzem, Stefan; Kwo, Paul Y; Sulkowski, Mark; Bräu, Norbert; Hernandez, Dennis; McPhee, Fiona; Wind-Rotolo, Megan; Liu, Zhaohui; Noviello, Stephanie; Hughes, Eric A; Yin, Philip D; Schnittman, Steven

    2015-06-01

    To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNAdaclatasvir/peginterferon-alfa-2a/ribavirin for 24 weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12 weeks. Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48. Primary efficacy endpoints were undetectable HCV-RNA at Weeks 4 and 12 (extended rapid virologic response, eRVR) and at 24 weeks post-treatment (sustained virologic response, SVR24) among genotype 1-infected patients. Overall, eRVR was achieved by 54.4% (80/147) of genotype 1-infected patients receiving daclatasvir 20 mg, 54.1% (79/146) receiving 60 mg versus 13.9% (10/72) receiving placebo. SVR24 was achieved among 87 (59.2%), 87 (59.6%), and 27 (37.5%) patients in these groups, respectively. Higher proportions of genotype 4-infected patients receiving daclatasvir 20 mg (66.7%; 8/12) or 60 mg (100.0%; 12/12) achieved SVR24 versus placebo (50.0%; 3/6). A majority of daclatasvir-treated patients achieved PDR and experienced less virologic failure and higher SVR24 rates with a shortened 24-week treatment duration. Adverse events occurred with similar frequency across all treatment groups. The combination of daclatasvir/peginterferon-alfa/ribavirin was generally well tolerated and achieved higher SVR24 rates compared with placebo/peginterferon-alfa/ribavirin among patients infected with HCV genotype 1 or 4. NCT01125189. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  16. Treatment of conjunctival and corneal epithelial neoplasia with retinoic acid and topical interferon alfa-2b: long-term follow-up.

    Science.gov (United States)

    Krilis, Matthew; Tsang, Hughie; Coroneo, Minas

    2012-10-01

    To evaluate the long-term recurrence rate of conjunctival and corneal intraepithelial neoplasia (CIN) treated with retinoic acid and topical interferon alfa-2b. Retrospective, noncomparative, interventional case series. A total of 89 eyes of 89 patients from 1 institution who were treated between September 2003 and February 2010 for CIN lesions used topical interferon alfa 1 million IU/ml drops 4 times daily and retinoic acid 0.01% once every second day. Diagnosis was made by biopsy and impression cytology. Patients' notes and clinical photographs were reviewed, and data were analyzed. All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution. All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution. Complete clinical resolution of the CIN lesions was achieved in 87 of the 89 eyes treated (97.75%). Two of the 89 eyes treated (2.25%) had only a partial response to treatment; of these 2 patients, 1 was taking cyclosporine for keratitis sicca. For the 87 eyes with complete response, resolution occurred after a mean of 1.69 months (range, 19 days to 6.5 months). Mean follow-up after clinical resolution (tumor-free period) was 51.5 months (range, 11-84 months). Four of the 87 patients with complete response developed a mild allergic papillary conjunctivitis that settled on halving the interferon dose to 0.5 million IU drops and reducing the frequency to 3 times daily. Side effects were limited to 1 case of epithelial microcysts and 1 case of marginal keratitis. In this group of patients observed with CIN lesions, combination treatment of topical retinoic acid and interferon alfa-2b was effective in treating lesions with minimal self-limited side effects with faster and greater resolution and a longer tumor-free period compared with studies using interferon alfa-2b alone. We hypothesize that topical

  17. Chikungunya Virus: In Vitro Response to Combination Therapy With Ribavirin and Interferon Alfa 2a.

    Science.gov (United States)

    Gallegos, Karen M; Drusano, George L; D Argenio, David Z; Brown, Ashley N

    2016-10-15

    We evaluated the antiviral activities of ribavirin (RBV) and interferon (IFN) alfa as monotherapy and combination therapy against chikungunya virus (CHIKV). Vero cells were infected with CHIKV in the presence of RBV and/or IFN alfa, and viral production was quantified by plaque assay. A mathematical model was fit to the data to identify drug interactions for effect. We ran simulations using the best-fit model parameters to predict the antiviral activity associated with clinically relevant regimens of RBV and IFN alfa as combination therapy. The model predictions were validated using the hollow fiber infection model (HFIM) system. RBV and IFN alfa were effective against CHIKV as monotherapy at supraphysiological concentrations. However, RBV and IFN alfa were highly synergistic for antiviral effect when administered as combination therapy. Simulations with our mathematical model predicted that a standard clinical regimen of RBV plus IFN alfa would inhibit CHIKV burden by 2.5 log10 following 24 hours of treatment. In the HFIM system, RBV plus IFN alfa at clinical exposures resulted in a 2.1-log10 decrease in the CHIKV burden following 24 hours of therapy. These findings validate the prediction made by the mathematical model. These studies illustrate the promise of RBV plus IFN alfa as a potential therapeutic strategy for the treatment of CHIKV infections. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. ALFA detector, Background removal and analysis for elastic events

    CERN Document Server

    Belaloui, Nazim

    2017-01-01

    I worked on the ALFA project, which has the aim to measure the total cross section in PP collisions as a function of t, the momentum transfer by measuring the scattering angle of the protons. This measurement is done for all available energies; so far 7, 8 and 13 TeV. There are many analysis steps and we have focused on enhancing the signal-to-noise ratio. First of all I tried to be more familiar with ROOT, worked on understanding the code used to access to the data, plotting histograms, then cutting-off background.

  19. Reconocimiento de expresiones faciales empleando memorias asociativas Alfa-Beta

    OpenAIRE

    Márquez Olivera, Moisés Vicente

    2016-01-01

    El presente trabajo de tesis orienta su atención en la compleja tarea del reconocimiento automático de las expresiones faciales, el propósito principal es probar la asertividad y competitividad de las memorias asociativas de tipo Alfa-Beta en el reconocimiento automático de expresiones faciales. La primera parte de la tesis brinda una breve introducción, la cual enfatiza la importancia de las expresiones faciales en la comunicación humana, incluyendo los estudios más relevantes dedicados a...

  20. Alternative method for quantification of alfa-amylase activity Alternativa para quantificação de alfa-amilase

    Directory of Open Access Journals (Sweden)

    DF. Farias

    2010-05-01

    Full Text Available A modification of the sensitive agar diffusion method was developed for macro-scale determination of alfa-amylase. The proposed modifications lower costs with the utilisation of starch as substrate and agar as supporting medium. Thus, a standard curve was built using alfa-amylase solution from Aspergillus oryzae, with concentrations ranging from 2.4 to 7,500 U.mL-1. Clear radial diffusion zones were measured after 4 hours of incubation at 20 °C. A linear relationship between the logarithm of enzyme activities and the area of clear zones was obtained. The method was validated by testing α-amylase from barley at the concentrations of 2.4; 60; 300 and 1,500 U.mL-1. The proposed method turned out to be simpler, faster, less expensive and able to determine on a macro-scale α-amylase over a wide range (2.4 to 7,500 U.mL-1 in scientific investigation as well as in teaching laboratory activities.Modificações foram propostas ao método sensível de difusão em ágar para a macrodeterminação de alfa-amilase. As modificações propostas diminuem os custos, com a utilização de amido como substrato e ágar como meio solidificante. Assim, foi construída uma curva padrão utilizando uma solução de alfa-amilase de Aspergillus oryzae com concentrações variando de 2,4 a 7.500 U.mL-1. Em seguida, as zonas claras de difusão radial foram mensuradas depois de 4 horas de incubação a 20 °C. Foi obtida uma relação linear entre o logaritmo da atividade enzimática e os diâmetros das zonas claras. O método foi validado utilizando-se soluções de alfa-amilase de cevada nas concentrações de 2,4; 60; 300 e 1.500 U.mL-1. O método tornou-se mais simples, rápido, com baixo custo e passível de ser utilizado para macrodeterminação de alfa-amilase em ampla faixa (2,4 a 7.500 U.mL-1 na investigação científica e para fins didáticos em aulas práticas.

  1. Alternative method for quantification of alfa-amylase activity

    Directory of Open Access Journals (Sweden)

    DF. Farias

    Full Text Available A modification of the sensitive agar diffusion method was developed for macro-scale determination of alfa-amylase. The proposed modifications lower costs with the utilisation of starch as substrate and agar as supporting medium. Thus, a standard curve was built using alfa-amylase solution from Aspergillus oryzae, with concentrations ranging from 2.4 to 7,500 U.mL-1. Clear radial diffusion zones were measured after 4 hours of incubation at 20 °C. A linear relationship between the logarithm of enzyme activities and the area of clear zones was obtained. The method was validated by testing α-amylase from barley at the concentrations of 2.4; 60; 300 and 1,500 U.mL-1. The proposed method turned out to be simpler, faster, less expensive and able to determine on a macro-scale α-amylase over a wide range (2.4 to 7,500 U.mL-1 in scientific investigation as well as in teaching laboratory activities.

  2. Stock footage ATLAS-ALFA experiment November 2016

    CERN Multimedia

    2016-01-01

    This footage shows an ALFA station of the ATLAS experiment in the LHC tunnel. This detector aims to measure the elastic proton scattering and to determine from these data the elastic and total cross sections, as well as the luminosity. Altogether there are two times two stations at both sides of ATLAS at Point 1 in a distance of about 240m. Each station consist of two Roman Pots which are equipped with scintillating fiber detectors. They are used under special beam conditions (high beta*) when the detectors are moved close to the circulating LHC beams (as close as 1mm). In standard high intensity LHC runs the Pots remain in parking position. The movie records the composition of an ALFA station at the C-side of ATLAS in the tunnel section *** 7L1. All stations are placed on the outgoing beams where scattered protons are expected. That's why the station mechanics is partly covered by the tubes of incoming beam lines. The stations are placed in between the large boxes with DQR resistors to absorb the magnet curr...

  3. IFN Alfa-2B and BCG Therapy Is An Effective Method In Superficial Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmet Ozdemir

    2012-04-01

    Full Text Available Aim: The initial therapy for superficial bladder carcinoma is the transurethral resection of the tumor. In spite of successful resections, there are 60-79% recurrence and 15% progression rates. Additional therapies are suggested for the treatment of superficial bladder carcinoma. We compared the efficacy of interferon alfa-2b monotherapy with interferon alfa-2b plus Bacillus Calmette Guerin (BCG combination therapy with urine interleukin (IL 2, 6 and 10 levels of patients with superficial bladder carcinoma. Material and Method: The patients who underwent TUR-BT for superficial bladder tumor (pathological staging Ta-T1 between 2004 and 2007 at our hospital included in this prospective study. Intravesical immunotherapy was administered once a week for 6 weeks and there after a month for 6 months, starting 4 weeks after TUR-BT. IL levels were measured. Results: IL-2, IL-6 and IL- 10 levels in urine samples were taken at 2nd and 4th hours of intravesical therapy. A statistically significant difference was observed between mean urine IL-2 levels of patients treated with IFN%u03B1-2b monotherapy and IFN%u03B1- 2b plus BCG combination both at 2nd and 4th hours. (p=0.05 In IFN%u03B1-2b plus BCG combination group, there was a statistical significant difference between stages regarding IL-2 and IL-6 levels (p=0.05. Among patients with G3 tumors, IL-2 levels were higher at 2 and 4 hours (p=0.05 but there was no significant difference in IL-6 and IL-10 levels in this group of patients regardless of intravesical therapy received (p=0.05. Discussion: IFN%u03B1-2b and BCG combination therapy is a reliable and effective therapy in the management of superficial bladder tumors.

  4. Evaluating the transport layer of the ALFA framework for the Intel® Xeon Phi™ Coprocessor

    Science.gov (United States)

    Santogidis, Aram; Hirstius, Andreas; Lalis, Spyros

    2015-12-01

    The ALFA framework supports the software development of major High Energy Physics experiments. As part of our research effort to optimize the transport layer of ALFA, we focus on profiling its data transfer performance for inter-node communication on the Intel Xeon Phi Coprocessor. In this article we present the collected performance measurements with the related analysis of the results. The optimization opportunities that are discovered, help us to formulate the future plans of enabling high performance data transfer for ALFA on the Intel Xeon Phi architecture.

  5. AFP and ALFA detectors as a momentum spectrometer system - feasibility study

    CERN Document Server

    ABDUL KHALEK, Rabah

    2015-01-01

    We consider a possibility to measure a leading proton momentum using simultaneously the AFP and ALFA detectors. The idea is based on the simple fact that the proton trajectory through the magnetic field between the AFP and ALFA$_{1}$ detectors, depends on the proton's momentum loss $\\xi$. The feasibility of the proton momentum measurement is directly related to the availability of the magnetic fields and their configuration, the overlap between ALFA and AFP detectors and their resolutions as well as energy losses and the multiple scattering effect that could wash away little actions from the magnets on the proton.

  6. Etude structurale et chimique de la lignine d'Alfa et sa valorisation comme macromonomère et/ou précurseur du charbon actif

    OpenAIRE

    Berrima, Besma

    2015-01-01

    Lignin precipitated from black liquor of alfa (Stipa tenacissima) soda cooking before being carefully characterized and valorized following two different approaches: (i) its utilization after chemical modification in view of preparing rigid polyurethane foams; and (ii) its simple pyrolysis simple, in order to prepare charcoal. In fact, a comparative study concerning the careful characterization of the hydroxyl functions was realized using several methods and techniques, namely: the conductime...

  7. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial.

    Science.gov (United States)

    Eggermont, Alexander M M; Suciu, Stefan; Santinami, Mario; Testori, Alessandro; Kruit, Wim H J; Marsden, Jeremy; Punt, Cornelis J A; Salès, François; Gore, Martin; Mackie, Rona; Kusic, Zvonko; Dummer, Reinhard; Hauschild, Axel; Musat, Elena; Spatz, Alain; Keilholz, Ulrich

    2008-07-12

    Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00006249. All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3.8-33.4) months. At 3.8 (3.2-4.2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0.82, 95% CI 0.71-0.96; p=0.01); the 4-year rate of recurrence-free survival was 45.6% (SE 2.2) in the interferon group and 38.9% (2.2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in

  8. Fast Radio Burst Discovered in the Arecibo Pulsar ALFA Survey

    Science.gov (United States)

    Spitler, L. G.; Cordes, J. M.; Hessels, J. W. T.; Lorimer, D. R.; McLaughlin, M. A.; Chatterjee, S.; Crawford, F.; Deneva, J. S.; Kaspi, V. M.; Wharton, R. S.; Allen, B.; Bogdanov, S.; Brazier, A.; Camilo, F.; Freire, P. C. C.; Jenet, F. A.; Karako-Argaman, C.; Knispel, B.; Lazarus, P.; Lee, K. J.; van Leeuwen, J.; Lynch, R.; Ransom, S. M.; Scholz, P.; Siemens, X.; Stairs, I. H.; Stovall, K.; Swiggum, J. K.; Venkataraman, A.; Zhu, W. W.; Aulbert, C.; Fehrmann, H.

    2014-08-01

    Recent work has exploited pulsar survey data to identify temporally isolated, millisecond-duration radio bursts with large dispersion measures (DMs). These bursts have been interpreted as arising from a population of extragalactic sources, in which case they would provide unprecedented opportunities for probing the intergalactic medium; they may also be linked to new source classes. Until now, however, all so-called fast radio bursts (FRBs) have been detected with the Parkes radio telescope and its 13-beam receiver, casting some concern about the astrophysical nature of these signals. Here we present FRB 121102, the first FRB discovery from a geographic location other than Parkes. FRB 121102 was found in the Galactic anti-center region in the 1.4 GHz Pulsar Arecibo L-band Feed Array (ALFA) survey with the Arecibo Observatory with a DM = 557.4 ± 2.0 pc cm-3, pulse width of 3.0 ± 0.5 ms, and no evidence of interstellar scattering. The observed delay of the signal arrival time with frequency agrees precisely with the expectation of dispersion through an ionized medium. Despite its low Galactic latitude (b = -0.°2), the burst has three times the maximum Galactic DM expected along this particular line of sight, suggesting an extragalactic origin. A peculiar aspect of the signal is an inverted spectrum; we interpret this as a consequence of being detected in a sidelobe of the ALFA receiver. FRB 121102's brightness, duration, and the inferred event rate are all consistent with the properties of the previously detected Parkes bursts.

  9. Factor de necrosis tumoral alfa en pacientes con preeclampsia a término y pretérmino

    Directory of Open Access Journals (Sweden)

    Eduardo Reyna Villasmil

    2012-07-01

    necrosis tumoral alfa, preeclampsia, citokinas. Tumor necrosis factor alpha in term and pre-term preeclamptic patients Abstract The objective of research was to know and compare concentrations of tumor necrosis factor alpha in term and pre-term preeclamptic patients. Fifty patients were selected. Twenty pre-term preeclamptic patients (group A and thirty term preeclamptic patients (group B were selected. Blood samples for tumor necrosis factor alpha was collected in all patients before labor and immediately after diagnosis of preeclampsia. There were not significant differences related to a maternal age and body mass index at the moment of collecting samples. There were significant differences between groups in gestational age (p < 0,00001. Mean value of systolic blood pressure in group A was 149.4 ± 11.3 mmHg while in patients of group B was 148.1 ± 12.3 mmHg (p = 0.7071 and mean value od diastolic blood pressure in group A was 103.8 ± 8,6 mmHg and in group B was 102.7 ± 7.9 mmHg (p = 0,6436. Tumor necrosis factor alpha concentrations were similar in study group A (98.2 ± 45.1 pg/mL compared with group B (96.6 ± 48.7 pg/mL; p = 0.9072. When correlation was calculated between values of necrosis tumor factor alpha with values of blood pressure there was observed that there was no correlation with systolic blood pressure (r = 0.129; p = 0.374 nor diastolic blood pressure (r = 0.158; p = 0.273. It is concluded that blood concentrations of tumor necrosis factor alfa were similar in preeclamptic patients wit pre-term and term pregnacy. Correlation of tumor necrosis factor alfa with values of systolic and diastolic blood pressure were not significant.

  10. Metodos para promediar coeficientes alfa en los estudios de generalizacion de la fiabilidad

    National Research Council Canada - National Science Library

    Lopez-Pina, Jose A; Sanchez-Meca, Julio; Lopez-Lopez, Jose A

    2012-01-01

    ... que factores de los estudios pueden explicar su variabilidad. Se han propuesto en la literatura diferentes procedimientos para promediar un conjunto de coeficientes alfa independientes y no existe un consenso actual sobre que metodos son los mejores...

  11. Towards a Total Cross Section Measurement with the ALFA Detector at ATLAS

    CERN Document Server

    Trzebiński, Maciej

    2013-01-01

    The main goals of the Absolute Luminosity For ATLAS (ALFA) detector is to provide an absolute luminosity and total cross section measurement. The measurement method used, the detector alignment and the quality of the collected data are discussed.

  12. Factor de necrosis tumoral alfa en una población infanto-juvenil con sobrepeso

    National Research Council Canada - National Science Library

    Teresita del R. Carrizo; Elba I. Díaz; María S. Velarde; María M. Prado; María C. Bazán; Adela V. Abregú

    2013-01-01

    El sobrepeso infantil está asociado a sobrepeso/obesidad en la edad adulta. El tejido adiposo en obesos produce una cantidad incrementada de citoquinas proinflamatorias como el factor de necrosis tumoral alfa (TNF...

  13. Alfa tahab TeliaSonerat Türgis üle pakkuda / Tõnis Arnover

    Index Scriptorium Estoniae

    Arnover, Tõnis, 1952-

    2005-01-01

    TeliaSoneraga, kellele kuulub 37 protsenti Türgi operaatorfirma Turkcell aktsiatest, konkureerib täiendava 27 protsendise aktsiapaki ostmises Venemaa operaatorfirmaga Alfa Telecom. Lisa: Kaasosanike huvid põrkuvad. Diagramm: Konkurendid Vene MegaFonis

  14. Measurement of the total cross section with ALFA Detector at ATLAS

    CERN Document Server

    Trzebinski, M; The ATLAS collaboration

    2017-01-01

    The main goals of the Absolute Luminosity For ATLAS (ALFA) detector is to provide an absolute luminosity and total cross section measurement. The measurement method used, the detector alignment and the quality of the collected data are discussed.

  15. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

    Science.gov (United States)

    McMurray, John J.V.; Anand, Inder S.; Diaz, Rafael; Maggioni, Aldo P.; O'Connor, Christopher; Pfeffer, Marc A.; Solomon, Scott D.; Tendera, Michal; van Veldhuisen, Dirk J.; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B.; Amuchastegui, M.; Belziti, C.; Bluguermann, J.; Caccavo, M.; Cartasegna, L.; Colque, R.; Cuneo, C.; Fernandez, A.; Gabito, A.; Goicochea, R.; Gonzalez, M.; Gorosito, V.; Grinfeld, L.; Hominal, M.; Kevorkian, R.; Litvak Bruno, M.; Llanos, J.; Mackinnon, I.; Manuale, O.; Marzetti, E.; Nul, D.; Perna, E.; Riccitelli, M.; Sanchez, A.; Santos, D.; Schygiel, P.; Toblli, J.; Vogel, D.; Aggarwal, A.; Amerena, J.; De Looze, F.; Fletcher, P.; Hare, D.; Ireland, M.; Krum, H.; Lattimore, J.; Marwick, T.; Sindone, A.; Thompson, P.; Waites, J.; Altenberger, J.; Ebner, C.; Lenz, K.; Pacher, R.; Poelzl, G.; Charlier, F.; de Ceuninck, M.; De Keulenaer, G.; Dendale, P.; Maréchal, P.; Mullens, W.; Thoeng, J.; Vanderheyden, M.; Vanhaecke, J.; Weytjens, C.; Wollaert, B.; Albuquerque, D.; Almeida, D.; Aspe y Rosas, J.; Bocchi, E.; Bordignon, S.; Clausell, N.; Kaiser, S.; Leaes, P.; Martins Alves, S.; Montera, M.; Moura, L.; Pereira de Castro, R.; Rassi, S.; Reis, A.; Saraiva, J.; Simões, M.; Souza Neto, J.; Teixeira, M.; Benov, H.; Chompalova, B.; Donova, T.; Georgiev, P.; Gotchev, D.; Goudev, A.; Grigorov, M.; Guenova, D.; Hergeldjieva, V.; Ivanov, D.; Kostova, E.; Manolova, A.; Marchev, S.; Nikolov, F.; Popov, A.; Raev, D.; Tzekova, M.; Czarnecki, W.; Giannetti, N.; Haddad, H.; Heath, J.; Huynh, T.; Lepage, S.; Liu, P.; Lonn, E.; Ma, P.; Manyari, D.; Moe, G.; Parker, J.; Pesant, Y.; Rajda, M.; Ricci, J.; Roth, S.; Sestier, F.; Sluzar, V.; Sussex, B.; Vizel, S.; Antezana, G.; Bugueno, C.; Castro, P.; Conejeros, C.; Manriquez, L.; Martinez, D.; Potthoff, S.; Stockins, B.; Vukasovic, J.; Gregor, P.; Herold, M.; Jerabek, O.; Jirmar, R.; Kuchar, R.; Linhart, A.; Podzemska, B.; Soucek, M.; Spac, J.; Spacek, R.; Vodnansky, P.; Bronnum-Schou, J.; Clemmensen, K.; Egstrup, K.; Jensen, G.; Kjoller-Hansen, L.; Kober, L.; Markenvard, J.; Rokkedal, J.; Skagen, K.; Torp-Pedersen, C.; Tuxen, C.; Videbak, L.; Laks, T.; Vahula, V.; Harjola, V.; Kettunen, R.; Kotila, M.; Bauer, F.; Cohen Solal, A.; Coisne, D.; Davy, J.; De Groote, P.; Dos Santos, P.; Funck, F.; Galinier, M.; Gibelin, P.; Isnard, R.; Neuder, Y.; Roul, G.; Sabatier, R.; Trochu, J.; Anker, S.; Denny, S.; Dreykluft, T.; Flesch, M.; Genth-Zotz, S.; Hambrecht, R.; Hein, J.; Jeserich, M.; John, M.; Kreider-Stempfle, H.; Laufs, U.; Muellerleile, K.; Natour, M.; Sandri, M.; Schäufele, T.; von Hodenberg, E.; Weyland, K.; Winkelmann, B.; Tse, H.; Yan, B.; Barsi, B.; Csikasz, J.; Dezsi, C.; Edes, I.; Forster, T.; Karpati, P.; Kerekes, C.; Kis, E.; Kosa, I.; Lupkovics, G.; Nagy, A.; Preda, I.; Ronaszeki, A.; Tomcsanyi, J.; Zamolyi, K.; Agarwal, D.; Bahl, V.; Bordoloi, A.; Chockalingam, K.; Chopda, M.; Chopra, V.; Dugal, J.; Ghaisas, N.; Ghosh, S.; Grant, P.; Hiremath, S.; Iyengar, S.; Jagadeesa Subramania, B.; Jain, P.; Joshi, A.; Khan, A.; Mullasari, A.; Naik, S.; Oomman, A.; Pai, V.; Pareppally Gopal, R.; Parikh, K.; Patel, T.; Prakash, V.; Sastry, B.; Sathe, S.; Sinha, N.; Srikanthan, V.; Subburamakrishnan, P.; Thacker, H.; Wander, G.; Admon, D.; Katz, A.; Klainman, E.; Lewis, B.; Marmor, A.; Moriel, M.; Mosseri, M.; Shotan, A.; Weinstein, J.; Zimlichman, R.; Agostoni, P.; Albanese, M.; Alunni, G.; Bini, R.; Boccanelli, A.; Bolognese, L.; Campana, C.; Carbonieri, E.; Carpino, C.; Checco, L.; Cosmi, F.; D'Angelo, G.; De Cristofaro, M.; Floresta, A.; Fucili, A.; Galvani, M.; Ivleva, A.; Marra, S.; Musca, G.; Peccerillo, N.; Perrone Filardi, P.; Picchio, E.; Russo, T.; Scelsi, L.; Senni, M.; Tavazzi, L.; Erglis, A.; Jasinkevica, I.; Kakurina, N.; Veze, I.; Volans, E.; Bagdonas, A.; Berukstis, E.; Celutkiene, J.; Dambrauskaite, A.; Jarasuniene, D.; Luksiene, D.; Rudys, A.; Sakalyte, G.; Sliaziene, S.; Aguilar-Romero, R.; Cardona-Muñoz, E.; Castro-Jimenez, J.; Chavez-Herrera, J.; Chuquiure Valenzuela, E.; De la Pena, G.; Herrera, E.; Leiva-Pons, J.; Lopez Alvarado, A.; Mendez Machado, G.; Ramos-Lopez, G.; Basart, D.; Buijs, E.; Cornel, J.; de Leeuw, M.; Dijkgraaf, R.; Dunselman, P.; Freericks, M.; Hamraoui, K.; Lenderlink, T.; Linssen, G.; Lodewick, P.; Lodewijks, C.; Lok, D.; Nierop, P.; Ronner, E.; Somsen, A.; van Dantzig, J.; van der Burgh, P.; van Kempen, L.; van Vlies, B.; Voors, A.; Wardeh, A.; Willems, F.; Dickstein, K.; Gundersen, T.; Hole, T.; Thalamus, J.; Westheim, A.; Dabrowski, M.; Gorski, J.; Korewicki, J.; Kuc, K.; Miekus, P.; Musial, W.; Niegowska, J.; Piotrowski, W.; Podolec, P.; Polonski, L.; Ponikowski, P.; Rynkiewicz, A.; Szelemej, R.; Trusz-Gluza, M.; Ujda, M.; Wojciechowski, D; Wysokinski, A.; Camacho, A.; Fonseca, C.; Monteiro, P.; Apetrei, E.; Bruckner, I.; Carasca, E.; Coman, I.; Datcu, M.; Dragulescu, S.; Ionescu, P.; Iordachescu-Petica, D.; Manitiu, I.; Popa, V.; Pop-Moldovan, A.; Radoi, M.; Stamate, S.; Tomescu, M.; Vita, I.; Aroutiounov, G.; Ballyuzek, M.; Bart, B.; Churina, S.; Glezer, M.; Goloshchekin, B.; Ivleva, A.; Kobalava, Z.; Kostenko, V.; Lopatin, Y.; Martynov, A.; Orlov, V.; Semernin, E.; Shogenov, Z.; Sidorenko, B.; Skvortsov, A.; Storzhakov, G.; Sulimov, V.; Talibov, O.; Tereshenko, S.; Tsyrline, V.; Zadionchenko, V.; Zateyshchikov, D.; Dzupina, A.; Hranai, M.; Kmec, J.; Micko, K.; Murin, J.; Pella, D.; Sojka, G.; Spisak, V.; Vahala, P.; Vinanska, D.; Badat, A.; Bayat, J.; Dawood, S.; Delport, E.; Ellis, G.; Garda, R.; Klug, E.; Mabin, T.; Naidoo, D.; Pretorius, M.; Ranjith, N.; Van Zyl, L.; Weich, H.; Anguita, M.; Berrazueta, J.; Bruguera i Cortada, J.; de Teresa, E.; Gómez Sánchez, M.; González Juanatey, J.; Gonzalez-Maqueda, I.; Jordana, R.; Lupon, J.; Manzano, L.; Pascual Figal, D.; Pulpón, L.; Recio, J.; Ridocci Soriano, F.; Rodríguez Lambert, J.; Roig Minguell, E.; Roig Minguell, E.; Romero, J.; Valdovinos, P.; Klintberg, L.; Kronvall, T.; Lycksell, M.; Morner, S.; Rydberg, E.; Swedberg, K.; Timberg, I.; Wikstrom, G.; Moccetti, T.4; Ashok, J.; Banerjee, P.; Carr-White, G.; Cleland, J.; Connolly, E.; Francis, M.; Greenbaum, R.; Kadr, H.; Lindsay, S.; McMurray, J.; Megarry, S.; Memon, A.; Murdoch, D.; Senior, R.; Squire, I.; Tan, L.; Witte, K.; Adams, K.; Adamson, P.; Adler, A.; Altschul, L.; Altschuller, A.; Amirani, H.; Anand, I.; Andreou, C.; Ansari, M.; Antonishen, M.; Banchs, H.; Banerjee, S.; Banish, D.; Bank, A.; Barbagelata, A.; Barnard, D.; Bellinger, R.; Benn, A.; Berk, M.; Berry, B.; Bethala, V.; Bilazarian, S.; Bisognano, J.; Bleyer, F.; Blum, M.; Boehmer, J.; Bouchard, A.; Boyle, A.; Bozkurt, B.; Brown, C.; Burlew, B.; Burnham, K.; Butler, J.; Call, J.; Cambier, P.; Cappola, T.; Carlson, R.; Chandler, B.; Chandra, R.; Chandraratna, P.; Chernick, R.; Colan, D.; Colfer, H.; Colucci, W.; Connelly, T.; Costantini, O.; Dadkhah, S.; Dauber, I.; Davis, J.; Davis, S.; Denning, S.; Drazner, M.; Dunlap, S.; Egbujiobi, L.; Elkayam, U.; Elliott, J.; El-Shahawy, M.; Essandoh, L.; Ewald, G.; Fang, J.; Farhoud, H.; Felker, G.; Fernandez, J.; Festin, R.; Fishbein, G.; Florea, V.; Flores, E.; Floro, J.; Gabris, M.; Garg, M.; Gatewood, R.; Geller, M.; Ghali, J.; Ghumman, W.; Gibbs, G.; Gillespie, E.; Gilmore, R.; Gogia, H.; Goldberg, L.; Gradus-Pizlo, I.; Grainger, T.; Gudmundsson, G.; Gunawardena, D.; Gupta, D.; Hack, T.; Hall, S.; Hamroff, G.; Hankins, S.; Hanna, M.; Hargrove, J.; Haught, W.; Hauptman, P.; Hazelrigg, M.; Herzog, C.; Heywood, J.; Hill, T.; Hilton, T.; Hirsch, H.; Hunter, J.; Ibrahim, H.; Imburgia, M.; Iteld, B.; Jackson, B.; Jaffrani, N.; Jain, D.; Jain, A.; James, M.; Jimenez, J.; Johnson, E.; Kale, P.; Kaneshige, A.; Kapadia, S.; Karia, D.; Karlsberg, R.; Katholi, R.; Kerut, E.; Khoury, W.; Kipperman, R.; Klapholz, M.; Kosinski, E.; Kozinn, M.; Kraus, D.; Krueger, S.; Krum, H.; Kumar, S.; Lader, E.; Lee, C.; Levy, W.; Lewis, E.; Light-McGroary, K.; Loh, I.; Lombardi, W.; Machado, C.; Maislos, F.; Mancini, D.; Markus, T.; Mather, P.; McCants, K.; McGrew, F.; McLaurin, B.; McMillan, E.; McNamara, D.; Meyer, T.; Meymandi, S.; Miller, A.; Minami, E.; Modi, M.; Mody, F.; Mohanty, P.; Moscoso, R.; Moskowitz, R.; Moustafa, M.; Mullen, M.; Naz, T.; Noonan, T.; O'Brien, T.; Oellerich, W.; Oren, R.; Pamboukian, S.; Pereira, N.; Pitt, W.; Porter, C.; Prabhu, S.; Promisloff, S.; Ratkovec, R.; Richardson, R.; Ross, A.; Saleh, N.; Saltzberg, M.; Sarkar, S.; Schmedtje, J.; Schneider, R.; Schuyler, G.; Shanes, J.; Sharma, A.; Siegel, C.; Siegel, R.; Silber, D.; Singh, V.; Singh, N.; Singh, J.; Sklar, J.; Small, R.; Smith, A.; Smith, E.; Smith, E.; Smull, D.; Sotolongo, R.; Staniloae, C.; Stapleton, D.; Steele, P.; Stehlik, J.; Stein, M.; Tang, W.; Thadani, U.; Torre-Amoine, G.; Trichon, B.; Tsai, C.; Tummala, R.; Van Bakel, A.; Vicari, R.; Vijay, N.; Vijayaraghavan, K.; Vittorio, T.; Vossler, M.; Wagoner, L.; Wallis, D.; Ward, N.; Widmer, M.; Wight, J.; Wilkins, C.; Williams, C.; Williams, G.; Winchester, M.; Winkel, E.; Wittmer, B.; Wood, D.; Wormer, D.; Wright, R.; Xu, Z.; Yasin, M.; Zolty, R.

    2013-01-01

    Aims This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Methods and results Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L. Conclusion The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity. PMID:23329651

  16. Corifollitropin alfa in a long GnRH agonist protocol: proof of concept trial.

    Science.gov (United States)

    Fatemi, Human M; Oberyé, Janine; Popovic-Todorovic, Biljana; Witjes, Han; Mannaerts, Bernadette; Devroey, Paul

    2010-10-01

    Fifty healthy women, aged 18-39 years with no known risk of ovarian hyperstimulation were treated with 100 or 150 μg corifollitropin alfa (dependent on body weight) in a long GnRH agonist protocol. At these doses, corifollitropin alfa initiated and supported growth of a large cohort of follicles during the first week of ovarian stimulation. Copyright © 2010. Published by Elsevier Inc.

  17. Treatment of indolent primary cutaneous B-cell lymphomas with subcutaneous interferon-alfa.

    Science.gov (United States)

    Vandersee, Staffan; Terhorst, Dorothea; Humme, Daniel; Beyer, Marc

    2014-04-01

    Interferon-alfa is used in the treatment of primary cutaneous B-cell lymphoma (PCBCL). Therapy with interferon-alfa has thus far been reported solely in case reports and small case series, mostly describing intralesional use. We sought to evaluate efficacy, response rate, time to response, duration of response, and safety of subcutaneously administered interferon-alfa for the treatment of cutaneous B-cell lymphoma. We conducted a retrospective chart analysis of patients given the diagnosis of PCBCL and treated with interferon-alfa subcutaneously at a tertiary referral center. Fifteen patients with indolent subtypes of PCBCL were identified. The overall response rate was 66.7%; all responding patients went into complete remission. Response was not significantly associated with the maximum tolerated dose. Within the median follow-up time of 40 months, 90% of the responders experienced a relapse; median duration of response was 15.5 months. Adverse events were predominantly mild and in no case led to cessation of therapy. Retrospective nature of the analysis and small number of patients because of scarcity of the disease are limitations. Treatment of indolent PCBCL with subcutaneously injected interferon-alfa demonstrated good response rates and tolerability. Response was not dose dependent. Relapses were observed in nearly all responding patients raising the question of interferon-alfa maintenance therapy in PCBCL. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  18. Cure of hepatitis C virus infection without interferon alfa: scientific basis and current clinical evidence.

    Science.gov (United States)

    Thomas, David L

    2014-01-01

    Cure of hepatitis C virus (HCV) infection is achievable without interferon alfa through the use of new direct-acting antiviral (DAA) drugs. In this era of interferon alfa-sparing therapy, however, interferon alfa sensitivity still matters, even as it turns out, if interferon alfa is not used. Inclusion of ribavirin in the treatment regimen remains a factor in treatment response, as does duration of treatment. HCV genotype and subtype remain relevant considerations in choosing a treatment regimen, and viral resistance may emerge when treatment fails. The potency and barrier to resistance of new DAAs and the use of appropriately designed interferon alfa-sparing combinations can overcome obstacles to cure posed by HCV resistance, interferon alfa resistance, and differences in response based on HCV genotype and subtype. Studies demonstrating the use of new DAAs to overcome these obstacles are discussed. This article summarizes a presentation by David L. Thomas, MD, MPH, at the IAS-USA continuing education program held in New York, New York, in June 2013.

  19. Topical interferon alfa-2b for management of ocular surface squamous neoplasia in 23 cases: outcomes based on American Joint Committee on Cancer classification.

    Science.gov (United States)

    Shah, Sanket U; Kaliki, Swathi; Kim, H Jane; Lally, Sara E; Shields, Jerry A; Shields, Carol L

    2012-02-01

    To evaluate the efficacy of topical interferon alfa-2b in the management of ocular surface squamous neoplasia (OSSN). Clinically visible OSSN in 20 patients (23 tumors) was managed with topical interferon alfa-2b, 1 million IU/mL, 4 times daily. Tumor control and complications were evaluated according to American Joint Committee on Cancer classification. Complete tumor resolution was achieved in 19 tumors (83%) following topical interferon alfa-2b treatment for a median period of 6 months (mean, 7 months; range, 1-12 months) and maintained for up to 24 months of follow-up. Of the 4 tumors with partial resolution (17%), tumor surface area was reduced 44% (median) during 4 months (median) without further response and alternative therapy was used. Based on American Joint Committee on Cancer classification, complete control was achieved in 2 of 3 Tis (67%), 17 of 20 T3 (85%), 19 of 23 N0 (83%), and 19 of 23 M0 (83%) category tumors. Tumors involving the cornea responded earlier compared with those without corneal involvement (P = .01). Initial tumor size did not correlate with time to response (P = .27). Recurrence was noted in 1 case (Tis, 4%) at 3 months. Adverse effects included conjunctival hyperemia (2 [10%]), follicular hypertrophy (2 [10%]), giant papillary conjunctivitis (1 [5%]), irritation (1 [5%]), corneal epithelial defect (1 [5%]), and flulike symptoms (1 [5%]); all resolved within 1 month of medication discontinuation. According to American Joint Committee on Cancer classification, complete control with topical interferon alfa-2b can be achieved in 67% of Tis, 85% of T3, and 83% of all OSSN.

  20. Efficacy of daclatasvir plus peginterferon alfa and ribavirin for patients with chronic hepatitis C genotype 4 infection

    Directory of Open Access Journals (Sweden)

    Hussien Ahmed

    2017-03-01

    Full Text Available Clinical trials evaluating the safety and efficacy of daclatasvir for chronic hepatitis C virus (HCV genotype 4 infection are scarce and yet with small sample sizes. Therefore, we conducted this systematic review to investigate the efficacy of daclatasvir in HCV genotype 4 treatment. A computer literature search of PubMed, Scopus, Embase, Ovid, Web of knowledge, and Cochrane central was conducted. We selected studies comparing daclatasvir plus peginterferon-alfa/ribavirin versus placebo plus peginterferon-alfa/ribavirin in patients with HCV genotype 4 infection. Pooling data from two randomized controlled trials (n = 154 patients showed that daclatasvir/peg-interferon/ribavirin treatment achieved a moderate sustained virologic response rate of 76% after 12 weeks and of 79% after 24 weeks. The daclatasvir containing regimen was superior to the placebo containing regimen in terms of virologic response rates after 12 weeks (RR=1.9% CI 1.3 to 2.6 and 24 weeks (RR=1.8% CI 1.3 to 2.5. More effective regimens are needed for HCV genotype 4.

  1. Combination of interferon alfa-2b and ribavirin in relapsed or nonresponding chronic hepatitis C patients following interferon therapy

    Directory of Open Access Journals (Sweden)

    Laurentius A. Lesmana

    2001-12-01

    Full Text Available Twenty six patients (pts with chronic hepatitis C (CHC who reLapsed or non-responded following.interferon (IFN therapy were given lFN alfa-2b 3   MIU three times a week for 48 weeks in combination with Ribavirin 800-1000 mg daily 2I (80,8% of the 26.pts completed the study consisted of 12 relapsers and 9 non-responders. Five pts dropped out due to drug adverse events in three pts and non-drug related reason in the other two. In the relapsed group complete response, relapse and sustained response rates were obtained in 9/12(75%, 2/2 (16,5% and 7/12(58,3% pts respectively. In the non- responding group, these figures were 3/9 (33,3%, 1/9(I1,1%, and 2/9(22,2% pts, respectively. The most frequent adverse event was flu-like syndrome, which was found in 18 pts (85,7%. Combination therapy of IFN alfa-2b and ribavirin may induce sustained virological response in relapsed and non-responding CHC patients. This combination therapy is more effective for relapsers compared to for non-responders. (Med J Indones 2001; 10: 214-8Keywords: Chronic hepatitis C, combination therapy, interferon, ribavirin

  2. Influence of wool and thermo-binder fibers relative fractions on the adhesion of non-woven Alfa fibers reinforced unsaturated polyester hybrid composites

    Science.gov (United States)

    Amin Omri, Med; Triki, A.; Ben Hassen, Med; Arous, M.; Bulou, A.

    2016-10-01

    Alfa/wool/thermo-binder fibers hybrid composites were investigated in order to analyze adhesion state. Bearing in mind the chemical structure of wool and thermo-binder fibers, this study revealed a good compatibility between the reinforcement and the matrix. Dielectric measurements revealed the presence of two dielectric relaxations in the composite. The first relaxation was attributed to the α mode relaxation and the second one was associated with the conductivity noted for high temperature. This study allowed the analysis of the interfacial polarization effect using the Havrilliak-Negami model in the electric modulus formalism. The lowness of this relaxation intensity revealed a good adhesion of the fibers in the matrix. Differential Scanning Calorimetry (DSC) showed a slow decrease of the Tg glass transition temperature compared to the matrix, which could be explained by the existence of interactions between the fibers and the matrix. Vibrational analysis, based on FTIR measurements, showed a less hydrophilic character of Alfa fibers owing to a basic dissociation that occurs between the wool fibers and the water molecules associated with Alfa fibers. Furthermore, adhesion mechanism in the composite material was established by covalent and hydrogen bonds. Tensile testing performed on this composite confirmed that such adhesion was improved by increasing the thermo-binder fibers relative fraction.

  3. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study.

    Science.gov (United States)

    Omrani, Ali S; Saad, Mustafa M; Baig, Kamran; Bahloul, Abdelkarim; Abdul-Matin, Mohammed; Alaidaroos, Amal Y; Almakhlafi, Ghaleb A; Albarrak, Mohammed M; Memish, Ziad A; Albarrak, Ali M

    2014-11-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used χ(2) and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5·88 × 10(9)/L [SD 3·95] vs 9·88 × 10(9)/L [6·63]; p=0·023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0·004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0·54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4·32 g/L [SD 2·47] vs 2·14 g/L [1·90]; p=0·002). In patients with

  4. Incidence of neutropenia and infections during combination treatment of chronic hepatitis C with pegylated interferon alfa-2a or alfa-2b plus ribavirin.

    Science.gov (United States)

    Antonini, M G; Babudieri, S; Maida, I; Baiguera, C; Zanini, B; Fenu, L; Dettori, G; Manno, D; Mura, M S; Carosi, G; Puoti, M

    2008-06-01

    Combination therapy with pegylated interferon (peginterferon) plus ribavirin is associated with several side effects, including neutropenia and infection. To evaluate the incidence of neutropenia and infection between all consecutive patients with hepatitis C who were treated in two centers with peginterferon-alfa-2a and peginterferon-alfa-2b, in combination with ribavirin and actively monitored for occurrence of any infection. A total of 319 consecutive patients with chronic hepatitis C received once-weekly peginterferon alfa-2b at a weight-adjusted dose (n=162) or peginterferon alfa-2a at a flat dose (n=157), plus ribavirin. Neutropenia was observed in 53 patients overall (17%). There were 73 infections in 73 subjects (23% of the treated population); 4/73 required hospitalization. Infections included respiratory infections (n=23), cellulitis (n=17), dental abscesses (n=13), gastroenteric infections (n=2), and other types of infections (n=18). The incidence of all infections was significantly associated with age, especially over 60 years (pinterferon. During the treatment with pegylated interferons and ribavirin, we did not find a correlation between neutropenia and infections. This result provides a support for the notion that current guidelines for pegylated interferons dose reduction in the treatment of chronic hepatitis C for hematologic toxicity could be overly strict.

  5. Forward Detectors in ATLAS: ALFA, ZDC and LUCID

    CERN Document Server

    Fabbri, L; The ATLAS collaboration

    2009-01-01

    In order to determine the experimental cross sections for the observed physics processes, an estimation of the absolute luminosity is needed. In fact a careful study of “well known” processes will be one of the first steps of the LHC experiments as it can provide possible signatures of new physics which consist in deviations with respect to the Standard Model (SM) predictions. The methodologies for luminosity monitoring and total cross section estimation at the LHC will be reviewed in this talk along with the dedicated detectors of the ATLAS experiment. ATLAS will make extensive usage of the detectors in the forward region each one with a different task: LUCID (LUminosity measurement using Cherenkov Integrating Detector) is a system of 40 (2 x 20) Cherenkov tubes, surrounding the beam pipe at about 17 m from the interaction region. It will be able to monitor the collision-by-collision luminosity by detecting and counting the number of charged particles coming from the impact point. ALFA (Absolute Luminosi...

  6. The clinical effectiveness and cost-effectiveness of peginterferon alfa and ribavirin for the treatment of chronic hepatitis C in children and young people: a systematic review and economic evaluation.

    Science.gov (United States)

    Hartwell, Debbie; Cooper, Keith; Frampton, Geoff K; Baxter, Louise; Loveman, Emma

    2014-10-01

    Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children. To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years. Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched from inception to November 2012. Bibliographies of retrieved papers, key hepatitis C websites and symposia and manufacturers' submissions to the National Institute for Health and Care Excellence were also searched, and clinical experts were contacted. Systematic reviews of clinical effectiveness and cost-effectiveness were conducted, including studies of health-related quality of life (HRQoL), following standard guidelines to ensure methodological rigour. Clinical effectiveness studies were included if they were in children and young people aged 3-17 years with chronic compensated HCV of any severity, including those with human immunodeficiency virus co-infection and those who were treatment naive or had been previously treated. Eligible interventions were peginterferon alfa-2a or peginterferon alfa-2b, each in combination with RBV, compared against best supportive care (BSC) or against each other, and study designs were randomised controlled trials (RCTs) or non-RCTs, or uncontrolled cohort studies. Outcomes included sustained virological response (SVR) and adverse events. Previously published Markov state-transition economic models of chronic HCV in adults were adapted to estimate the cost-effectiveness of peginterferon alfa-2a and -2b (in combination with RBV), compared with BSC and with one another in children. The model extrapolated the impact of SVR on life expectancy, quality-adjusted life

  7. Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin.

    Science.gov (United States)

    Tawara, Shunsuke; Sakai, Takumi; Matsuzaki, Osamu

    2016-11-01

    Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro. CPB2 activity and tissue factor-induced thrombin generation was examined by a chromogenic assay. C5a inactivation was evaluated by C-terminal cleavage of C5a and inhibition of C5a-induced human neutrophil migration. Clot lysis time prolongation was examined by a tissue-type plasminogen activator-induced clot lysis assay. CPB2 activity in human plasma was increased by TM alfa and thrombin in a concentration-dependent manner. TM alfa inhibited tissue factor-induced thrombin generation and enhanced pro-CPB2 activation in human plasma simultaneously. The mass spectrum of C5a treated with TM alfa, thrombin, and pro-CPB2 was decreased at 156m/z, indicating that TM alfa enhanced the processing of C5a to C-terminal-cleaved C5a, an inactive form of C5a. C5a-induced human neutrophil migration was decreased after C5a treatment with TM alfa, thrombin, and pro-CPB2. TM alfa prolonged the clot lysis time in human plasma, and this effect was completely abolished by addition of a CPB2 inhibitor. TM alfa exerts anti-inflammatory and anti-fibrinolytic effects through CPB2 in the presence of thrombin in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.

  9. Moving beyond interferon alfa: investigational drugs for hepatitis C virus infection.

    Science.gov (United States)

    Wyles, David L

    2010-01-01

    Numerous direct-acting drugs to treat hepatitis C virus (HCV) infection are in development, offering the potential for substantial improvement over current interferon alfa-based therapy and the possibility of effective interferon alfa-sparing regimens in achieving cure of HCV infection. Drugs furthest along in clinical development include HCV nonstructural protein 3 (NS3) protease inhibitors (eg, telaprevir, boceprevir), which have potent anti-HCV activity but low barriers to resistance and considerable likelihood of cross-resistance. Nucleoside analogue nonstructural protein 5B (NS5B) polymerase inhibitors exhibit a high barrier to resistance and cross-HCV genotype and subtype activity. Nonnucleoside analogue polymerase inhibitors have a low barrier to resistance and are characterized by a substantial frequency of preexisting resistance mutations. The initial use of direct-acting drugs will be as add-on treatment to interferon alfa and ribavirin regimens. The success of interferon alfa-sparing regimens will depend on presenting a sufficiently high barrier to resistance with direct-acting drugs and whether the immunomodulatory effects of interferon alfa are needed for cure of HCV infection.

  10. Testing stable boundary layer parameterizations against the BASE:ALFA measurements

    Science.gov (United States)

    Bonafè, G.; Tampieri, F.; di Giuseppe, F.; Caporaso, L.

    2010-09-01

    The Po valley in the Northern Italy is a large plain in a semi-closed basin surrounded by complex orography; the Alps to the North and Apennines to the South-East, and closed to the east by the Adriatic sea. As a flatland basin shielded by mountains, calm wind is very frequent and strong temperature inversions are often observed near the ground, during the night and in the winter period the occurrence of a extremely stable boundary layer is common. A complete set of surface and atmospheric measurements have been collected during a four month observational program carried out at San Pietro Capofiume meteo station, in the middle of the Po Valley. The long term dataset has been collected in the contest of the project BASE:ALFA with the main aim of creating a data pool of micro-meteorological /soil data to test and validate numerical weather prediction PBL schemes. The measurement periods span summer, winter and spring and allows to analyse a wide range of PBL stability conditions. Different parameterizations of first and second order moments of velocity and temperature are tested against the collected data. A particular focus is given to stable boundary layer and the values of its height obtained from Nieuwstadt 1984 and Zilitinkievich et al 2005 formulas will be provided and compared against radiosounding profile estimates.

  11. Analyse af forventet energiforbrug og indeklima via et ALFA og BETA koncept - Københavns Energi som Case

    DEFF Research Database (Denmark)

    Tøgersen, Michael; Brohus, Henrik; Jensen, Rasmus Lund

    udgangspunkt i, hvordan bygningen styres i dag samt forventningsklassen1, hvor der udvælges et udsnit af bygningen, der giver et tilstrækkeligt detaljeret billede af bygningens virkemåde. Herefter defineres et såkaldt ALFA og BETA koncept, hvor ALFA-konceptet svarer til en bygning med naturlig ventilation...

  12. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection

    DEFF Research Database (Denmark)

    Hézode, Christophe; Hirschfield, Gideon M; Ghesquiere, Wayne

    2015-01-01

    OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30......) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA... rerandomised at Week 12 to continue daclatasvir/peginterferon-alfa-2a/ribavirin for 24 weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12 weeks. Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48. Primary efficacy endpoints were...

  13. ESTABILIZACIÓN DE HOLO-alfa-LACTOALBÚMINA EN PRESENCIA DE POLIOLES

    Directory of Open Access Journals (Sweden)

    Alberto Albis

    2010-02-01

    Full Text Available En este trabajo se presenta un estudio sistemático sobre el efecto de las soluciones acuosas de eritritol, xilitol, sorbitol e inositol con diferentes concentraciones, sobre la estabilidad térmica de la holo- alfa-lactoalbúmina bovina con pH 6,5 usando espectroscopia UV-VIS. Los resultados obtenidos muestran que los polioles usados estabilizan la holo-alfa-lactoalbúmina en un grado significativamente menor al reportado para otras proteínas. Se sugiere que este menor efecto de estabilización ocurre debido a que esta proteína presenta un estado desnaturalizado parcialmente desdoblado.

  14. VizieR Online Data Catalog: Arecibo Pulsar-ALFA (PALFA) survey. IV. (Lazarus+, 2015)

    Science.gov (United States)

    Lazarus, P.; Brazier, A.; Hessels, J. W. T.; Karako-Argaman, C.; Kaspi, V. M.; Lynch, R.; Madsen, E.; Patel, C.; Ransom, S. M.; Scholz, P.; Swiggum, J.; Zhu, W. W.; Allen, B.; Bogdanov, S.; Camilo, F.; Cardoso, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Ferdman, R.; Freire, P. C. C.; Jenet, F. A.; Knispel, B.; Lee, K. J.; van Leeuwen, J.; Lorimer, D. R.; Lyne, A. G.; McLaughlin, M. A.; Siemens, X.; Spitler, L. G.; Stairs, I. H.; Stovall, K.; Venkataraman, A.

    2016-02-01

    The Arecibo Pulsar-ALFA (PALFA) survey observations have been restricted to the two regions of the Galactic plane (|b|<5°) visible from the Arecibo observatory, the inner Galaxy (32°<~l<~77°), and the outer Galaxy (168°<~l<~214°). Integration times are 268s and 180s for inner and outer Galaxy observations, respectively. Observations conducted with the 7-beam Arecibo L-band Feed Array (ALFA) receiver of the Arecibo Observatory William E. Gordon 305m Telescope have a bandwidth of 322MHz centered at 1375MHz. PALFA survey data have been recorded with the Mock spectrometers since 2009. (2 data files).

  15. The ATLAS ALFA and AFP detectors - the experimental challenge of measuring forward protons at the LHC

    CERN Document Server

    Trzebinski, M; The ATLAS collaboration

    2013-01-01

    The Absolute Luminosity For ATLAS (ALFA) and ATLAS Forward Protons (AFP) detectors are introduced. The forward proton trajectories are shown. The similarities and differences between these two detector systems are described. Finally, the physics possible to be done in these forward detectors is discussed. In particular, in case of ALFA the elastic scattering and exclusive di-pion production are described. In case of AFP, the hard diffractive processes like: Single Diffractive Jet, Double Pomeron Exchange Jet, Exclusive Jet and anomalous coupling production are described.

  16. Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients.

    Science.gov (United States)

    Beiraghdar, Fatemeh; Panahi, Yunes; Einollahi, Behzad; Nemati, Eghlim; Sahebkar, Amirhossein; Hassanzadeh, Arash; Khosroshahi, Hamid T; Azar, Sima A; Safa, Javid; Hashemi, Sadroddin R; Etemadi, Jalal; Marzony, Eisa T; Noshad, Hamid

    2015-10-01

    The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin(®)) and compare it with the innovator product Eprex(®), as a standard rHuEPO. One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80-120 IU/kg/week in 2-3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p  0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.

  17. A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B.

    Science.gov (United States)

    Xie, Qing; Zhou, Huijuan; Bai, Xuefan; Wu, Shuhuan; Chen, Jian-Jie; Sheng, Jifang; Xie, Yao; Chen, Chengwei; Chan, Henry Lik-Yuen; Zhao, Mianzhi

    2014-12-15

    Treatment with pegylated interferon (peg-IFN) alfa-2a (40KD) results in hepatitis B "e" antigen (HBeAg) seroconversion 6 months after treatment in up to 36% of HBeAg-positive chronic hepatitis B patients. This study explored the efficacy of a novel combination of peg-IFN alfa-2a and entecavir (ETV), a potent nucleoside analogue. In total, 218 treatment-naive Chinese HBeAg-positive patients were randomized to peg-IFN alfa-2a (180 µg/week) for 48 weeks, either as monotherapy (n = 72), or with 24 weeks of ETV (0.5 mg/daily) added at week 13 (ETV add-on, n = 73), or pretreatment with a 24-week course of ETV, starting peg-IFN alfa-2a at week 21 (ETV pretreatment, n = 73). The primary endpoint was reduction in quantitative HBeAg from baseline to 24 weeks posttreatment. Significant reductions in HBeAg from baseline were achieved in all treatment groups 24 weeks posttreatment; reductions were comparable across treatment arms (shown as log10 Paul Ehrlich international units [PEIU]/mL): monotherapy: -1.4 (SD, 1.8); ETV add-on: -1.6 (SD, 1.8); ETV pretreatment: -1.3 (SD, 1.7). Rates of HBeAg seroconversion were similar across treatment groups posttreatment (monotherapy: 22 [31%]; ETV add-on: 18 [25%]; ETV pretreatment: 19 [26%]). Significantly greater reductions of hepatitis B virus DNA were achieved with ETV add-on while on treatment, but were not sustained posttreatment. Safety profiles were comparable between treatment groups; adverse events were experienced by 62 (86%) monotherapy, 65 (89%) ETV add-on, and 58 (81%) ETV pretreatment patients. Neither ETV add-on nor ETV pretreatment demonstrated superiority compared with 48 weeks of peg-IFN alfa-2a monotherapy. The optimal treatment strategy using nucleos(t)ide analogues and peg-IFN alfa-2a remains to be determined. Clinical Trials Registration. NCT00614471. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e

  18. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders.

    Science.gov (United States)

    Jensen, Donald; Sherman, Kenneth E; Hézode, Christophe; Pol, Stanislas; Zeuzem, Stefan; de Ledinghen, Victor; Tran, Albert; Elkhashab, Magdy; Younes, Ziad H; Kugelmas, Marcelo; Mauss, Stefan; Everson, Gregory; Luketic, Velimir; Vierling, John; Serfaty, Lawrence; Brunetto, Maurizia; Heo, Jeong; Bernstein, David; McPhee, Fiona; Hennicken, Delphine; Mendez, Patricia; Hughes, Eric; Noviello, Stephanie

    2015-07-01

    Improved therapies for peginterferon/ribavirin null or partial responders are needed. This study evaluated daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) plus peginterferon alfa-2a and ribavirin in this patient population. This open-label, phase 3 study (HALLMARK-QUAD; NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. Patients received daclatasvir 60 mg once-daily plus asunaprevir 100mg twice-daily, with weekly peginterferon alfa-2a and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients. Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90-96) in prior non-responders infected with HCV genotype 1. SVR12 rates among genotype 4-infected patients were 98% (95% CI 93-100); one patient had a missing post-treatment week-12 HCV-RNA measurement, but achieved an SVR at post-treatment week 24, yielding a 100% SVR rate in genotype 4 patients. Prior peginterferon/ribavirin response, sex, age, IL28B genotype, or cirrhosis status did not influence SVR12 rates. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%), and ALT/AST elevations (3% each). Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Management of chronic hepatitis C patients who have relapsed or not responded to pegylated interferon alfa plus ribavirin.

    Science.gov (United States)

    Dieterich, D T; Rizzetto, M; Manns, M P

    2009-12-01

    Development of therapeutic strategies for patients with chronic hepatitis C who experience virological breakthrough, relapse or nonresponse lag behind those for treatment-naïve patients. The probability of a previously treated patient responding to re-treatment depends on the nature of the previous regimen, the magnitude of the response to previous treatment and the patient's characteristics. Relapsers have higher sustained virological response rates than nonresponders when re-treated with pegylated interferon plus ribavirin. Re-treatment of nonresponders to pegylated interferon plus ribavirin with the standard 48-week regimen resulted in an approximate 6% sustained response rate in the EPIC-3 program. In the REPEAT trial, the sustained response rate was significantly higher in nonresponders to pegylated interferon alfa-2b (12 kD) plus ribavirin randomized to 72 weeks of peginterferon alfa-2a (40 kD) plus ribavirin, compared with a 48-week regimen (16%vs 8%, P = 0.0006). Based on available data, extended treatment is the best option for these individuals. Undetectable viral RNA at week 12 is an important criterion for re-treatment in the REPEAT and EPIC studies. Maintenance therapy with pegylated interferon is generally ineffective in nonresponders and cannot be recommended. Directly acting antivirals may increase response rates and the burden of adverse events when combined with the standard of care, but will not be available for some years. In conclusion, after careful evaluation of an individual's benefit-risk ratio, a 72-week regimen is the preferred strategy for optimizing sustained response rates in patients who have not responded to the standard of care, provided that viral RNA is undetectable at week 12 of re-treatment.

  20. Durability of Response in Children Treated With Pegylated Interferon alfa [corrected] 2a ± Ribavirin for Chronic Hepatitis C.

    Science.gov (United States)

    Schwarz, Kathleen B; Molleston, Jean P; Jonas, Maureen M; Wen, Jessica; Murray, Karen F; Rosenthal, Philip; Gonzalez-Peralta, Regino P; Lobritto, Steven J; Mogul, Douglas; Pavlovic, Vedran; Warne, Charles; Wat, Cynthia; Thompson, Bruce

    2016-01-01

    No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C. This prospective, multicenter, long-term follow-up (LTFU) study aimed to assess long-term durability of sustained virological response (SVR), long-term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa-2a ± ribavirin (RBV) in the PEDS-C trial. A total of 93 patients were assessed for enrollment, and 38 enrolled in the study. Patients attended 2 study visits: 5 (mean 5.6, range 4.1-6.6) and 6 (6.6, 5.1-7.7) years after treatment cessation. Standardized medical history, physical examination, and laboratory testing were performed at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit. The LTFU cohort was the representative of the original PEDS-C cohort because both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS-C trial and 17 had not (nonresponders). All 21 responders maintained undetectable hepatitis C virus RNA during the LTFU (4.4-7.0 years after achieving SVR) in contrast to the nonresponders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67% vs 30% in non-CC, P = 0.028). Long-term durability of SVR is excellent following PegIFN alfa-2a treatment in children with chronic hepatitis C; SVR is higher in those with IL28B CC versus non-CC.

  1. Induction pegylated interferon alfa-2b in combination with ribavirin in patients with genotypes 1 and 4 chronic hepatitis C: a prospective, randomized, multicenter, open-label study.

    Science.gov (United States)

    Brady, Daniel E; Torres, Dawn M; An, Jong W; Ward, John A; Lawitz, Eric; Harrison, Stephen A

    2010-01-01

    Standard of care (SOC) treatment for chronic hepatitis C (CHC) involves weekly pegylated (PEG) interferon plus weight-based ribavirin with resultant sustained virologic response (SVR) rates at or near 50% for genotypes 1 and 4 virus. Induction therapy with higher doses of PEG interferon may improve first-phase viral kinetics and thus improve the overall SVR in genotypes 1 and 4 patients. This multicenter, randomized, open-label trial enrolled treatment-naive genotypes 1- and 4-infected CHC patients to either initial induction therapy versus SOC. The induction group received PEG interferon alfa-2b 3.0 mcg/kg/wk for 12 weeks followed by PEG interferon alfa-2b 1.5 mcg/kg/wk for 36 weeks and 13 +/- 2 mg/kg ribavirin daily for 48 weeks. SOC patients received PEG interferon alfa-2b 1.5 mcg/kg weekly for 48 weeks and 13 +/- 2 mg/kg ribavirin daily for 48 weeks. The primary end point was SVR. There were 610 patients enrolled throughout the United States. Complete early virologic response was 62.6% versus 57.7% in induction versus SOC (NS). Overall SVR was 32% in induction versus 29% in SOC group (NS). Dose reduction of either PEG interferon (24.1% vs 23.8%) or ribavirin (26.8% vs 25.1%) was similar between the 2 groups. There was a trend toward a significant difference when comparing the SVR in induction therapy in patients weighing more than 85 kg versus those receiving SOC (38% vs 28%; P = .08). Induction therapy does not enhance complete early virologic response or SVR rates in a predominantly genotype 1 CHC population compared with SOC therapy. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Valorization of Tunisian alfa fibres and sumac tannins for the elaboration of biodegradable insulating panels

    Science.gov (United States)

    Saad, Houda; Charrier, Bertrand; Ayed, Naceur; Charrier-El-Bouhtoury, Fatima

    2017-10-01

    Alfa leaves are important renewable raw materials in Tunisia where they are used basically in handcrafts and paper industry. Sumac is also an abundant species in Tunisia known for its high tannin content and is basically used in traditional medicine. To valorize these natural resources, we studied, for the first time, the possibility of making insulating panels based on alfa fibres and sumac tannins based adhesive. Firstly, alfa leaves were treated with an alkali solution as it is one of the standard procedures commonly used in the paper industry to extract cellulosic fibres. Mercerization effects were studied by characterizing fibres thermal properties and fibres surface morphology. Secondly, the sumac tannin based resin was formulated and characterized. Finally, the insulating panel was elaborated and characterized by determining its thermal conductivity. The thermal gravimetric analysis results show improvement in the thermal stability of fibres after alkali treatment. Environmental Scanning Electron Microscopy showed changes on treated alfa surface which could promote the fibre-matrix adhesion. The reactivity of sumac tannins to formaldehyde test (Stiasny number) showed the possible use of sumac tannins in wood adhesive formulation. Thermomechanical analysis and strength analysis of sumac tannin/hexamin based resin highlighted acceptable bonding properties. The thermal conductivity measurement showed an average value equal to 0.110 W/m K. Contribution to the topical issue "Materials for Energy harvesting, conversion and storage II (ICOME 2016)", edited by Jean-Michel Nunzi, Rachid Bennacer and Mohammed El Ganaoui

  3. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Lamm, D.; Brausi, M.; O'Donnell, M.A.; Witjes, J.A.

    2014-01-01

    OBJECTIVES: In this article, we review the various options for and the potential role of interferon alfa (IFN-alpha) in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: PubMed was searched for journal articles on IFN-alpha use in treating bladder cancer. The references listed in

  4. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated)

    NARCIS (Netherlands)

    Levi, Marcel; Levy, Mitchell; Williams, Mark D.; Douglas, Ivor; Artigas, Antonio; Antonelli, Massimo; Wyncoll, Duncan; Janes, Jonathan; Booth, Frank V.; Wang, Dazhe; Sundin, David P.; Macias, William L.

    2007-01-01

    RATIONALE: Patients with severe sepsis frequently receive prophylactic heparin during drotrecogin alfa (activated) (DrotAA) treatment due to risk of venous thromboembolic events (VTEs). Biological plausibility exists for heparin to reduce DrotAA efficacy and/or increase bleeding. OBJECTIVES:

  5. Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a

    NARCIS (Netherlands)

    V. Carreño (Vicente); P. Marcellin (Patrick); S. Hadziyannis (Stephanos); J. Salmerón (Javier); M. Diago (Moisés); G. Kitis; I. Vafiadis (Irene); S.W. Schalm (Solko); F. Zahm (Friederike); F. Manzarbeitia (Félix); F. Javier Jiménez (F.); J.A. Quiroga (Juan Antonio)

    1999-01-01

    textabstractFifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-α) therapy were included in a multicenter prospective randomized

  6. The safety and tolerability of darbepoetin alfa in patients with anaemia and symptomatic heart failure

    NARCIS (Netherlands)

    Klapholz, Marc; Abraham, William T.; Ghali, Jalal K.; Ponikowski, Piotr; Anker, Stefan D.; Knusel, Beat; Sun, Yan; Wasserman, Scott M.; van Veldhuisen, Dirk J.

    2009-01-01

    To assess the safety and tolerability of darbepoetin alfa (DA) in the treatment of anaemia in heart failure (HF). In this pooled analysis of three randomized, double-blind, placebo-controlled studies of anaemic [haemoglobin (Hb) <12.0 g/dL or <12.5 g/dL] symptomatic HF subjects, DA was administered

  7. Fluorouracil continuous infusion plus alfa interferon plus oral folinic acid in advanced colorectal cancer

    NARCIS (Netherlands)

    Punt, C. J.; de Mulder, P. H.; Burghouts, J. T.; Wagener, D. J.

    1992-01-01

    Several reports on fluorouracil (5-FU) and alfa interferon (IFN-alpha) combination therapy in patients with advanced colorectal cancer have been published. In our study high-dose continuous infusion 5-FU (60 mg/kg per 48 hours), oral folinic acid (FA) (8 x 90 mg during 5-FU), and IFN-alpha three

  8. Interferon alfa for chronic hepatitis B infection: Increased efficacy of prolonged treatment

    NARCIS (Netherlands)

    H.L.A. Janssen (Harry); G. Gerken (Guido); V. Carreño (Vicente); P. Marcellin (Patrick); N.V. Naoumov (Nikolai); A. Craxi (Antonio); H. Ring-Larsen (Helmer); G. Kitis; J. van Hattum (Jan); R.A. de Vries (Richard); P.P. Michielsen (Peter); F.J.W. ten Kate (Fiebo); W.C.J. Hop (Wim); R.A. Heijtink; P. Honkoop (Pieter); S.W. Schalm (Solko)

    1999-01-01

    textabstractInterferon alfa (IFN-a) is the primary treatment for chronic hepatitis B. The standard duration of IFN-a therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-a treatment in patients

  9. Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

    NARCIS (Netherlands)

    Forestier, Nicole; Reesink, Hendrik W.; Weegink, Christine J.; McNair, Lindsay; Kieffer, Tara L.; Chu, Hui-May; Purdy, Susan; Jansen, Peter L. M.; Zeuzem, Stefan

    2007-01-01

    Telaprevir (VX-950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa-2a for 14

  10. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors

    NARCIS (Netherlands)

    Connolly, Stuart J.; Milling, Truman J.; Eikelboom, John W.; Gibson, C. Michael; Curnutte, John T.; Gold, Alex; Bronson, Michele D.; Lu, Genmin; Conley, Pamela B.; Verhamme, Peter; Schmidt, Jeannot; Middeldorp, Saskia; Cohen, Alexander T.; Beyer-Westendorf, Jan; Albaladejo, Pierre; Lopez-Sendon, Jose; Goodman, Shelly; Leeds, Janet; Wiens, Brian L.; Siegal, Deborah M.; Zotova, Elena; Meeks, Brandi; Nakamya, Juliet; Lim, W. Ting; Crowther, Mark; Connolly, S. C.; Crowther, M.; Eikelboom, J.; Gibson, M.; Milling, T. J.; Albaladejo, P.; Cohen, A.; Lopez-Sendon, J.; Schmidt, J.; Verhamme, P.; Beyer-Westendorf, J.; Wyse, D. G.; Garcia, D.; Prins, M. [=Martin H.; Nakamya, J.; Büller, H. R.; Mahaffey, K.; Alexander, J.; Demchuk, A.; Raskob, G.; Schulman, S.; Meeks, B.; Zotova, E.; Holadyk-Gris, I.; Pinto, T.; Behr, M.; Lim, T.; Anand, R.; Bastani, A.; Caterino, J.; Clark, C.; Concha, M.; Cornell, J.; Eriksson, E.; Fermann, G.; Fulmer, J.; Goldstein, J.; Kereiakes, D.; Lotfipour, S.; Milling, T.; Moll, S.; Pallin, D.; Patel, N.; Refaai, M.; Rehman, M.; Schmaier, A.; Schwarz, E.; Shillinglaw, W.; Sinert, R.; Singer, A.; Takata, T.; Venkat, A.; Weinstein, D.; Welker, J.; Welsby, I.; Wiener, S.; Wilson, J.; Blostein, M.; van Keer, L.; Verschuren, F.; Coppens, M.; van Wissen, S.; Alikhan, R.; Breen, K.; Hall, R.

    2016-01-01

    Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major

  11. Safety of drotrecogin alfa (activated) in the treatment of patients with severe sepsis.

    Science.gov (United States)

    McCoy, Christopher

    2004-11-01

    While severe sepsis continues to plague hospitals worldwide, new treatment modalities, including activated recombinant protein C (drotrecogin alfa, Xigris, Lilly), have become a standard treatment alternative in many institutional algorithms. Drotrecogin alfa was shown to have a beneficial effect on mortality versus placebo in the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial (p = 0.005), but its use is not completely without risk. An increased risk of bleeding, including severe bleeding episodes, exists ranging 3.5 - 5.2% in the drotrecogin alfa treatment group versus 2.0 - 5.0% in the placebo group. Patients at risk include those on concomitant heparin therapy (> 15,000 units/day), those with platelet counts market, the reported incidence of severe bleeding episodes has risen only slightly from the pre-marketing era, at that time notable for restrictive treatment protocols, devoid of at-risk patients. Drotrecogin alfa, while a promising agent for severe sepsis, requires prudent patient evaluation for bleeding risks.

  12. Arecibo Pulsar Survey Using ALFA. III. Precursor Survey and Population Synthesis

    NARCIS (Netherlands)

    Swiggum, J.K.; Lorimer, D.R.; McLaughlin, M.A.; Bates, S.D.; Champion, D.J.; Ransom, S.M.; Lazarus, P.; Brazier, A.; Hessels, J.W.T.; Nice, D.J.; Ellis, J.; Senty, T.R.; Allen, B.; Bhat, N.D.R.; Bogdanov, S.; Camilo, F.; Chatterjee, S.; Cordes, J.M.; Crawford, F.; Deneva, J.S.; Freire, P.C.C.; Jenet, F.A.; Karako-Argaman, C.; Kaspi, V.M.; Knispel, B.; Lee, K.J.; van Leeuwen, J.; Lynch, R.; Lyne, A.G.; Scholz, P.; Siemens, X.; Stairs, I.H.; Stappers, B.W.; Stovall, K.; Venkataraman, A.; Zhu, W.W.

    2014-01-01

    The Pulsar Arecibo L-band Feed Array (PALFA) Survey uses the ALFA 7-beam receiver to search both inner and outer Galactic sectors visible from Arecibo (32° lsim ℓ lsim 77° and 168° lsim ℓ lsim 214°) close to the Galactic plane (|b| lsim 5°) for pulsars. The PALFA survey is sensitive to sources

  13. Virological escape in HCV genotype-1-infected patients receiving daclatasvir plus ribavirin and peginterferon alfa-2a or alfa-2b.

    Science.gov (United States)

    McPhee, Fiona; Hernandez, Dennis; Zhou, Nannan; Yu, Fei; Ueland, Joseph; Monikowski, Aaron; Chayama, Kazuaki; Toyota, Joji; Izumi, Namiki; Yokosuka, Osamu; Kawada, Norifumi; Osaki, Yukio; Hughes, Eric A; Watanabe, Hideaki; Ishikawa, Hiroki; Kumada, Hiromitsu

    2014-01-01

    Daclatasvir (DCV; BMS-790052) is a picomolar inhibitor of HCV non-structural protein 5A (NS5A) and has demonstrated efficacy in patients chronically infected with HCV. In the double-blind, randomized studies AI444021 and AI444022, 71 Japanese patients chronically infected with HCV genotype 1 (predominantly genotype 1b) received DCV (10 mg or 60 mg) plus peginterferon alfa-2b or alfa-2a and ribavirin. Virological failure occurred in 14% (5/36) of treatment-naive patients and 54% (19/35) of prior alfa/ribavirin non-responders. Resistance testing was performed on baseline samples and samples with HCV RNA≥1,000 IU/ml at week 1 through post-treatment week 24. Baseline NS5A resistance-associated polymorphisms had less impact on virological response rates than IL28B genotype. All patients with virological failure had NS5A DCV-resistant variants at the time of failure. The predominant NS5A variants were L31V/M/I plus Y93H; this combination was detected in 100% (5/5) of treatment-naive patients and 74% (14/19) of non-responders with failure. Emergent resistance variants in prior non-responders (four viral breakthroughs, one relapse) were more varied with novel combinations such as L31F-ΔP32 and L28M-R30Q-A92K detected. Significant loss in DCV antiviral activity was generally only seen with ≥ two resistance-associated NS5A substitutions. All DCV-resistant variants were still detected at end of study. Virological failure in HCV genotype 1b treatment-naive Japanese patients receiving DCV plus alfa-2a/ribavirin or alfa-2b/ribavirin was associated with enrichment of NS5A resistance variants L31V/M-Y93H. In prior non-responders, emergent variants associated with failure also included NS5A-A92K or NS5A-ΔP32. As with L31-Y93 variants, these variants persisted.

  14. Spotlight on taliglucerase alfa in the treatment of pediatric patients with type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Gupta P

    2017-06-01

    Full Text Available Punita Gupta,1 Gregory M Pastores2 1Division of Genetics, Department of Pediatrics, St. Joseph’s Children’s Hospital, Paterson, New Jersey, USA; 2National Center for Inherited Metabolic Disorders, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland Abstract: Gaucher disease (GD is a heritable storage disorder caused by functional defects of the lysosomal acid β-glucosidase and the accumulation of glucosylceramide within macrophages, resulting in multiple organ dysfunction. There are three commercially available enzyme replacement therapy (ERT products for the treatment of GD type 1 (GD1: imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems; imiglucerase requires postproduction deglycosylation to expose terminal α-mannose residues, which are required for mannose receptor-mediated uptake by target macrophages. These steps are critical to the success of ERT for the treatment of visceral and hematologic manifestations of GD. Taliglucerase alfa is the first US Food and Drug Administration-approved plant-cell-expressed recombinant human protein, using carrot root cell cultures. Furthermore, it does not require postproduction glycosidic modifications. It is indicated for treatment of adults with GD1 in the US, Israel, Australia, Canada, Chile, Brazil, and other countries, and it is additionally approved for the treatment of pediatric patients in the US, Australia, and Canada and for the treatment of hematologic manifestations in pediatric patients with Type 3 GD in Canada and other countries. Our review focuses on the role of taliglucerase alfa in the pediatric population. A literature search through PubMed (from 1995 up till November 2016 of English language articles was performed with the following terms: Gaucher disease, lysosomal storage disease, taliglucerase. Secondary and tertiary references were obtained by reviewing

  15. 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.

  16. Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance in athletes

    Directory of Open Access Journals (Sweden)

    Karila Tuomo AM

    2010-01-01

    Full Text Available Abstract Background Alfa-Hydroxy-isocaproic acid (HICA is an end product of leucine metabolism in human tissues such as muscle and connective tissue. According to the clinical and experimental studies, HICA can be considered as an anti-catabolic substance. The present study investigated the effects of HICA supplementation on body composition, delayed onset of muscle soreness (DOMS and physical performance of athletes during a training period. Methods Fifteen healthy male soccer players (age 22.1+/-3.9 yr volunteered for the 4-week double-blind study during an intensive training period. The subjects in the group HICA (n = 8 received 583 mg of sodium salt of HICA (corresponding 500 mg of HICA mixed with liquid three times a day for 4 weeks, and those in the group PLACEBO (n = 7 received 650 mg of maltodextrin mixed with liquid three times a day for the same period. According to a weekly training schedule, they practiced soccer 3 - 4 times a week, had strength training 1 - 2 times a week, and had one soccer game during the study. The subjects were required to keep diaries on training, nutrition, and symptoms of DOMS. Body composition was evaluated with a dual-energy X-ray absorptiometry (DXA before and after the 4-week period. Muscle strength and running velocity were measured with field tests. Results As compared to placebo, the HICA supplementation increased significantly body weight (p th week of the treatment (p Conclusion Already a 4-week HICA supplementation of 1.5 g a day leads to small increases in muscle mass during an intensive training period in soccer athletes.

  17. Deficiência de alfa-1 antitripsina: diagnóstico e tratamento Alpha-1 antitrypsin deficiency: diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Aquiles A Camelier

    2008-07-01

    Full Text Available A deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que determina polimerização e acúmulo dentro dos hepatócitos. O acúmulo e a conseqüente redução dos níveis séricos de alfa-1 antitripsina determinam, respectivamente, doença hepática e pulmonar, sendo que esta se manifesta principalmente sob a forma de enfisema de aparecimento precoce, habitualmente com predomínio basal. O diagnóstico envolve a detecção de níveis séricos reduzidos de alfa-1 antitripsina e a confirmação fenotípica. Além do tratamento usual para doença pulmonar obstrutiva crônica, existe atualmente uma terapia específica com infusão de concentrados de alfa-1 antitripsina. Essa terapia de reposição, aparentemente segura, ainda não teve a eficácia clínica definitivamente comprovada, e o custo-efetividade também é um tema controverso e ainda pouco abordado. Apesar da sua importância, não existem dados epidemiológicos brasileiros a respeito da prevalência da doença ou da freqüência de ocorrência dos alelos deficientes. O subdiagnóstico também tem sido uma importante limitação tanto para o estudo da doença quanto para o tratamento adequado dos pacientes. Espera-se que a criação do Registro Internacional de Alfa-1 venha a resolver essas e outras importantes questões.Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical

  18. Stroke in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia treated with Darbepoetin Alfa

    DEFF Research Database (Denmark)

    Skali, Hicham; Parving, Hans-Henrik; Parfrey, Patrick S

    2011-01-01

    More strokes were observed in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) among patients assigned to darbepoetin alfa. We sought to identify baseline characteristics and postrandomization factors that might explain this association....

  19. THE AUTHOR’S EXPERIENCE IN USING BEVACIZUMAB PLUS INTERFERON ALFA-2A IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2010-01-01

    Full Text Available Target therapy is a main approach to treating metastatic renal cell carcinoma. Bevacizumab plus interferon alfa-2A is now standard first-line options for patients with previously untreated, good or intermediate prognosis (using the Memorial Sloan-Kettering Cancer Center criteria. We have presented our experience in using bevacisumab plus interferon alfa-2A in patients with metastatic renal cell carcinoma. Median progression-free survival and overall survival were 10 months and 22 months, respectively.

  20. THE AUTHOR’S EXPERIENCE IN USING BEVACIZUMAB PLUS INTERFERON ALFA-2A IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2014-08-01

    Full Text Available Target therapy is a main approach to treating metastatic renal cell carcinoma. Bevacizumab plus interferon alfa-2A is now standard first-line options for patients with previously untreated, good or intermediate prognosis (using the Memorial Sloan-Kettering Cancer Center criteria. We have presented our experience in using bevacisumab plus interferon alfa-2A in patients with metastatic renal cell carcinoma. Median progression-free survival and overall survival were 10 months and 22 months, respectively.

  1. Erythropoiesis-stimulating agents in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2012-04-01

    Full Text Available Anemia is a frequent complication of chronic kidney disease (CKD due to the inability of the kidneys to release sufficient erythropoietin to regulate the production of red blood cells. Administration of erythropoiesis-stimulating agents (ESAs is highly effective in correcting anemia of CKD. The ESAs currently approved in Italy are epoetin alfa, epoetin beta, epoetin theta, darbepoetin alfa, CERA and biosimilars epoetin alfa and epoetin zeta. All the ESAs are effective in correcting renal anemia and increasing hemoglobin levels, but the choice of which to use should also take into account their pharmacokinetics and pharmacodynamics, their administration route, and economic issues. However, regarding the optimal use of ESAs an issue that remains controversial is the most appropriate dose conversion between epoetin alfa and darbepoetin alfa. In fact clinical experience demonstrates that the dose relationship between epoetin alfa and darbepoetin alfa is non proportional across the dosing spectrum. In this review is presented an update on the latest available evidence in the treatment of anemia in CKD patients, with particular reference to the definition of the correct conversion ratio EPO:DARB.

  2. Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1.

    Science.gov (United States)

    Izumi, Namiki; Yokosuka, Osamu; Kawada, Norifumi; Osaki, Yukio; Yamamoto, Kazuhide; Sata, Michio; Ishikawa, Hiroki; Ueki, Tomoko; Hu, Wenhua; McPhee, Fiona; Hughes, Eric A; Kumada, Hiromitsu

    2014-01-01

    New direct-acting antiviral agents are currently being developed to treat chronic HCV. The efficacy and safety of daclatasvir combined with peginterferon alfa-2a (alfa-2a) and ribavirin were assessed in a randomized, double-blind Phase IIa study of Japanese patients with chronic HCV genotype-1 infection. Japanese patients who were treatment-naive (n=25) or prior null (n=12) or partial (n=5) responders received once-daily daclatasvir 10 mg or 60 mg or placebo in combination with alfa-2a and ribavirin. Daclatasvir recipients with a protocol-defined response (HCV RNAdaclatasvir 10 mg and 60 mg, respectively, versus 75% in placebo recipients. Virological failure was more frequent in prior non-responder patients, with 50% and 78% achieving SVR24 in daclatasvir 10 mg and 60 mg groups, respectively. Adverse events occurred with similar frequency among treatment groups and were consistent with the adverse event profile of alfa-2a/ribavirin alone. The most commonly reported adverse events included pyrexia, alopecia, anaemia, lymphopenia, neutropenia, pruritus and diarrhoea. Three patients discontinued treatment due to anaemia. Daclatasvir combined with alfa-2a/ribavirin in treatment-naive patients showed greater efficacy than alfa-2a/ribavirin alone and was generally well tolerated. The 60-mg dose of daclatasvir achieved the highest rates of SVR24 in both treatment-naive and non-responder populations and will be evaluated in a Phase III clinical trial.

  3. Estudo comparativo do uso isolado de plasma rico em plaquetas e combinado com cimento de alfa-fosfato tricálcico no reparo ósseo em ratos Comparative study on use of platelet-rich plasma alone and in combination with alpha-tricalcium phosphate cement for bone repair in rats

    Directory of Open Access Journals (Sweden)

    Alessandra Deise Sebben

    2012-01-01

    Full Text Available OBJETIVOS: Avaliar o efeito do cimento α-TCP combinado com PRP sobre a osteogênese, comparando os resultados com PRP utilizado isoladamente. MÉTODOS: Foi confeccionado defeito bilateral no fêmur de ratos e preenchido com um dos dois tipos de tratamentos (PRP ou α-TCP+PRP, sendo avaliado em quatro e oito semanas. As imagens radiográficas forneceram valores da área da lesão, e a histologia (coloração Picrosirius indicou a área de neoformação óssea. RESULTADOS: As médias referentes à área de lesão do grupo α-TCP+PRP (2,64mm² ± 2,07 e 1,91mm² ± 0,93; quatro e oito semanas, respectivamente demonstraram numericamente melhores resultados, porém não significativos (p > 0,05, em comparação com aqueles observados no grupo PRP (5,59mm² ± 2,69 e 3,23mm² ± 1,46; quatro e oito semanas, respectivamente. As médias de neoformação óssea foram de 62,7% ± 12,1% e 79,01% ± 6,25 no grupo PRP, e 73,3% ± 12,7 e 85,86% ± 10,45 no grupo α-TCP+PRP, em quatro e oito semanas, respectivamente (p > 0,05. CONCLUSÃO: Os dados deste estudo sugerem que o tratamento com cimento α-TCP combinado com PRP não demonstra diferença significativa quando comparado ao PRP isolado. Entretanto, há um possível efeito precoce sobre a regeneração óssea quando os dois biomateriais são aplicados em conjunto.OBJECTIVES: To evaluate the effect of alpha-tricalcium phosphate (α-TCP cement combined with platelet-rich plasma (PRP on osteogenesis, and to compare the results with use of PRP alone. METHODS: A bilateral defect was produced in rat femurs and was filled with one of two types of treatments (PRP or α-TCP + PRP. The outcomes were evaluated after four and eight weeks. Radiographic images provided values for the lesion area, and histology (picrosirius staining indicated the area of ​​new bone formation. RESULTS: The means relating to the lesion area of the α-TCP + PRP group (2.64 ± 2.07 and 1.91 ± 0.93 mm², after four and eight weeks

  4. A Study of Diffractive Scattering with the ATLAS and ALFA Experiment

    CERN Document Server

    AUTHOR|(CDS)2097773

    This thesis presents a study of diffractive scattering of high-energy protons. Hadronic diffraction is not well-understood and many alternative approaches exist. The Monte Carlo event generator Pythia 8 follows a Pomeron-based approach, where the invariant mass of the diffractive system and the squared momentum transfer $t$ of the system is set up according to a phenomenological Pomeron flux parameterization, which is parameterized by the super-critical Pomeron trajectory, $\\alpha(t) = 1 + \\varepsilon + \\alpha' t$, where the intercept parameter $\\varepsilon$ and the slope parameter $\\alpha'$ can be tuned by the user. A fast detector response simulation of the ALFA and ATLAS detectors has been developed in the Rivet toolkit for the purposes of this thesis. The developed simulation framework is able to handle the beam transport of diffractively scattered protons as well as impose the kinematic acceptance of the ALFA detector which was found to be approximately $\\xi \\lesssim 0.22$, with a pseudorapidity coverag...

  5. A Severe Case of Lymphomatoid Papulosis Type E Successfully Treated with Interferon-Alfa 2a

    Directory of Open Access Journals (Sweden)

    Aslı Bilgiç Temel

    2017-01-01

    Full Text Available Lymphomatoid papulosis (LyP is a benign papulonodular skin eruption with histologic features of malignant lymphoma. A new variant of LyP which was termed “type E” was recently described with similar clinical and histological features to angiocentric and angiodestructive T-cell lymphoma. LyP type E is characterized with recurrent papulonodular lesions which rapidly turn into hemorrhagic necrotic ulcers and spontaneous regression by leaving a scar. None of the available treatment modalities affects the natural course of LyP. For therapy various modalities have been used such as topical and systemic steroids, PUVA, methotrexate, bexarotene, and IFN alfa-2b. Here we present a severe and devastating case with a very rare variant of LyP type E, which is, to our knowledge, the first case successfully treated with IFN alfa-2a. Now disease has been maintaining its remission status for six months.

  6. Extensive psoriasis induced by interferon alfa treatment for chronic hepatitis C

    OpenAIRE

    Taylor, C; Burns, D; Wiselka, M

    2000-01-01

    A 47 year old man with chronic hepatitis C was treated with interferon alfa, 3 million units three times a week, and developed widespread plaque psoriasis within weeks of starting interferon therapy. There was no previous history of psoriasis. The psoriasis was characterised by extensive nail involvement and plaques at the interferon injection sites. The patient relapsed after a total of 12 months of interferon and was subsequently treated with interferon and tribavirin (ribavirin) with recur...

  7. Impact of Elosulfase Alfa on Pain in Patients with Morquio A Syndrome over 52 Weeks

    Directory of Open Access Journals (Sweden)

    Marsha Treadwell

    2017-07-01

    Full Text Available Patients with mucopolysaccharidosis (MPS, and Morquio A syndrome (MPS IVA in particular, often report substantial pain burden. MOR-008 was a randomized, double-blind, pilot study assessing the safety and efficacy, including impact on patient-reported pain, of 52 weeks of treatment with elosulfase alfa (at a dose of 2.0 or 4.0 mg/kg/week in patients with Morquio A syndrome (≥7 years old. Assessment of pain at baseline revealed that patients (N = 25 had a mean number of pain locations of 5.7, mean pain intensity score of 4.6 (indicative of medium pain, and a mean number of selected pain descriptors of 7.4 words. Treatment with elosulfase alfa improved subjective pain score (reduced to 3.2, pain locations (reduced by a mean of 1 location, and pain descriptor words (reduced to 4.9 words over 1 year (52 weeks, suggesting that elosulfase alfa can reduce pain in some patients with Morquio A.

  8. Human factors engineering and design validation for the redesigned follitropin alfa pen injection device.

    Science.gov (United States)

    Mahony, Mary C; Patterson, Patricia; Hayward, Brooke; North, Robert; Green, Dawne

    2015-05-01

    To demonstrate, using human factors engineering (HFE), that a redesigned, pre-filled, ready-to-use, pre-asembled follitropin alfa pen can be used to administer prescribed follitropin alfa doses safely and accurately. A failure modes and effects analysis identified hazards and harms potentially caused by use errors; risk-control measures were implemented to ensure acceptable device use risk management. Participants were women with infertility, their significant others, and fertility nurse (FN) professionals. Preliminary testing included 'Instructions for Use' (IFU) and pre-validation studies. Validation studies used simulated injections in a representative use environment; participants received prior training on pen use. User performance in preliminary testing led to IFU revisions and a change to outer needle cap design to mitigate needle stick potential. In the first validation study (49 users, 343 simulated injections), in the FN group, one observed critical use error resulted in a device design modification and another in an IFU change. A second validation study tested the mitigation strategies; previously reported use errors were not repeated. Through an iterative process involving a series of studies, modifications were made to the pen design and IFU. Simulated-use testing demonstrated that the redesigned pen can be used to administer follitropin alfa effectively and safely.

  9. Efficacy of Alfa EEG wave biofeedback in the management of anxiety

    Directory of Open Access Journals (Sweden)

    Pookala Bhat

    2010-01-01

    Full Text Available Background: Biofeedback is a technique in which people are trained to improve their health by learning to control certain internal bodily processes that normally occur involuntarily. Various studies in the past have shown usefulness of Alfa electroencephalographic (EEG biofeedback in the alleviation of anxiety symptoms. Though most of the psychiatric centers in the armed forces have this facility, not much work has been done in our setup to assess its efficacy in the management of anxiety. Hence this study was undertaken. Materials and Methods: This study was carried out in a multispecialty Command Hospital by enrolling 100 patients with psychiatric diagnosis from both inpatient and outpatient services. The anxiety level was assessed clinically and by using Hamilton Anxiety Scale and Taylor′s Manifest Anxiety Scale. One group of 50 patients was treated with Alfa EEG biofeedback sessions only, 5 times in a week for 8 weeks, along with specific pharmacotherapy. The other group was treated with appropriate dose of anxiolytics. The anxiety level was reassessed after 4 weeks and 8 weeks. Results: The response was better for mixed anxiety and depressive disorder with pharmacotherapy than with the biofeedback, but female patients showed better response with EEG biofeedback. Conclusion: In the short term, Alfa EEG biofeedback therapy is almost as efficacious as pharmacological intervention in the management of anxiety symptoms, and relatively more useful in females.

  10. The role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency.

    Science.gov (United States)

    Erwin, Angelika L

    2017-07-01

    Lysosomal acid lipase deficiency (LALD) is a lysosomal storage disorder (LSD) characterized either by infantile onset with fulminant clinical course and very poor prognosis or childhood/adult-onset disease with an attenuated phenotype. The disorder is often misdiagnosed or remains undiagnosed in children and adults due to a rather unspecific clinical presentation with dyslipidemia and steatohepatitis. Until recently, no good treatment options were available for LALD. Despite supportive and symptomatic therapies, death occurred before 1 year of age in patients with infantile-onset disease and patients with childhood/adult-onset LALD suffered from significant complications, such as liver cirrhosis, requiring liver transplantation and early-onset cardiovascular disease. With the recent approval of sebelipase alfa for clinical use in infantile- as well as childhood/adult-onset LALD, a new treatment era for this disorder has begun. Sebelipase alfa is a recombinant human lysosomal acid lipase (LAL), which is administered via the intravenous route. Clinical trials have shown significant improvement of disease parameters such as liver transaminases, hepatomegaly, and dyslipidemia in childhood/adult-onset LALD patients. Treatment of infants with the severe infantile-onset form of the disease has led to improved survival beyond the age of 1 year, and also showed improvement of hepatic and gastrointestinal symptoms, as well as growth. Overall, sebelipase alfa has a favorable safety profile and promises to be a good long-term treatment option for patients with LALD, with significant reduction of disease burden and increased life expectancy.

  11. Coste-efectividad de drotrecogina alfa (activada en el tratamiento de la sepsis grave en España Cost-effectiveness of drotrecogin alpha [activated] in the treatment of severe sepsis in Spain

    Directory of Open Access Journals (Sweden)

    José A Sacristán

    2004-02-01

    grupo de pacientes con 2 o más fallos orgánicos. En el análisis de sensibilidad, los resultados oscilaron desde 7.322 a 16.493 euros por AVG. Los factores que más influyeron en los resultados fueron la modificación de la eficacia de drotrecogina alfa (activada, el ajuste de la supervivencia según la comorbilidad inicial y la aplicación de descuento a los AVG. Conclusiones: El tratamiento con drotrecogina alfa (activada presenta una relación coste-efectividad favorable en comparación con otras intervenciones sanitarias comúnmente utilizadas en España.Introduction: The PROWESS clinical trial has shown that treatment with drotrecogin alpha (activated in patients with severe sepsis is associated with a reduction in the absolute risk of death compared with standard treatment. The aim of the present study was to assess the cost-effectiveness of drotrecogin alpha (activated versus that of standard care in the treatment of severe sepsis in Spain. Patients and methods: A decision analysis model was drawn up to compare costs to hospital discharge and the long-term efficacy of drotrecogin alpha (activated versus those of standard care in the treatment of severe sepsis in Spain from the perspective of the health care payer. Most of the information for creating the model was obtained from the PROWESS clinical trial. A two-fold baseline analysis was performed: a for all patients included in the PROWESS clinical trial and b for the patients with two or more organ failures. The major variables for clinical assessment were the reduction in mortality and years of life gained (YLG. Cost-effectiveness was expressed as cost per YLG. A sensitivity analysis was applied using 3% and 5% discount rates for YLG and by modifying the patterns of health care, intensive care unit costs, and life expectancy by initial co-morbidity and therapeutic efficacy of drotrecogin alpha (activated. Results: Treatment with drotrecogin alfa (activated was associated with a 6.0% drop in the absolute risk

  12. Arecibo pulsar survey using ALFA. III. Precursor survey and population synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Swiggum, J. K.; Lorimer, D. R.; McLaughlin, M. A.; Bates, S. D.; Senty, T. R. [Department of Physics and Astronomy, West Virginia University, Morgantown, WV 26506 (United States); Champion, D. J.; Lazarus, P. [Max-Planck-Institut für Radioastronomie, D-53121 Bonn (Germany); Ransom, S. M. [NRAO, Charlottesville, VA 22903 (United States); Brazier, A.; Chatterjee, S.; Cordes, J. M. [Astronomy Department, Cornell University, Ithaca, NY 14853 (United States); Hessels, J. W. T. [ASTRON, Netherlands Institute for Radio Astronomy, Postbus 2, 7990 AA, Dwingeloo (Netherlands); Nice, D. J. [Department of Physics, Lafayette College, Easton, PA 18042 (United States); Ellis, J.; Allen, B. [Physics Department, University of Wisconsin-Milwaukee, Milwaukee WI 53211 (United States); Bhat, N. D. R. [Center for Astrophysics and Supercomputing, Swinburne University, Hawthorn, Victoria 3122 (Australia); Bogdanov, S.; Camilo, F. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Crawford, F. [Department of Physics and Astronomy, Franklin and Marshall College, Lancaster, PA 17604-3003 (United States); Deneva, J. S. [Arecibo Observatory, HC3 Box 53995, Arecibo, PR 00612 (United States); and others

    2014-06-01

    The Pulsar Arecibo L-band Feed Array (PALFA) Survey uses the ALFA 7-beam receiver to search both inner and outer Galactic sectors visible from Arecibo (32° ≲ ℓ ≲ 77° and 168° ≲ ℓ ≲ 214°) close to the Galactic plane (|b| ≲ 5°) for pulsars. The PALFA survey is sensitive to sources fainter and more distant than have previously been seen because of Arecibo's unrivaled sensitivity. In this paper we detail a precursor survey of this region with PALFA, which observed a subset of the full region (slightly more restrictive in ℓ and |b| ≲ 1°) and detected 45 pulsars. Detections included 1 known millisecond pulsar and 11 previously unknown, long-period pulsars. In the surveyed part of the sky that overlaps with the Parkes Multibeam Pulsar Survey (36° ≲ ℓ ≲ 50°), PALFA is probing deeper than the Parkes survey, with four discoveries in this region. For both Galactic millisecond and normal pulsar populations, we compare the survey's detections with simulations to model these populations and, in particular, to estimate the number of observable pulsars in the Galaxy. We place 95% confidence intervals of 82,000 to 143,000 on the number of detectable normal pulsars and 9000 to 100,000 on the number of detectable millisecond pulsars in the Galactic disk. These are consistent with previous estimates. Given the most likely population size in each case (107,000 and 15,000 for normal and millisecond pulsars, respectively), we extend survey detection simulations to predict that, when complete, the full PALFA survey should have detected 1000{sub −230}{sup +330} normal pulsars and 30{sub −20}{sup +200} millisecond pulsars. Identical estimation techniques predict that 490{sub −115}{sup +160} normal pulsars and 12{sub −5}{sup +70} millisecond pulsars would be detected by the beginning of 2014; at the time, the PALFA survey had detected 283 normal pulsars and 31 millisecond pulsars, respectively. We attribute the deficiency in normal pulsar

  13. Arecibo Pulsar Survey Using ALFA. III. Precursor Survey and Population Synthesis

    Science.gov (United States)

    Swiggum, J. K.; Lorimer, D. R.; McLaughlin, M. A.; Bates, S. D.; Champion, D. J.; Ransom, S. M.; Lazarus, P.; Brazier, A.; Hessels, J. W. T.; Nice, D. J.; Ellis, J.; Senty, T. R.; Allen, B.; Bhat, N. D. R.; Bogdanov, S.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Freire, P. C. C.; Jenet, F. A.; Karako-Argaman, C.; Kaspi, V. M.; Knispel, B.; Lee, K. J.; van Leeuwen, J.; Lynch, R.; Lyne, A. G.; Scholz, P.; Siemens, X.; Stairs, I. H.; Stappers, B. W.; Stovall, K.; Venkataraman, A.; Zhu, W. W.

    2014-06-01

    The Pulsar Arecibo L-band Feed Array (PALFA) Survey uses the ALFA 7-beam receiver to search both inner and outer Galactic sectors visible from Arecibo (32° <~ l <~ 77° and 168° <~ l <~ 214°) close to the Galactic plane (|b| <~ 5°) for pulsars. The PALFA survey is sensitive to sources fainter and more distant than have previously been seen because of Arecibo's unrivaled sensitivity. In this paper we detail a precursor survey of this region with PALFA, which observed a subset of the full region (slightly more restrictive in l and |b| <~ 1°) and detected 45 pulsars. Detections included 1 known millisecond pulsar and 11 previously unknown, long-period pulsars. In the surveyed part of the sky that overlaps with the Parkes Multibeam Pulsar Survey (36° <~ l <~ 50°), PALFA is probing deeper than the Parkes survey, with four discoveries in this region. For both Galactic millisecond and normal pulsar populations, we compare the survey's detections with simulations to model these populations and, in particular, to estimate the number of observable pulsars in the Galaxy. We place 95% confidence intervals of 82,000 to 143,000 on the number of detectable normal pulsars and 9000 to 100,000 on the number of detectable millisecond pulsars in the Galactic disk. These are consistent with previous estimates. Given the most likely population size in each case (107,000 and 15,000 for normal and millisecond pulsars, respectively), we extend survey detection simulations to predict that, when complete, the full PALFA survey should have detected 1000^{+330}_{-230} normal pulsars and 30^{+200}_{-20} millisecond pulsars. Identical estimation techniques predict that 490^{+160}_{-115} normal pulsars and 12^{+70}_{-5} millisecond pulsars would be detected by the beginning of 2014; at the time, the PALFA survey had detected 283 normal pulsars and 31 millisecond pulsars, respectively. We attribute the deficiency in normal pulsar detections predominantly to the radio frequency interference

  14. Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in adult patients with Pompe disease.

    Science.gov (United States)

    Kanters, Tim A; van der Ploeg, Ans T; Kruijshaar, Michelle E; Rizopoulos, Dimitris; Redekop, W Ken; Rutten-van Mӧlken, Maureen P M H; Hakkaart-van Roijen, Leona

    2017-12-13

    Pompe disease is a rare, progressive, metabolic disease, and the first treatable inheritable muscle disorder. Enzyme replacement therapy (ERT) with alglucosidase alfa is disease specific and the only medicinal product authorized for the treatment of Pompe disease. Costs of ERT are very high as for most orphan drugs. This study investigates the cost-effectiveness of ERT compared to supportive treatment in adult patients with Pompe disease. Survival probabilities were estimated from an international observational dataset (n = 283) using a time-dependent Cox model. Quality of life was estimated on a Dutch observational dataset using a previously developed conceptual model which links clinical factors to quality of life. Costs included costs of ERT, costs of drug administration and other healthcare costs. Cost-effectiveness was estimated using a patient-level simulation model (n = 90), synthesising the information from underlying models for survival, quality of life and costs. The cost-effectiveness model estimated the (difference in) lifetime effects and costs for both treatments. Two scenarios were modelled: (1) a worse case scenario with no extrapolation of the survival gain due to ERT beyond the observed period (i.e. from 10 years onwards); and (2) a best case scenario with lifetime extrapolation of the survival gain due to ERT. Effects were expressed in (quality adjusted) life years (QALYs). Costs were discounted at 4.0% and effects at 1.5%. Substantial increases in survival were estimated - discounted incremental life years of ERT ranged from 1.9 years to 5.4 years in the scenarios without and with extrapolation of survival gains beyond the observed period. Quality of life was also significantly better for patients receiving ERT. Incremental costs were considerable and primarily consisted of the costs of ERT. Incremental costs per QALY were €3.2 million for scenario 1 and €1.8 million for scenario 2. The availability of extended, prospectively

  15. A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for HCV genotype 1 infection.

    Science.gov (United States)

    Suzuki, Fumitaka; Toyota, Joji; Ikeda, Kenji; Chayama, Kazuaki; Mochida, Satoshi; Hayashi, Norio; Ishikawa, Hiroki; Miyagoshi, Hidetaka; Hu, Wenhua; McPhee, Fiona; Hughes, Eric A; Kumada, Hiromitsu

    2014-01-01

    Daclatasvir-containing regimens have the potential to address limitations of current regimens combining peginterferon alfa and ribavirin with first-generation protease inhibitors for treatment of chronic HCV genotype 1 infection. In this randomized, double-blind study, 27 Japanese treatment-naive patients received once-daily daclatasvir 10 mg or 60 mg or placebo, each combined with peginterferon alfa-2b/ribavirin; 18 prior null (n=9) or partial (n=9) responders received the same daclatasvir-containing regimens without a placebo arm. Daclatasvir recipients with protocol-defined response (HCV RNAdaclatasvir 10 mg, 60 mg and placebo groups, respectively. Prior non-responders had more frequent virological failure; 22.2% and 33.3% of daclatasvir 10 mg and 60 mg recipients, respectively, achieved SVR24. Adverse events were similar across groups and were typical of peginterferon alfa-2b/ribavirin. Pyrexia, headache, alopecia, decreased appetite and malaise were the most common adverse events; two daclatasvir recipients discontinued due to adverse events. Daclatasvir 60 mg combined with peginterferon alfa-2b and ribavirin achieved a high rate of SVR24 in treatment-naive patients with HCV genotype 1 infection, with tolerability similar to that of peginterferon alfa-2b/ribavirin alone. However, regimens with greater antiviral potency are needed for prior non-responders.

  16. Interferon alfa combined with azathioprine for the uveitis of Behçet's disease: an open study.

    Science.gov (United States)

    Hamuryudan, Vedat; Ozyazgan, Yilmaz; Fresko, Yzzet; Mat, Cem; Yurdakul, Sebahattin; Yazici, Hasan

    2002-11-01

    Eye involvement is the main cause of morbidity in Behçet's syndrome. The efficacy of the combined use of azathioprine and interferon alfa in treating this condition has not been studied. Ten male BD patients with retinal involvement but no irreversible structural changes were treated with azathioprine 2.5 mg/kg/day and IFN alpha 2b three times weekly for 24 weeks in an open trial. At week 24, IFN alpha was stopped and the patients continued to use azathioprine or received other immunosuppressives as indicated. Clinical response was assessed by visual acuity changes of either eye under the combination treatment and during the follow-up after stopping interferon. As compared to the study entry, the mean visual acuities of either eye increased significantly at the end of the combination treatment (right eye 5.8 +/- 1.26 vs. 8.3 1.14; P = 0.043; left eye 6.3 1.15 SEM vs. 9.1 +/- 0.9 SEM; P = 0.027). The improvement in visual acuity persisted in the nine patients who were followed for 7.2 +/- 1.6 SEM months after stopping interferon. Reversible hematologic toxicity, mostly in the form of leukopenia, was detected in six patients during the combination treatment. The combination of IFN alpha and azathioprine appears to be effective for eye involvement of BD. However, the frequent occurrence of myelosuppression mandates close monitoring.

  17. Diversidade alfa e beta no cerrado sensu strictu da Chapada Pratinha, Brasil Alfa and Beta diversity in the cerrado sensu stricto

    Directory of Open Access Journals (Sweden)

    Maria Cristina Felfili

    2001-08-01

    Full Text Available O bioma cerrado possui uma das mais ricas floras dentre as savanas mundiais com mais de 6000 espécies, abrange uma vasta extensão territorial, contém as três maiores bacias hidrográficas sul americanas, e se destaca pela elevada biodiversidade. O objetivo deste trabalho, que faz parte do Projeto Biogeografia do Bioma Cerrado, foi analisar as diversidades alfa e beta em comunidades de cerrado sensu stricto. Foram amostrados o Parque Nacional de Brasília, a Estação Ecológica de Águas Emendadas, a Area de Proteção Ambiental (APA Gama-Cabeça de Veado, Silvânia-GO, Paracatu-MG e Patrocínio-MG. A amostragem foi aleatória com 10 parcelas de 20x50m em cada área de estudo. Foram incluídas plantas lenhosas, exceto lianas, que tivessem no mínimo 5cm de diâmetro. Foi calculada a diversidade alfa pelo teste de Shannon & Wienner e o de Simpson. A diversidade beta foi calculada pelo índice de Whittaker que mede a mudança ou taxa de substituição na composição de espécies de um local para outro. Foi efetuada a curva espécie-área para as 60 parcelas amostradas e efetuada a classificação por TWINSPAN. O cerrado sensu stricto da Chapada Pratinha pode ser diferenciado em duas zonas fitogeográficas: Distrito Federal-Silvânia e Paracatu-Patrocínio. Estas coincidem com um zoneamento por sistemas de terra que classifica a primeira zona como terras altas em contraposição à segunda.The cerrado flora is one of the richest among the world's savannas with more than 6000 species. The cerrado covers a large territory, contains the three most important hydrographycal basins in South America and a high diversity. The objective of this work, that is part of the project Biogeography of the Cerrado Biome, was to analyse alfa and beta diversity in the cerrado sensu stricto. The sampled places were: Brasília National Park -- DF, Águas Emendadas Ecological Station -- DF, Environmentally protected Area of Gama-Cabeça de Veado -- DF, Silv

  18. Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study.

    Science.gov (United States)

    Artaç, Mehmet; Çoşkun, Hasan Şenol; Korkmaz, Levent; Koçer, Murat; Turhal, Nazım Serdar; Engin, Hüseyin; Dede, İsa; Paydaş, Semra; Öksüzoğlu, Berna; Bozcuk, Hakan; Demirkazık, Ahmet

    2016-08-01

    We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma. This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS). The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months. This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. GSI Helmholz Centre for Heavy Ion Research - ALFA: Next generation concurrent framework for ALICE and FAIR experiments

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    FAIR is a new, unique international accelerator facility for the research with antiprotons and ions. It is being built at the GSI Darmstadt in Hesse, Germany. The commonalities between the ALICE and FAIR experiments and their computing requirements led to the development of a common software framework in an experiment independent way; ALFA (ALICE-FAIR framework). ALFA is designed for high quality parallel data processing and reconstruction on heterogeneous computing systems. It provides a data transport layer and the capability to coordinate multiple data processing components. ALFA is a flexible, elastic system which balances reliability and ease of development with performance by using a message based multi-processing in addition to multi-threading. The framework allows for usage of heterogeneous computing architectures by offloading (portions of code are accelerated on the device) or natively (where the full program is executed on the device ).

  20. Unmasking of myasthenia gravis during pegylated Alfa 2 a interferon and ribavirin therapy for chronic hepatitis C.

    Science.gov (United States)

    Saleem, Ayesha

    2016-05-01

    Over last few decades, hepatitis C has emerged as a serious infection that has threatened the health and budgets of millions in the world. The objective of health professionals to treat it with recommended therapy of Alfa interferon and Ribavirin combination presents certain risks. One of the alarms is the ability of interferon to stimulate the production of autoantibodies in the body resulting in expression of autoimmune diseases in few who develop these antibodies. The case presented here is about unmasking of myasthenia gravis in a patient who received alfa interferon therapy for her chronic hepatitis C. Alfa interferon probably plays an important role in manifestation of the diseases in susceptible patients and all autoimmune diseases cannot be taken as mere side effects of the therapy. Clinicians need to be alert to pick up these diseases earlier so that the prompt management is possible.

  1. Economic and clinical effects of evaluating rapid viral response to peginterferon alfa-2b plus ribavirin for the initial treatment of chronic hepatitis C.

    Science.gov (United States)

    Wong, John B; Davis, Gary L; McHutchison, John G; Manns, Michael P; Albrecht, Janice K

    2003-11-01

    Evaluation of 12-wk viral response to initial antiviral therapy for chronic hepatitis C has been recommended to minimize antiviral-associated morbidity and costs. The aim of this study was to examine the economic and clinical effects of evaluating rapid viral response during antiviral therapy for treatment naive chronic hepatitis C patients. We applied viral response and drug dosage from an international randomized clinical trial of ribavirin plus peginterferon alfa-2b or ribavirin plus interferon alfa-2b to a previously published computer cohort simulation to project lifelong clinical and economic outcomes. Natural history and economic estimates were based on published literature, expert panel estimates, and actual variable and reimbursement cost data. The assessment of 12-wk rapid viral response reduced antiviral treatment duration by 40-44% and antiviral costs by 44-45% (savings of $15,116-16,268 for peginterferon plus ribavirin and $8300 for interferon plus ribavirin) compared to full 48-wk dosing. With the 12-wk evaluation, the marginal cost-effectiveness of peginterferon plus ribavirin versus interferon plus ribavirin was $13,600-22,800 compared with $14,600-25,000 per discounted quality adjusted life-year gained with the 24-wk evaluation. For genotype 1, hepatitis C infected patients, 12-wk testing for peginterferon plus ribavirin remaining preferred and cost-effective compared with interferon plus ribavirin. For genotype 2 or 3, hepatitis C infected patients, 12-wk testing yielded similar results to those of 24-wk treatment. Assessment of 12-wk viral response in genotype 1, hepatitis C infected patients should reduce peginterferon plus ribavirin morbidity and costs and improve its cost-effectiveness; however, for genotype 2 and 3, hepatitis C infected patients, 12-wk testing and 24-wk treatment have similar outcomes. Decisions regarding continuation of antiviral treatment should also consider the variability in the accuracy of quantitative viral assays as

  2. Darbepoetin alfa administered every 4 weeks for anemia in patients with advanced prostate cancer.

    Science.gov (United States)

    Beer, Tomasz M; Bergenstock, Misty; Birt, Karlee; Higano, Celestia S

    2007-06-01

    Anemia is a common morbidity of advanced prostate cancer, and prostate cancer treatment and has been associated with a worse overall survival and reduced quality of life in patients with prostate cancer. We sought to determine if infrequent dosing of darbepoetin alfa is safe and effective in treating anemia in patients receiving systemic therapy for prostate cancer. Sixteen patients with histologically confirmed prostate cancer with bone metastases on androgen deprivation therapy with or without chemotherapy; and a baseline hemoglobin (Hb) or = 12.5 g/dL and the proportion whose baseline Hb increased by > or = 1 g/dL. Patients were initially treated with 300 microg of darbepoetin alfa every 4 weeks. The dose was increased to 500 microg, 800 microg, and 1000 microg at each subsequent visit if the baseline Hb was not at target and had not increased by > or = 1 g/dL during the previous 4 weeks. Treatment was planned for 6 months. Treatment was well tolerated with no grade > or = 3 toxicities. Fourteen patients were assessable. The median Hb at study entry was 10.7 g/dL (range, 8.4-12). Serum Hb increased by > or = 1 g/dL in 10 patients (71%; 95% confidence interval, 42%-92%) and 7 patients (50%; 95% confidence interval, 23%-77%) reached an Hb of > or = 12.5 g/dL after treatment with doses that ranged from 300 microg to 1000 microg. Darbepoetin alfa administration every 4 weeks is feasible and well tolerated. Target Hb increases were achieved in approximately half of the patients and required doses that ranged from 300 microg to 1000 microg.

  3. Amniotic membrane transplantation with topical interferon alfa-2b after excision of ocular surface squamous neoplasia

    Directory of Open Access Journals (Sweden)

    Hua-Tao Xie

    2018-01-01

    Full Text Available To evaluate the outcome of amniotic membrane transplantation (AMT after tumor excision followed by topical interferon alfa-2b (IFNα2b drops for primary ocular surface squamous neoplasia (OSSN. Twelve eyes of 12 patients with a mean age of 66±10y were included. The average follow-up was 23±10mo. All 12 patients had limbal involvement. Smooth ocular surface and transparent cornea were achieved in all cases. No sign of inflammation, neovascularization, symblepharon or recurrence was noted at the last follow-up. We conclude that AMT with topical IFNα2b drops restores a healthy ocular surface in OSSN without recurrence.

  4. Pegylated interferon-alfa plus ribavirin therapies for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    T Kanda

    2011-03-01

    Full Text Available Until HCV NS3/4A protease inhibitors become available at the end of 2011, the combination pegylated-interferon (PEG-IFN-alfa and ribavirin (RBV will remain the standard treatment for chronic hepatitis C patients. In some hepatitis C virus-infected patients, PEG-IFN plus RBV treatment against HCV should continue to be used because of side effects of new drugs such as anemia. Our Japanese experiences should provide new information for the treatment of chronic hepatitis C. Keywords: Direct-acting antiviral agents (DAA, HCV, pegylated interferon, ribavirin, standard of care (SOC .

  5. Managing infertility with the follitropin alfa prefilled pen injector – patient considerations

    Directory of Open Access Journals (Sweden)

    Bühler K

    2015-06-01

    Full Text Available Klaus Bühler Centre for Gynaecological Endocrinology and Reproductive Medicine, Stuttgart, Germany Abstract: Gonadotropin treatment has been used in fertility treatment since the 1930s. First, preparations coming from animals were injected, then, gonadotropins prepared from the pituitary glands of human cadavers. A great step was achieved with the introduction of human menopausal gonadotropin extracted from the urine of postmenopausal women. When cases of Creutzfeld-Jacob disease were recognized after the use of human pituitary-derived hormone injections, urinary gonadotropins were increasingly purified and then produced by the use of recombinant DNA technology. Recombinant gonadotropins were characterized by the extreme high specificity and the nearly 100% purity. This allows for follitropin alfa, the first recombinant-human follicle stimulating hormone (r-hFSH approved, to be quantified and filled by mass, with a small variance of only ±2% and no more with a bioassay with a variance of 45%. With recombinant preparations, it is also possible to cover the tremendous growing demand for gonadotropins. Ovarian stimulation has become a self-injecting procedure for the patients. Accurate and easy-to-use injection devices which minimize pain, difficulty, and stress are essential for patient compliance. So, two pen injectors adapted from the well-known insulin pen were introduced in fertility treatment, one as a multiple-use device rechargeable with premixed, prefilled cartridges with r-hFSH (follitropin β and the other a disposable, prefilled drug delivery system with a liquid formulation of follitropin alfa filled by mass. The efficacy in comparison to the quite more cumbersome handling with ampoules and syringes has been proven very quickly. In several studies, it has been shown that patients had a preference to the prefilled follitropin alfa pen due to the faster preparation and were more confident of accurate dosing. The follitropin alfa

  6. Expressão local do fator de necrose tumoral alfa na ruptura prematura de membranas

    OpenAIRE

    Roveran,Valquíria; Silva,Maria Antonieta Longo Galvão; Yamano,Lucia; Rodrigues,Lilian Paiva; Vasquez,Mônica Lopez; Piato,Sebastião

    2009-01-01

    OBJETIVO: comparar a expressão do fator de necrose tumoral alfa (TNF-α) em membranas ovulares com ruptura prematura (RPM) e com ruptura oportuna das mesmas; verificar a associação entre a expressão do TNF-α em membranas ovulares e o grau de corioamnionite das mesmas e correlacionar a expressão do TNF-α e o tempo de ruptura das membranas. MÉTODOS: foram analisadas as membranas ovulares de 31 parturientes com RPM, com idade gestacional acima de 34 semanas, e de 14 parturientes co...

  7. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina Programa de infusión domiciliaria para la enfermedad de Fabry: experiencia con agalsidasa alfa en la Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X ocasionado por el déficit de la enzima alfa galactosidasa A. La terapia de reemplazo enzimático utilizando agalsidasa alfa reduce significativamente el dolor, mejora la función cardíaca y la calidad de vida y enlentece el deterioro renal. Sin embargo, es un tratamiento de por vida que requiere infusiones intravenosas regulares y supone una gran carga para los pacientes. Nuestro objetivo fue evaluar retrospectivamente la

  8. The ALFA (Activity Log Files Aggregation) toolkit: a method for precise observation of the consultation.

    Science.gov (United States)

    de Lusignan, Simon; Kumarapeli, Pushpa; Chan, Tom; Pflug, Bernhard; van Vlymen, Jeremy; Jones, Beryl; Freeman, George K

    2008-09-08

    There is a lack of tools to evaluate and compare Electronic patient record (EPR) systems to inform a rational choice or development agenda. To develop a tool kit to measure the impact of different EPR system features on the consultation. We first developed a specification to overcome the limitations of existing methods. We divided this into work packages: (1) developing a method to display multichannel video of the consultation; (2) code and measure activities, including computer use and verbal interactions; (3) automate the capture of nonverbal interactions; (4) aggregate multiple observations into a single navigable output; and (5) produce an output interpretable by software developers. We piloted this method by filming live consultations (n = 22) by 4 general practitioners (GPs) using different EPR systems. We compared the time taken and variations during coded data entry, prescribing, and blood pressure (BP) recording. We used nonparametric tests to make statistical comparisons. We contrasted methods of BP recording using Unified Modeling Language (UML) sequence diagrams. We found that 4 channels of video were optimal. We identified an existing application for manual coding of video output. We developed in-house tools for capturing use of keyboard and mouse and to time stamp speech. The transcript is then typed within this time stamp. Although we managed to capture body language using pattern recognition software, we were unable to use this data quantitatively. We loaded these observational outputs into our aggregation tool, which allows simultaneous navigation and viewing of multiple files. This also creates a single exportable file in XML format, which we used to develop UML sequence diagrams. In our pilot, the GP using the EMIS LV (Egton Medical Information Systems Limited, Leeds, UK) system took the longest time to code data (mean 11.5 s, 95% CI 8.7-14.2). Nonparametric comparison of EMIS LV with the other systems showed a significant difference, with EMIS

  9. De-squeeze the beams: the TOTEM and ATLAS/ALFA experiments

    CERN Multimedia

    Stefania Pandolfi

    2016-01-01

    A special week-long proton–proton run with larger beam sizes at the interaction point is intended to probe the p-p elastic scattering regime at small angles.   Nicola Turini, deputy spokesperson for TOTEM, in front of one of the experiment’s ‘Roman Pot’ detectors in the LHC tunnel. (Photo: Maximilien Brice/CERN) Usually, the motto of the LHC is “maximum luminosity”. But for a few days per year, the LHC ignores its motto to run at very low luminosity for the forward experiments. This week, the LHC will provide the TOTEM and ATLAS/ALFA experiments with data for a broad physics programme. The TOTEM experiment at Point 5 and the ATLAS/ALFA experiment at Point 1 study the elastic scattering of protons, which are not observable in normal operation runs. In the elastic scattering process, the two protons survive their encounter intact and only change directions by exchanging momentum. To allow this special run, the operators play with the so-c...

  10. Mango resistance to fruit flies. II - resistance of the alfa cultivar

    Energy Technology Data Exchange (ETDEWEB)

    Rossetto, C.J.; Bortoletto, N., E-mail: rossetto@iac.sp.gov.b [Agencia Paulista de Tecnologia dos Agronegocios (APTA), Votuporanga, SP (Brazil). Polo Regional do Noroeste Paulista; Walder, J.M.M.; Mastrangelo, T. de A., E-mail: jmwalder@cena.usp.b [Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil); Carvalho, C.R.L.; Castro, J.V. de, E-mail: climonta@iac.sp.gov.b, E-mail: josalba@iac.sp.gov.b [Instituto Agronomico de Campinas, SP (Brazil); Pinto, A.C. de Q. [EMBRAPA, Brasilia, DF (Brazil); Cortelazzo, A.L., E-mail: angelo@unicamp.b [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Biologia

    2006-07-01

    The percentage of infested mango fruits of five selected mango varieties was evaluated during three years under field conditions. Three varieties with field resistance to fruit flies had less then 10% of fruits infested. Tommy Atkins, the susceptible commercial check, had 42,9% and the susceptible check had 98.9 % of infested fruits. The three field resistant varieties plus the susceptible commercial check, Tommy Atkins, were further tested in laboratory, under caged conditions, with artificial infestation of Anastrepha obliqua. The attempts of oviposition and the number of pupae developed from each fruit were evaluated. Under caged conditions, the cultivar Alfa maintained its field resistance and Espada Stahl and IAC 111 lost the field resistance and were as susceptible as Tommy Atkins. The attempts of oviposition were positively and highly correlated with the number of pupae developed in the fruits. Non preference for oviposition was confirmed as the main mechanism of resistance of mango fruits to fruit flies. In the absence of a more susceptible variety (no choice test) the cultivar Alfa has kept the resistance (author)

  11. Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis.

    Science.gov (United States)

    Kim, V; Abreu, R M; Nakagawa, D M; Baldassare, R M; Carrilho, F J; Ono, S K

    2016-03-01

    Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNα) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases--PubMed, EMBASE, Cochrane Library and LILACS--for randomized controlled trials evaluating PEG-IFNα therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies. © 2015 The Authors Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

  12. Immunogenicity of glycans on biotherapeutic drugs produced in plant expression systems-The taliglucerase alfa story.

    Directory of Open Access Journals (Sweden)

    Bonita Rup

    Full Text Available Plants are a promising alternative for the production of biotherapeutics. Manufacturing in-planta adds plant specific glycans. To understand immunogenic potential of these glycans, we developed a validated method to detect plant specific glycan antibodies in human serum. Using this assay, low prevalence of pre-existing anti-plant glycan antibodies was found in healthy humans (13.5% and in glucocerebrosidase-deficient Gaucher disease (GD patients (5%. A low incidence (9% in naïve patient and none in treatment experienced patients of induced anti-plant glycan antibodies was observed in GD patients after up to 30 months replacement therapy treatment with taliglucerase alfa, a version of human glucocerebrosidase produced in plant cells. Detailed evaluation of clinical safety and efficacy endpoints indicated that anti-plant glycan antibodies did not affect the safety or efficacy of taliglucerase alfa in patients. This study shows the benefit of using large scale human trials to evaluate the immunogenicity risk of plant derived glycans, and indicates no apparent risk related to anti-plant glycan antibodies.

  13. FTIR spectroscopy and X-ray powder diffraction characterization of microcrystalline cellulose obtained from alfa fibers

    Directory of Open Access Journals (Sweden)

    Trache D.

    2013-07-01

    Full Text Available Many cereal straws have been used as raw materials for the preparation of microcrystalline cellulose (MCC. These raw materials were gradually replaced with wood products; nevertheless about 10% of the world overall pulp production is obtained from non-wood raw material. The main interest in pulp made from straw is that it provides excellent fibres for different industries with special properties, and that it is the major available source of fibrous raw material in some geographical areas. The aim of the present work was to characterize microcrystalline cellulose prepared from alfa fibers using the hydrolysis process. The products obtained are characterized with FTIR spectroscopy and X-ray powder diffraction. As a result, FTIR spectroscopy is an appropriate technique for studying changes occurred by any chemical treatment. The spectrum of alfa grass stems shows the presence of lignin and hemicelluloses. However, the cellulose spectrum indicates that the extraction of lignin and hemicellulose was effective. The X-ray analysis indicates that the microcrystalline cellulose is more crystalline than the source material.

  14. Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis.

    Science.gov (United States)

    Druyts, Eric; Thorlund, Kristian; Wu, Ping; Kanters, Steve; Yaya, Sanni; Cooper, Curtis L; Mills, Edward J

    2013-04-01

    A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin (RBV) in children and adolescents with chronic hepatitis C virus (HCV). Medline, Embase, and Cochrane Central Register of Controlled Trials were searched. Clinical trials examining peg-IFN alfa-2a or peg-IFN alfa-2b plus RBV among persons ages 3-18 years with HCV were included. Data were abstracted for complete early virologic response (EVR), sustained virologic response (SVR), relapse, treatment discontinuations, hematologic and dermatologic adverse events, and growth inhibition. Eight trials met the inclusion criteria. Results indicate that 70% of subjects (95% confidence interval [CI], 58%-81%) achieved EVR, and 58% (95% CI, 53%-64%) achieved SVR. EVR and SVR were higher for those with HCV genotypes 2/3 than 1/4. Discontinuation due to adverse events and discontinuation due to viral breakthrough were each 4%, discontinuation due to a lack of response was 15%, and relapse was 7%. Anemia, neutropenia, leukopenia, and thrombcytopenia were 11%, 32%, 52%, and 5%, respectively. Alopecia, injection site erythema, and pruritus were 13%, 27%, and 10%, respectively. Small growth inhibitions were observed during treatment. The results of this meta-analysis indicate that peg-IFN/RBV combination treatment is effective and safe in treating children and adolescents with HCV.

  15. Diversidad alfa y beta de la comunidad de reptiles en el complejo cenagoso de Zapatosa, Colombia

    Directory of Open Access Journals (Sweden)

    Guido Fabián Medina-Rangel

    2011-06-01

    Full Text Available La diversidad es una propiedad de las comunidades, permite describir, caracterizar y entender el funcionamiento de los ecosistemas. Para estudiar la riqueza, abundancia y el recambio de especies de reptiles entre hábitats circundantes al complejo cenagoso de Zapatosa, se realizaron cuatro salidas de campo (noviembre de 2006 y octubre de 2007. Se invirtieron 640h/hombre de muestreo repartido en cinco tipos de hábitat: bosque casmófito, bosque seco, bosque de ribera, palmar y sabana arbolada. Se encontraron 847 individuos de 48 especies, la familia más rica fue Colubridae, se registraron cinco especies endémicas y ocho con algún grado de amenaza en conservación a nivel nacional. El hábitat más diverso fue el bosque de ribera. La representatividad del muestreo en total y para cada hábitat fue superior al 80%, con excepción del palmar (Alfa and beta diversity of reptilian assemblages in Zapatosa wetland complex, Colombia. Diversity is a property of community that can described, characterized, and understood according to the functioning of ecosystems. To study the richness and local abundance and species replacement between habitats around the Zapatosa’s wetland complex (El Cesar Department, I carried out four field trips between November of 2006 and October of 2007. A total of 640 sampling hours/man analyzed five habitat types chasmophyte forest, dry forest, riparian forest, palm-grove and tree-lined savanna; with the exception of the palm-grove sampled at its 75%, the others were sampled up to their 80%. I found 847 reptiles that were distributed in 48 species. The group with the highest number of species was Colubridae with 14, followed by Gekkonidae with five. Five endemic species and eight with some conservation threat grade at a national level a re reported. The riparian forest was the richest and most abundant habitat with 34 species and 196 individuals. For each habitat, Colubridae had the highest number of species, followed by

  16. Early virologic response to сеpeginterferon alfa-2b in combination with ribavirin in treatment of patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    O. O. Znoyko

    2013-01-01

    Full Text Available Algeron (cepeginterferon alfa-2b is a new pegylated form of interferon alfa containing linear polyethylene glycol (molecular weight 20 kDa. Pharmacokinetic profile of Algeron allows once weekly administration. In phase II–III study 150 treatment-naive patients with compensated liver function were randomized into 3 groups: Algeron 1,5 μg/kg/week, Algeron 2,0 μg/kg/week, and a reference group of PegIntron 1.5 μg/kg/week in combination with ribavirin 800– 1400 mg/day. Comparative ITT -analysis of early virologic response (EVR showed absence of differences between groups in frequency of EVR. In Algeron groups (regardless of a dose – 1,5 or 2,0 μg/kg EVR was observed in 94%, in PegIntron group – – in 88% of patients. Complete EVR (HCV RNA≤15 I I U/mL was recorded in 88% and 84% of patients receiving Algeron 1,5 and 2,0 μg/kg, respectively, in the reference group – – in 84% of patients. There were no statistically significant differences between groups where patients received Algeron in different doses and the reference group, with or without genotype stratification. Adverse events occurring during the treatment with Algeron are dose-dependent; however, their frequency is no more than in patients receiving standard doses of PegIntron. Based on the absence of differences in efficacy and more favorable safety profile of a lower dose of the study drug, the therapeutic dose of Algeron was selected to be 1,5 μg/kg/week.

  17. Efficacy and safety of pegylated interferon alfa-2b and ribavirin combination therapy versus pegylated interferon monotherapy in hemodialysis patients: a comparison of 2 sequentially treated cohorts.

    Science.gov (United States)

    Tseng, Po-Lin; Chen, Te-Chuan; Chien, Yu-Shu; Hung, Chao-Hung; Yen, Yi-Hao; Chang, Kuo-Chin; Tsai, Ming-Chao; Lin, Ming-Tsung; Lee, Chien-Te; Shen, Chien-Heng; Hu, Tsung-Hui

    2013-10-01

    Pegylated interferon (peginterferon; interferon with an attached polyethylene glycol molecule) monotherapy is the recommended treatment for chronic hepatitis C virus (HCV) infection in hemodialysis patients. Limited data concerning peginterferon alfa-2b and ribavirin treatment in this population are available. 2 prospective observational cohort studies. From 2007-2009, a total of 26 patients received peginterferon alfa-2b monotherapy. From 2009-2012, an additional 26 patients were treated with peginterferon alfa-2b and ribavirin. Peginterferon alfa-2b monotherapy, 1.0 μg/kg/wk, versus peginterferon alfa-2b, 1.0 μg/kg/wk, and ribavirin, 200 mg, 3 times per week. Treatment durations were 24 and 48 weeks for HCV genotypes non-1 and 1, respectively. End-of-treatment virologic response and sustained virologic response (SVR) were undetectable HCV RNA at the end of treatment and 24 weeks after treatment ended, respectively. SVR and treatment-related withdrawal rate were evaluated by intention-to-treat (ITT) and per-protocol (PP) analyses. Severe anemia was defined as nadir hemoglobin level alfa-2b and ribavirin combination therapy provided a higher SVR rate than peginterferon alfa-2b monotherapy for treatment-naive dialysis patients with chronic HCV infection through careful monitoring of hematologic parameters and ribavirin dose modification. Severe anemia was significantly higher in patients receiving combination therapy than patients treated with monotherapy. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. Characterization of IXINITY® (Trenonacog Alfa, a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

    Directory of Open Access Journals (Sweden)

    Dougald M. Monroe

    2016-01-01

    Full Text Available The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148 polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant]. Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX both with and without factor VIIIa (FVIIIa and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed 97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa; once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX.

  19. Interferon alfa for chronic hepatitis B infection: increased efficacy of prolonged treatment. The European Concerted Action on Viral Hepatitis (EUROHEP)

    NARCIS (Netherlands)

    Janssen, H. L.; Gerken, G.; Carreño, V.; Marcellin, P.; Naoumov, N. V.; Craxi, A.; Ring-Larsen, H.; Kitis, G.; van Hattum, J.; de Vries, R. A.; Michielsen, P. P.; ten Kate, F. J.; Hop, W. C.; Heijtink, R. A.; Honkoop, P.; Schalm, S. W.

    1999-01-01

    Interferon alfa (IFN-alpha) is the primary treatment for chronic hepatitis B. The standard duration of IFN-alpha therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-alpha treatment in patients

  20. Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels

    DEFF Research Database (Denmark)

    Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo

    2015-01-01

    Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre...

  1. alfa-Deuterium kinetic isotope effects in reactions of methyllithium. Is better aggregation the cause of lower reactivity?

    DEFF Research Database (Denmark)

    Holm, Torkil

    1996-01-01

    The value of kH/kD for alfa deuterium kinetic isotope effects for the reaction of methyllithium and methylmagnesium iodid with a series of substrates are consistently ca. 10-15 % higher for the lithium reagent. This may indicate a pre-equilibrium...

  2. Study of forward elastic pp scattering at √ i>s> = 8 TeV with the ALFA detector

    DEFF Research Database (Denmark)

    Stark, Simon Holm

    The elastic proton-proton scattering data analyzed in this thesis was taken at the LHC with the ALFA detector at sqrt(s) = 8 TeV with a beta* collision optics which gave access to the Coulomb-Nuclear-Interference region. An improved procedure was used to fit the observed number of elastic events ...

  3. Successi artigianali e promesse mancate. La progettazione auto all’Alfa Romeo negli anni Trenta e Quaranta.

    OpenAIRE

    Italiano, Patrick

    2011-01-01

    L'article examine le rapport entre les projets de rationalisation industrielle mis en oeuvre par l'Ing. Gobbato et l'activité du bureau d'études automobile d'Alfa-Romeo entre 1933 et 1945. Peer reviewed

  4. Switch from agalsidase beta to agalsidase alfa in the enzyme replacement therapy of patients with Fabry disease in Latin America

    Directory of Open Access Journals (Sweden)

    Diego Ripeau

    2017-06-01

    Full Text Available There are currently two available enzyme replacement therapies for Fabry disease and little information regarding efficacy and safety of switching therapies. Between 2009 and 2012 there was a worldwide shortage of agalsidase beta and patients on that enzyme were switched to agalsidase alfa. This retrospective observational study assessed a 2-year period of efficacy and safety in a population of Fabry patients, in Argentina (30 patients and Venezuela (3 patients, who switched therapies from algasidase beta to agalsidase alfa. Thirty-three patients completed 24-months follow-up after the switch (age 32.4 ± 2.0, range 10.0-55.9 years; male: female 23:10. Measures of renal function such as estimated glomerular filtration rate remained almost unchanged in 31 patients without end stage renal disease over the 2 years after switching and urine protein excretion continued stable. Cardiac functional parameters: left ventricular mass index, interventricular septum, left ventricular posterior wall showed no significant change from baseline in the 33 patients. Quality of life, pain and disease severity scores were mostly unchanged after 24-months and agalsidase alfa was generally well tolerated. Our findings showed there is no significant change in the efficacy measured through the renal or cardiac function, quality of life, pain, disease severity scoring and safety for at least 2 years after switching from agalsidase beta to agalsidase alfa.

  5. Arecibo Pulsar Survey Using ALFA. IV. Mock Spectrometer Data Analysis, Survey Sensitivity, and the Discovery of 40 Pulsars

    NARCIS (Netherlands)

    Lazarus, P.; Brazier, A.; Hessels, J.W.T.; Karako-Argaman, C.; Kaspi, V.M.; Lynch, R.; Madsen, E.; Patel, C.; Ransom, S.M.; Scholz, P.; Swiggum, J.; Zhu, W.W.; Allen, B.; Bogdanov, S.; Camilo, F.; Cardoso, F.; Chatterjee, S.; Cordes, J.M.; Crawford, F.; Deneva, J.S.; Ferdman, R.; Freire, P.C.C.; Jenet, F.A.; Knispel, B.; Lee, K.L.; van Leeuwen, J.; Lorimer, D.R.; Lyne, A.G.; McLaughlin, M.A.; Siemens, X.; Spitler, L.G.; Stairs, I.H.; Stovall, K.; Venkataraman, A.

    2015-01-01

    The on-going Arecibo Pulsar-ALFA (PALFA) survey began in 2004 and is searching for radio pulsars in the Galactic plane at 1.4 GHz. Here we present a comprehensive description of one of its main data reduction pipelines that is based on the PRESTO software and includes new interference-excision

  6. Dificuldades na identificação laboratorial da talassemia alfa Difficulty on laboratory identification of alpha thalassemia

    Directory of Open Access Journals (Sweden)

    Karlla Greick Batista Dias-Penna

    2010-04-01

    Full Text Available Introdução: Talassemia alfa é uma síndrome associada à redução da síntese de cadeias de globina do tipo alfa. A gravidade das manifestações clínicas está relacionada com a quantidade de globinas produzida e a estabilidade das cadeias beta presentes em excesso. A talassemia alfa mínima resulta da deleção de apenas um dos quatro genes a (-α/αα. Clinicamente apresenta anemia leve com microcitose ou ausência de anemia, sendo o diagnóstico realizado por meio de visualização da hemoglobina (Hb H por eletroforese alcalina em acetato de celulose ou por identificação de inclusões celulares de Hb H coradas pelo azul de crezil brilhante. Objetivo: Avaliar portadores de talassemia alfa e seus respectivos progenitores, correlacionando perfil hematológico e presença de Hb H, utilizando procedimentos laboratoriais clássicos em três diferentes amostragens. Discussão e conclusão: Os dados obtidos mostram que a presença de Hb H, indicativo de talassemia alfa, pode não ser confirmada em uma análise posterior. Entre os fatores que podem influenciar no não aparecimento de Hb H em pessoa comprovadamente com talassemia alfa está a deficiência de ferro. A talassemia alfa está associada a defeitos envolvendo os genes codificadores da cadeia alfa, mas também pode estar relacionada com desbalanciamento temporário na expressão dos genes globina, diminuição de alfa ou aumento de beta, o que poderia explicar o aparecimento de tetrâmeros de cadeia beta (Hb H, sugerindo diagnóstico de talassemia alfa mínima.Introduction: Alpha thalassemia is a syndrome with associated with the reduction of alpha globin chain synthesis. The severity of clinical manifestations is related to the amount of globins produced and the stability of beta chains that are present in excess. Alpha thalassemia minor is caused by the deletion of one of the four genes a (-α/αα. Clinically, it presents mild anemia with microcytosis or absence of anemia. The

  7. Recommendations for the clinical practice: Standards, options and recommendations 2003 for the use of recombinant erythropoietin (alpha and beta epoetine, alpha darbepoetine, EPO) in the taking charge of anemia in oncology for the patients treated by radiotherapy, update; Recommandations pour la pratique clinique: Standards, Options et Recommandations 2003 pour l'utilisation de l'erythropoietine recombinante (epoetine alfa et beta, darbepoetine alfa, EPO) dans la prise en charge de l'anemie en cancerologie pour les patients traites par radiotherapie, mise a jour

    Energy Technology Data Exchange (ETDEWEB)

    Marchal, Ch. [Centre Alexis-Vautrin, oncologue-radiotherapeute, 54 - Nancy (France); Spaeth, C. [Centre Alexis-Vautrin, oncologue medical, 54 - Nancy (France); Casadevall, N. [Hopital Hotel-Dieu, hematologue, 75 - Paris (France); Daouphars, M. [Hopital Notre-Dame-de-Bon-Secours, pharmacien, 57 - Metz (France); Marec-Berard, P. [Centre Leon-Berard, oncologue-pediatre, 69 - Lyon (France); Fabre, N. [FNCLCC, methodologiste, 75 - Paris (France); Haugh, M. [FNCLCC, methodologiste, 75 - Paris (France)

    2004-06-01

    Standards, Options and Recommendations for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy - UPDATE 2003. Context. - 'The Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the twenty French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives. - To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy. Methods. - The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomized clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002. Results. - There is no standard attitude for use of rHuEPO in patients undergoing radiotherapy. There is no evidence to support use of rHuEPO in patients with ENT cancer receiving radiotherapy alone. In patients undergoing curative radiotherapy, it is recommended to correct anaemia under 10 g/dL using transfusion rather than rHuEPO. When the haemoglobin concentration is between 12 g/dL and 14 g/dL initial use of rHuEPO can be an option under certain conditions for radio-chemotherapy if the risk of anaemia is high with the chemotherapy regimen used. Anemic patients should be included in clinical trials to clarify the impact of rHuEPO in terms of local control of the tumour and survival. (authors)

  8. Peginterferon alfa-2b and ribavirin in thalassaemia/chronic hepatitis C virus-co-infected non-responder to standard interferon-based.

    Science.gov (United States)

    Hamidah, A; Thambidorai, C R; Jamal, R

    2005-10-01

    We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.

  9. Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macrometastatic nodes: an open-label, randomised, phase 3 European Association for Dermato-Oncology (EADO) study.

    Science.gov (United States)

    Grob, Jean Jacques; Jouary, Thomas; Dréno, Brigitte; Asselineau, Julien; Gutzmer, Ralf; Hauschild, Axel; Leccia, Marie Thérèse; Landthaler, Michael; Garbe, Claus; Sassolas, Bruno; Herbst, Rudolf A; Guillot, Bernard; Chene, Genevieve; Pehamberger, Hubert

    2013-01-01

    Both low-dose interferon (IFN) alfa-2b and pegylated interferon (Peg-IFN) alfa-2b have been shown to be superior to observation in the adjuvant treatment of melanoma without macrometastatic nodes, but have never been directly compared. Peg-IFN facilitates prolongation of treatment, which could provide additional benefit. This multicentre, open-label, randomised, phase 3 trial compared standard low-dose interferon IFN and prolonged treatment with Peg-IFN. Patients with resected melanoma ≥1.5mm thick and without clinically detectable node metastases were randomised 1:1 to treatment with IFN 3 MU subcutaneously (SC) three times weekly for 18 months or Peg-IFN 100 μg SC once weekly for 36 months. Sentinel lymph node dissection (SLND) was optional. The primary endpoint was disease-free survival (DFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS) and adverse events (AEs) grade 3-4. Of 898 patients enrolled, 896 (443 Peg-IFN, 453 IFN) were eligible for evaluation (median follow-up 4.7 years). SLND was performed in 68.2% of patients. There were no statistical differences between the two arms for the primary outcome of DFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.73-1.15) or the secondary outcomes of DMFS (HR 1.02, 95% CI 0.80-1.32) and OS (HR 1.09, 95% CI 0.82-1.45). Peg-IFN was associated with higher rates of grade 3-4 AEs (47.3% versus 25.2%; p<0.0001) and discontinuations (54.3% versus 30.4%) compared with IFN. This trial did not show superiority for adjuvant Peg-IFN over conventional low-dose IFN in melanoma patients without clinically detectable nodes. ClinicalTrials.gov identifier: NCT00221702. Copyright © 2012. Published by Elsevier Ltd.

  10. Health-related quality of life in patients with high-risk melanoma randomised in the Nordic phase 3 trial with adjuvant intermediate-dose interferon alfa-2b.

    Science.gov (United States)

    Brandberg, Y; Aamdal, S; Bastholt, L; Hernberg, M; Stierner, U; von der Maase, H; Hansson, J

    2012-09-01

    To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN). A total of 855 patients with histologically verified resected cutaneous melanoma in AJCC stage IIb (T4 N0 M0) or stage III (Tx N1-3 M0) were randomised to: Arm A: observation only (n = 284); Arm B: 1-year treatment: induction: IFN alfa-2b, 10 MU (flat dose), SC, 5 days/week, 4 weeks, maintenance: IFN alfa-2b, 10 MU (flat dose), SC, 3 days/week for 12 months (n = 285); or Arm C: 2 years of same treatment as Arm B. HRQoL was assessed using The European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) before randomisation and at 8 pre-defined time-points during 2 years. IFN-related side-effects were assessed by a study-specific questionnaire. > 80% of eligible patients returned questionnaires at the different assessment points. Statistically significant interactions between randomisation arm and time after randomisation were found for almost all EORTC QLQ-30 variables. While patients in Arm A improved or remained at baseline levels; patients in Arms B and C reported decreased functioning and quality of life, and an increase in side-effects during their treatment. Patients in Arm B improved after the 12th month assessment, when IFN treatment was scheduled to end, to the 16th month assessment (p interferon-related side-effects. A significant negative impact on HRQoL of IFN treatment was demonstrated, however the impact were reversible when treatment was stopped. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Using ALFA for high throughput, distributed data transmission in the ALICE O2 system

    Science.gov (United States)

    Wegrzynek, A.; ALICE Collaboration

    2017-10-01

    ALICE (A Large Ion Collider Experiment) is a heavy-ion detector designed to study the physics of strongly interacting matter (the Quark–Gluon Plasma at the CERN LHC (Large Hadron Collider). ALICE has been successfully collecting physics data in Run 2 since spring 2015. In parallel, preparations for a major upgrade of the computing system, called O2 (Online-Offline), scheduled for the Long Shutdown 2 in 2019-2020, are being made. One of the major requirements of the system is the capacity to transport data between so-called FLPs (First Level Processors), equipped with readout cards, and the EPNs (Event Processing Node), performing data aggregation, frame building and partial reconstruction. It is foreseen to have 268 FLPs dispatching data to 1500 EPNs with an average output of 20 Gb/s each. In overall, the O2 processing system will operate at terabits per second of throughput while handling millions of concurrent connections. The ALFA framework will standardize and handle software related tasks such as readout, data transport, frame building, calibration, online reconstruction and more in the upgraded computing system. ALFA supports two data transport libraries: ZeroMQ and nanomsg. This paper discusses the efficiency of ALFA in terms of high throughput data transport. The tests were performed with multiple FLPs pushing data to multiple EPNs. The transfer was done using push-pull communication patterns and two socket configurations: bind, connect. The set of benchmarks was prepared to get the most performant results on each hardware setup. The paper presents the measurement process and final results – data throughput combined with computing resources usage as a function of block size. The high number of nodes and connections in the final set up may cause race conditions that can lead to uneven load balancing and poor scalability. The performed tests allow us to validate whether the traffic is distributed evenly over all receivers. It also measures the behaviour

  12. Diversidad alfa y beta de los artrópodos en diferentes ambientes del Parque Nacional Los Cardones, Salta (Argentina

    Directory of Open Access Journals (Sweden)

    María Belén Cava

    2013-12-01

    Full Text Available El Parque Nacional Los Cardones ubicado en la provincia de Salta protege las ecorregiones de Puna, Monte y Pastizal Altoandino Nublado de la Yungas. Nuestro objetivo es evaluar la diversidad alfa y beta de artrópodos en las ecorregiones del Parque. Se muestrearon tres sitios en cada ecorregión utilizando Pit-fall y G-Vac. Se calcularon estimadores no paramétricos de riqueza de especies, la diversidad entre ecorregiones se comparó a través de los “perfiles de diversidad” y “números efectivos de especies”, se analizó el recambio de especies y la complementariedad entre las ecorregiones y sitios de una misma ecorregión. Se registraron 469 spp/morfoespecies, la diversidad en el Parque fue alta, siendo mayor en los Pastizal Altoandino Nublado, y la más baja en la Puna. El inventario llegó al 81% de completitud. El recambio de especies entre ecorregiones fue alto, de esa manera los diferentes ambientes del Parque contribuyen a conservar la diversidad regional de artrópodos. Las ensambles de artrópodos en sitios de una misma ecorregión mostraron mayor similitud entre sí que con sitios más distantes. Se pudo reconocer tres grupos de artrópodos (arañas, dípteros e himenópteros que son diversos y abundantes, los que podrían ser utilizados en futuros estudios como grupos focales.

  13. Dornase Alfa

    Science.gov (United States)

    ... down the thick secretions in the airways, allowing air to flow better and preventing bacteria from building ... of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, ...

  14. Interferon alfa-2b in the management of recurrent conjunctival papillomatosis.

    Science.gov (United States)

    Singh, Manpreet; Gautam, Natasha; Gupta, Adit; Kaur, Manpreet

    2016-10-01

    A 2-year-old boy presented with a recurrent strawberry-like reddish mass arising from the left caruncular region for 8 months. An incisional biopsy was performed elsewhere 2 months earlier, followed by an increase in size of mass, significant epiphora, and intermittent bleeding. On examination, exuberant exophytic gelatinous mass with multifocal origin was observed arising from inferior forniceal conjunctiva and caruncle. Clinical differential of multifocal conjunctival papilloma was kept, and topical interferon alfa-2b (INFα-2b) was started. No clinical reduction in mass or symptomatology was observed over 6 weeks. Excision biopsy with cryotherapy and subconjunctival injection of INFα-2b was performed over all foci. Conjunctival papilloma was confirmed on histopathology, and topical INFα-2b was continued in postoperative period for 3 months. At 14 months of follow-up, no recurrence, epiphora, or bleeding was noticed. We advocate a possible role of local INF therapy in managing and preventing recurrences of conjunctival papillomatosis.

  15. VizieR Online Data Catalog: UV counterparts in HI clouds using ALFA surveys (Donovan+, 2015)

    Science.gov (United States)

    Donovan Meyer, J.; Peek, J. E. G.; Putman, M.; Grcevich, J.

    2017-10-01

    GALFA-HI is a survey of Galactic HI conducted with the ALFA seven-beam feed array on the 305 m Arecibo antenna. The survey has both high spatial (FWHM~4') and velocity (0.18 km/s) resolution over 13000 (7520 in DR1) degrees2 of sky between -650 and 650 km/s. Details of the observations and data reduction can be found in Peek et al. (2011ApJS..194...20P). The ALFALFA HI-line survey, now 40% complete, also uses the Arecibo Observatory and its seven-beam feed array to detect potential dwarf galaxies in the vicinity of the Milky Way. The survey, which covers over 7000 (2800 in α.40) deg2 of sky out to 18000 km/s, has the sensitivity to detect 105 Mȯ clouds with 20 km/s linewidths at a distance of 1 Mpc. (2 data files).

  16. The ATLAS Forward Detectors - LUCID, ALFA and AFP: Past, Present and Future

    CERN Document Server

    Caforio, D; The ATLAS collaboration

    2013-01-01

    LUCID is a gas Cerenkov detector deployed near to the beam‐pipe at 17 m either side of the ATLAS Intersection point. The LUCID detector ‐ when calibrated via a Van der Meer scan – is now measuring absolute luminosity on a bunch‐by‐bunch basis. It is now measuring integrated luminosity up to high luminosity with a precision of around 3%. The technical challenges that had to faced to make this measurement as well as upgrade plans for LUCID will be presented. In addition to LUCID, we will discuss that ALFA detector (Absolute Luminosity for ATLAS) and its status as well as the progress on the ATLAS Forward Protons project (AFP) that plans to deploy detectors to tag and measure, with 3‐D silicon detectors, both protons in exclusive central diffractive processes.

  17. ALGLUCOSIDASE ALFA — A NEW STAGE IN THE THERAPY OF INFANTILE POMPE DISEASE

    Directory of Open Access Journals (Sweden)

    E. N. Basargina

    2014-01-01

    Full Text Available Pompe disease is a rare severe hereditary disease caused by excessive glycogen storage in organs and target tissues due to the acid α-glucosidase gene mutation. Infantile and adult Pompe disease is characterized by involvement of cardiovascular, respiratory and muscular systems in the pathological process. The only specific method of treating Pompe disease is enzyme replacement therapy (intravenous administration of recombinant human acid glucosidase, the effectiveness whereof depends on the time the therapy started. Since such a therapy was introduced into practice, Pompe disease mortality decreased by 79%. 6 children with infantile Pompe disease were observed and treated at the cardiovascular care unit of the Scientific Center of Children’s Health in 2011‑2014. The article presents a clinical case demonstrating capabilities of diagnosing infantile Pompe disease in Russia and effective application of alglucosidase alfa in 4-month-old child. 

  18. A large, multicentre, observational, post-marketing surveillance study of the 2:1 formulation of follitropin alfa and lutropin alfa in routine clinical practice for assisted reproductive technology.

    Science.gov (United States)

    Bühler, Klaus; Naether, Olaf G J; Bilger, Wilma

    2014-01-14

    Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) both have a role to play in follicular development during the natural menstrual cycle. LH supplementation during controlled ovarian stimulation (COS) for assisted reproductive technology (ART) is used for patients with hypogonadotropic hypogonadism. However, the use of exogenous LH in COS in normogonadotropic women undergoing ART is the subject of debate. The aim of this study was to investigate characteristics of infertile women who received the 2:1 formulation of follitropin alfa and lutropin alfa (indicated for stimulation of follicular development in women with severe LH and FSH deficiency) in German clinical practice. A 3-year, multicentre, open-label, observational/non-interventional, post-marketing surveillance study of women (21-45 years) undergoing ART. Primary endpoint: reason for prescribing the 2:1 formulation of follitropin alfa and lutropin alfa. Secondary variables included: COS duration/dose; oocytes retrieved; fertilization; clinical pregnancy; ovarian hyperstimulation syndrome (OHSS). In total, 2220 cycles were assessed; at least one reason for prescribing the 2:1 formulation was given in 1834/2220 (82.6%) cycles. Most common reasons were: poor ovarian response (POR) (39.4%), low baseline LH (17.8%), and age (13.8%). COS: mean dose of the 2:1 formulation on first day, 183.1/91.5 IU; mean duration, 10.8 days. In 2173/2220 (97.9%) cycles, human chorionic gonadotrophin was administered. Oocyte pick-up (OPU) was attempted in 2108/2220 (95.0%) cycles; mean (standard deviation) 8.0 (5.4) oocytes retrieved/OPU cycle. Fertilization (≥1 oocyte fertilized) rates: in vitro fertilization (IVF), 391/439 (89.1%) cycles; intracytoplasmic sperm injection (ICSI)/IVF + ICSI, 1524/1613 (94.5%) cycles. Clinical pregnancy rate: all cycles, 25.9%; embryo transfer cycles, 31.3%. OHSS: hospitalization for OHSS, 8 (0.36%) cycles, Grade 2, 60 (2.7%), and Grade 3, 1 (0.05%). In German routine clinical

  19. Efficacy of pegylated interferon alfa-2a or alfa-2b in combination with ribavirin in the treatment of chronic hepatitis caused by hepatitis C virus genotype 1b.

    Science.gov (United States)

    Mach, Tomasz H; Cieśla, Andrzej; Warunek, Wioleta; Janas-Skulina, Urszula; Cibor, Dorota; Owczarek, Danuta; Ciećko-Michalska, Irena

    2011-12-01

    Treatment of chronic hepatitis C (CHC) with pegylated interferon (Peg-IFN) and ribavirin leads to sustained virological response (SVR) in approximately 50% of the patients. SVR depends on hepatitis C virus (HCV) and host factors, including IL28B genotypes. The aim of the study was to investigate the therapeutic efficacy of the difficult-to-treat HCV genotype 1b in patients from the south of Poland. A total of 260 adult patients with CHC and HCV genotype 1b were treated with Peg-IFN alfa-2a or Peg-IFN alfa-2b with ribavirin for 48 weeks. Efficacy was assessed at 12 weeks (early virological response - EVR), 48 weeks (end-of-treatment response - ETR), and at 6 months (SVR). HCV-RNA, alanine transaminase (ALT), and other biochemical parameters were measured in serum at baseline and at 12, 48, and 72 weeks of therapy. HCV-RNA levels were 3.72 ±1.17 × 106 IU/ml at baseline and decreased significantly at 12 weeks (0.02 ±0.17 × 106 IU/ml); there were no differences between the group treated with Peg-INF alfa-2a and the group treated with Peg-INF alfa-2b. ALT was 94.1 ±7.6 IU/l at baseline and decreased significantly at 12 weeks (42.5 ±3.1 IU/l). The overall EVR, ETR, and SVR were achieved by 63.9%, 77.7%, and 48.1% of the patients, respectively. Tolerance of therapy was similar in both groups. Efficacy of Peg-IFN alfa-2a with ribavirin is not significantly different from that of Peg-IFN alfa-2b with ribavirin, and SVR was achieved in 48.3% and 44.3% of the patients, respectively. Our study confirms that the efficacy of treatment of patients with HCV genotype 1b from the southern region of Poland is similar to that observed in the overall Polish population.

  20. Decline in pulmonary function during chronic hepatitis C virus therapy with modified interferon alfa and ribavirin.

    Science.gov (United States)

    Foster, G R; Zeuzem, S; Pianko, S; Sarin, S K; Piratvisuth, T; Shah, S; Andreone, P; Sood, A; Chuang, W-L; Lee, C-M; George, J; Gould, M; Flisiak, R; Jacobson, I M; Komolmit, P; Thongsawat, S; Tanwandee, T; Rasenack, J; Sola, R; Messina, I; Yin, Y; Cammarata, S; Feutren, G; Brown, K K

    2013-04-01

    Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg-IFNα-2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research. © 2013 Blackwell Publishing Ltd.

  1. Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.

    Science.gov (United States)

    Case, Laura E; Bjartmar, Carl; Morgan, Claire; Casey, Robin; Charrow, Joel; Clancy, John P; Dasouki, Majed; DeArmey, Stephanie; Nedd, Khan; Nevins, Mary; Peters, Heidi; Phillips, Dawn; Spigelman, Zachary; Tifft, Cynthia; Kishnani, Priya S

    2015-04-01

    Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 2 or 3.

    Science.gov (United States)

    Nelson, David R; Benhamou, Yves; Chuang, Wan-Long; Lawitz, Eric J; Rodriguez-Torres, Maribel; Flisiak, Robert; Rasenack, Jens W F; Kryczka, Wiesław; Lee, Chuan-Mo; Bain, Vincent G; Pianko, Stephen; Patel, Keyur; Cronin, Patrick W; Pulkstenis, Erik; Subramanian, G Mani; McHutchison, John G

    2010-10-01

    A phase 3 active-controlled study was conducted to assess the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of recombinant human albumin and interferon alfa-2b, in patients with chronic hepatitis C virus (HCV) genotype 2/3. In all, 933 patients were randomized to open-label subcutaneous treatment with pegylated interferon-alfa-2a (Peg-IFNalfa-2a) 180 μg/wk, or albIFN 900 or 1200 μg every 2 weeks for 24 weeks, each administered with oral ribavirin 800 mg/day. The primary end point of the study was sustained virologic response (SVR) (HCV-RNA level, alfa-2b 900 μg every 2 weeks provides an alternative efficacious treatment option in patients with chronic HCV genotype 2 or 3. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Hauser, Goran

    2010-01-01

    A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha-2a or peginterferon alfa-2b...... alfa-2b plus ribavirin. Overall, peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa-2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04-1.19; P = 0.004 [eight trials]). Subgroup analyses......-2a is associated with higher SVR than peginterferon alfa-2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one peginterferon over the other, because any potential benefit must outweigh the risk of harm....

  4. Stroke in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia treated with Darbepoetin Alfa: the trial to reduce cardiovascular events with Aranesp therapy (TREAT) experience

    National Research Council Canada - National Science Library

    Skali, Hicham; Parving, Hans-Henrik; Parfrey, Patrick S; Burdmann, Emmanuel A; Lewis, Eldrin F; Ivanovich, Peter; Keithi-Reddy, Sai Ram; McGill, Janet B; McMurray, John J V; Singh, Ajay K; Solomon, Scott D; Uno, Hajime; Pfeffer, Marc A

    2011-01-01

    .... A multivariate logistic regression model was used to identify baseline predictors of stroke in 4038 patients with diabetes mellitus, chronic kidney disease, and anemia randomized to receive darbepoetin alfa or placebo...

  5. [Position statements regarding usage of biosimilars of Epoetins. Position paper of the Société de néphrologie, Société francophone de dialyse, and Société de néphrologie pédiatrique].

    Science.gov (United States)

    Bouchet, Jean-Louis; Brunet, Philippe; Canaud, Bernard; Chanliau, Jacques; Combe, Christian; Deray, Gilbert; Houillier, Pascal; Kourilsky, Olivier; Ledneva, Elena; Niaudet, Patrick; Ortiz, Jean-Paul; Pavlovic, Mira; Ryckelynck, Jean-Philippe; Singlas, Eric; Verhelst, David

    2009-02-01

    The European patents for epoetin alpha recently expired. Biosimilars (i.e. "a medicine which is similar to a biological medicine that has already been authorized" [EMEA 2007]) of epoetins have thus been released on the market in Europe. Because of the complexity of the processes that are required to produce medicinal products containing biotechnology-derived proteins as active substances and to characterize the physicochemical properties of these compounds, the guidelines that have been developed for generic drugs cannot be used for approval of biosimilar products. The EMEA guidelines do not answer all questions that have been raised for the development of biosimilars, and in some cases, decisions will have to be taken at a national level. This is why the Society of Nephrology (Société de néphrologie), the French-speaking Society of Dialysis (Société francophone de dialyse) and the Pediatric Society of Nephrology (Société de néphrologie pédiatrique) established guidelines for the usage of biosimilar epoetins concerning approval, identification, substitution of an innovator drug, post-marketing surveillance, extension of indication and pharmacovigilance plan.

  6. Efficacy and safety of peginterferon alfa-2a and ribavirin treatment of chronic hepatitis C in the Republic of Serbia

    Directory of Open Access Journals (Sweden)

    Božić Milena

    2012-01-01

    Full Text Available Introduction. Hepatitis C virus (HCV infection is one of the main causes of chronic liver disease worldwide. Pegylated interferon alfa-2a or 2b (PEG IFN alfa-2a or 2b and ribavirin (RBV represent a standard treatment of chronic hepatitis C (CHC. Sustained virological response (SVR, defined as continued undetectable HCV RNA 24 weeks after completion of treatment, is universally considered as an indicator of treatment efficacy. Objective. The aim of this study was to determine efficacy and safety of PEG IFN alfa-2a and RBV treatment in patients with CHC in Serbia. Methods. One hundred seventy-six patients with CHC were included in this multicenter trial from 8 reference centers in Serbia. The patients were treated with standard PEG IFN alfa- 2a and RBV protocol. We performed the following virological testing: anti-HCV (ELISA, HCV RNK (quantitative PCR, HCV genotype (type-specific PCR, HBsAg, anti-HBs, anti-HBc and anti-HIV (ELISA. Histological activity and the degree of fibrosis were determined according to the Metavir scoring system. Potential predictors for achieving SVR were evaluated using multivariable logistic regression analysis. Results. Of the treated patients with CHC 65.9% were male, and 60.2% of them aged over 40 years. Of the treated patients 68.2% had infection over 5 years, 63% had HCV RNA >400.000 IU/mL, 76.1% had HCV G1/4, and 60.1% had a mild to moderate liver fibrosis. SVR was achieved in 78.9% of patients (G1/4 79.1%; G2/3 78.1%. The factors that indicated a poorer efficacy of the treatment were age >40 (p<0.05, high basal viremia (p=0.013, and the reduction of PEG IFN alfa-2a and RBV doses, with interruption of therapy (p<0.001. Of the treated patients 45.9% had adverse affects (G1/4 50.8%; G2/3 29.7%. Conclusion. Treatment of CHC with PEG IFN alfa-2a and RBV was efficient in 78.9% of patients. The safety profile of therapy was satisfactory. Longer therapy increases the possibility of the development of adverse affects. No

  7. Propiedades electrofisiológicas de las variantes normales de actividad alfa en el continuo vigilia-sueño

    Directory of Open Access Journals (Sweden)

    José Luis Cantero

    2001-01-01

    Full Text Available El estudio de los ritmos cerebrales puede ser abordado mediante el análisis de sus propiedades electrofisiológicas usando técnicas de EEG cuantitativo. En aquellos casos donde una misma actividad aparece espontáneamente en diferentes estados de activación cerebral, el estudio de estas propiedades ayudaría a establecer diferencias funcionales asociadas a cada uno de estos estados. El presente trabajo revisa aquellos estudios que han determinado las propiedades electrofisiológicas de las diferentes variantes normales de alfa que aparecen en el continuo vigilia-sueño, más concretamente en vigilia relajada, somnolencia y durante la fase REM del sueño. Los resultados indican que cada variante normal de alfa, aun mostrando una distribución topográfica similar en cada uno de los estados cerebrales, presenta características diferenciales atendiendo a su composición espectral, relaciones funcionales entre regiones corticales, y micro-estados cerebrales subyacentes. De acuerdo con estos hallazgos, cada variante de alfa desempeñaría diferentes funciones cerebrales. El ritmo alfa de vigilia parece ser el resultado de una máxima sincronización neuronal como consecuencia de la ausencia de procesamiento sensorial, mientras que la presencia de actividad alfa durante la somnolencia estaría más asociada al procesamiento de las imágenes hipnagógicas que ocurren al comienzo del sueño. Los brotes de alfa de REM, sin embargo, constituirían un punto de contacto entre el cerebro dormido y el ambiente externo. Esta caracterización electrofisiológica encuentra su campo de aplicación más directo en el diseño de algoritmos para clasificar el sueño de forma automática, así como en el diagnóstico y evaluación de determinadas patologías donde pudieran verse afectados los mecanismos cerebrales de generación de esta actividad a lo largo del continuo vigilia-sueño.

  8. Long-term efficacy and safety of low-dose and dose-escalating interferon alfa-2a therapy in refractory Behçet uveitis.

    Science.gov (United States)

    Onal, Sumru; Kazokoglu, Haluk; Koc, Aylin; Akman, Mehmet; Bavbek, Tayfun; Direskeneli, Haner; Yavuz, Sule

    2011-03-01

    To investigate the long-term efficacy and safety of low-dose and dose-escalating therapy of interferon alfa-2a in the treatment of Behçet uveitis. This study included 37 patients with refractory Behçet panuveitis unresponsive to conventional immunosuppressive therapy. Induction interferon alfa-2a therapy was given as a daily dose of 3.0 million IU (MIU) subcutaneously for 14 days. Maintenance dose was achieved with 3.0 MIU 3 times per week given subcutaneously. The dosage was increased sequentially to 4.5, 6.0, and 9.0 MIU 3 times per week if uveitis relapses occurred. Total therapy duration was 24 months. Primary outcome measure was control of uveitis with quiescence during maintenance therapy. Ocular relapses per patient-year before and after initiation of interferon alfa-2a therapy and a corticosteroid-sparing effect were secondary outcomes. We also estimated the rate of remission after discontinuing interferon alfa-2a therapy. During maintenance therapy, interferon alfa-2a controlled uveitis in 35 patients (95%). In 15 patients (41%), a maintenance dosage of 3.0 MIU 3 times per week controlled uveitis without any relapse. The rate of uveitis relapses decreased from 3.52 per patient-year before to 0.75 per patient-year after initiating interferon alfa-2a therapy. Seventeen patients were receiving systemic corticosteroids at the time of initiation of interferon therapy. During the maintenance stage, 9 patients were able to discontinue and 8 to taper systemic corticosteroid therapy. Survival analysis estimated that the rate of remission after discontinuation of interferon alfa-2a therapy was 76% by 3 months. The rate of remission remained stable thereafter. A treatment protocol using a low-dose and dose-escalating therapy with interferon alfa-2a was able to control and achieve remission of uveitis in most patients with refractory ocular Behçet disease.

  9. Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial.

    Science.gov (United States)

    Hansson, Johan; Aamdal, Steinar; Bastholt, Lars; Brandberg, Yvonne; Hernberg, Micaela; Nilsson, Bo; Stierner, Ulrika; von der Maase, Hans

    2011-02-01

    Adjuvant high-dose interferon alfa-2b improves relapse-free survival (RFS) in patients with high-risk melanoma, although benefits in overall survival are uncertain. Because of the toxic effects of high-dose regimens, intermediate doses are being explored. We investigated whether adjuvant therapy with intermediate-dose interferon alfa-2b for 1 or 2 years would improve outcomes in patients with stage IIB-IIC or III resected cutaneous melanoma. This randomised, open-label, phase 3, parallel-group trial was undertaken between 1996 and 2004. 855 patients were randomly assigned at 35 centres in the Nordic countries by block randomisation to three groups: observation only (group A); 4 weeks of induction (interferon alfa-2b 10 million units flat dose subcutaneously 5 days per week) followed by 12 months of maintenance therapy (interferon alfa-2b 10 million units flat dose subcutaneously 3 days per week; group B); or 1 month of induction and 24 months of maintenance (group C). Neither investigators nor patients were masked to treatment assignment. Patients were stratified for country and tumour stage; patients with stage III disease were further stratified for presence of metastatic lymph nodes at primary diagnosis versus at relapse, palpable versus non-palpable lymph-node metastases, and number of metastatic lymph nodes. The primary endpoint was overall survival in the two interferon alfa-2b groups combined. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01259934. 284 patients were assigned to group A, 285 to group B, and 286 to group C; all patients were analysed. The median follow-up time was 72·4 months (IQR 46·9-98·0). We recorded no significant improvement in overall survival in patients given interferon alfa-2b compared with observation: median overall survival was 56·1 months (IQR 22·3 to >120·0) in group A, 72·1 months (25·8 to >120) in group B, and 64·3 months (24·7 to >120) in group C (p=0·600). Hazard

  10. JAK-inhibitor tofacitinib suppresses interferon alfa production by plasmacytoid dendritic cells and inhibits arthrogenic and antiviral effects of interferon alfa.

    Science.gov (United States)

    Boor, Patrick P C; de Ruiter, Petra E; Asmawidjaja, Patrick S; Lubberts, Erik; van der Laan, Luc J W; Kwekkeboom, Jaap

    2017-10-01

    Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections. Using in vitro culture models with human cells, we studied the effects of tofacitinib on PDC survival and IFNα production, and on arthrogenic and antiviral effects of IFNα. Tofacitinib inhibited the expression of antiapoptotic BCL-A1 and BCL-XL in human PDC and induced PDC apoptosis. TLR7 stimulation upregulated the levels of antiapoptotic Bcl-2 family members and prevented the induction of PDC apoptosis by tofacitinib. However, tofacitinib robustly inhibited the production of IFNα by toll like receptor-stimulated PDC. In addition, tofacitinib profoundly suppressed IFNα-induced upregulation of TLR3 on synovial fibroblasts, thereby inhibiting their cytokine and protease production in response to TLR3 ligation. Finally, tofacitinib counteracted the suppressive effects of IFNα on viral replication. Tofacitinib inhibits PDC survival and IFNα production and suppresses arthrogenic and antiviral effects of IFNα signaling. Inhibition of the IFNα pathway at 2 levels may contribute to the beneficial effects of tofacitinib in autoimmune diseases and explain the increased viral infection rates observed during tofacitinib treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease.

    Science.gov (United States)

    Saglimbene, Valeria M; Palmer, Suetonia C; Ruospo, Marinella; Natale, Patrizia; Craig, Jonathan C; Strippoli, Giovanni Fm

    2017-08-07

    Continuous erythropoiesis receptor activator (CERA) is a newer, longer acting ESA which might be preferred to other ESAs (epoetin or darbepoetin) based on its lower frequency of administration. Different dosing requirements and molecular characteristics of CERA compared with other ESAs may lead to different health outcomes (mortality, cardiovascular events, quality of life) in people with anaemia and chronic kidney disease (CKD). To assess benefits and harms of CERA compared with other epoetins (darbepoetin alfa and epoetin alfa or beta) or placebo/no treatment or CERA with differing strategy of administration for anaemia in individuals with CKD. We searched the Cochrane Kidney and Transplant Specialised Register to 13 June 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised controlled trials (RCTs) of at least three months' duration, comparing CERA with a different ESA (darbepoetin alfa or epoetin alfa or beta) or placebo or standard care or versus CERA with different strategies for administration in people with any stage of CKD. Data were extracted by two independent investigators. We summarised patient-centred outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events, red cell blood transfusion, iron therapy, cancer, hypertension, seizures, dialysis vascular access thrombosis, drug injection-related events, hyperkalaemia and health-related quality of life and haemoglobin levels) using random effects meta-analysis. Treatment estimates were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean differences or standardized mean difference with

  12. 13,845 home therapy infusions with velaglucerase alfa exemplify safety of velaglucerase alfa and increased compliance to every-other-week intravenous enzyme replacement therapy for Gaucher disease.

    Science.gov (United States)

    Elstein, Deborah; Abrahamov, Aya; Oz, Anat; Arbel, Naama; Baris, Hagit; Zimran, Ari

    2015-12-01

    Lifelong intravenous (IV) enzyme replacement therapy (ERT) every other week for Gaucher disease is appreciated as decreasing quality of life in a palpable way. To review the Israeli experience with the home therapy option for IV velaglucerase alfa (Shire, Lexington MA USA) infusions every-other-week in the clinical trial context, in the early access program (EAP) during a shortage with the standard commercial ERT, and currently with the commercially available drug (VPRIV, Shire). Among 24 patients participating in trials, 1654 infusions were at home; in the EAP and commercial setting, 12,191 infusions were performed at home for a total of 154 patients with 98.4% compliance. There were no incidents of serious adverse events. This is the first review of experience of 174 patients and 13,845 intravenous infusions of velaglucerase alfa for Gaucher in the home setting, underscoring its safety. Copyright © 2015. Published by Elsevier Inc.

  13. Intensification of treatment with pegylated interferon alfa in patients coinfected with HIV and HBV genotype H or G being treated with a tenofovir/emtricitabine-containing regimen.

    Science.gov (United States)

    Mata-Marín, José Antonio; Mata-Marín, Luis Alberto; Arroyo-Anduiza, Carla Ileana; Huerta-García, Gloria; Sandoval-Ramirez, J L; Manjarrez-Tellez, Bulmaro; Gaytán-Martínez, J E

    2014-01-01

    The most common HBV genotypes in HIV-coinfected patients in Mexico are H and G; the response to treatment for these genotypes is unknown. The aim of the study was to examine the effectiveness of intensification with pegylated interferon (PEG-IFN) alfa-2a or alfa-2b in HBV/HIV-coinfected patients treated with a tenofovir/emtricitabine (TDF/FTC) backbone in an HIV clinic in Mexico City. We performed a single-arm open-label trial involving HBV/HIV-coinfected patients. Patients with chronic hepatitis B who were HBeAg positive were treated with TDF/FTC-containing regimen. Treatment was intensified by addition of PEG-IFN alfa-2b or alfa-2a for 24 weeks. The primary endpoint of effectiveness, assessed after 24 weeks, was suppression of HBV DNA to alfa-2a or alfa-2b is effective and well tolerated in patients with chronic hepatitis B who are HBeAg positive, have genotype H or G, and are coinfected with HIV while they are being treated with TDF/FTC-containing regimen.

  14. Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1.

    Science.gov (United States)

    Jacobson, Ira; Zeuzem, Stefan; Flisiak, Robert; Knysz, Brygida; Lueth, Stefan; Zarebska-Michaluk, Dorota; Janczewska, Ewa; Ferenci, Peter; Diago, Moises; Zignego, Anna Linda; Safadi, Rifaat; Baruch, Yaacov; Abdurakhmanov, Dzhamal; Shafran, Stephen; Thabut, Dominique; Bruck, Rafael; Gadano, Adrian; Thompson, Alexander James; Kopit, Justin; McPhee, Fiona; Michener, Tracy; Hughes, Eric A; Yin, Philip D; Noviello, Stephanie

    2016-03-28

    To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin (pegIFN/RBV), in treatment-naive hepatitis C virus (HCV) genotype (GT) 1-infected patients. In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned (2:1) to daclatasvir vs telaprevir, stratified by IL28B rs12979860 host genotype (CC vs non-CC), cirrhosis status (compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype (GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus pegIFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus pegIFN/RBV; those without an extended rapid virologic response (eRVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of pegIFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus pegIFN/RBV followed by 12 (with eRVR) or 36 (no eRVR) wk of pegIFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12 (SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia (hemoglobin daclatasvir + pegIFN/RBV than with telaprevir + pegIFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/mL, to investigate any link between NS5A polymorphisms associated with daclatasvir resistance and virologic outcome. Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups (6.0% and 8.2% in the GT1b and GT1a groups, respectively) than in the telaprevir groups (2.2% and 3.0%). Among GT1b-infected patients, daclatasvir plus pegIFN/RBV was

  15. Mucoproteína versus alfa-1-glicoproteína ácida: o que quantificar?

    OpenAIRE

    Geraldo Picheth; Bresolin, Paula L.; Osmar Pereira Jr.; Jaworski, Maria Cristina G.; Santos,Celso M.; Pinto, Adriana P.; Marileia Scartezini; Alcântara, Vânia M.; Fadel-Picheth, Cyntia M.T.

    2002-01-01

    A quantificação sérica da alfa-1-glicoproteína (GPA) ácida é útil no diagnóstico e no acompanhamento dos processos agudos resultantes de múltiplas causas. Esta proteína também pode ser estimada pela quantificação da mucoproteína (Muco), ensaio que reflete as glicoproteínas com elevado teor de açúcar, entre as quais a GPA é majoritária. O objetivo deste trabalho é verificar a correlação e a performance analítica das determinações de mucoproteína (Muco) e alfa-1-glicoproteína ácida (GPA), propo...

  16. Efek Pemberian Seduhan Teh Hijau terhadap Gelombang Alfa Otak pada Mahasiswa Tingkat Akhir Fakultas Kedokteran Universitas Islam Bandung

    Directory of Open Access Journals (Sweden)

    Helga Marwa Afifah

    2015-09-01

    Full Text Available Abstrak Teh merupakan bahan alam yang sudah dikenal memiliki banyak manfaat salah satunya sebagai zat relaksan. Sifat relaksan diperoleh dari kandungan senyawa pada teh terutama teh hijau yaitu L-teanin yang memicu peningkatan aktivitas gamma-aminobutyric acid (GABA, produksi serotonin dan dopamin, serta menghambat kerja glutamat. Efek keseluruhan L-teanin pada otak memicu seseorang menjadi rileks, kondisi rileks dapat dinilai dari aktivitas gelombang alfa otak. Tujuan penelitian ini menilai efek pemberian seduhan teh hijau terhadap gelombang alfa otak pada mahasiswa tingkat akhir Fakultas Kedokteran Unisba. Penelitian menggunakan metode eksperimental, melalui dua kali perekaman gelombang alfa otak sebelum dan setelah pemberian seduhan teh hijau yang mengandung 50 mg L-teanin dengan menggunakan brain wave sensors. Hasil penelitian dianalisis melalui Uji Wilcoxon. Penelitian dilakukan di Fakultas Kedokteran Unisba pada bulan April–Mei 2014. Sampel yang digunakan adalah mahasiswa tingkat akhir Fakultas Kedokteran Unisba yaitu sebanyak 30 orang, terdiri atas 13 laki-laki dan 17 perempuan. Hasil penelitian menunjukkan bahwa pada 28 dari 30 orang memperlihatkan peningkatan gelombang alfa otak setelah pemberian seduhan teh hijau dan hanya 2 orang yang memperlihatkan gelombang alfa otak yang lebih rendah. Hasil Uji Wilcoxon menunjukkan nilai signifikansi <0,001. Berdasarkan hasil penelitian, dapat disimpulkan bahwa pemberian seduhan teh hijau memiliki efek meningkatkan gelombang alfa otak pada mahasiswa tingkat akhir Fakultas Kedokteran Unisba. Hal ini dapat disebabkan karena aktivitas L-teanin dalam teh hijau yang dapat memicu aktivitas GABA, serotonin, dan dopamin serta menghambat kerja glutamat sehingga memicu kondisi relaksasi yang dinilai dalam gelombang alfa otak. Kata kunci: Gelombang alfa otak, L-teanin, teh, teh hijau   The Effect of Green Tea to Alpha Brain Waves of Final Students of Faculty of Medicine Universitas Islam Bandung Abstract

  17. Successful management of transfusion-dependent congenital dyserythropoietic anemia type 1b with interferon alfa-2a

    DEFF Research Database (Denmark)

    Rathe, Mathias; Møller, Michael Boe; Greisen, Pernille Wied

    2018-01-01

    The congenital dyserythropoietic anemias (CDAs) are a group of rare inherited blood disorders characterized by ineffective erythropoiesis as the principal cause of anemia. We present a child with CDA 1b-the rarest and least well-described type-due to a mutation in the C15orf41 gene. The patient...... deformities. The patient responded to treatment with pegylated interferon alfa-2a....

  18. A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease.

    Science.gov (United States)

    Byrne, Barry J; Geberhiwot, Tarekegn; Barshop, Bruce A; Barohn, Richard; Hughes, Derralynn; Bratkovic, Drago; Desnuelle, Claude; Laforet, Pascal; Mengel, Eugen; Roberts, Mark; Haroldsen, Peter; Reilley, Kristin; Jayaram, Kala; Yang, Ke; Walsh, Liron

    2017-08-24

    Late-onset Pompe disease is a rare genetic neuromuscular disorder caused by lysosomal acid alpha-glucosidase (GAA) deficiency that ultimately results in mobility loss and respiratory failure. Current enzyme replacement therapy with recombinant human (rh)GAA has demonstrated efficacy in subjects with late-onset Pompe disease. However, long-term effects of rhGAA on pulmonary function have not been observed, likely related to inefficient delivery of rhGAA to skeletal muscle lysosomes and associated deficits in the central nervous system. To address this limitation, reveglucosidase alfa, a novel insulin-like growth factor 2 (IGF2)-tagged GAA analogue with improved lysosomal uptake, was developed. This study evaluated the pharmacokinetics, safety, and exploratory efficacy of reveglucosidase alfa in 22 subjects with late-onset Pompe disease who were previously untreated with rhGAA. Reveglucosidase alfa plasma concentrations increased linearly with dose, and the elimination half-life was Pompe disease. ISRCTN01435772 and ISRCTN01230801 , registered 27 October 2011.

  19. Asociación de la actividad alfa-amilasa salivar matutina con índices de psicopatología internalizante en niñas de 8-11 años

    OpenAIRE

    Maldonado-Montero, Enrique Francisco

    2014-01-01

    ANTECEDENTES: Recientemente, se ha observado una reducción estadísticamente significativa en los niveles de actividad de la alfa-amilasa salivar en mujeres adolescentes diagnosticadas de depresión mayor (Cubala & Landowski, 2014). OBJETIVO: El objetivo del presente estudio ha sido analizar la relación entre índices de psicopatología internalizada y niveles matutinos de cortisol, de alfa-amilasa salivar y de sus respectivos ratios (cortisol/alfa-amilasa y alfa-amilasa/cortisol) en 45 niños y 5...

  20. [Short-term curative effect of ribavirin combination therapy with pegylated interferon alfa-2a vs. interferon alfa-2a in patients with chronic hepatitis C].

    Science.gov (United States)

    Wang, Meng; Zheng, Weiyang; Zhang, Hongyu; Li, Zhiqin; Jiang, Dong; Liu, Yanhong; Zhou, Rong; Li, Xiao-Gang; Zhang, Yingying; Zhang, Zhen; Wu, Shuhuan; Zhang, Yi; Li, Jiansheng

    2014-04-01

    To perform a retrospective cohort study in order to determine the differences in short-term curative effect of ribavirin in combination with interferon alfa (IFNa)-2a vs. pegylated (Peg)-IFNa-2a in patients with chronic hepatitis C (CHC). One-hundred-and-eighty-eight treatment of the CHC patients who were administered combination therapy of ribavirin with IFNa from 2010 to 2012. One-hundred-and-thirty-three of the patients received the therapy with IFNa-2a and the remaining 55 received Peg-IFNa-2a. Hepatitis C virus (HCV) load and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at treatment weeks 4, 12, 24, and 48. Adverse reactions were recorded. Differences between the groups were assessed by statistical analysis. The patients in the Peg-IFNa-2a group and the IFNa-2a group showed no significant difference in sex distribution, age, smoking habits, or drinking habits at baseline (all P more than 0.05). Both antiviral therapies significantly reduced the HCV load and levels of ALT and AST (baseline levels vs. all treatment weeks examined, P less than 0.05); however, the reduction in the HCV load at week 4 was significantly more robust with the Peg-IFNa-2a therapy (2.96 ± 0.66) log10 IU/ ml vs. (3.47 ± 1.42)1og10 IU/ml; F =4.14, P=0.04). The Peg-IFNa-2a group also showed a significant higher rate of rapid virological response (RVR) than the IFNa-2a group (72.72% vs .57.14%; x²=4.37, P=0.04), but there were no statistically significant differences found between the two groups for early virological response rate (EVR), endpoint antiviral treatment virologic response rate (ETR), biochemical response rate, or rate of adverse reactions (all P more than 0.05). Ribavirin in combination with Peg-IFNa-2a produces a better RVR than in combination with IFNa-2a .Yet, the EVR, ETR, biochemical response rate, and rate of adverse reactions is similar for the two forms of IFNa-2a. Further studies are required to determine the potential

  1. Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery

    DEFF Research Database (Denmark)

    Poulsen, Troels Dirch; Andersen, Lars Willy; Steinbrüchel, Daniel

    2009-01-01

    concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p ... for coronary artery bypass graft surgery with CPB. INTERVENTIONS: EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: CPB in both groups greatly increased plasma...

  2. Importance of a 5- versus 7-day pill-free interval in a GnRH antagonist protocol using corifollitropin alfa: a prospective cohort study in oocyte donors.

    Science.gov (United States)

    Pérez-Calvo, Alicia; Martínez, Francisca; Blockeel, Christophe; Clúa, Elisabeth; Rodríguez, Ignacio; Barri, Pere N; Coroleu, Buenaventura

    2017-10-01

    In this prospective cohort study, oocyte donors were recruited prospectively and assigned to receive corifollitropin alfa: 5 days after pill discontinuation (group D5; 42 donors), or 7 days after pill discontinuation (group D7; 50 donors) in a gonadotrophin-releasing hormone antagonist protocol. Fixed additional daily doses of 200 IU recombinent FSH (rFSH) were started after 7 days of corifollitropinalfa, until triggering. No significant differences in basal characteristics were observed between both groups. In group D5, mean (SD) total additional rFSH dose was 659 (452) IU; in group D7, total rFSH dose was 459 (356) IU (P = 0.022). Duration of stimulation was significantly longer in group D5 compared with group D7 (P = 0.002). No differences were found in total number of oocytes obtained. Total number of injections was significantly lower in group D7 compared with group D5 (9.8 [3.2] versus 11.9 [3.9], respectively; P = 0.004). Total cost of medication used for donor treatment was significantly higher in group D5 than in group D7 (P = 0.015). After more than 22 days of pill-taking, extending the pill-free interval to 7 days significantly reduces the total dose of gonadotrophins, duration of stimulation, total cost of medication and total number of injections. Copyright © 2017. Published by Elsevier Ltd.

  3. Peg-Interferon Alfa 2-b Related Cellulitis in a 40 Years Man

    Directory of Open Access Journals (Sweden)

    Shahnaaz Sali

    2016-01-01

    Full Text Available Background: Pegylated interferon and ribavirin are currently one of the accepted treatment for chronic Hepatitis C. Dermatologic complications of interferon have been reported, but to date a few cases of bacterial cellulitis; a rare and severe complication, have been published. Cellulitis is a common infectious process affecting the skin and subcutaneous tissues which results in significant morbidity and holds considerable healthcare costs.Cases Report: Herein, we report a case of chronic hepatitis C genotype 1a who was on medication since 8 weeks prior to developing leg cellulitis, an uncommon pegylated interferon injection site. Considering no other possible risk factors were found to be in favor of bacterial cellulitis, our case is unique in its kind. Some reports reveal necrotizing vasculitis as basis for cutaneous lesions, which could be due to the high concentrations of drug at the injection site, a toxic effect of the diluents, or an immunological reaction.Conclusion: According to the latter mechanism patients could develop bacterial cellulitis in their different organs. Conclusively, we propose the hypothesis of a possible association between cellulitis to occur at any site as the complication of pegylated interferon Alfa 2b and would highlight the role of a careful skin examination that could be an asset in preventing local skin infections.

  4. Development of solar energy education IASEE-Argentina, Arquisur and Alfa-built

    Energy Technology Data Exchange (ETDEWEB)

    Schiller, S. de; Evans, J.M. [Buenos Aires Univ. (Argentina). Faculty of Architecture

    1997-02-01

    Three educational experiences are presented in this paper on the development of national and regional networks to incorporate renewable energy in curricular programmes. IASEE-Argentina, established in 1990 as the National Section of IASEE, the International Association for Solar Energy Education, was designated in 1993 as the Education Working Group of ASADES, the Argentine Association of Solar Energy. It holds annual meetings to coincide with the ASADES conference. Arquisur is a regional network established by Architectural Faculties of State Universities within the Mercosur Region, covering Argentina, southern Brazil, Paraguay and Uruguay, to promote exchange and development between the 19 faculties involved. A Working Group set up by Arquisur with members from four countries developed the programme for short post-graduate courses on bioclimatic design and rational energy use in buildings, which has been given in Argentina and Uruguay. Alfa-Built, a project supported by the European Union for promoting academic exchange in the field of energy efficient building is also introduced. This paper presents the development and initial results of these educational experiences. (author)

  5. LHC Report: special run with de-squeezed beams for ATLAS/ALFA and TOTEM

    CERN Multimedia

    Helmut Burkhardt for the LHC team

    2015-01-01

    The main high-luminosity proton-proton run of the LHC is complemented by one week per year of special proton-proton runs. The special runs are performed with larger beam sizes at the interaction points to allow the forward physics experiments, TOTEM and ATLAS/ALFA, the chance to make precise measurements of protons as they emerge from collisions at small angles.   In standard high-luminosity operation, the beams are squeezed to give small beam sizes at the interaction points to maximise the collision rates. The “squeeze” takes place at top energy and the beam size at the centre of ATLAS (IP1) and CMS (IP5) is reduced from 66 micrometres at the top of the ramp to 18 micrometres before colliding beams are established. Protons that avoid the fate of an inelastic collision but yet still interact – in elastic or diffractive events – are scattered and emerge in the forward direction. The reduction in beam size has a side effect of increasing the an...

  6. Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation.

    Science.gov (United States)

    Desai, Ankit K; Walters, Crista K; Cope, Heidi L; Kazi, Zoheb B; DeArmey, Stephanie M; Kishnani, Priya S

    2017-12-23

    Patients with Pompe disease have realized significant medical benefits due to enzyme replacement therapy (ERT) infusions with alglucosidase alfa. However, regular infusions are time-consuming. Utilizing recommended infusion rates, infusion duration is 3h 45min for a patient receiving the standard dose of 20mg/kg, not including additional time needed for preparation of ERT, assessment of vital signs, intravenous access, and post-infusion monitoring. Recent studies have demonstrated increased effectiveness of higher dose of ERT (40mg/kg) in infantile-onset Pompe disease (IOPD), which increases the infusion duration to 6h 36min. Increased infusion durations compound the psychosocial burden on patients and families and potentially further disrupt family activities and obligations. We developed a stepwise infusion rate escalation protocol to administer higher dose ERT safely while decreasing infusion duration, which has been implemented in 15 patients to date. Reported here in detail are five patients with IOPD on 40mg/kg/weekly ERT in whom infusion duration was decreased with individualized, stepwise rate escalation. All patients tolerated rate escalations above the recommended rates without experiencing any infusion associated reactions and experienced a reduction in infusion duration by 1h and 24min with a corresponding increase in reported satisfaction. Our experience with ERT rate escalation is presented. A careful stepwise method of enzyme replacement therapy (ERT) rate escalation can safely reduce infusion duration in patients with Pompe disease. Copyright © 2017. Published by Elsevier Inc.

  7. The influence of treatment with pegylated interferon-alfa and ribavirin on neutrophil function and death in patients with HIV/HCV coinfection.

    Science.gov (United States)

    Jablonowska, Elzbieta; Wojcik, Kamila; Nocun, Marek

    2012-04-01

    In patients with human immunodeficiency virus (HIV) as well as in patients with hepatitis C virus (HCV) infection the impairment of neutrophil activity is observed. We decided to analyze how treatment with pegylated interferon-alfa (Peg-IFN-alfa) and ribavirin affects neutrophil function in HIV/HCV coinfected patients. The study group consisted of 18 patients with HIV/HCV coinfection, on combination antiretroviral treatment (cART), aged between 27 and 42 y (mean 33.1±4.5 y). At the beginning of treatment with Peg-IFN-alfa and ribavirin all patients had an undetectable HIV viral load, and CD4 T-cell counts higher than 350 cells/μL. At two time points, before and after 12 wk of treatment with Peg-IFN-alfa and ribavirin, we examined intracellular levels of reactive oxygen species (ROS), and expression of selected adhesion molecules on whole blood neutrophils, along with apoptosis and necrosis of these cells. These analyses were done with flow cytometry. During anti-HCV therapy undetectable HIV levels were maintained in all patients. Treatment with PEG-IFN-alfa and ribavirin resulted in increases in the expression of CD11b and CD18, and decreases of CD16 and CD62L. However, only the change in CD62L expression was statistically significant (palfa and ribavirin treatment caused an activation of neutrophil function, yet it did not affect the suppression of HIV replication.

  8. LONG TERM MUCOLYTIC THERAPY WITH DORNASE ALFA AT NOVOSIBIRSK CENTER FOR DIAGNOSTICS, TREATMENT, RHEABILITATION AND ADAPTATION OF CHILDREN WITH CYSTIC FIBROSIS

    Directory of Open Access Journals (Sweden)

    N.I. Romanenko

    2006-01-01

    Full Text Available The center for diagnostic, treatment, rehabilitation and social adaptation of patients with cystic fibrosis was established in pulmonology department of the children's clinical hospital № 3 of Novosibirsk in 1994. Since 1995 the database of the center has registered 23 patients. the center has carried out an open prospective study of clinical efficacy and safety of dornase alfa (pulmozyme, «F. hoffmannala roche ltd.», basel in 10 patients with cystic fibrosis. The patients have received mucolytic therapy with dornase alfa for 2 years (2003–2005. They have been administered a daily inhalation of 2.5 ml of the solution (pulmozyme inhalation solution containing 2.5 of dornaza alfa. The study has shown an improvement of pulmonary function and elevation of oxygen saturation. The number of respiratory infections have dropped by 33%, the administration of intravenous antibiotics has shortened by 25%, the nutrition status has trended towards improvement. regardless of it's high price, dornasa alfa has proven its' benefits in the treatment of cystic fibrosis in patients of any age and disease severity.Key words: dornase alfa, children, cystic fibrosis, treatment.

  9. Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial

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    Picardi Antonio

    2010-02-01

    Full Text Available Abstract Background In patients with chronic hepatitis C virus (HCV genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha and ribavirin induces a sustained virological response (SVR in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR. The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. Methods Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week and ribavirin (800-1200 mg/day for 4 weeks. Patients with a RVR (HCV RNA not detectable were randomized (1:1 to either 12 (group A1 or 24 (group A2 weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B. HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. Results At study end, end of treatment response (ETR was observed in 62 (86% patients of group A1 and in 55 (77% patients of group A2 (p Conclusion In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. Trial registration Trial number ISRCTN29259563

  10. Interferon alfa-2b for recurrent and metastatic giant cell tumor of the spine: report of two cases.

    Science.gov (United States)

    Wei, Feng; Liu, Xiaoguang; Liu, Zhongjun; Jiang, Liang; Dang, Gengting; Ma, Qingjun; Dang, Lei

    2010-11-15

    Case report. To demonstrate that interferon alfa-2b is a therapeutic option for obtaining long-term control of recurrent and metastatic giant cell tumor of spine. Interferon alfa served as angiogenesis inhibitor and has been successfully used to treat giant cell tumor of long bones and facial bones. Up to date, no report is found with regard to the use of interferon as a stand-alone treatment for unresectable, recurrent, and metastatic giant cell tumor originated from the spine. A 29-year-old woman with C1 and C2 giant cell tumor was treated by radiotherapy, intralesional curet, and chemotherapy orderly. Tumor recurred after 2 years. A second curet was undertaken. Tumor recurred second time and caused severe spinal cord compression. Lung metastasis was diagnosed simultaneously. A 24-year-old man with recurrent giant cell tumor of T5 and T6 was treated by spondylectomy of T5 and T6. Six months later, a giant metastatic lesion was found in sacrococcygeal region, which was excised and proved to be giant cell tumor of bone. Four months later, 2 recurrent lesions were found beside the rectum. Interferon alfa-2b at a dose of 3,000,000 U/m was then administered subcutaneously everyday for both patients for 3.5 and 3 years, respectively. No major complications related to the use of interferon occurred. The lesion in C1-C2 of the first patient regressed steadily and was restricted and encircled within the lateral mass. The metastatic lesions in the lungs also significantly reduced. The pararectal lesions of the second patient disappeared completely. Interferon therapy may be an effective and safe treatment for spine giant cell tumor recurrence and metastasis in soft tissue. The effectiveness may be time and dosage dependent.

  11. Nebulizing poractant alfa versus conventional instillation: Ultrastructural appearance and preservation of surface activity.

    Science.gov (United States)

    Minocchieri, Stefan; Knoch, Stephan; Schoel, W Michael; Ochs, Matthias; Nelle, Mathias

    2014-04-01

    Nebulized surfactant therapy has been proposed as an alternative method of surfactant administration. The use of a perforated vibrating membrane nebulizer provides a variety of advantages over conventional nebulizers. We investigated the molecular structure and integrity of poractant alfa pre- and post-nebulization. Curosurf® was nebulized using an Investigational eFlow® Nebulizer System. Non-nebulized surfactant ("NN"), recollected surfactant droplets from nebulization through an endotracheal tube ("NT") and nebulization of surfactant directly onto a surface ("ND") were investigated by transmission electron microscopy. Biophysical characteristics were assessed by the Langmuir-Wilhelmy balance and the Captive Bubble Surfactometer. Volume densities of lamellar body-like forms (LBL) and multi-lamellar forms (ML) were high for "NN" and "NT" samples (38.8% vs. 47.7% for LBL and 58.2% vs. 47.8% for ML). In the "ND" sample, we found virtually no LBL's, ML's (72.6%) as well as uni-lamellar forms (16.4%) and a new structure, the "garland-like" forms (9.4%). Surface tension for "NN" and "NT" was 23.33 ± 0.29 and 25.77 ± 1.12 mN/m, respectively. Dynamic compression-expansion cycling minimum surface tensions were between 0.91 and 1.77 mN/m. The similarity of surfactant characteristics of nebulized surfactant via a tube and the non-nebulized surfactant suggests that vibrating membrane nebulizers are suitable for surfactant nebulization. Alterations in surfactant morphology and characteristics after nebulization were transient. A new structural subtype of surfactant was identified. © 2013 Wiley Periodicals, Inc.

  12. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Lamm, Donald; Brausi, Maurizio; O'Donnell, Michael A; Witjes, J Alfred

    2014-01-01

    In this article, we review the various options for and the potential role of interferon alfa (IFN-α) in the treatment of non-muscle-invasive bladder cancer (NMIBC). PubMed was searched for journal articles on IFN-α use in treating bladder cancer. The references listed in the National Comprehensive Cancer Network guidelines were used as a guide to identify relevant publications on treatments for NMIBC. Transurethral resection with adjuvant intravesical chemotherapy or immunotherapy is the standard treatment option for NMIBC. Adjuvant IFN-α therapy has limited efficacy in preventing recurrences in intermediate-risk and high-risk patients; bacillus Calmette-Guérin (BCG) monotherapy is the recommended first-line treatment in these patients. Unfortunately, cancer progression or recurrence is a common outcome; radical cystectomy, which is often the lifesaving approach in such a scenario, is associated with significant morbidity, mortality, and decreased quality of life. Current alternatives to cystectomy include repeat intravesical immunotherapy, conventional instillation chemotherapy, and device-assisted intravesical chemotherapy. The efficacy of any chemotherapy after BCG failure, either conventional or device assisted, has not been established. BCG and IFN-α combination intravesical therapy has not been investigated thoroughly; based on available data, combination therapy appears to be most effective in patients with carcinoma in situ and may be preferentially considered as an alternative to radical cystectomy for patients with intermediate-risk or high-risk NMIBC who do not tolerate the standard BCG dose or experience BCG failure after 1 year of therapy. However, this approach requires close follow-up and should only be chosen after careful consideration of all risk factors. There is a lack of efficacious treatment options for patients with NMIBC recurrence or progression after initial BCG treatment. There is a need for well-designed clinical trials

  13. Induction pegylated interferon alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads.

    Science.gov (United States)

    Reddy, K Rajender; Shiffman, Mitchell L; Rodriguez-Torres, Maribel; Cheinquer, Hugo; Abdurakhmanov, Djamal; Bakulin, Igor; Morozov, Viacheslav; Silva, Giovanni Faria; Geyvandova, Natalia; Stanciu, Carol; Rabbia, Michael; McKenna, Michael; Thommes, James A; Harrison, Stephen A

    2010-12-01

    Patients infected with hepatitis C virus (HCV) genotype 1, body weight ≥85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight ≥85 kg and HCV RNA titer ≥400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Sustained virologic response rates (HCV RNA level alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.83-1.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.79-1.28; P = .974). In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight ≥85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Secondary bronchiolitis obliterans organizing pneumonia during treatment of chronic hepatitis C: role of pegylated interferon alfa-2a

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    Ronaldo Soares Martins

    2012-10-01

    Full Text Available The treatment of chronic hepatitis C has frequent side effects such as cytopenias and neuropsychiatric symptoms. However, pulmonary toxicity associated with interferon is rarely described. This paper describes the clinical case of a 67-year-old female patient with chronic hepatitis C who presented an acute onset of dry cough, dyspnoea, and fever 36 weeks after the use of pegylated interferon alfa-2a and ribavirin. The lung biopsy confirmed the diagnosis of a bronchiolitis obliterans organizing pneumonia (BOOP. Corticotherapy was initiated, with clinical and radiological improvement. This paper aims to advise physicians to this occasional, though severe, adverse event related to hepatitis C virus (HCV treatment.

  15. Comportamiento de glicinina, beta-conglicinina y alfa-amilasa en semillas de soja deterioradas y no deterioradas

    OpenAIRE

    Salinas,Adriana Rita; Yoldjian,Ana Maria; Dietrich,María Lucrecia; Craviotto,Roque Mario; Bisaro,Vilma

    2002-01-01

    El objetivo del trabajo fue estudiar el comportamiento de glicinina y beta-conglicinina y la actividad de alfa-amilasa en semillas deterioradas y no deterioradas de 10 cultivares de soja [Glycine max (L.) Merr.]. Las semillas se sometieron a dos tratamientos: deterioradas por envejecimiento acelerado y no deterioradas. Se determinó la presencia de las proteínas de reserva a partir de semillas con 0, 3 y 8 días de germinadas por electroforesis en geles de poliacrilamida (SDS-PAGE). La activida...

  16. Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy.

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    Carmel M McVicar

    Full Text Available BACKGROUND: Erythropoiesis stimulating agents (ESAs are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDINGS: The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml. ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal neovascularisation in comparison to controls (p<0.05. Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05. This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05. Darbepoetin alfa induced retinal TNFalpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001. CONCLUSIONS: This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs.

  17. Los hendidores de la capa musteriense «Alfa» de la Cueva del Castillo (Santander. Estudio tipológico

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    Luis BENITO DEL REY

    2009-10-01

    Full Text Available Al interés que supone la sola presencia de hendidores en la capa musteriense «Alfa» de la cueva del Castillo, en Puente Viesgo, provincia de Santander, hay que añadir la originalidad de sus tipos y de ciertos caracteres observados. Forma también una parte importante de toda la industria lítica, por lo que nos parece oportuno darla a conocer mientras publicamos el conjunto de toda la industria de piedra de la capa «Alfa».

  18. Los hendidores de la capa musteriense «Alfa» de la Cueva del Castillo (Santander). Estudio tipológico

    OpenAIRE

    Luis BENITO DEL REY

    2009-01-01

    Al interés que supone la sola presencia de hendidores en la capa musteriense «Alfa» de la cueva del Castillo, en Puente Viesgo, provincia de Santander, hay que añadir la originalidad de sus tipos y de ciertos caracteres observados. Forma también una parte importante de toda la industria lítica, por lo que nos parece oportuno darla a conocer mientras publicamos el conjunto de toda la industria de piedra de la capa «Alfa».

  19. El ácido alfa lipoico y su poder antioxidante frente al cáncer y las patologías de sensibilización central

    OpenAIRE

    Durand, Marisa

    2013-01-01

    El objetivo del presente trabajo es reunir y contrastar información sobre las propiedades antioxidantes del ácido alfa lipoico (ALA) en la prevención y desarrollo de las patologías relacionadas con el estrés oxidativo. L'objectiu del present treball és reunir i contrastar informació sobre les propietats antioxidants de l'àcid alfa lipoico (ALA) en la prevenció i desenvolupament de les patologies relacionades amb l'estrès oxidatiu.

  20. Uso de la tierra y diversidades alfa, beta y gamma de diplópodos en la cuenca del río Otún, Colombia

    OpenAIRE

    Ruiz-Cobo, Darío Hernán; Grupo Gestión en Agroecosistemas Tropicales Andinos (GATA), Facultad de Ciencias Ambientales, Universidad Tecnológica de Pereira. Vereda La Julita A.A. 97, Pereira; Bueno-Villegas, Julián; Laboratorio de Sistemática Animal, Centro de Investigaciones Biológicas, Universidad Autónoma del Estado de Hidalgo. Km. 4.5 carretera Pachuca - Tulancingo S/N. Colonia Carboneras, Mineral de la Reforma, Hidalgo, 42184; Feijoo-Martínez, Alexander; Grupo Gestión en Agroecosistemas Tropicales Andinos (GATA), Facultad de Ciencias Ambientales, Universidad Tecnológica de Pereira. Vereda La Julita A.A. 97, Pereira

    2010-01-01

    Objetivo: Determinar la relación entre los cambios promovidos por la intervención humana en ecosistemas y grosistemas y la diversidad alfa, beta y gamma de Diplopoda de la cuenca media del río Otún. Materiales y métodos: Se utilizó un diseño sistemático estratificado con la selección de siete ventanas y 16 puntos de muestreo. Se separaron los diplópodos en familias y morfotipos para calcular la diversidad alfa, beta y gamma relacionada con la heterogeneidad de usos del terreno. Resultados: Se...

  1. Evidencia de la eficacia de los fármacos anti-TNF Alfa en el tratamiento de la espondilitis anquilosante

    OpenAIRE

    Montilla Salas, Juan Manuel

    2011-01-01

    OBJETIVO Establecer la evidencia de los estudios clínicos sobre la eficacia de las terapias anti-TNF alfa para el tratamiento de la espondilitis anquilosante (EA). MÉTODOS Se realizó una búsqueda con los diferentes fármacos anti-NTF alfa actualmente utilizados en terapia de la espondilitis anquilosante (Infiximab, Etanercept y Adalimumab). La revisión bibliográfica se realizó en Medline, Embase y la librería Cochrane para los estudios controlados y randomizados publicados hasta 1-enero-2005. ...

  2. La técnica de seguimiento Instruccional Alfa para el manejo de desobediencia infantil en una triada madre-hija-hija

    OpenAIRE

    Hernández Hernández, María de Jesús; Moreno Cervantes, Dolores Alejandra; González Zepeda, Adriana Patricia; Fulgencio Juárez, Mónica

    2016-01-01

    Se presenta un estudio de caso, cuyo propósito es explorar la afectividad de una variación del entrenamiento en el uso de instrucciones Alfa, el cual generalmente se realiza con diadas madre-hijo. En este caso se realizó una intervención psicológica con una triada madre-hija.hija consistente en un entrenamiento a la madre, mediante retroalimentación y modelamiento, en el uso de instrucciones Alfa (IA), para reducir problemas de desobediencia en sus dos niñas. Recurriendo a un diseño AB, se vi...

  3. The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa

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    Rena C. Baek

    2016-09-01

    Full Text Available Correlations between angiotensin-converting enzyme (ACE genotype (I/I, I/D, D/D, disease severity at baseline and response to enzyme replacement therapy (ERT were assessed in the Pompe disease Late-Onset Treatment Study (LOTS. No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation.

  4. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

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    Goláň L

    2015-07-01

    Full Text Available Lubor Goláň,1 Ozlem Goker-Alpan,2 Myrl Holida,3 Ikka Kantola,4 Mariusz Klopotowski,5 Johanna Kuusisto,6 Aleš Linhart,1 Jacek Musial,7 Kathleen Nicholls,8 Derlis Gonzalez-Rodriguez,9 Reena Sharma,10 Bojan Vujkovac,11 Peter Chang,12 Anna Wijatyk12 1First Faculty of Medicine, Department of Cardiovascular Medicine, Charles University, Prague, Czech Republic; 2Lysosomal Research and Treatment Unit, Fairfax, VA, USA; 3Stead Family Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Division of Medicine, Turku University Hospital, Turku, Finland; 5Institute of Cardiology, Warsaw, Poland; 6Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; 8Department of Nephrology, Royal Melbourne Hospital and the University of Melbourne, VIC, Australia; 9Instituto Privado de Hematologia E Investigacion Clinica (IPHIC, Asuncion, Paraguay; 10Salford Royal NHS Foundation Trust, Salford, UK; 11General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia; 12Shire, Lexington, MA, USA Purpose: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW. Exploratory analyses were performed for 0.4 mg/kg weekly.Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643 in treatment-naïve adults (≥18 years with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New

  5. Informe sobre el Proyecto Alfa Biblioteca de Babel: ¿Un atajo para la administración de bibliotecas universitarias? Biblioteca de Babel Alfa Project Report: A shortcut for the academic libraries management?

    Directory of Open Access Journals (Sweden)

    Liliana Laura Rega

    2006-12-01

    Full Text Available El Proyecto Alfa Biblioteca de Babel que reúne bibliotecas universitarias de América Latina y Europa comenzó en marzo de 2005 y prevé su conclusión en marzo de 2007. El presente trabajo intenta describir los objetivos y los resultados esperados, e informa las actividades realizadas por la Red Biblioteca de Babel. Finalmente se analizan las propuestas del proyecto en cuanto al rol de las bibliotecas universitarias, y su relación con la innovación en las prácticas pedagógicas.Biblioteca de Babel Alfa Project that assembles academic libraries from Latin America and Europe was approved on March, 2005 and its conclusion is foreseen on March, 2007. This article attempts to describe the aims and the expected results, and reports the activities of the Biblioteca de Babel Network. Finally it analizes the proposals of the project about the role of academic libraries and their relationship with innovations in pedagogical practices.

  6. Factor de necrosis tumoral alfa en una población infanto-juvenil con sobrepeso

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    Teresita del R. Carrizo

    2013-08-01

    Full Text Available El sobrepeso infantil está asociado a sobrepeso/obesidad en la edad adulta. El tejido adiposo en obesos produce una cantidad incrementada de citoquinas proinflamatorias como el factor de necrosis tumoral alfa (TNF-a, ejerciendo un efecto deletéreo sobre la función vascular. El objetivo de este trabajo fue evaluar niveles de TNF-a en una población infantojuvenil con sobrepeso y su relación con otras variables. Se estudiaron 30 niños con sobrepeso (12 varones de edades entre 8-13 años, se midió circunferencia de cintura (CC e índice de masa corporal (IMC y fueron comparados con 20 controles de edad y sexo semejantes. Se consideró criterio de inclusión un IMC = 85 < 95 percentilo para edad y sexo. En ambos grupos se determinó: glucemia en ayunas (método glucosa oxidasa, insulina plasmática (ECLIA, fibrinógeno (Fg, método de Clauss, proteína C reactiva ultrasensible (uPCR, método inmunoturbidimétrico, TNF-a (ELISA, perfil lipídico (métodos enzimáticos, eritrosedimentación y se calculó el índice HOMA. Los datos se expresaron como mediana y rango intercuartil y con el coeficiente de Spearman se investigaron las correlaciones entre variables, considerándose significativo un p < 0.05. Los niveles de TNF-a fueron mayores en los sujetos con sobrepeso [15.4 (13.2-24.0 vs. 12.7 (11.2-14.8 pg/ml; p = 0.028]. También resultaron más elevados los valores de Fg, insulina plasmática, índice HOMA, uPCR y triglicéridos. El TNF-a se correlacionó con la CC (r = 0.654; p = 0.021. Los niveles elevados de TNF-a, uPCR y Fg encontrados confirman un estado proinflamatorio asociado a obesidad abdominal en la población estudiada.

  7. Estimadores de consistencia interna en las investigaciones en salud: el uso del coeficiente alfa

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    Franciele Cascaes da Silva

    Full Text Available La producción académica ha aumentado en el área de la salud, exigiendo cada vez más calidad en las publicaciones de gran impacto. Una de las formas de considerar la calidad es por medio de procedimientos que aumentan la consistencia del análisis de los datos, como la confiabilidad, que dependiendo del tipo de datos, puede ser evaluada por diferentes coeficientes, en especial el coeficiente alfa. Basados en lo anterior, la presente revisión reúne sistemáticamente artículos científicos producidos en los últimos cinco años, que de manera metodológica hicieron uso psicométrico del coeficiente α como un estimador de consistencia interna y de confiabilidad en procesos de construcción, adaptación y validación de instrumentos. La identificación de los estudios fue realizada sistemáticamente en las bases de datos Biomed Central Journals, Google Scholar, Web of Science, Wiley Online Library, Medline via Pubmed, Scielo, Scopus, Journals@Ovid, BMJ y Springer por medio del Portal de Periódicos CAPES, utilizando criterios de inclusión y exclusión. El análisis de los datos fue realizado por medio de triangulación, análisis de contenido y análisis descriptivo. Se obtuvo que la mayoría de los estudios fueron realizados principalmente en Irán (f=3, España (f=2 y Brasil (f=2, estos estudios tuvieron como objetivo testar las propiedades psicométricas de instrumentos, siendo que ocho estudios utilizaron el coeficiente α para evaluar la confiabilidad y nueve para evaluar la consistencia interna. Todos los estudios fueron clasificados como investigaciones metodológicas al analizar sus objetivos. Adicionalmente, cuatro estudios también fueron clasificados como correlacionales y uno como descriptivo-correlacional. Se puede concluir que a pesar de que el coeficiente α es ampliamente utilizado como uno de los principales parámetros para la evaluación de consistencia interna de instrumentos de medición del tipo cuestionario en el

  8. Reduction of circulating regulatory T cells by intravenous high-dose interferon alfa-2b treatment in melanoma patients.

    Science.gov (United States)

    Mozzillo, Nicola; Ascierto, Paolo

    2012-10-01

    High-dose interferon alfa-2b (IFNα-2b) is the only approved adjuvant systemic therapy for resected, high risk melanoma in the United States (Fecher and Flaherty, in Natl Compr Cancer Netw 7:295-304, 2009). Recently, two important meta-analyses of randomized trials (Wheatley et al., in J Clin Oncol, 2007; Mocellin et al. in J Natl Cancer Inst, 2010) investigating IFNα-2b versus observation in high risk melanoma patients, showed that adjuvant IFNα-2b has an impact both on relapse-free survival (RFS) and overall survival (OS) independently by dosage, duration and route compared with observation in high risk melanoma patients. Despite of an absolute benefits of 3 % (Wheatley et al., in J Clin Oncol, 2007), this treatment is associated with significant toxicity, which impacts on patient quality of life. A better understanding of the mechanism of action may help to potentiate the clinical efficacy and reduce the toxicity of IFNα-2b/Peg-IFNα-2b. Numerous studies suggest that interferon's mechanism of action in melanoma is primarily immunomodulatory (Table 1) (de La Salmoniere, in Clin Cancer Res 6:4713-4718, 2000; Stuckert, in J Clin Oncol 25:8506, 2007; Gogas et al., in N Engl J Med 354:709-718, 2006; Moschos et al., in J Clin Oncol 24:3164-3171, 2006; Ascierto and Kirkwood, in J Transl Med 6:62, 2008) Recent efforts to elucidate the mechanism of action for interferon have focused upon signal transducers and activators of transcription (STAT) (Simons et al., in J Transl Med 9:52, 2011) signaling and immunoregulatory responses mediated by regulatory T cells (Tregs) (Wang et al., in Clin Cancer Res 13:1523-1531, 2007; Clin Cancer Res 14:8314-8320, 2008). Tregs are a suppressive CD4+ T cell population that is present, along with primed effector T cells, in tumor and tumor-draining lymph nodes (Hiura et al. in J Immunol 175:5058-5066, 2005). Tregs express high levels of surface antigens such as CD25, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), and

  9. Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.

    Science.gov (United States)

    Dasgupta, Nupur; Xu, You-Hai; Oh, Sunghee; Sun, Ying; Jia, Li; Keddache, Mehdi; Grabowski, Gregory A

    2013-01-01

    Gaucher disease type 1, an inherited lysosomal storage disorder, is caused by mutations in GBA1 leading to defective glucocerebrosidase (GCase) function and consequent excess accumulation of glucosylceramide/glucosylsphingosine in visceral organs. Enzyme replacement therapy (ERT) with the biosimilars, imiglucerase (imig) or velaglucerase alfa (vela) improves/reverses the visceral disease. Comparative transcriptomic effects (microarray and mRNA-Seq) of no ERT and ERT (imig or vela) were done with liver, lung, and spleen from mice having Gba1 mutant alleles, termed D409V/null. Disease-related molecular effects, dynamic ranges, and sensitivities were compared between mRNA-Seq and microarrays and their respective analytic tools, i.e. Mixed Model ANOVA (microarray), and DESeq and edgeR (mRNA-Seq). While similar gene expression patterns were observed with both platforms, mRNA-Seq identified more differentially expressed genes (DEGs) (∼3-fold) than the microarrays. Among the three analytic tools, DESeq identified the maximum number of DEGs for all tissues and treatments. DESeq and edgeR comparisons revealed differences in DEGs identified. In 9V/null liver, spleen and lung, post-therapy transcriptomes approximated WT, were partially reverted, and had little change, respectively, and were concordant with the corresponding histological and biochemical findings. DEG overlaps were only 8-20% between mRNA-Seq and microarray, but the biological pathways were similar. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were most altered with the Gaucher disease process. Imig and vela differentially affected specific disease pathways. Differential molecular responses were observed in direct transcriptome comparisons from imig- and vela-treated tissues. These results provide cross-validation for the mRNA-Seq and microarray platforms, and show differences between the molecular effects of two highly structurally similar ERT biopharmaceuticals.

  10. Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.

    Directory of Open Access Journals (Sweden)

    Nupur Dasgupta

    Full Text Available Gaucher disease type 1, an inherited lysosomal storage disorder, is caused by mutations in GBA1 leading to defective glucocerebrosidase (GCase function and consequent excess accumulation of glucosylceramide/glucosylsphingosine in visceral organs. Enzyme replacement therapy (ERT with the biosimilars, imiglucerase (imig or velaglucerase alfa (vela improves/reverses the visceral disease. Comparative transcriptomic effects (microarray and mRNA-Seq of no ERT and ERT (imig or vela were done with liver, lung, and spleen from mice having Gba1 mutant alleles, termed D409V/null. Disease-related molecular effects, dynamic ranges, and sensitivities were compared between mRNA-Seq and microarrays and their respective analytic tools, i.e. Mixed Model ANOVA (microarray, and DESeq and edgeR (mRNA-Seq. While similar gene expression patterns were observed with both platforms, mRNA-Seq identified more differentially expressed genes (DEGs (∼3-fold than the microarrays. Among the three analytic tools, DESeq identified the maximum number of DEGs for all tissues and treatments. DESeq and edgeR comparisons revealed differences in DEGs identified. In 9V/null liver, spleen and lung, post-therapy transcriptomes approximated WT, were partially reverted, and had little change, respectively, and were concordant with the corresponding histological and biochemical findings. DEG overlaps were only 8-20% between mRNA-Seq and microarray, but the biological pathways were similar. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were most altered with the Gaucher disease process. Imig and vela differentially affected specific disease pathways. Differential molecular responses were observed in direct transcriptome comparisons from imig- and vela-treated tissues. These results provide cross-validation for the mRNA-Seq and microarray platforms, and show differences between the molecular effects of two highly structurally similar ERT

  11. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma

    NARCIS (Netherlands)

    A.M.M. Eggermont (Alexander); S. Suciu (Stefan); A. Testori (Alessandro); M. Santinami (Mario); W.H.J. Kruit (Wim); J. Marsden (Jeremy); C.J.A. Punt (Cornelis); F. Salès (François); R. Dummer (Reinhard); C. Robert (Caroline); D. Schadendorf (Dirk); P. Patel (Poulam); G. de Schaetzen (Gaetan); A. Spatz (Alan); U. Keilholz (Ulrich)

    2012-01-01

    textabstractPurpose: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods: In all, 1,256 patients with resected stage III melanoma were randomly

  12. The ALFA4Hearing Model (At-a-Glance Labeling for Features of Apps for Hearing Health Care) to Characterize Mobile Apps for Hearing Health Care.

    Science.gov (United States)

    Paglialonga, Alessia; Pinciroli, Francesco; Tognola, Gabriella

    2017-10-12

    The aim of the study was to analyze, by using the ALFA4Hearing model (At-a-Glance Labeling for Features of Apps for Hearing Health Care), a sample of apps over a wide range of services in the hearing health care (HHC) domain in order to take a first picture of the current scenario of apps for HHC. We tested 120 apps, and we characterized them by using the ALFA4Hearing model, which includes 29 features in 5 components (Promoters, Services, Implementation, Users, and Descriptive Information). We analyzed (a) the distribution of the 29 features in the sample, (b) the relationship between the Implementation features and the Services provided by the apps, and (c) the distribution of the 29 features in apps for professional use. The analysis of our sample of apps by means of the ALFA4Hearing model highlighted interesting trends and emerging challenges. Also, results suggested many potential opportunities for research and clinical practice, such as greater involvement of stakeholders, improved evidence base, higher technical quality, and usability. The ALFA4Hearing model is able to represent, at a glance, a large amount of information about apps for HHC, highlighting trends and challenges. It might be useful to HHC professionals as a basis for app characterization and informed decision making.

  13. Debulking surgery followed by intraarterial 5-fluorouracil chemotherapy plus subcutaneous interferon alfa for massive hepatocellular carcinoma with multiple intrahepatic metastases: a pilot study.

    Science.gov (United States)

    Tanaka, K; Yabushita, Y; Nakagawa, K; Kumamoto, T; Matsuo, K; Taguri, M; Endo, I

    2013-12-01

    The prognosis in advanced hepatocellular carcinoma (HCC) with multiple intrahepatic metastases is extremely poor. Combination therapy with subcutaneous interferon (IFN) alfa and intraarterial 5-fluorouracil was reported to be effective against such advanced HCC. We describe results of debulking surgery followed by combination therapy with IFN alfa and 5-FU for massive HCC with multiple intrahepatic metastases. In 27 HCC patients with massive tumors and multiple intrahepatic metastases, we performed combination therapy with IFN alfa and 5-FU after maximal liver tumor resection. Mean patient age was 63.3 years. Including intrahepatic metastases, tumors numbered 5 or more in 17 patients (63%). Portal or hepatic vein branches were invaded in 22 (81%). The mean maximum tumor diameter was 102 mm. Among 24 patients whose results were analyzed, an objective response by residual intrahepatic metastases was observed in 13 (54%; complete response in 12, and partial response in 1). Overall 1-, 3-, and 5-year survival was 73.2%, 38.7%, and 38.7%, respectively; 1-, 3-, and 5-year progression-free rates were 38.2%, 22.3%, and 22.3%. Debulking surgery followed by IFN alfa and 5-FU combination chemotherapy offers possibility of long-term survival despite massive HCC with multiple intrahepatic metastases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. European Concerted Action on Viral Hepatitis (EUROHEP)

    DEFF Research Database (Denmark)

    Fattovich, G; Giustina, G; Realdi, G

    1997-01-01

    The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated virological and biochemical remission improves survival in a cohort of 90 white patients with compensated cirrhosis caused by hepatitis B (Child A) followed for a mean period of 7 years. Inclusion...

  15. Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial.

    NARCIS (Netherlands)

    Eggermont, A.M.M.; Suciu, S.; MacKie, R.; Ruka, W.; Testori, A.; Kruit, W.; Punt, C.J.A.; Delauney, M.; Sales, F.; Groenewegen, G.; Ruiter, D.J.; Jagiello, I.; Stoitchkov, K.; Keilholz, U.; Lienard, D.

    2005-01-01

    BACKGROUND: Individuals affected by melanoma with thick primary tumours or regional node involvement have a poor outlook, with only 30-50% alive at 5 years. High-dose and low-dose interferon alfa have been assessed for the treatment of these patients, with the former having considerable toxicity and

  16. Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C. European Concerted Action on Viral Hepatitis (EUROHEP)

    DEFF Research Database (Denmark)

    Fattovich, G; Giustina, G; Degos, F

    1997-01-01

    The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate. The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C....

  17. Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration.

    Science.gov (United States)

    Azzoni, Livio; Foulkes, Andrea S; Papasavvas, Emmanouil; Mexas, Angela M; Lynn, Kenneth M; Mounzer, Karam; Tebas, Pablo; Jacobson, Jeffrey M; Frank, Ian; Busch, Michael P; Deeks, Steven G; Carrington, Mary; O'Doherty, Una; Kostman, Jay; Montaner, Luis J

    2013-01-15

    Antiretroviral therapy (ART)-mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication. A total of 23 HIV type 1 (HIV-1)-infected, virologically suppressed subjects receiving ART (CD4(+) T-cell count, >450 cells/μL) were randomly assigned to have 180 μg/week (for arm A) or 90 μg/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg-interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, ≥ 400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed. At week 12 of Peg-interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication. NCT00594880.

  18. Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial

    NARCIS (Netherlands)

    Eggermont, Alexander M. M.; Suciu, Stefan; Mackie, Rona; Ruka, Wlodzimierz; Testori, Alessandro; Kruit, Wim; Punt, Cornelis J. A.; Delauney, Michelle; Sales, François; Groenewegen, Gerard; Ruiter, Dirk J.; Jagiello, Izabella; Stoitchkov, Konstantin; Keilholz, Ulrich; Lienard, Danielle

    2005-01-01

    Individuals affected by melanoma with thick primary tumours or regional node involvement have a poor outlook, with only 30-50% alive at 5 years. High-dose and low-dose interferon alfa have been assessed for the treatment of these patients, with the former having considerable toxicity and a

  19. Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia

    NARCIS (Netherlands)

    van Veldhuisen, Dirk J.; Dickstein, Kenneth; Cohen-Solal, Alain; Lok, Dirk J. A.; Wasserman, Scott M.; Baker, Nigel; Rosser, Dylan; Cleland, John G. F.; Ponikowski, Piotr

    Aims Anaemia is common in chronic heart failure (CHF) and associated with worse outcome. This randomized, double-blind, placebo -controlled study evaluated the effect of two darbepoetin alfa dosing regimens on haemoglobin (Hb) rate of rise and clinical effects in patients with CHF and anaemia.

  20. Desarrollo de Aspergillus niger ATCC 11414 en un sustrato con base en la goma de Anacardium occidentale. Produccion de [alfa]-D-galactosidasa

    National Research Council Canada - National Science Library

    Mesa C., Luz Mila; Graterol, Eugenia; Rodriguez-Valero, Sofia; Araujo, Karelen; Clamens, Carmen; Leon-Pinto, Gladys

    2007-01-01

    .... El mejor crecimiento del hongo, observado en pH 4,5 y 6,2 y en presencia de iones magnesio, se selecciono para estudiar la interaccion hongo-sustrato, la cual se demostro por la actividad enzimatica. La produccion de [alfa...

  1. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

    Science.gov (United States)

    Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

    2017-03-07

    Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10 6 /mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10 6 /mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

  2. Estudios sobre alfa-amilasa en saliva como marcador de estrés en la especie humana y otras especies animales= Studies on salivary alpha-amylase as a maker of stress in human and different animal species

    OpenAIRE

    Fuentes Rubio, María

    2014-01-01

    OBJETIVOS 1. Evaluar el uso de la alfa amilasa salivar como marcador de estrés usando técnicas tradicionales (ensayos enzimáticos) en humana, usando como modelo experimental a estudiantes de veterinaria que tenían que realizar una presentación oral de un trabajo en lengua extranjera. 2. Evaluar el uso de la alfa amilasa salivar como marcador de estrés usando técnicas tradicionales (ensayos enzimáticos) en cerdos. 3. Implementar nuevos enfoques para la medición de la alfa-amilasa e...

  3. Effects of multiple-dose pegylated interferon alfa-2b on the activity of drug-metabolizing enzymes in persons with chronic hepatitis C.

    Science.gov (United States)

    Gupta, Samir K; Kolz, Karen; Cutler, David L

    2011-06-01

    To examine the effect of pegylated interferon (PEG-IFN) alfa-2b on the activity of major drug-metabolizing enzymes. This nonrandomized, open-label, multiple-dose study examined the effects of PEG-IFN alfa-2b on the activity of CYP450 1A2, 2 C8/9, 2D6, and 3A4 enzymes and N-acetyltransferase in subjects with chronic hepatitis C. Eligible subjects received PEG-IFN alfa-2b 1.5 μg/kg subcutaneously once weekly for 4 weeks (days 3, 10, 17, and 24). Oral probe substrates (dextromethorphan hydrobromide 45 mg, caffeine 200 mg, tolbutamide 500 mg, and dapsone 100 mg) were administered after a 10-h fast on days 1 and 25. Midazolam 4 mg was administered orally on days 2 and 26. Enzyme activity for each CYP450 isozyme and for N-acetyltransferase was estimated based on the ratios of the observed concentrations of the substrates and metabolites in plasma or urine samples. Twenty-six subjects enrolled in the study. Mean age was 44.3 years, mean weight was 78.9 kg, and mean body mass index was 26.3 kg/m(2). Multiple doses of PEG-IFN alfa-2b inhibited CYP1A2 activity to a limited extent (point estimate = 84.2%, 90% confidence interval [CI] 79-90), increased CYP2C8/9 activity to a limited extent (point estimate = 127.6%, 90% CI 115-142), increased CYP2D6 activity (point estimate = 167%, 90% CI 125-223), and had no effect on the activity of CYP3A4 or N-acetyltransferase. Weekly administration of PEG-IFN alfa-2b to subjects with chronic hepatitis C increased CYP2C8/9 and CYP2D6 activity in some individuals.

  4. Randomized, double-blind, placebo-controlled trial of every-3-week darbepoetin alfa 300 micrograms for treatment of chemotherapy-induced anemia.

    Science.gov (United States)

    Hernandez, Enrique; Ganly, Peter; Charu, Veena; Dibenedetto, Joseph; Tomita, Dianne; Lillie, Tom; Taylor, Kerry

    2009-09-01

    Darbepoetin alfa is effective in treating chemotherapy-induced anemia (CIA). Administration of subcutaneous darbepoetin alfa every 3 weeks (Q3W) could simplify treatment through synchronization with common Q3W chemotherapy regimens. We report results from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA. Patients aged > or = 18 years with anemia (hemoglobin subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be adjusted per prespecified rules. The primary endpoint was the proportion of patients who received > or =1 red blood cell (RBC) transfusion between week 5 and the end of the treatment period (EOTP). The study also analyzed the proportions of patients achieving a hemoglobin concentration > or =11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL, and the change in hemoglobin concentration over time. The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group (24 vs. 41% of patients, a 16.3% difference, p protocol deviations (primarily dosing errors) occurred in approximately one-half of the patients in both treatment groups. In this study, fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA. Study 20030232; ClinicalTrials.Gov Identifier: NCT00110955.

  5. Intermittent High-Dose Intravenous Interferon Alfa-2b for Adjuvant Treatment of Stage III Melanoma: Final Analysis of a Randomized Phase III Dermatologic Cooperative Oncology Group Trial.

    Science.gov (United States)

    Mohr, Peter; Hauschild, Axel; Trefzer, Uwe; Enk, Alexander; Tilgen, Wolfgang; Loquai, Carmen; Gogas, Helen; Haalck, Thomas; Koller, Josef; Dummer, Reinhard; Gutzmer, Ralf; Brockmeyer, Norbert; Hölzle, Erhard; Sunderkötter, Cord; Mauch, Cornelia; Stein, Annette; Schneider, Lars A; Podda, Maurizio; Göppner, Daniela; Schadendorf, Dirk; Weichenthal, Michael

    2015-12-01

    To evaluate the efficacy, safety, tolerability, and quality of life (QoL) in patients receiving intravenous, intermittent high-dose interferon alfa-2b (IFN-α-2b [iHDI]) compared with standard high-dose IFN-α-2b (HDI). Patients with stage III resected lymph node or in-transit metastasis from cutaneous malignant melanoma were randomly assigned to receive either a standard HDI regimen or three courses of IFN-α-2b 20 MIU/m(2) administered intravenously 5 days a week for 4 weeks then repeated every 4 months. Distant metastasis-free survival was the primary end point for efficacy analysis. In addition, relapse-free survival, overall survival, safety as determined by Common Terminology Criteria for Adverse Events criteria, and QoL were secondary end points. Of 649 patients enrolled, 22 patients were excluded from the intent-to-treat analysis. The remaining 627 patients were well balanced between the arms according to sex, age, and stage. After a median follow-up of 55 months, a multivariable Cox model revealed no significant differences for distant metastasis-free survival (hazard ratio [HR], 1.21; P = .12) or overall survival (HR, 1.01; P = .85). In contrast, the difference for relapse-free survival was significant (HR, 1.27; P = .03), favoring standard HDI. Early termination of treatment because of adverse events or QoL occurred significantly more often with HDI than with iHDI (26.0% v 14.8%; P < .001). Although the safety and QoL profiles for the intermittent regimen were favorable, no significant difference was observed for survival while the HR for relapse with iHDI was increased. Therefore, an iHDI regimen, as tested here, cannot be recommended as adjuvant treatment for high-risk melanoma. © 2015 by American Society of Clinical Oncology.

  6. PEMBUATAN ETANOL DARI BIJI CEMPEDAK (Artocarpus champeden sp. DENGAN HIDROLISIS MENGGUNAKAN ENZIM ALFA AMILASE DAN GLUKOLASE FERMENTASI Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Wahyu Teguh Santoso

    2016-06-01

    Full Text Available Telah dilakukan penelitian yang bertujuan untuk mengetahui potensi dari biji cempedak (Artocarpus champedan sp. sebagai bahan baku pembuatan etanol, sekaligus mengetahui apakah variasi penambahan nutrisi ammonium sulfat dan lamanya waktu fermentasi dapat meningkatkan konsentrasi etanol yang dihasilakan. Proses hidrolisis pati dilakukan secara  enzimatis melalui tahap liquifikasi dan sakarifikasi dengan menggunakan enzim alfa-amilase dan glukolase yang akan mengkonversi pati menjadi glukosa. Hasil hidrolisis ditambahkan amonium sulfat sebagai sumber nutrisi dengan variasi 0,1 %, 0,3 % dan 0,5 % (b/v kemudian difermentasi dengan variasi waktu 4, 5 dan 6 hari. Konsentrasi etanol tertinggi berada pada penambahan nutrisi amonium sulfat 0,3 % (b/v dengan waktu fermentasi 6 hari sebesar 8,233 %   Kata Kunci: Etanol, Biji Cempedak (Artocarpus champedan sp. dan Fermentasi.

  7. A multi-centre phase 3 study comparing efficacy and safety of Bemfola® versus Gonal-f® in women undergoing ovarian stimulation for IVF

    DEFF Research Database (Denmark)

    Rettenbacher, M; Andersen, A N; Garcia-Velasco, J A

    2015-01-01

    Bemfola (follitropin alfa) (Finox AG, Switzerland), a new recombinant FSH, has a comparable pharmacological profile to that of Gonal-f (Merck Serono, Germany), the current standard for ovarian stimulation. A randomized, multi-centre, Phase 3 study in women undergoing IVF or intracytoplasmic sperm...

  8. Serum levels of interleukin-6, tumor necrosis factor-alpha and interferon-gama in infants with and without dengue Níveis séricos de interleucina-6, fator de necrose tumoral-alfa e interferon-gama em crianças menores de um ano com e sem dengue

    Directory of Open Access Journals (Sweden)

    Berta Nelly Restrepo

    2008-02-01

    Full Text Available This study compared the serum levels of IL-6, TNF-alpha and IFN-gamma, in children under 1 year of age with and without dengue. Sera were collected from a total of 41 children living in the Department of Antioquia, Colombia (27 patients with dengue and 14 controls. The results showed higher cytokine levels in children with dengue than without dengue, with statistically significant differences for IL-6 and IFN-gamma. No statistically significant differences were found between clinical forms, although IL-6 and IFN-gamma levels were higher in dengue fever cases than in dengue hemorrhagic fever cases. On the other hand, TNF-alpha levels were higher in dengue hemorrhagic fever than in dengue fever. The levels of IL-6 and TNF-alpha were higher in secondary infection than in primary infection, although IFN-gamma levels were higher in primary infection. These results suggest that IL-6, TNF-alpha and IFN-gamma are involved in dengue infection independently of the clinical form.Este estudo comparou os níveis séricos de IL-6, TNF-alfa e IFN-gama, em crianças menores de um ano com e sem dengue. Os soros foram coletados de um total de 41 crianças residentes no Departamento de Antioquia, Colômbia (27 pacientes com dengue e 14 controles. Os resultados mostraram níveis de citoquinas mais elevadas em crianças com dengue do que naquelas sem dengue, com diferenças estatisticamente significativas para IL-6 and IFN-gama. Não houve diferenças estatisticamente significativas entre formas clínicas, embora os níveis de IL-6 e IFN-gama estivessem mais elevados nos casos de febre do dengue que nos casos de febre hemorrágica do dengue. Por outro lado, os níveis de TNF-alfa estavam mais elevados na febre hemorrágica do dengue que na febre do dengue. Os níveis de IL-6 and TNF-alfa estavam mais elevados em infecções secundárias que em infecções primarias, embora os níveis de IFN-gama estivessem mais elevados em infecções primárias. Estes resultados

  9. Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia: Results from a Japanese clinical trial.

    Science.gov (United States)

    Kitaoka, Taichi; Tajima, Toshihiro; Nagasaki, Keisuke; Kikuchi, Toru; Yamamoto, Katsusuke; Michigami, Toshimi; Okada, Satoshi; Fujiwara, Ikuma; Kokaji, Masayuki; Mochizuki, Hiroshi; Ogata, Tsutomu; Tatebayashi, Koji; Watanabe, Atsushi; Yatsuga, Shuichi; Kubota, Takuo; Ozono, Keiichi

    2017-07-01

    Hypophosphatasia (HPP) is a rare skeletal disease characterized by hypomineralization and low alkaline phosphatase activity. Asfotase alfa (AA) has been recently developed to treat HPP complications. This study evaluated its safety and efficacy in Japan. Open-label, multicentre, prospective trial. Patients were enrolled in 11 hospitals from June 2014 to July 2015. Thirteen patients (9 females, 4 males) ages 0 days to 34 years at baseline were enrolled and treated with AA (2 mg/kg three times weekly subcutaneously in all but one patient). All had ALPL gene mutations. HPP forms were perinatal (n=6), infantile (n=5), childhood (n=1) and adult (n=1). Safety determined from adverse events (AEs) and laboratory data was the primary outcome measure. Efficacy was assessed as a secondary outcome measure from overall survival, respiratory status, rickets severity and gross motor development. Injection site reactions were the most frequent AEs. Serious AEs possibly related to treatment were convulsion and hypocalcaemia observed in a patient with the perinatal form. In addition, hypercalcaemia and/or hyperphosphatemia was observed in three patients with the infantile form and a low-calcium and/or low-phosphate formula was given to these patients. With respect to efficacy, all patients survived and the radiographic findings, developmental milestones and respiratory function improved. Asfotase alfa therapy improved skeletal, respiratory and physical symptoms with a few serious AEs in patients with HPP. Our results add support to the safety and efficacy of AA therapy for HPP patients. © 2017 John Wiley & Sons Ltd.

  10. Ensaio de potência da alfaepoetina: Comparação de camundongos Swiss Webster, NIH, C57BL/6, BALB/c com o híbrido B6D2F1 /Potency assay of epoetin alpha: Comparison of Swiss Webster, NIH, C57BL/6, BALB/c mice with the hybrid B6D2F1

    Directory of Open Access Journals (Sweden)

    Igor Barbosa da Silva

    2013-08-01

    Full Text Available Neste estudo comparamos os resultados de ensaios de potência da alfaepoetina (EPOhr realizados com camundongos de diferentes colônias e linhagens (Swiss Webster, NIH, C57BL/6 e BALB/c com aqueles de ensaios conduzidos com o híbrido B6D2F1, o úni-co camundongo recomendado pela Farmacopeia Europeia (FE. Fêmeas de diferentes colônias e linhagens, pesando 16-18 gramas, receberam uma única dose de EPOhr por via subcutânea (30, 90 ou 270 UI/animal, 0,2 mL/camundongo. As potências biológi-cas de apresentações de 4.000 UI/mL da EPOhr foram avaliadas utilizando um material de referência de trabalho de alfaepoetina (3.773 UI/mL anteriormente testado junto ao padrão de referência internacional BRP (European Pharmacopeia Biological Refe-rence Preparation. Os resultados indicaram que camundongos das colônias e linhagens examinadas atingiram critérios estatísticos (FE para um ensaio válido de potência da eritropoietina e, portanto, podem ser considerados como alternativas ao uso do híbrido B6D2F1. Os ensaios com camundongos BALB/c, entretanto, foram os que produziram re-sultados mais semelhantes aos obtidos com os híbridos B6D2F1, em relação à contagem média de reticulócitos em resposta a 30, 90 e 270 UI/camundongo, e aos coefi cientes angulares (inclinação e lineares (intersecção da curva dose-resposta (curvas paralelas praticamente superpostas. --------------------------------------------------------------------------- In this study we compared the outcomes of epoetin alpha (rhEPO potency assays per-formed with Swiss Webster, NIH, C57BL/6 and BALB/c mice with those of the assay conducted with the B6D2F1 hybrid, the only mice recommended by the European Phar-macopoeia (EP. Female mice from different breeding stocks and strains, weighing 16-18 g, received a single subcutaneous injection of (30, 90 or 270 IU per mouse, 0.2 mL per mouse of rhEPO. Biological potencies 4000 IU/mL rhEPO pharmaceutical forms from di-fferent batches

  11. Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial

    DEFF Research Database (Denmark)

    Hansson, Johan; Aamdal, Steinar; Bastholt, Lars

    2011-01-01

    Adjuvant high-dose interferon alfa-2b improves relapse-free survival (RFS) in patients with high-risk melanoma, although benefits in overall survival are uncertain. Because of the toxic effects of high-dose regimens, intermediate doses are being explored. We investigated whether adjuvant therapy...... with intermediate-dose interferon alfa-2b for 1 or 2 years would improve outcomes in patients with stage IIB-IIC or III resected cutaneous melanoma....

  12. Défice de alfa-1 antitripsina. A propósito de dois casos clínicos

    Directory of Open Access Journals (Sweden)

    Sónia Serra

    2008-03-01

    Full Text Available Resumo: O defice de alfa-1 antitripsina e uma doenca hereditaria autossomica codominante. O fenotipo Pi ZZ esta associado com maior frequencia a doenca pulmonar, sendo responsavel pelo aparecimento precoce de enfisema, sobretudo nos fumadores. Os autores apresentam dois casos de diagnostico tardio e em que estiveram presentes outros factores que terao contribuido para o aparecimento de manifestacoes clinicas. Abstract: The alpha-1 antitrypsin deficiency is an hereditary autosomic codominant disease. The phenotype Pi ZZ is associated more frequently with pulmonary disease and is responsible for the presence of emphysema early in life, particularly in smokers. The author's present two cases which diagnosis were performed later in life and in which other factors could be also responsible for clinical manifestations. Palavras-chave: Defice de alfa-1 antitripsina, fenotipo Pi ZZ, enfisema, Key-words: Alpha-1 antitrypsin deficiency, phenotype Pi ZZ, emphysema

  13. AVALIAÇÃO DA PREVALÊNCIA DE TALASSEMIA ALFA EM UMA POPULAÇÃO COM ANEMIA MICROCÍTICA E HIPOCRÔMICA.

    OpenAIRE

    Mesquita, Mauro Meira de

    2006-01-01

    As anemias hereditárias são as mais comuns das doenças determinadas geneticamente e são freqüentes na população brasileira (WHO, 1982). A razão para isso se deve ao processo de miscigenação ocorrido desde o inicio do povoamento e colonização do Brasil, e consequentemente da dispersão dos genes anormais que determinam doenças como as hemoglobinopatias (Naoum, 1997b). A talassemia alfa é uma doença hereditária resultante da síntese deficiente de cadeias alfa, provocando um exc...

  14. Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alfa-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

    Czech Academy of Sciences Publication Activity Database

    Khainar, A.; Latta, P.; Dražanová, Eva; Rudá-Kučerová, J.; Szabó, N.; Arab, A.; Hutter-Paier, B.; Havas, D.; Windisch, M.; Šulcová, A.; Starčuk jr., Zenon; Rektorová, I.

    2015-01-01

    Roč. 28, č. 4 (2015), 281-289 ISSN 1029-8428 R&D Projects: GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : diffusion kurtosis imaging * alfa-Synuclein * TNWT-61 * Parkinson’s disease * Transgenic mice * TBSS Subject RIV: BH - Optics, Masers, Lasers Impact factor: 3.140, year: 2015

  15. Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open‐label, phase 2 study

    Science.gov (United States)

    Mengel, Eugen; Geberhiwot, Tarekegn; Muschol, Nicole; Hendriksz, Christian J.; Burton, Barbara K.; Jameson, Elisabeth; Berger, Kenneth I.; Jester, Andrea; Treadwell, Marsha; Sisic, Zlatko; Decker, Celeste

    2016-01-01

    Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open‐label, phase 2, multi‐national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6‐min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25‐foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug‐related adverse events, the other was not drug‐related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID:27774754

  16. Recombinant Factor VIIa (Eptacog Alfa): A Pharmacoeconomic Review of its Use in Haemophilia in Patients with Inhibitors to Clotting Factors VIII or IX

    OpenAIRE

    Katherine A. Lyseng-Williamson; Greg L. Plosker

    2007-01-01

    Recombinant factor VIIa (NovoSeven(R); also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of succe...

  17. Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON).

    Science.gov (United States)

    Chi, Heng; Hansen, Bettina E; Guo, Simin; Zhang, Ning Ping; Qi, Xun; Chen, Liang; Guo, Qing; Arends, Pauline; Wang, Ji-Yao; Verhey, Elke; de Knegt, Robert J; Xie, Qing; Janssen, Harry L A

    2017-04-01

    We studied whether 48 weeks of pegylated interferon alfa-2b (peginterferon) add-on therapy increases serological response in hepatitis B virus (HBV) envelope antigen (HBeAg)-positive patients receiving nucleos(t)ide analogue (NA) therapy, compared with continued NA monotherapy. This randomized trial included HBeAg-positive patients with compensated liver disease who were treated with entecavir/tenofovir for >12 months and had an HBV DNA load of interferon-naive patients, add-on therapy led to a greater frequency of HBeAg seroconversion (30% vs 7%; P = .034) and response (26% vs 7%; P = .068) at week 96, compared with monotherapy. Among 8 responders at week 48 who discontinued NA therapy at week 72, 6 patients (75%) maintained a response until week 96 (4 of 6 [67%] in the add-on therapy group vs 2 of 2 [100%] in the monotherapy group; P = 1.00). Adverse events were mainly related to peginterferon. The primary end point was negative, but peginterferon add-on therapy appeared to result in a greater frequency of HBeAg seroconversion, compared with NA monotherapy, in interferon-naive patients receiving NA therapy. NCT01532843.

  18. Anaphylactic reactions to a cow's milk whey protein hydrolysate (Alfa-Ré, Nestlé) in infants with cow's milk allergy.

    Science.gov (United States)

    Businco, L; Cantani, A; Longhi, M A; Giampietro, P G

    1989-04-01

    It has been shown in an animal model that cow's milk (CM) protein hydrolysates do not elicit an antibody response to CM proteins and do not induce passive cutaneous anaphylaxis. In addition, babies fed with these formulae during the first months of life do not show antibodies to betalactoglobulin (BLG). These data suggest that these hydrolysates are not antigenic, therefore they have been employed as CM substitutes for the management of infants with CM allergy (CMA). We report five exclusively breast fed infants aged 3 to 8 months (median age = 5 mo) with IgE-mediated CMA, who experienced allergic reactions when they were first fed (median age = 5 months) with a small amount of CM whey protein hydrolysate (Alfa-Ré, Nestlé). Family history was positive for atopy in 3/5 babies. All infants had atopic dermatitis during breastfeeding, positive skin tests, and RAST to CM proteins as well as to Alfa-Ré. Total IgE levels ranged from 45 to 2,990 U/mL. These data show that Alfa-Ré, a CM whey protein trypsin hydrolysate, can trigger severe allergic reactions in children with CMA and it should be employed with great caution as a CM substitute in the management of CMA.

  19. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  20. Uso tópico do inteferon alfa-2b para neoplasia escamosa da superficie ocular em um caso de paciente com xeroderma pigmentoso

    Directory of Open Access Journals (Sweden)

    Nayara Queiroz Cardoso Pinto

    Full Text Available Resumo Relato de um caso clínico de Xeroderma Pigmentoso com carcinoma espinocelular de conjuntiva bilateral que apresentou regressão importante das dimensões tumorais com o uso de Interferon alfa-2b tópico. Relato de caso: Paciente feminina com Xeroderma Pigmentoso em estágio avançado, com ausência de pele sadia, tendo sido submetida a cerca de 60 exéreses de lesões de pele malignas. A paciente compareceu com tumoração conjuntival em ambos os olhos, correspondendo a carcinoma espinocelular de conjuntiva e neoplasia intraepitelial de conjuntiva em olho esquerdo. Devido as dificuldades cirúrgicas, alta taxa de recidiva e elevada probabilidade de formação de simbléfaro foi-se iniciado terapêutica com Interferon alfa-2beta 1.000.000 unidades tópico, obtendo-se bons resultados com importante regressão do tamanho da lesão e resolução dos sintomas. Conclusão: O uso tópico de interferon alfa-2beta em neoplasia escamosa de conjuntiva, mostrou-se uma boa opção terapêutica em situações de elevado risco cirúrgico e de complicações pós operatórias.

  1. The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

    Science.gov (United States)

    Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

    2017-08-01

    Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

  2. Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 1.

    Science.gov (United States)

    Zeuzem, Stefan; Sulkowski, Mark S; Lawitz, Eric J; Rustgi, Vinod K; Rodriguez-Torres, Maribel; Bacon, Bruce R; Grigorescu, Mircea; Tice, Alan D; Lurie, Yoav; Cianciara, Janusz; Muir, Andrew J; Cronin, Patrick W; Pulkstenis, Erik; Subramanian, G Mani; McHutchison, John G

    2010-10-01

    The current standard of care for patients with chronic hepatitis C virus (HCV) genotype 1 is once-weekly pegylated interferon-α (Peg-IFNα) plus daily ribavirin for 48 weeks. We evaluated the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of albumin and IFNα-2b. In the phase 3 ACHIEVE-1 trial, 1331 patients were assigned equally to 3 open-label, 48-week treatment groups: Peg-IFNα-2a 180 μg every week, or albIFN 900 or 1200 μg every 2 weeks administered subcutaneously, with weight-based oral ribavirin 1000-1200 mg/day. During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg because of increased pulmonary adverse events (AEs) in the 1200-μg arms of both ACHIEVE studies. Main outcome measure was sustained virologic response (SVR; undetectable serum HCV RNA at week 72). Intention-to-treat SVR rates were 51.0% (225/441), 48.2% (213/442), and 47.3% (208/440) with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. The primary objective of showing noninferiority of albIFN 900 μg (P < .001) and 1200 μg (P = .003) vs Peg-IFNα-2a for SVR was achieved. Multivariate modeling indicated consistency of treatment effect across subgroups. Serious/severe AE rates were 23.1%, 24.0%, 28.2%; treatment discontinuation rates because of AEs were 4.1%, 10.4%, 10.0%; discontinuation rates because of respiratory AEs were 0%, 0.9%, 1.6%; with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. Hematologic abnormality rates were comparable across the Peg-IFNα-2a and albIFN 900-μg groups. albIFN 900 μg every 2 weeks showed comparable efficacy, with similar serious/severe AE rates, although with a higher discontinuation rate, vs Peg-IFNα-2a in patients with chronic HCV genotype 1. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Central nervous system frontiers for the use of erythropoietin

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    2003-01-01

    Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous...... system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical...

  4. Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC of hepatitis C patients during the first 10 weeks of treatment

    Directory of Open Access Journals (Sweden)

    Edenberg Howard J

    2008-11-01

    Full Text Available Abstract Background and Aims This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron™ and ribavirin (administered by weight in HCV patients and compared it with the recently completed Virahep C study 12 in which Peginterferon-alfa2a (Pegasys™ and ribavirin were administered. Methods RNA was isolated from peripheral blood monocytes (PBMC from twenty treatment-naïve patients just before treatment (day 1 and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. Results The expression of many genes differed significantly (p ≤ 0.001 and changed at least 1.5-fold at days 3 (290 probes and 10 (255 probes, but the number dropped at days 6 (165 and 13 (142. Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1, TRAIL, IL1Rα and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1 was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. Conclusion The response to Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our

  5. Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.

    Science.gov (United States)

    Taylor, Milton W; Tsukahara, Takuma; McClintick, Jeanette N; Edenberg, Howard J; Kwo, Paul

    2008-11-05

    This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron) and ribavirin (administered by weight) in HCV patients and compared it with the recently completed Virahep C study 12 in which Peginterferon-alfa2a (Pegasys) and ribavirin were administered. RNA was isolated from peripheral blood monocytes (PBMC) from twenty treatment-naïve patients just before treatment (day 1) and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. The expression of many genes differed significantly (p changed at least 1.5-fold) at days 3 (290 probes) and 10 (255 probes), but the number dropped at days 6 (165) and 13 (142). Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1), TRAIL, IL1Ralpha and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1) was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR) was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. The response to Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our data suggest that more than once a week dosing might be desirable early during

  6. Tratamento de hemangioma gigante com interferon alfa: relato de dois casos Treatment of giant hemangioma with interferon-alpha: report of two cases

    Directory of Open Access Journals (Sweden)

    Ana Julia Balau

    2007-12-01

    Full Text Available O objetivo do trabalho é descrever o uso de interferon alfa no tratamento de pacientes com hemangioma gigante. Os autores relatam e analisam dois casos de hemangioma gigante em tratamento com interferon alfa. IBS, 3 anos, em acompanhamento no Ambulatório de Hematologia desde um ano de idade com quadro de lesão angiomatosa em praticamente toda hemiface direita, acompanhada de sangramentos gengivais importantes. Após a realização de exames complementares (Angiorressonância magnética e feito o diagnóstico de hemangioma gigante em face, foi iniciado tratamento com prednisona e, posteriormente, associação com interferon alfa e observada importante melhora do quadro, resultando na diminuição dos episódios de sangramento e no tamanho do tumor. C.N.P., 12 anos, apresentando nódulo em região lateral de joelho esquerdo há 2 anos, com aumento progressivo do tamanho e dor local. Fez uso de prednisona e, sem melhora do quadro, introduzido interferon alfa com regressão importante do tamanho do tumor. O tratamento com interferon alfa deve ser considerado no tratamento de hemangiomas, pois apresenta bons resultados em relação à diminuição do tamanho do tumor e, conseqüentemente, reduz as intercorrências clínicas associadas à sua presença, principalmente os sangramentos.The aim of this study is to describe the treatment using interferon-alpha of giant hemangiomas in children. The authors report two cases of children presenting with giant hemangiomas treated using interferon-alpha and analyze the results. IBS, 3 years-old, has been followed up in Famema Hemathology Service since she was 1 year-old with a tumor on the face and persistent bleeding. After clinical and radiologic evaluations and suggested the diagnosis of giant hemangioma, she started treatment with interferon-alpha. A great clinical improvement was observed a reducing of the number of episodes of bleedings and a decrease in of the tumor size. CNP, 12 years-old, came to

  7. Influence of Ginkgo Biloba extract (EGb 761) on expression of IL-1 Beta, IL-6, TNF-alfa, HSP-70, HSF-1 and COX-2 after noise exposure in the rat cochlea.

    Science.gov (United States)

    Dogan, Remzi; Sjostrand, Alev Pektas; Yenıgun, Alper; Karatas, Ersin; Kocyigit, Abdurrahim; Ozturan, Orhan

    2017-10-14

    The objective of this study was to investigate the influence of Ginkgo Biloba in early treatment of noise induced hearing loss on expression of IL-6, IL-1 Beta, TNF-alfa, HSP-70, HSF-1 and COX-2 in the rat cochlea. Thirty two female rats were randomly divided into four groups (Acoustic Trauma, Ginkgo Biloba, Acoustic Trauma+Ginkgo Biloba, Non Treatment). Auditory brainstem response (ABR) was applied in all the groups. At the end of the study, IL-1Beta, IL-6, TNF-alpha, HSP-70, HSF-1 and COX-2 were studied in cochlear tissue with ELISA and Western blot analysis. There were significant increases in ABR values measured at days 1 and 7 compared to baseline values in Group 3. IL-1 Beta, IL-6 and TNF-alpha values were significantly higher in Group 1 than in the other groups. Whereas HSP-70 and HSF-1 values were found to be significantly lower in Group 1 compared to those in Group 2 and Group 3. COX-2 of Group 1 was significantly higher than the other groups. Ginkgo Biloba is helpful in the treatment of noise induced hearing loss and exerts its effect by inhibiting expression of IL-1 Beta, IL-6, TNF-alpha and COX-2 and increasing HSP-70 and HSF-1 values in rat cochlea. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Neuregulinas 1-alfa e 1-beta na regeneração de nervos periféricos Neuregulins 1-alpha and 1-beta on the regeneration the peripheral nerves

    Directory of Open Access Journals (Sweden)

    Fabiano Inácio de Souza

    2010-01-01

    Full Text Available OBJETIVO: Avaliar o efeito das neuregulinas 1-alfa e 1-beta na regeneração de nervos ciáticos de camundongos C57BL/6J, adultos, machos, através da técnica de tubulização. MÉTODOS: Utilizaram-se 18 animais, divididos em 3 grupos, implantando-se prótese de polietileno em falhas de 4,0 mm no nervo ciático esquerdo: grupo 1 contendo apenas colágeno purificado (Vitrogen®; grupo 2, colágeno associado a neuregulina 1-alfa; grupo 3 com colágeno e neuregulina 1-beta. O grupo controle foi formado por 6 segmentos de nervos ciáticos direitos. Após 4 semanas, os animais foram sacrificados; extraiu-se segmento do ponto médio do nervo regenerado no interior das próteses, padronizaram-se cortes histológicos e confecção das lâminas para análise histomorfométrica. Confrontaram-se os resultados estatisticamente. RESULTADOS: Os animais tratados com neuregulinas tiveram maior número de axônios mielinizados, com diferença estatisticamente significante quando comparados ao grupo colágeno. Não houve diferença estatística entre os grupos de neuregulinas 1-alfa e 1-beta. CONCLUSÃO: a adição de neuregulinas proporcionou aumento significativo do número de fibras mielinizadas.OBJECTIVE: to evaluate the effect of the neuregulins 1-alpha and 1-beta on the regeneration the sciatic nerves of male adult C57BL/6J mice, using the tubulization technique. METHODS: eighteen animals were used, divided into three groups. A polyethylene prosthesis was implanted in a 4.0 mm defect of the left sciatic nerve, as follows: group 1 containing only purified collagen (Vitrogen®; group 2, collagen with neuregulin 1-alpha; group 3, collagen with neuregulin 1-beta. The control group consisted of six segments of right sciatic nerves. After four weeks, the animals were sacrificed. A segment from the midpoint of the nerve regenerated inside the prostheses was extracted; histological sections were standardized, and slides were made up for histomorphometric analysis

  9. Lichen planus induced by pegylated interferon alfa-2a therapy in a patient monitored for delta hepatitis.

    Science.gov (United States)

    Kaya, Safak; Arslan, Eyup; Baysal, Birol; Baykara, Sule Nergiz; Uzun, Ozlem Ceren; Kaya, Sehmuz

    2015-01-01

    Interferons are used for treatment of chronic hepatitis B. They can induce or exacerbate some skin disorders, such as lichen planus. In this study, as we know, we presented the first case developing lichen planus while receiving interferon treatment due to delta hepatitis. A 31-year-old male patient presented to our outpatient clinic with HBsAg positivity. With his analyses, HBV DNA was negative, anti-delta total was positive, ALT was 72 U/L (upper limit 41 U/L), and platelet was 119 000/mm(3). He was therefore started on subcutaneous pegylated interferon alfa-2a therapy at 180 mcg/week for delta hepatitis. At month 4 of therapy, the patient developed diffuse eroded lace-like lesions in oral mucosa, white plaques on lips, and itchy papular lesions in the hands and feet. Lichen planus was considered by the dermatology clinic and topical treatment (mometasone furoate) was given. The lesions persisted at month 5 of therapy and biopsy samples were obtained from oral mucosal lesions and interferon dose was reduced to 135 mcg/week. Biopsy demonstrated nonkeratinized stratified squamous epithelium; epithelial acanthosis, spongiosis, and apoptotic bodies were observed in the epidermis and therefore lichen planus was considered. At month 6 of therapy, lesions did not improve and even progressed and interferon treatment was therefore discontinued.

  10. Complex treatment of allergic eye diseases using interferon alfa-2b and loratadine gel for topical and external use

    Directory of Open Access Journals (Sweden)

    A. V. Surov,

    2014-01-01

    Full Text Available Aimis to determine the efficacy of Allergoferon® — combined medicine composed of interferon alfa-2b and loratadine gel for topical and external use — in ocular allergies treatment.Materials and methods. 60 patients with allergic eye diseases were treated. Allergoferon® gel applied QID on upper and lower eyelids was used as a first-line therapy. Efficacy was measured using the following criteria: chemozis, eyelid edema, conjunctival redness and discharge, the presence of conjunctival follicles and papillae. All symptoms were scored using a 4‑point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe.Results. Topical administration of Allergoferon® was associated with significant symptoms reduction, i.e., chemozis by 82 %, eyelid edema by 91 %, conjunctival redness by 79 %, eyelid redness by 88 %, conjunctival discharge by 95 %, the presence of conjunctival follicles and papillae by 76 %.Conclusion. Allergoferon® gel for topical and external use quickly reduces tissue allergic reactions and, consequently, terms of treatment. This medication is highly-effective as a therapy of ocular allergies owing to its antihistamine, anti-inflammatory and anti-exudative effects.

  11. Study of forward elastic $pp$ scattering at $\\sqrt{s}=8\\text{ TeV}$ with the ALFA detector

    CERN Document Server

    Stark, Simon Holm; Hansen, Jørgen Beck

    The elastic $pp$ scattering data analyzed in this thesis was taken at the LHC with the ALFA detector at $\\sqrt{s}=8\\text{ TeV}$ with a $\\beta^*=1\\text{ km}$ collision optics which gave access to the Coulomb-Nuclear-Interference region. An improved procedure was used to fit the observed number of elastic events as a function of the four-momentum transfer with a simulation based on theoretical expectations including experimental effects. The data can not exclude any of the investigated parametrizations for the modulus of the nuclear amplitude. The fit results for the total $pp$ cross section, $\\sigma_\\text{tot}$, and the ratio of the real to imaginary forward elastic scattering amplitude, $\\rho$, are: \\begin{align*} \\sigma_\\text{tot} &= 99.1\\pm 0.3 \\text{ (stat.)}\\pm1.6\\text{ (syst.)} \\text{ mb}\\;,\\\\ \\rho &= 0.166\\pm0.017\\text{ (stat.)}\\pm0.019\\text{ (syst.)}\\;, \\end{align*} which are in agreement with previous measurements. As part of the analysis, the detector distance to the beam was determined with ...

  12. Proton-Proton Central Exclusive Pion Production at $\\sqrt{13}$ TeV with the ALFA and ATLAS Detector

    CERN Document Server

    Bols, Emil Sorensen

    The cross section for proton-proton central exclusive dipion production, $pp\\rightarrow p + \\pi^+ \\pi^- + p$, has been measured at the center of mass energy $\\sqrt{s}=13\\mathrm{TeV}$, where double Pomeron exchange is expected to dominate. The LHC was used to create the central diffractive events, and all the final state particles were measured using the ATLAS and ALFA detector. After correcting for detector inefficiencies and proton acceptance using the Donnachie-Landshoff model with $\\alpha'=0.126\\mathrm{GeV}^{-2}$ and $\\epsilon=0.085$, the cross section was found to be: \\begin{equation} \\sigma_{pp\\rightarrow p+\\pi^+\\pi^-+p}=18.754\\pm0.048(\\mathrm{stat}.)\\pm0.770(\\mathrm{syst}.)\\mu\\mathrm{b} , \\quad |\\eta_{\\pi}| 100\\mathrm{MeV} \\end{equation} The invariant mass spectrum of the pions has been analyzed in order to extract the widths and masses of the $f_0(500)$, $f_0(980)$, $f_2(1275)$ and $f_0(1500)$ mesons. A correlation between the two outgoing protons has been observed, which is not in agreement with Pom...

  13. Um imunoensaio rápido para a detecção de alfa-trembolona em urina bovina

    Directory of Open Access Journals (Sweden)

    Keila Maria Roncato Duarte

    2006-12-01

    Full Text Available O Brasil está entre os países que mantêm o uso de anabolizantes proibido, o que gera dificuldades muito grandes no monitoramento destas substâncias, uma vez que possui o maior rebanho bovino. Contudo, diversas substâncias são largamente utilizadas, entre as quais o acetato de trembolona. Com o consentimento do Ministério da Agricultura, Pecuária e Abastecimento, foram produzidos anticorpos policlonais para um teste baseado em ELISA ("enzyme linked immunosorbent assay" capazes de detectar acetato de trembolona na urina de bovinos tratados com trembolona. O teste apresentou baixo custo e de fácil execução para a detecção de alfa-trembolone, o principal metabólito na absorção do acetato de trembolona, liberado na urina dos animais. Os resultados foram similares aos obtidos com o "kit" comercial usado pelo Ministério da Agricultura, Pecuária e Abastecimento do Brasil.

  14. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Jacobson, Ira M; Dore, Gregory J; Foster, Graham R; Fried, Michael W; Radu, Monica; Rafalsky, Vladimir V; Moroz, Larysa; Craxi, Antonio; Peeters, Monika; Lenz, Oliver; Ouwerkerk-Mahadevan, Sivi; De La Rosa, Guy; Kalmeijer, Ronald; Scott, Jane; Sinha, Rekha; Beumont-Mauviel, Maria

    2014-08-02

    Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus ribavirin has improved sustained virological response (SVR) in treatment-naive and treatment-experienced patients infected with hepatitis C virus (HCV) genotype 1, the regimens have a high pill burden and are associated with increased rates and severity of adverse events, such as anaemia and rash. The efficacy and safety of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in treatment-naive patients with HCV genotype 1 infection. In QUEST-1, a phase 3, randomised, double-blind multicentre trial undertaken in 13 countries (Australia, Europe, North America, Puerto Rico, and New Zealand), 394 patients (aged ≥18 years) with chronic HCV genotype 1 infection and no history of HCV treatment, stratified by HCV subtype and host IL28B genotype, were randomly assigned in a 2:1 ratio with a computer-generated allocation sequence to receive simeprevir (150 mg once daily, orally) plus peginterferon alfa 2a plus ribavirin for 12 weeks, followed by peginterferon alfa 2a plus ribavirin (simeprevir group), or placebo orally plus peginterferon alfa 2a plus ribavirin for 12 weeks, followed by peginterferon alfa 2a plus ribavirin (placebo group). Treatment duration was 24 weeks or 48 weeks in the simeprevir group according to criteria for response-guided therapy (ie, HCV RNA alfa 2a, and ribavirin was superior to placebo, peginterferon alfa 2a, and ribavirin (SVR12 in 210 [80%] patients of 264 vs 65 [50%] of 130, respectively, adjusted difference 29·3% [95% CI 20·1-38·6; palfa 2a and ribavirin shortens therapy in treatment-naive patients with HCV genotype 1 infection without worsening the adverse event profiles associated with peginterferon alfa 2a plus ribavirin. Janssen Infectious Diseases-Diagnostics. Copyright © 2014 Elsevier Ltd. All rights

  15. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial.

    Science.gov (United States)

    Manns, Michael; Marcellin, Patrick; Poordad, Fred; de Araujo, Evaldo Stanislau Affonso; Buti, Maria; Horsmans, Yves; Janczewska, Ewa; Villamil, Federico; Scott, Jane; Peeters, Monika; Lenz, Oliver; Ouwerkerk-Mahadevan, Sivi; De La Rosa, Guy; Kalmeijer, Ronald; Sinha, Rekha; Beumont-Mauviel, Maria

    2014-08-02

    Pegylated interferon (peginterferon) alfa 2a or 2b plus ribavirin regimens were the standard of care in patients with hepatitis C virus (HCV) infection, but the sustained virological response can be suboptimum in patients with HCV genotype 1 infection. The efficacy, safety, and tolerability of the combination of simeprevir, a one-pill, once-daily, oral HCV NS3/4A protease inhibitor versus placebo, plus peginterferon alfa 2a or 2b plus ribavirin was assessed in treatment-naive patients with HCV genotype 1 infection. In the QUEST-2, phase 3 study, done at 76 sites in 14 countries (Europe, and North and South Americas), patients with confirmed chronic HCV genotype 1 infection and no history of HCV treatment were randomly assigned with a computer-generated allocation sequence in a ratio of 2:1 and stratified by HCV genotype 1 subtype and host IL28B genotype to receive simeprevir (150 mg once daily, orally), peginterferon alfa 2a (180 μg once weekly, subcutaneous injection) or 2b (according to bodyweight; 50 μg, 80 μg, 100 μg, 120 μg, or 150 μg once weekly, subcutaneous injection), plus ribavirin (1000-1200 mg/day or 800-1400 mg/day, orally; simeprevir group) or placebo (once daily, orally), peginterferon alfa 2a or 2b, plus ribavirin (placebo group) for 12 weeks, followed by just peginterferon alfa 2a or 2b plus ribavirin. Total treatment duration was 24 weeks or 48 weeks (simeprevir group) based on criteria for response-guided therapy (ie, HCV RNA alfa used. The most common adverse events were headache, fatigue, pyrexia, and influenza-like illness at 12 weeks (95 [37%) vs 45 [34%], 89 [35%] vs 52 [39%], 78 [30%] vs 48 [36%], and 66 [26%] vs 34 [25%], respectively) and for the entire treatment (100 [39%] vs 49 [37%], 94 [37%] vs 56 [42%], 79 [31%] vs 53 [40%], and 66 [26%] vs 35 [26%], respectively). Rash and photosensitivity frequencies were higher in the simeprevir group than in the placebo group (61 [24%] vs 15 [11%] and ten [4%] vs one [alfa 2a or

  16. Unidades fototérmicas e temperatura-base inferior de frutos de Mangueira Alfa, na Baixada Cuiabana Photothermal units and lower base temperature for alfa mango fruit on the Baixada Cuiabana

    Directory of Open Access Journals (Sweden)

    Marcelo Paes de Barros

    2010-06-01

    Full Text Available O objetivo deste trabalho foi determinar a temperatura-base inferior (Tb a partir da unidade fototérmica (UF para o cultivo experimental de manga Alfa sob condições de cerrado. Foram utilizados dados diários da temperatura do ar disponibilizados pela Estação Agrometeorológica Padre Ricardo Remetter, localizada em Santo Antônio do Leverger-MT (15,8° S e 56,1° W, 140 m, e avaliação sensorial do estádio de maturação dos frutos de manga. A Tb foi determinada pelo método da menor variabilidade das unidades fototérmicas (UF acumuladas do período da floração à colheita dos frutos, variabilidade avaliada pelo coeficiente de variação (cv simulado para diferentes valores da Tb. De julho a novembro de 2007, em três plantas de um pomar demonstrativo irrigado, foram identificados 82 frutos para o acompanhamento do crescimento e maturação. Entre esses frutos, em meados de dezembro de 2007, foi possível identificar 13 frutos que atingiram a maturidade fisiológica, após um período médio de observação de 112 dias. Para exigência fototérmica de 1.878.166,1 UF, encontrou-se Tb de 10 °C, valor consistente com os apresentados na literatura para a cultivar de manga, o que comprova a eficiência do método que combina a ação da temperatura e do fotoperíodo sobre a maturação dos frutos e que confere um caráter mais racional que o método tradicional da soma térmica.In this study was to determine the lower base temperature (Tb for Alfa mango fruit, using the photothermal units (PTU method in cerrado conditions. The meteorological data for the study were acquired from "Padre Ricardo Remetter" meteorological station located at Santo Antonio do Leverger, MT, Brazil (15,8° S and 56,1° W, 140 m, and the fruit data was acquired by sensorial evaluation of mango fruit maturation state. The Tb was determined by less variability of the coefficient of variation (cv method applied to the PTU sum, from flowering to harvest, simulated for

  17. Cost-effectiveness analysis of darbepoetin after switch from epoetin-beta in patients on hemodialysis: an Italian single-center retrospective study

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2006-03-01

    Full Text Available Darbepoetin (DARB, a human erythropoietin with improved pharmacological parameters (longer half life and a dose-response relationship independent from the route of administration is a new treatment option for chronic nephropathy-induced anemia that in many Italian dialysis centers is substituting older erythropoietins, mainly due to greater ease of use. At current prices and at the theoretical and recommended 200:1 dose conversion factor, DARB pharmaceutical cost ranges from –9% to +17% of EPO cost. In this monocentric study, real drug consumption and related actual costs of a pre-switch semester with EPO were analysed and compared to the first two post-switch semesters with DARB therapy. Furthermore, erythropoetic response was recorded and related to drug exposition levels, in order to establish a real life EPO:DARB dose conversion factor. In this experience, the conversion factor was estimated in at least 250-280:1, depending on the method adopted for the estimation. The initial dose, chosen on the basis of the recommended conversion factor, induced an excessive erythropoietic response, which was generally followed by a dose reduction and successive titration to target desired Hb levels, generating the spiraliform dose-response curve associated with delayed feed-back mechanisms. The pharmacoeconomical analysis, conducted in the perspective of the public health service, indicated that the choice of substituting DARB for EPO in the treatment of chronic kidney failure-associated anemia is univocally convenient, the former being less costly and more effective.

  18. Simeprevir with pegylated interferon alfa 2a plus ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a meta-analysis and historical comparison.

    Science.gov (United States)

    Andersohn, Frank; Claes, Anne-Kathrin; Kulp, Werner; Mahlich, Jörg; Rockstroh, Jürgen Kurt

    2016-01-11

    About one third of patients infected with human immunodeficiency virus (HIV) also have chronic hepatitis due to hepatitis C virus (HCV). HCV therapy with simeprevir, pegylated interferon alfa (PegIFNα) and ribavirin (RBV) have been shown to be superior to PegIFNα + RBV alone in non-HIV patients, but no randomized trials in patients with HCV genotype 1 (HCV-1)/HIV coinfection are available. This was a historical comparison of study C212 (simeprevir + PegIFNα-2a + RBV in patients with HCV-1/HIV coinfection) with studies in which HCV-1/HIV coinfected patients were treated with PegIFNα-2a + RBV alone. A systematic literature search was performed to identify eligible studies. Efficacy and safety results of PegIFNα-2a + RBV studies were combined in random- and fixed-effects inverse-variance weighted meta-analyses of proportions using the Freeman-Tukey double arcsin transformation method, and compared with the results of study C212. The literature search revealed a total of 2392 records, with 206 articles selected for full-text review. Finally, 11 relevant articles reporting on 12 relevant study groups were included. Results on sustained virologic response 24 weeks after end of treatment (SVR24) were available from all 12 study groups. Pooled SVR24 for PegIFNα-2a + RBV from the random-effects meta-analysis was 28.2% (95% CI 23.8% to 32.9%). The comparison between study C212 (SVR24 = 72.6%; 95% CI 63.1% to 80.9%) revealed substantial superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV alone, with an absolute risk difference of 45% (95% CI 34 to 55). This finding was robust in a sensitivity analysis that only included historical studies with a planned treatment duration of at least 48 weeks and the same RBV dose as in study C212. No increases in the frequency of important adverse event categories including anemia were identified, but these analyses were limited by the low number of studies. This

  19. Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double‐blind, pilot study

    Science.gov (United States)

    Burton, Barbara K.; Berger, Kenneth I.; Lewis, Gregory D.; Tarnopolsky, Mark; Treadwell, Marsha; Mitchell, John J.; Muschol, Nicole; Jones, Simon A.; Sutton, V. Reid; Pastores, Gregory M.; Lau, Heather; Sparkes, Rebecca; Genter, Fred; Shaywitz, Adam J.

    2015-01-01

    The primary treatment outcomes of a phase 2, randomized, double‐blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6‐min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3‐min stair climb test [3MSCT]), exercise capacity (cardio‐pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty‐five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0–4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID:26069231

  20. An Alpha spectrometer for measuring radon daughter individual activity concentration; Spettrometro Alfa per la misura delle concentrazioni individuali in attivita' della progenie del radon

    Energy Technology Data Exchange (ETDEWEB)

    Berico, M.; Formignani, M. [ENEA, Div. Protezione dell' Uomo e degli Ecosistemi, Centro Ricerche E. Clementel, Bologna (Italy); Mariotti, F. [Bologna Univ., Bologna (Italy). Dipt. di Fisica

    2001-07-01

    In the frame of the program of the Institute for Radiation Protection of ENEA, related to the evaluation of dose from radon and thoron progeny, an alpha spectrometer for the continuous air monitoring (CAM type) of radon and thoron has been realized. The constructive characteristics of the device are here presented together with energy and efficiency calibration. The device allows, by means of a screen type diffusion battery and a filter, to determinate the single radioactivity of each radionuclide of the progeny selecting them in relation to their diffusive behaviour (dichotomous particle size selection). The three-count filter method has been employed to measure the concentrations of {sup 218}Po, {sup 214}Pb and {sup 214}Bi in air. Radon and thoron effective doses using a dosimetric, instead of an epidemiologic approach, will be then evaluated. [Italian] Presso l'Istituto per la Radioprotezione, nell'ambito del programma di valutazione di dose da radon e' stato progettato e realizzato uno spettrometro alfa per il monitoraggio continuo in aria (CAM) della progenie del radon e del toron. Le caratteristiche costruttive dello strumento permettono, tramite l'utilizzo di batterie a diffusione a reti, di determinare l'attivita' individuale della progenie per diverse dimensioni granulometriche in particolare per la frazione attaccata e non al particolato amosferico con un taglio granulometrico di qualche nanometro. E' stato inoltre applicato un metodo spettrometrico a tre conteggi per il calcolo delle concentrazioni individuali della progenie del radon, {sup 218}Po, {sup 214}Pb and {sup 214}Bi, effettuando un conteggio alfa di {sup 218}Po e due conteggi alfa di {sup 214}Po. Tale informazione consentira' una valutazione della dose di radon utilizzando il modello dosimetrico in alternativa a quello epidemiologico.

  1. Peginterferon alfa-2a is associated with elevations in alanine aminotransferase at the end of treatment in chronic hepatitis C patients with sustained virologic response.

    Directory of Open Access Journals (Sweden)

    Chih-Wei Tseng

    Full Text Available The purpose of this study was to investigate the incidence and demographic/clinical factors of alanine aminotransferase (ALT abnormalities at the end of treatment (EOT in chronic hepatitis C (CHC patients with sustained virologic response (SVR.Seven hundred naïve CHC patients who underwent combination treatment between January 2003 and December 2010 were included in the study. The patients with SVR and serum ALT>upper limit of normal (ULN at the EOT were further analyzed. The effects of clinical characteristics, treatment regimen, and virologic variables were evaluated by logistic regression. Of the 700 included patients, 488 (69.7% achieved an SVR after treatment, and 235 (33.6% had serum ALT levels>ULN at the EOT. Of those 488 patients, 137 (28.1% had abnormal ALT values at the EOT. A multivariate analysis showed that the occurrence of ALT abnormalities at the EOT was significantly associated with pegylated interferon (PEG-IFN alfa-2a (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.45-3.45; P<0.001, baseline fatty liver (OR, 1.76; 95% CI, 1.16-2.76; P = 0.007, and baseline liver cirrhosis (OR, 2.35; 95% CI, 1.35-4.09; P = 0.002.Use of PEG-IFN-alfa-2a, fatty liver, and cirrhosis are important factors associated with EOT-ALT abnormality in CHC patients receiving combination therapy that achieve an SVR. PEG-IFN-alfa-2a-related EOT-ALT elevation will become normal at the end of follow-up, but fatty liver and cirrhosis-related ALT elevation will not be resolved.

  2. Phase 2 trial of paclitaxel, 13-cis retinoic acid, and interferon alfa-2b in the treatment of advanced stage or recurrent cervical cancer.

    Science.gov (United States)

    Song, Mihae; DiPaola, Robert S; Cracchiolo, Bernadette M; Gibbon, Darlene G; Hellmann, Mira; Nieves-Neira, Wilberto; Vaidya, Ami; Wagreich, Allison R; Shih, Weichung J; Rodriguez-Rodriguez, Lorna

    2014-11-01

    Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m, days 1 to 4, and intravenous paclitaxel, 175 mg/m, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. Thirty-three patients were enrolled between March 2001 and June 2009. Thirty-one patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0-7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5-26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.

  3. Health management program: factors influencing completion of therapy with high-dose interferon alfa-2b for high-risk melanoma

    Science.gov (United States)

    Levesque, N.; Mitchinson, K.; Lawrie, D.; Fedorak, L.; MacDonald, D.; Normand, C.; Pouliot, J.F.

    2008-01-01

    The goal of the 1-year observational, multicentre, open-label study reported here was to identify factors influencing adherence to high-dose interferon alfa-2b adjuvant therapy in patients at high risk of recurrence following surgical excision of malignant melanoma. The study was carried out in 23 tertiary-care centres across Canada. The 225 patients enrolled in the study all had malignant melanoma that was surgically excised and that required adjuvant treatment with interferon alfa-2b. Of these patients, 64% were men. Mean age was 51.7 years. All patients received interferon alfa-2b treatment during a 4-week induction phase (20 MU/m2 intravenously 5 days per week) followed by a 48-week maintenance phase (10 MU/m2 subcutaneously 3 days per week). Oncology nurses reviewed side-effect management with the patients before the induction and maintenance phases. Patients were provided with daily diaries, comprehensive educational materials, and ongoing nursing support. Data on side effects and discontinuations were obtained from patient interviews and diaries. The main outcome measurements were related to treatment discontinuation: rate, timing, reason, and prevention. Of the 225 patients, 75 (33.3%) discontinued interferon during the induction phase, and 58 (25.8%) discontinued during the maintenance phase. The main reasons for discontinuation were adverse events (58%) and disease progression (26%). Patients with a daily fluid intake greater than 1.5 L were more likely to complete therapy than were those with an intake less than 1.5 L (64% vs. 36%, p 1.5 L daily) was associated with increased adherence to therapy. PMID:18317583

  4. Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin.

    Science.gov (United States)

    Petersen, Tess; Lee, Yu-Jin; Osinusi, Anu; Amorosa, Valerianna K; Wang, Crystal; Kang, Minhee; Matining, Roy; Zhang, Xiao; Dou, Diana; Umbleja, Triin; Kottilil, Shyam; Peters, Marion G

    2016-07-01

    A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500 mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ.

  5. Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease.

    Science.gov (United States)

    Park, Ji-Youn; Chung, Yoo-Ri; Lee, Kihwang; Song, Ji Hun; Lee, Eun-So

    2015-07-01

    Behçet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

  6. Arecibo Pulsar Survey Using ALFA. IV. Mock Spectrometer Data Analysis, Survey Sensitivity, and the Discovery of 40 Pulsars

    Science.gov (United States)

    Lazarus, P.; Brazier, A.; Hessels, J. W. T.; Karako-Argaman, C.; Kaspi, V. M.; Lynch, R.; Madsen, E.; Patel, C.; Ransom, S. M.; Scholz, P.; Swiggum, J.; Zhu, W. W.; Allen, B.; Bogdanov, S.; Camilo, F.; Cardoso, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Ferdman, R.; Freire, P. C. C.; Jenet, F. A.; Knispel, B.; Lee, K. J.; van Leeuwen, J.; Lorimer, D. R.; Lyne, A. G.; McLaughlin, M. A.; Siemens, X.; Spitler, L. G.; Stairs, I. H.; Stovall, K.; Venkataraman, A.

    2015-10-01

    The on-going Arecibo Pulsar-ALFA (PALFA) survey began in 2004 and is searching for radio pulsars in the Galactic plane at 1.4 GHz. Here we present a comprehensive description of one of its main data reduction pipelines that is based on the PRESTO software and includes new interference-excision algorithms and candidate selection heuristics. This pipeline has been used to discover 40 pulsars, bringing the survey’s discovery total to 144 pulsars. Of the new discoveries, eight are millisecond pulsars (MSPs; P\\lt 10 ms) and one is a Fast Radio Burst (FRB). This pipeline has also re-detected 188 previously known pulsars, 60 of them previously discovered by the other PALFA pipelines. We present a novel method for determining the survey sensitivity that accurately takes into account the effects of interference and red noise: we inject synthetic pulsar signals with various parameters into real survey observations and then attempt to recover them with our pipeline. We find that the PALFA survey achieves the sensitivity to MSPs predicted by theoretical models but suffers a degradation for P≳ 100 ms that gradually becomes up to ˜10 times worse for P\\gt 4 {{s}} at {DM}\\lt 150 pc cm-3. We estimate 33 ± 3% of the slower pulsars are missed, largely due to red noise. A population synthesis analysis using the sensitivity limits we measured suggests the PALFA survey should have found 224 ± 16 un-recycled pulsars in the data set analyzed, in agreement with the 241 actually detected. The reduced sensitivity could have implications on estimates of the number of long-period pulsars in the Galaxy.

  7. El ácido alfa lipoico y su poder antioxidante frente al cáncer y las patologías de sensibilización central

    OpenAIRE

    Marisa Durand; Núria Mach

    2013-01-01

    Introducción: El ácido alfa lipoico (ALA) puede controlar y limitar la cantidad de radicales libres, influyendo el desarrollo de patologías como el cáncer o las enfermedades de sensibilización central, aunque los mecanismos moleculares implicados en este proceso aún están dilucidándose. Objetivo: Reunir y contrastar información sobre las propiedades antioxidantes del ALA en la prevención y desarrollo de las patologías relacionadas con el estrés oxidativo. Material y métodos: En este trabajo, ...

  8. Efeitos do levosimendan sobre TNF-alfa, PNB e MMP-1 em pacientes com insuficiência cardíaca com anemia

    Directory of Open Access Journals (Sweden)

    Mutlu Büyüklü

    2012-07-01

    Full Text Available FUNDAMENTO: O levosimendan é conhecido pelo seu efeito bilateral de fortalecimento contração das miofibrilas sem aumentar a demanda de oxigênio no miocárdio. A anemia é uma deterioração que causa aumento da dosagem de fármacos em pacientes com insuficiência cardíaca. OBJETIVO: No presente estudo comparamos a eficácia do tratamento com levosimendan em pacientes com insuficiência cardíaca descompensada com ou sem anemia. MÉTODOS: Foram incluídos no estudo 23 pacientes anêmicos com insuficiência cardíaca classe 3 ou 4, segundo a New York Heart Association (NYHA e fração de ejeção abaixo de 35%. Outros 23 pacientes com o mesmo diagnóstico cardíaco, mas sem anemia, serviu como grupo controle. Ao tratamento da insuficiência cardíaca tradicional desses pacientes foi acrescido um tratamento de 24 horas de levosimendan. Amostras foram tomadas para dosar os níveis séricos do fator de necrose tumoral alfa sérico (TNF-alfa, peptídeo natriurético cerebral aminoterminal (NT-proPNB e metaloproteinase da matriz 1 (MMP-1, antes e após a administração. RESULTADOS: Não houve diferença significativa entre os níveis séricos de TNF-alfa e MMP-1, antes e depois do tratamento (p > 0,05. Embora o nível de NT-proBNP tenha diminuído em ambos os grupos após o tratamento, não foi estatisticamente significativo (p = 0,531 e p = 0,913 para os grupos de anemia e de controle, respectivamente. Uma restauração significativa da capacidade funcional foi observada em ambos os grupos avaliados, de acordo com a NYHA (p < 0,001 e p = 0,001 para os grupos de anemia e controle, respectivamente. CONCLUSÃO: O tratamento com levosimendan apresenta efeitos semelhantes em pacientes com insuficiência cardíaca, com anemia e sem anemia. No entanto, o efeito precoce desse tratamento sobre os níveis de TNF-alfa, NT-proPNB e MMP-1 não é evidente. Ele oferece uma melhora significativa na capacidade funcional, sem a influência da anemia.

  9. Effect of darbepoetin alfa on physical function in patients undergoing surgery for colorectal cancer. A randomized, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Norager, C B; Jensen, Martin Bach; Rørbæk Madsen, Mogens

    2007-01-01

    OBJECTIVE: To study whether perioperative treatment with darbepoetin alfa (DA) improves physical performance following colorectal cancer surgery. METHODS: Patients admitted for planned colorectal cancer surgery were randomized to receive either weekly placebo or DA 300 or 150 microg depending...... on the hemoglobin (Hb) concentration. Patients were assessed 10 days before, as well as 7 and 30 days after surgery for work capacity, postural sway, muscle strength, fatigue and quality of life (QoL). The primary outcome measure were the changes in patients' physical performance from preoperative to postoperative...

  10. Terapia combinada de criocirugía e interferón alfa-2b humano recombinante en el condiloma acuminado

    OpenAIRE

    Alfonso Trujillo , Israel

    2015-01-01

    Las continuas recidivas de lcondiloma acuminado hace necesario la búsqueda constante de alternativas terapéuticas. Para evaluar la eficacia terapéutica y seguridad del interferón alfa-2b asociado a criocirugía en el condiloma acuminado fue realizado un ensayo clínico abierto en 170 pacientes del hospital “Hermanos Ameijeiras” que fueron aleatorizados a recibir durante 6 semanas (grupo A) 3 x 106 UI de interferón subcutáneo, 3 veces por semana y aplicación quincenal de criocirugía o (grupo B) ...

  11. Tratamento clínico do linfangioma com alfa-2a-interferon Treatment of lymphangioma with interferon-alpha-2a

    Directory of Open Access Journals (Sweden)

    Reynaldo J.S.P. de Souza

    2001-04-01

    Full Text Available OBJETIVO: descrever os resultados obtidos com o uso do alfa-2a-interferon no tratamento de pacientes pediátricos com linfangiomas irressecáveis ou refratários a outros tratamentos. MÉTODO: após revisão da literatura sobre a patogenia e os tratamentos disponíveis para os linfangiomas, utilizamos o alfa-2a-interferon na dosagem de 3 milhões de unidades/m2/dia, via subcutânea, para tratamento de pacientes que apresentavam lesões irressecáveis. Para avaliar o grau de resposta e os efeitos colaterais foram realizadas avaliações clínicas e laboratoriais periódicas. RESULTADOS: observamos que os 6 pacientes com linfangiomas irressecáveis que utilizaram alfa-2a-interferon obtiveram uma resposta clínica satisfatória associada a efeitos colaterais mínimos. Cinco destes evoluíram com regressão parcial de suas lesões e 1 com estabilização da doença. CONCLUSÃO: concluímos que o alfa-2a-interferon constitui uma das armas disponíveis para o tratamento dos linfangiomas inoperáveis na infância.OBJECTIVE: to describe the results of the use of alpha-2a-interferon in the treatment of inoperable childhood lymphangiomas refractory to other therapeutic management. METHOD: we reviewed the literature about pathogenic events and the treatments available for lymphangiomas. Based on that, we used alpha-2a-interferon at a dose of 3 million units/m2/day administered subcutaneously to patients with inoperable disease and no response to other treatments. We conducted periodic clinical and laboratory control to evaluate the response and the adverse reactions to alpha-2a-interferon administration. RESULTS: we observed that the 6 patients with inoperable lymphangiomas who used alpha-2a-interferon had a satisfactory clinical response associated with minimum adverse reactions. Of these patients, 5 had partial regression of their lesions, and 1 remained stable. CONCLUSION: alpha-2a-interferon may be one more available treatment for inoperable childhood

  12. Acercamiento a la selección de materiales mediante la valoración del rendimiento y el uso de procedimientos correctos de reciclaje (red alfa AMEPAR).

    OpenAIRE

    Chiné-Polito, Bruno

    2006-01-01

    Proyecto: VIE-5402-1801-0400 El proyecto ha sido desarrollado para llevar a cabo actividades de movilidad de investigadores, investigación y entrenamiento avanzado en instituciones de la red ALFA AMEPAR, siendo esta misma financiada por la Unión Europea. Las actividades han interesado el área del diseño-ecológico y de la producción más limpia, con atención especial al suporto industrial, al análisis de nuevas soluciones y a la planificación del ciclo de vida del material (LC...

  13. Influência da vitamina D associada ao interferon alfa-peguilado e ribavirina na resposta virológica sustentada na hepatite C crônica

    OpenAIRE

    Luiza Vitelo ANDRIGHETTO; Jacqueline Shaurich dos SANTOS; Graziella NICOLETTI; Patricia Martins BOCK

    2016-01-01

    O objetivo deste trabalho foi avaliar a influência da vitamina D no tratamento de hepatite C com interferon-alfa peguilado e ribavirina. Foram utilizados artigos científicos relevantes publicados entre os anos de 2000 e 2015. Em diversos estudos foi observado que níveis mais elevados de vitamina D estavam associados à rápida resposta ao tratamento e à maior taxa de RVS, sugerindo que a deficiência de vitamina D pode estar ligada a uma falta de resposta ao tratamento antiviral. A i...

  14. PURIFICACIÓN Y CARACTERIZACIÓN DE alfa-AMILASA DE PENICILLIUM COMMUNE PRODUCIDA MEDIANTE FERMENTACIÓN EN FASE SÓLIDA

    OpenAIRE

    Esperanza Espinel; Elizabeth López

    2010-01-01

    Este estudio reporta la purificación y caracterización parcial de una alfa-amilasa producida por Penicillium commune mediante fermentación en fase sólida, empleandoyuca blanca colombiana (Manihot esculenta Crantz) como soporte. La enzima fue purificada por precipitación fraccionada con sulfato de amonio, cromatografía de intercambio aniónico (DEAE-Sephadex A-50), cromatografía de filtración por gel (Sephadex G-75) y cromatografía de intercambio catiónico (CM-Sephadex C-50) obteniendo una acti...

  15. Uso de los interferones en Dermatología: experiencia con el alfa-interferon en la micosis fungoide Use of interferons in Dermatology: experience with alpha-interferon in mycosis fungoides

    OpenAIRE

    Edelisa Moredo Romo; Marisela Moreira Preciado; Aylet Pérez López

    2004-01-01

    Se revisó la literatura y se constató la amplia utilización de los interferones (INFs) en Dermatología. Se presenta un estudio retrospectivo de 7 pacientes con diagnóstico de micosis fungoides tratados con alfa-interferón recombinante (alfa-INFR) y se concluye su efectividad en el tratamiento de esta enfermedad y su disponibilidad en el tratamiento en Cuba. Los efectos adversos observados a las dosis utilizadas fueron fundamentalmente fiebre, escalofríos y malestar general que cedieron con tr...

  16. Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China.

    Science.gov (United States)

    Chen, Nan; Qian, Jiaqi; Chen, Jianghua; Yu, Xueqing; Mei, Changlin; Hao, Chuanming; Jiang, Gengru; Lin, Hongli; Zhang, Xinzhou; Zuo, Li; He, Qiang; Fu, Ping; Li, Xuemei; Ni, Dalvin; Hemmerich, Stefan; Liu, Cameron; Szczech, Lynda; Besarab, Anatole; Neff, Thomas B; Peony Yu, Kin-Hung; Valone, Frank H

    2017-08-01

    FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD). In the NDD study, 91 participants were randomized to low (1.1-1.75 mg/kg) or high (1.50-2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1-1.8 mg/kg), medium (1.5-2.3 mg/kg) and high (1.7-2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed. In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P < 0.0001, both). In the DD study, 59.1%, 88.9% (P = 0.008) and 100% (P = 0.0003) of the low-, medium- and high-dose subjects maintained their Hb levels after 5- and 6-weeks versus 50% of the epoetin alfa-treated subjects. In both studies, significant reductions in cholesterol were noted in FG-4592-treated subjects, with stability or increases in serum iron, total iron-binding capacity (TIBC) and transferrin (without intravenous iron administration). In the NDD study, hepcidin levels were significantly reduced across all FG-4592-treated arms as compared with no change in the placebo arm. In the DD study, hepcidin levels were also reduced in a statistically significant dose-dependent manner in the highest dose group as compared with the epoetin alfa-treated group. Adverse events were similar for FG-4592-treated and control subjects. FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being

  17. O papel do Fator de Necrose Tumoral Alfa (TNF-alfa no processo de erosão óssea presente no colesteatoma adquirido da orelha média The role of Tumor Necrosis Factor -Alpha (TNF- alpha in bone resorption present in middle ear cholesteatoma

    Directory of Open Access Journals (Sweden)

    Rodrigo Faller Vitale

    2007-02-01

    Full Text Available O colesteatoma adquirido da orelha média causa erosão óssea, com altas taxas de morbidade e mortalidade. O TNF-alfa (TNF-alfa lambda uma das principais citocinas envolvidas neste processo. OBJETIVO: Avaliar o papel do TNF-alfa na reabsorsão óssea e a ação dele no colesteatoma. MATERIAL E MÉTODOS: Foi realizado um levantamento e uma revisão crítica da literatura. RESULTADOS: Todos os autores estudados concordam com a importância do TNF-alfa no processo de reabsorção óssea presente no colesteatoma e com o grau de destruição observado. Diferentes trabalhos demonstraram que o TNF-alfa é capaz de provocar erosão óssea, através de diferentes vias de ação. Ele pode estimular a diferenciação e a maturação dos osteoclastos ou, ainda, agir na matriz óssea expondo-a à ação dos osteoclastos. Existe a possibilidade de inibir a ação do TNF-alfa, diminuindo seus efeitos e prevenindo a perda óssea em doenças como a artrite reumatóide. Não existe, entretanto, trabalhos específicos em colesteatoma. Não existe consenso sobre a sua localização. Estas diferenças, provavelmente, ocorrem devido à distribuição dos receptores. CONCLUSÃO: O TNF-alfa, presente no colesteatoma promove a reabsorsão óssea, juntamente com outras citocinas (RANKL e IL-1, estando relacionado com a presença de complicações.Cholesteatoma may cause bone erosion, with high morbidity and mortality rates. Tumor Necrosis Factor -Alpha (TNF-a is one of the main cytokines involved in this process. Our goal was to evaluate the role of TNF-a in Bone Resorption and its effect on cholesteatoma. MATERIAL AND METHODS: analysis and critical literature review. RESULTS: Different studies have demonstrated that TNF-a is capable of causing bone erosion. It may stimulate the differentiation and maturation of osteoclasts or it may act on the bone matrix, exposing it to the action of the osteoclasts. It is possible to inhibit TNF-a, reducing its effects and prevent

  18. Measurement of elastic proton-proton scattering at $\\sqrt{s} = 7$ TeV with the ALFA sub-detector of ATLAS at the LHC

    CERN Document Server

    Kreutzfeldt, Kristof; Stenzel, Hasko

    The ATLAS experiment with the ALFA sub-detector, provides a unique opportunity to measure elastic proton--proton scattering at the LHC at a centre-of-mass energy of $\\sqrt{s} = 7$ TeV, that has never been reached before. The ALFA detector is a tracking detector housed in Roman Pots, which makes it possible to measure elastically scattered protons down to very small scattering angles. From the proton tracks, measured during a LHC fill with special $\\beta^{*} = 90$ m beam optics, the differential elastic cross-section as a function of the four-momentum transfer squared $t$ is determined, and the total hadronic cross-section $\\sigma_\\text{tot}$, the nuclear slope parameter $B$ and further derived quantities are extracted by utilizing the optical theorem. The total hadronic cross-section is a fundamental parameter of strong interaction depending on the centre-of-mass energy. It has been measured for more than 50 years at different energies and accelerators, where a rise with energy was observed. A newly developed...

  19. [24 weeks treatment with pegylated interferon alfa plus ribavirin may be possible in genotype 1 chronic hepatitis C patients with rapid virological response who have low pretreatment viremia].

    Science.gov (United States)

    Moon, Sung Soo; Kang, Hyoun Gu; Seo, Jeong Ah; Jung, Eun Uk; Lee, Sang Heon; Park, Sung Jae; Lee, Youn Jae; Seol, Sang Yong

    2010-07-01

    The standard treatment for chronic hepatitis C infected with hepatitis C virus (HCV) genotype 1 is a combination of pegylated interferon alfa and ribavirin over a 48 weeks period. It is unclear if 24 weeks treatment is possible for patients showing a rapid virological response (RVR) without compromising the sustained virological response (SVR) in Korea. Between June 2005 and September 2008, among patients chronically infected with the HCV genotype 1 who were treated with pegylated interferon alfa subcutaneously once weekly plus ribavirin based on body weight, 55 patients who had low pretreatment viral load (<600,000 IU/mL) and RVR were enrolled. A total of 55 patients were divided into 24 weeks treatment group (n=29) and the standard treatment group (n=26). The HCV RNA was quantitatively assessed before treatment, and after 12 weeks of treatment, and also qualitatively assessed after 4 weeks of treatment, at end of treatment (24 weeks), and 24 weeks after end of treatment. RVR was defined as undetectable HCV RNA at the 4 weeks of treatment. Among the 55 patients, SVR was achieved in 100% (29/29) of the patients in 24 weeks treatment and 96.2% (25/26) of the patients in the standard treatment (p=0.473). HCV genotype 1 infected patients with a low baseline HCV RNA concentration who become HCV RNA negative at week 4 may be treated for 24 weeks without compromising sustained virological response. However, an additional trial will be needed to optimize the treatment duration.

  20. Severe adverse events from the treatment of advanced melanoma: a systematic review of severe side effects associated with ipilimumab, vemurafenib, interferon alfa-2b, dacarbazine and interleukin-2.

    Science.gov (United States)

    Ma, Chelsea; Armstrong, April W

    2014-10-01

    Current immunomodulatory agents for stage III and IV melanoma exert different mechanisms of action that manifest in distinct adverse events. This systematic review aims to synthesize safety data from clinical trials on ipilimumab, vemurafenib, interferon (IFN) alfa-2b, dacarbazine and interleukin (IL)-2 to elucidate the severe adverse events associated with each melanoma therapy. Through a systematic search using MEDLINE, EMBASE and the Cochrane Central Register between January 1, 2010 and June 1, 2012, we identified 32 clinical trials with 5802 subjects that met the inclusion criteria. Ipilimumab was associated with immune-mediated diarrhea and colitis, with an incidence rate of 0.0017 cases per 100 person-years. Patients receiving vemurafenib developed keratoacanthomas and cutaneous squamous cell carcinoma at an incidence rate of 0.0025 cases per 100 person-years. Treatment with IFN alfa-2b precipitated depression at an incidence rate of 0.0002 cases per 100 person-years. Dacarbazine was associated with respiratory toxicity and dyspnea, with incidence rates of 0.0001 and 0.00008 cases per 100 person-years, respectively. IL-2 treatment induced vascular leak syndrome (VLS), with symptoms of hypotension and oliguria, was observed at incidence rates of 0.17 and 0.15 cases per 100 person-years, respectively. Findings may serve as a foundation for future research in this area and guide clinical recommendations.

  1. Peginterferon Alfa-2a plus ribavirin in Japanese patients infected with hepatitis C virus genotype 2 who failed previous interferon therapy.

    Science.gov (United States)

    Kanda, Tatsuo; Nakamoto, Shingo; Nishino, Takayoshi; Takada, Nobuo; Tsubota, Akihito; Kato, Keizo; Miyamura, Tatsuo; Maruoka, Daisuke; Wu, Shuang; Tanaka, Takeshi; Arai, Makoto; Mikami, Shigeru; Fujiwara, Keiichi; Imazeki, Fumio; Yokosuka, Osamu

    2013-01-01

    Some patients infected with hepatitis C virus (HCV) genotype 2 could be cured with treatment shorter than 24 weeks using peginterferon plus ribavirin, but there are still treatment-refractory patients. Direct-acting antivirals (DAAs) are not currently available for HCV genotype 2 patients, different from genotype 1 patients, in clinical practice. We investigated 29 HCV genotype 2-infected Japanese patients who had been previously treated and failed to clear HCV. We retreated them with peginterferon alfa-2a plus ribavirin and measured HCV RNA level to assess the efficacy and safety of this treatment in patients who had failed previous therapy. We found that retreatment of HCV genotype 2-infected Japanese patients with peginterferon alfa-2a plus ribavirin for 24-48 weeks led to 60 to 66.6% sustained virological response (SVR) in patients previously treated with (peg-)interferon monotherapy and to 69.9% SVR in relapsers previously treated with peginterferon plus ribavirin. Attention should be paid to certain patients with unique features. Selection of patients according to their previous treatment could lead to optimal therapy in HCV genotype 2 treatment-experienced patients.

  2. Défice de alfa-1 antitripsina. A propósito de dois casos clínicos

    Directory of Open Access Journals (Sweden)

    Sónia Serra

    2008-03-01

    Full Text Available Resumo: O défice de alfa-1 antitripsina é uma doença hereditária autossómica codominante. O fenótipo Pi ZZ está associado com maior frequência à doença pulmonar, sendo responsável pelo aparecimento precoce de enfisema, sobretudo nos fumadores. Os autores apresentam dois casos de diagnóstico tardio e em que estiveram presentes outros factores que terão contribuído para o aparecimento de manifestações clínicas.Rev Port Pneumol 2007; XIV (2: 295-302 Abstract: The alpha-1 antitrypsin deficiency is an hereditary autosomic codominant disease. The phenotype Pi ZZ is associated more frequently with pulmonary disease and is responsible for the presence of emphysema early in life, particularly in smokers. The author’s present two cases which diagnosis were performed later in life and in which other factors could be also responsible for clinical manifestations.Rev Port Pneumol 2007; XIV (2: 295-302 Palavras-chave: Défice de alfa-1 antitripsina, fenótipo Pi ZZ, enfisema, Key-words: Alpha-1 antitrypsin deficiency, phenotype Pi ZZ, emphysema

  3. Tuberculosis en pacientes tratados con antagonistas del factor de necrosis tumoral alfa en un área endémica, ¿vale la pena el riesgo?

    Directory of Open Access Journals (Sweden)

    Adriana Rojas-Villarraga

    2007-06-01

    Full Text Available Los antagonistas del factor de necrosis tumoral alfa (infliximab, adalimumab y etanercept son agentes biológicos utilizados en el tratamiento de enfermedades inflamatorias crónicas y autoinmunes. Sin embargo, su uso está asociado con el incremento de la tasa de tuberculosis, micosis endémicas e infecciones bacterianas intracelulares. Dado que la tuberculosis es moderada/altamente endémica en Colombia, el riesgo de esta infección en los pacientes tratados con estos agentes biológicos puede incrementarse y hacer dicha tasa mayor que la informada previamente (tanto en Colombia como en el mundo. Se presentan cuatro pacientes que desarrollaron tuberculosis durante el tratamiento con antagonistas del factor de necrosis tumoral alfa. La presentación de la tuberculosis ocurrió en promedio 15 meses después del inicio del agente biológico y fue independiente de la prueba de tuberculina. Se hace una revisión del tema y se plantea la necesidad de implementar guías y estrategias gubernamentales orientadas a la detección y profilaxis de tuberculosis en este grupo de pacientes.

  4. Isolation and molecular identification of a Serratia strain from ...

    African Journals Online (AJOL)

    ONOS

    2010-04-05

    Apr 5, 2010 ... Grohskopf LA, Roth VR, Feikin DR, Feikin DR, Arduino MJ, Carson LA,. Tokars JI, Holt SC, Jensen BJ, Hoffman RE, Jarvis WR (2001). Serratia liquefaciens bloodstream infections from contamination of epoetin alfa at a hemodialysis center. N.Engl. J. Med. 344: 1491-. 1497. Kampf G, Kramer A (2004).

  5. HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b.

    Science.gov (United States)

    Ma, Hui; Yang, Rui-Feng; Li, Xiao-He; Jin, Qian; Wei, Lai

    2016-09-20

    We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or pegylated IFN. Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored. The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were 110,245 kU/ml, 3760 kU/ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg <19,565 kU/ml at week 24, HBcrAg <34,225 kU/ml at 12-week follow-up, and HBcrAg decrease ≥0.565 log10kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all <31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.

  6. Tratamento da Doença de Pompe - deficiência da alfa-glicosidase ácida

    Directory of Open Access Journals (Sweden)

    Micaela Inês KUHN

    2014-12-01

    Full Text Available Este trabalho tem como objetivos descrever a patogênese e o tratamento da doença de Pompe. Foi realizado um estudo de revisão bibliográfica mediante busca de artigos científicos publicados entre 2004 e 2014. Portadores de deficiência na enzima alfa acido glicosidase, desenvolvem a doença de Pompe, que resulta em um acumulo de glicogênio dentro do lisossomo, originando danos e disfunções orgânicas no tecido muscular, ocasionando dificuldades na respiração, locomoção, fala e audição. A terapia de reposição enzimática é a alternativa de tratamento específica para Pompe, melhorando significativamente a função cardíaca e reduzindo a mortalidade. Contudo, a necessidade de injeção de altas doses da enzima, a perda de 80% da enzima por conta do metabolismo hepático e o alto custo do tratamento dificultam o seu uso. A dose que mostrou melhores resultados foi de 20 mg/kg da enzima a cada duas semanas. Todavia, apesar do alto custo do tratamento, os benefícios de diminuição de sintomas dos pacientes são importantes, como melhora na realização de atividades da vida diária, aumento da força muscular, redução da fadiga e incrementos na função pulmonar. Existem ainda, tratamentos alternativos, mas que ainda estão em fase de estudos. Dentre os tratamentos, aquele que possui um melhor prognóstico é a reposição com a enzima humana recombinante. A terapia de reposição enzimática trouxe sobrevida a diversos pacientes devido à diminuição da hipertrofia cardíaca e melhora nos sintomas motores.

  7. Neutron-induced alpha radiography; Radiografia com particulas alfa induzida por neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Marco Antonio Stanojev

    2008-07-01

    A new radiography technique to inspect thin samples was developed. Low energy alpha particles, generated by a boron based screen under thermal neutron irradiation, are used as penetrating radiation. The solid state nuclear track detector CR-39 has been used to register the image. The interaction of the {alpha} - particles with the CR-39 gives rise to damages which under an adequate chemical etching became tracks the basic units forming the image. A digital system was developed for data acquisition and data analysis as well as for image processing. The irradiation and etching conditions to obtain the best radiography are 1,3 hours and 25 minutes at 70 deg C respectively. For such conditions samples having 10 {mu}m in thickness can be inspected with a spatial resolution of 32 {mu}m. The use of the digital system has reduced the time spent for data acquisition and data analysis and has improved the radiography image visualization. Furthermore, by using the digital system, it was possible to study several new parameters regarding the tracks which are very important to understand and study the image formation theory in solid state nuclear track detectors, the one used in this thesis. Some radiography images are also shown which demonstrate the potential of the proposed radiography technique. When compared with the other radiography techniques already in use to inspect thin samples, the present one developed in the present paper allows a smaller time to obtain the image, it is not necessary to handle liquid radioactive substances, the detector is insensitive to {beta}, {gamma}, X-ray and visible light. (author)

  8. Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial

    DEFF Research Database (Denmark)

    Hansson, Johan; Aamdal, Steinar; Bastholt, Lars

    2011-01-01

    Adjuvant high-dose interferon alfa-2b improves relapse-free survival (RFS) in patients with high-risk melanoma, although benefits in overall survival are uncertain. Because of the toxic effects of high-dose regimens, intermediate doses are being explored. We investigated whether adjuvant therapy...

  9. 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, H.C.; Buck, G.; Cessie, S. le; Richards, S.; Beverloo, H.B.; Falkenburg, J.H.F.; Littlewood, T.; Muus, P.; Bareford, D.; Lelie, H. van der; Green, A.R.; Roozendaal, K.J.; Milne, A.E.; Chapman, C.S.; Shepherd, P.

    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

  10. 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

  11. A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study

    Directory of Open Access Journals (Sweden)

    Tatiana Rozov

    2013-12-01

    Full Text Available OBJECTIVE: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF patients. METHODS: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0, and at six (T2 and 12 (T4 months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated. RESULTS: Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase, hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1, in forced vital capacity (FVC, in oxygen saturation (SpO2, and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases. CONCLUSIONS: The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one

  12. Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C

    Directory of Open Access Journals (Sweden)

    Yoan Antonio Sánchez Rodríguez

    2011-03-01

    Full Text Available INTRODUCCIÓN: la hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales o definitivas de esta terapia. MÉTODOS: estudio de farmacovigilancia cuya serie estuvo conformada por 122 pacientes con hepatitis crónica C atendidos en el Instituto de Gastroenterología desde mayo de 2001 hasta mayo de 2006. Se utilizó interferón alfa 2b recombinante (3 millones de unidades 3 veces por semana más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal durante 48 semanas. RESULTADOS: el 88,5 % del total de casos presentó efectos adversos; de ellos el 79,5 % correspondió al síndrome seudogripal, seguido de manifestaciones hematológicas, neuropsiquiátricas, gastrointestinales, entre otras menos frecuentes. El 6,6 % de la serie presentó salidas temporales del tratamiento por efecto adverso distinto de la anemia y 4 pacientes, salidas definitivas del estudio, tres por anemia hemolítica severa y uno con hipertiroidismo no controlable. CONCLUSIONES: la terapia combinada interferón alfa 2b recombinante más ribavirina resulta segura, donde el mayor número de casos presentó síndrome seudogripal como efecto adverso más frecuente. Las manifestaciones hematológicas asociadas a las salidas definitivas del estudio permitieron recomendar seguimiento estricto de la hemoglobina y profundizar en el diagnóstico y tratamiento de los principales efectos adversos presentes en otros sistemas y asociados a esta terapia.

  13. Measurement of elastic proton-proton scattering at √(s)=7 TeV with the ALFA sub-detector of ATLAS at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Kreutzfeldt, Kristof

    2014-12-15

    The ATLAS experiment with the ALFA sub-detector, provides a unique opportunity to measure elastic proton-proton scattering at the LHC at a centre-of-mass energy of √(s)=7 TeV, that has never been reached before. The ALFA detector is a tracking detector housed in Roman Pots, which makes it possible to measure elastically scattered protons down to very small scattering angles. From the proton tracks, measured during a LHC fill with special β{sup *}=90 m beam optics, the differential elastic cross-section as a function of the four-momentum transfer squared t is determined, and the total hadronic cross-section σ{sub tot}, the nuclear slope parameter B and further derived quantities are extracted by utilizing the optical theorem. The total hadronic cross-section is a fundamental parameter of strong interaction depending on the centre-of-mass energy. It has been measured for more than 50 years at different energies and accelerators, where a rise with energy was observed. A newly developed fully data-driven method is used to determine the t-independent event reconstruction efficiency in the two spectrometer arms to be ε{sub rec}(Arm 1368)=0.8974±0.0005(stat.)±0.0061(syst.) and ε{sub rec}(Arm 2457)=0.8800±0.0005(stat.)±0.0092(syst.) by carefully selecting elastic-scattering events not reconstructed in the entire ALFA detector. Special care is also taken of other important aspects of the analysis like the determination of the luminosity and beam optics parameters. An integrated luminosity of L=80 μb{sup -1} is accumulated to measure the differential elastic cross-section from which the total hadronic cross-section is extracted from a fit in the range 0.01 GeV{sup 2}≤-t≤0.1 GeV{sup 2} to be σ{sub tot}=95.35±0.38(stat.)±1.25(exp.)±0.37(extr.) mb. In addition, the nuclear slope parameter at small vertical stroke t vertical stroke is determined to be B=19.73±0.14(stat.)±0.26(syst.) GeV{sup -2}.

  14. Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.

    Science.gov (United States)

    Asmuth, David M; Murphy, Robert L; Rosenkranz, Susan L; Lertora, Juan J L; Kottilil, Shyam; Cramer, Yoninah; Chan, Ellen S; Schooley, Robert T; Rinaldo, Charles R; Thielman, Nathan; Li, Xiao-Dong; Wahl, Sharon M; Shore, Jessica; Janik, Jennifer; Lempicki, Richard A; Simpson, Yaa; Pollard, Richard B

    2010-06-01

    To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection. Untreated HIV-1-infected volunteers without HCV infection received 180 microg of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferon-inducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed. Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/microL (90% CI, -95 to 85 cells/microL), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]). Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.

  15. PURIFICACIÓN Y CARACTERIZACIÓN DE alfa-AMILASA DE PENICILLIUM COMMUNE PRODUCIDA MEDIANTE FERMENTACIÓN EN FASE SÓLIDA

    Directory of Open Access Journals (Sweden)

    Esperanza Espinel

    2010-03-01

    Full Text Available Este estudio reporta la purificación y caracterización parcial de una alfa-amilasa producida por Penicillium commune mediante fermentación en fase sólida, empleandoyuca blanca colombiana (Manihot esculenta Crantz como soporte. La enzima fue purificada por precipitación fraccionada con sulfato de amonio, cromatografía de intercambio aniónico (DEAE-Sephadex A-50, cromatografía de filtración por gel (Sephadex G-75 y cromatografía de intercambio catiónico (CM-Sephadex C-50 obteniendo una actividad específica final de 314,82 U/mg, un grado de purificación del orden de 62 y un rendimiento de 9%. La purificación hasta la homogeneidad fue confirmada por SDS-PAGE. El peso molecular estimado fue 35 kDa. La enzima mostró máxima actividad de hidrólisis de almidón soluble con pH 6,0, y estabilidad en un intervalo de pH de 5,0-7,0. La estabilidad térmica de la enzima se presentó en el intervalo de temperatura 0-50 °C y su temperatura óptima fue 70 °C. Los iones Ca2+,Ba2+ y Ag+ aumentaron significativamente la actividad de la enzima, siendo el ión Ca2+ el que tuvo el más alto poder activador. Cu2+ no alteró significativamente la actividad de la enzima, mientras que Li+ y Fe3+ la disminuyeron ligeramente (13%, y Co2+ y Hg2+ la disminuyeron 25% y 40% respectivamente. Los valores de Km y Vmáx fueron calculados usando la linealización de Lineweaver- Burk, con el resultado Km= 0,48 mg/mL y Vmáx = 5,85 micromol glucosa/min. Entre los principales productos de hidrólisis del almidón de yuca se encuentran la maltosa y la glucosa, este resultado proporciona evidencia de que la enzima es capaz de romper los enlaces glicosídicos alfa-1,4 del almidón, comportamiento característico de una alfa-amilasa.

  16. Natural Killer Cell Characteristics in Patients With Chronic Hepatitis B Virus (HBV) Infection Are Associated With HBV Surface Antigen Clearance After Combination Treatment With Pegylated Interferon Alfa-2a and Adefovir.

    Science.gov (United States)

    Stelma, Femke; de Niet, Annikki; Tempelmans Plat-Sinnige, Marjan J; Jansen, Louis; Takkenberg, R Bart; Reesink, Hendrik W; Kootstra, Neeltje A; van Leeuwen, Ester M M

    2015-10-01

    The role of natural killer (NK) cells in the process of hepatitis B virus (HBV) surface antigen (HBsAg) clearance and whether their phenotype is related to treatment outcome in patients with chronic hepatitis B are currently unknown. Patients with chronic hepatitis B (HBV DNA load, >17 000 IU/mL) were treated with pegylated interferon alfa-2a and adefovir for 48 weeks. NK cell phenotype and function were analyzed in 7 responders (defined as individuals with HBsAg clearance by week 72; 3 HBV e antigen [HBeAg]-positive and 4 HBeAg-negative), 7 matched nonresponders, and 7 healthy controls. Subsequently, 34 baseline samples from HBeAg-positive patients with chronic hepatitis B were analyzed. During treatment, the percentage and absolute number of CD56(bright) NK cells increased significantly, whereas the percentage and absolute number of CD56(dim) NK cells decreased. At baseline, responders had a significantly lower expression of chemokine receptor CX3CR1 on CD56(bright) NK cells and inhibitory receptor NKG2A on CD56(dim) NK cells, compared with nonresponders. In addition, responders had higher CD56(bright) TRAIL expression and interferon γ production at end of treatment. These baseline differences were not found in HBeAg-positive patients who had HBeAg seroconversion without HBsAg clearance. Combination therapy significantly influences NK cell phenotype and function. Differences between patients with chronic hepatitis B with HBsAg clearance and nonresponders suggest that NK cells play a role in the clearance of HBsAg during interferon-based combination therapy. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. A Multicenter Study To Evaluate The Safety And Efficacy Of Heber On (Interferon Alfa-2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Iran

    Directory of Open Access Journals (Sweden)

    H. Mirmomen

    2005-05-01

    Full Text Available Combination therapy with interferon and ribavirin is the most effective treatment for chronic hepatitis C today. The aim of this study was to evaluate the efficacy and safety of thrice-weekly Heberon (interferon alfa-2b in combination with ribavirin as first -line treatment of chronic hepatitis C. Methods: A total of97 treatment-naive patients received Heberon three million units thrice-weekly subcutaneously in combination with ribavirin for 12 months. Serum HCV RNA levels were measured before and during therapy and 6 months after the end of therapy. End-of-treatment and sustained virological responses was defmed as an undetectable HCV-RNA level at the end of treatment, and 6 months after treatment was completed (end of follow-up, respectively. Results: In an intent-to-treat analysis, HCV-RNA was undetectable at the end of treatment in 49.5% of patients. At the end of follow-up, sustained virological response was 36.1 %. Combination treatment was generally well tolerated. Six patients stopped therapy because of side effects: severe cytopenia (n=4, depression (n=1, and hyperthyroidism (n= 1 . Common side effects of therapy include: Flu-like syndrome (85.6%, generalized alopecia (41.2% , injection site inflammation (37.1% , mood changes (36% , anorexia (34% and weight loss (32% . Conclusion: Heberon as an IFN product in combination with ribavirin for treat-ment of patients with chronic hepatitis Cis relatively safe, feasible, and potentially efficacious. It has comparable results in achieving end-of-treatment and sustained virological responses in chronic hepatitis C.

  18. Espectroscopia Mössbauer e refinamento estrutural no sistema cerâmico isomórfico (alfa-Fe2O3-(alfa-Al2O 3 Mössbauer spectroscopy and structural refinement in the isomorphic (alpha-Fe2O3-( alpha-Al2O3 ceramic system

    Directory of Open Access Journals (Sweden)

    J. A. Moreto

    2007-06-01

    Full Text Available Os multiferróicos são materiais em que duas ou três propriedades tais como ferroeletricidade, ferromagnetismo e ferroelasticidade são observadas em uma mesma fase. Em particular, os multiferróicos magnetoelétricos representam os materiais que são simultaneamente (antiferromagnéticos e ferroelétricos, com ou sem ferroelasticidade. Especificamente, o sistema hematita (alfa-Fe2O3-alumina (alfa-Al2O3 tem sido estudado, principalmente devido às suas potencialidades para aplicações em metalurgia e como catalisador na síntese de amônia. Contudo, compostos deste sistema também podem apresentar efeitos magnetoelétricos. Neste trabalho um estudo estrutural do composto (alfa-Fe2O30,25(alfa-Al2O 30,75 submetido à moagem em altas energias e tratamento térmico pós-moagem é apresentado. As amostras foram caracterizadas por difração de raios X, refinamento estrutural Rietveld e espectroscopia Mössbauer. A determinação e identificação das fases cristalográficas, parâmetros de rede e volume de celas unitárias nas amostras moída e tratada termicamente permitiu verificar as mudanças dos parâmetros, a formação de espinélios e possíveis deformações relativas advindas do processo de moagem em altas energias.Multiferroics are materials in which two or all three of the properties, ferroelectricity, ferromagnetism, and ferroelasticity occur in the same phase. In particular, multiferroic magnetoelectrics represent the materials that are simultaneously ferromagnetic and ferroelectric, with or without ferroelasticity. Specifically, the hematite (alpha-Fe2O3-alumina (alpha-Al2O3 system has been studied, mainly due to its potential applications in metallurgy and as catalyst of ammonia synthesis. However, compounds of this system also may present magnetoelectric effects. In this work, a structural study of the high-energy ball milled and annealed (alpha-Fe2O3 0.25(alpha-Al2O30.75 compound was carefully conducted. The samples were

  19. Measurement of the total cross section in pp collisions at $\\sqrt{s}=7$ TeV with the ALFA sub-detector of ATLAS

    CERN Document Server

    Adamczyk, Leszek; The ATLAS collaboration

    2015-01-01

    The total pp cross section is a fundamental parameter of the strong interaction which cannot be calculated in QCD but still can be measured using the optical theorem, which states that the total cross section can be obtained from the extrapolation to t=0 of the differential elastic cross section measured at small four-momentum transfer t. The ATLAS Collaboration has collected 80 mub-1 of elastic data in a dedicated run with high beta* optics at 7 TeV centre-of-mass energy with the ALFA Roman Pot detector in order to perform this measurement. From the extrapolation of the differential elastic cross section to t=0 using the optical theorem the total cross section is extracted with the luminosity-dependent method. In addition the nuclear slope of the elastic t-spectrum, the total elastic and inelastic cross sections are determined.

  20. L'alfa (Stipa tenacissima L.) dans la plaine de Midelt (haut bassin versant de la Moulouya, Maroc) – Éléments de climatologie

    OpenAIRE

    Mustapha Rhanem

    2009-01-01

    L'alfa (Stipa tenacissima L.) est représenté dans la haute plaine de Midelt par des touffes en bon état et de grande taille pouvant atteindre parfois des hauteurs allant jusqu'à 1,20 m, avec une densité moyenne à forte. Il y constitue un écosystème steppique intramontagnard spontané, caractérisé par une bonne régénération qui témoigne de conditions topo-édapho-climatiques propices à sa croissance et à sa reproduction.L'approche climatique utilisée pour caractériser cette steppe de plaine (par...

  1. L'alfa (Stipa tenacissima L. dans la plaine de Midelt (haut bassin versant de la Moulouya, Maroc – Éléments de climatologie

    Directory of Open Access Journals (Sweden)

    Mustapha Rhanem

    2009-01-01

    Full Text Available L'alfa (Stipa tenacissima L. est représenté dans la haute plaine de Midelt par des touffes en bon état et de grande taille pouvant atteindre parfois des hauteurs allant jusqu'à 1,20 m, avec une densité moyenne à forte. Il y constitue un écosystème steppique intramontagnard spontané, caractérisé par une bonne régénération qui témoigne de conditions topo-édapho-climatiques propices à sa croissance et à sa reproduction.L'approche climatique utilisée pour caractériser cette steppe de plaine (par opposition à la steppe de versant est fondée sur deux critères climatiques : la pluviosité (et plus généralement les précipitations et la température. Chacun des deux paramètres a été analysé sous différents angles en ayant recours à différents indicateurs. Ces critères ne sont pas les seuls facteurs climatiques agissant sur les conditions de vie de l'alfa et de son cortège d'espèces végétales steppiques ; mais ils sont prédominants. En effet, ces facteurs présentent d'étroites corrélations avec d'autres paramètres climatiques, tels que l'humidité relative, le vent et l'insolation. Enfin, le rapport P/2T de H. GAUSSEN a été utilisé pour cerner les modalités de la sécheresse.In Midelt high plain, alfa (Stipa tenacissima L. is formed by mean to high density good state of health and tall tufts that can sometimes reach up to 1.2 m height. It there builds up a spontaneous steppic intramountain ecosystem, characterized by a good regeneration that attests topo-edapho-climatic conditions are favorable to its growth and reproduction. Climatic approach used for characterizing this plain steppe (in contrast with slope steppe is based on two climatic criteria: raininess (and more generally rainfalls and temperature. Each of these two parameters has been analysed from different points of view using different indicators. These criteria are not the only climatic factors that act on the life conditions of alfa and its

  2. Mucoproteína versus alfa-1-glicoproteína ácida: o que quantificar? Mucoprotein versus alpha-1-acid glycoprotein: what should be measured?

    Directory of Open Access Journals (Sweden)

    Geraldo Picheth

    2002-01-01

    Full Text Available A quantificação sérica da alfa-1-glicoproteína (GPA ácida é útil no diagnóstico e no acompanhamento dos processos agudos resultantes de múltiplas causas. Esta proteína também pode ser estimada pela quantificação da mucoproteína (Muco, ensaio que reflete as glicoproteínas com elevado teor de açúcar, entre as quais a GPA é majoritária. O objetivo deste trabalho é verificar a correlação e a performance analítica das determinações de mucoproteína (Muco e alfa-1-glicoproteína ácida (GPA, propondo uma equação de regressão linear. Amostras de soros de 540 pacientes, com idades entre 10 e 79 anos (média de 34,6, predominando mulheres (71,3%, foram analisadas simultaneamente para Muco (Winzler, manual com reagentes próprios e GPA (imunoturbidimetria automatizada, Roche; Cobas mira. A análise de regressão, fixando a Muco como variável dependente, apresentou Muco (mg/dl em tirosina = 0,031 x GPA (mg/dl + 0,8 (r = 0,91; e, fixando o intercepto em zero, Muco = 0,039 x GPA (r = 0,98. A imprecisão interensaio foi de 23,4% e 5,2% (coeficiente de variação, respectivamente, para Muco e GPA. Conclusão: a elevada variabilidade analítica da quantificação da mucoproteína pelo método de Winzler recomenda que este ensaio seja substituído pela dosagem da alfa-1-glicoproteína ácida. Quando necessário, recomendamos estimar a mucoproteína, quantificando a alfa-1-glicoproteína ácida com ensaios de mesmo desempenho que o do utilizado neste trabalho, e usar a equação de regressão AGP (mg/dl x 0,039 = Muco (mg/dl em tirosina.The alpha-1-acid glycoprotein (AGP, orosomucoid serum measurement is useful in the diagnosis and management of acute processes of multiple causes. This protein can also be estimated by measuring the mucoprotein (Muco that reflects the serum glycoproteins with high levels of sugars, in which than AGP is the principal component. The analytical performance between Muco and AGP was analyzed and a linear

  3. Análisis de consistencia interna mediante Alfa de Cronbach: un programa basado en gráficos dinámicos

    OpenAIRE

    Ledesma,Rubén; Molina Ibañez,Gabriel; Valero Mora,Pedro

    2002-01-01

    En este trabajo se presenta una herramienta informática original que permite realizar análisis de consistencia interna (modelo Alfa de Cronbach) utilizando métodos gráficos dinámicos. Se trata de un módulo basado en la filosofía del Análisis Exploratorio de Datos y en métodos de visualización estadística, diseñado para asistir al analista en el proceso de construcción de pruebas psicológicas. La herramienta permite analizar la consistencia interna de la prueba, las propiedades de los ítems qu...

  4. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy

    Directory of Open Access Journals (Sweden)

    Goker-Alpan O

    2016-05-01

    Full Text Available Ozlem Goker-Alpan,1 Nicola Longo,2 Marie McDonald,3 Suma P Shankar,4,5 Raphael Schiffmann,6 Peter Chang,7 Yinghua Shen,7 Arian Pano7 1Lysosomal Disorders Unit, Fairfax, VA, 2University of Utah, Salt Lake City, UT, 3Department of Pediatrics, Duke University, Durham, NC, 4Department of Ophthalmology, 5Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 6Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, 7Shire, Lexington, MA, USA Background: Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT-naïve children with Fabry disease. Methods: In an open-label, multicenter, Phase II study (HGT-REP-084; Shire, 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring. Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI, midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life. Results: Among five boys (median 10.2 [range 6.7, 14.4] years and nine girls (14.8 [10.1, 15.9] years, eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2. One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms and no left ventricular hypertrophy: mean (SD baseline SDNN, 81.6 (20.9 ms; mean (95% confidence interval [CI] change from baseline to week 55, 17.4 (2.9, 31.9 ms. Changes in SDNN correlated with changes in LVMI (r=-0

  5. A Phase I, Single Ascending Dose Study of Cimaglermin Alfa (Neuregulin 1β3 in Patients With Systolic Dysfunction and Heart Failure

    Directory of Open Access Journals (Sweden)

    Daniel J. Lenihan, MD

    2016-12-01

    Full Text Available A first-in-human, phase 1, double blind, placebo-controlled, single ascending dose study examined the safety, tolerability, and exploratory efficacy of intravenous infusion of a recombinant growth factor, cimaglermin alfa, in patients with heart failure and left ventricular systolic dysfunction (LVSD. In these patients on optimal guideline-directed medical therapy, cimaglermin treatment was generally tolerated except for transient nausea and headache and a dose-limiting toxicity was noted at the highest planned dose. There was a dose-dependent improvement in left ventricular ejection fraction lasting 90 days following infusion. Thus, cimaglermin is a potential therapy to enhance cardiac function in LVSD and warrants further investigation.

  6. A phase-II study of combination of pegylated interferon alfa-2a and capecitabine in locally advanced or metastatic renal cell cancer.

    Science.gov (United States)

    Sunela, Kaisa Leea; Koskinen, Sanna; Kellokumpu-Lehtinen, Pirkko-Liisa

    2010-05-01

    Combination of capecitabine and interferon has shown activity in metastatic renal cell carcinoma. Pegylated interferons might have more clinical activity and fewer side effects. This study evaluated the efficacy, tolerability, and safety of the combination of capecitabine and pegylated interferon alfa-2a. In this open label, single institution, non-randomized phase-II first-line study, 26 patients were included. Capecitabine was administered 2,000 mg/m(2) daily for 14 days followed by 1 week rest. Pegylated interferon alfa-2a was given once as weekly injections with a fixed dose of 180 microg. Overall survival, progression-free survival, and response rates were evaluated; safety and tolerability were monitored. Response rate was 27, with 4% complete responses. Stable disease was achieved in 42%. The treatment discontinued in 4 (15%) patients before first response evaluation because of toxicity. The median progression-free survival was 7.5 months; the median overall survival was 17 months. Grades 3-4 toxicity was seen in 46% of patients, but in 93% of cycles no serious toxicity was experienced. Dose reductions had to be done, but in 81% of cycles intensity of 70% or more was possible. Quality of life was better in cycle five than in the base line. The combination had moderate, but manageable toxicity. In the future studies, lower dose for capecitabine is recommended. The combination was active and the response rates seen here were in line with phase-II studies on former combinations of non-pegylated interferons. One complete remission was achieved.

  7. Response to treatment with interferon-alfa in patients with chronic hepatitis C and high titers of -M2, -M4 and -M8 antimitochondrial antibodies.

    Science.gov (United States)

    Garrido Palma, G; Sánchez Cuenca, J M; Olaso, V; Pina, R; Urquijo, J J; López Viedma, B; Bustamante, M; Berenguer, M; Berenguer, J

    1999-03-01

    The prevalence of antimitochondrial antibodies (AMA) in chronic hepatitis C is 2%; titers of AMA are usually low ( 1:160). to undertake a preliminary analysis of the submitochondrial profile of AMA in three patients with chronic hepatitis C and positive AMA titers (> 1:160). we determined antibodies to submitochondrial particles (subtypes) -M2, -M4 and -M8 by ELISA, complement binding (CB) and western immunoblotting with Immunoblot-M2 or WIB-M2 (immunoreactive bands). two patients were positive for mitochondrial subtypes by ELISA (IgG/IgM subclass) and CB (ELISA M2 470/365 in patient 1 and 600/1370 in patient 2; M4 490/1200 in patient 2. CB M2 1:128, M4 1:64, M8 1:64 in patient 1, M2 1:128 in patient 2). Immunoreactive epitopes (bands) were detected with WIB-M2 for 70, 56, 51, 45 and 36-kDa molecules. Interferon-alfa treatment was unsuccessful, with biochemical exacerbation of cholestasis. In contrast, the patient with no submitochondrial particles according to ELISA, CB and WIB-M2 results responded favorable to this drug. these preliminary results suggest that analyses to detect antibodies to submitochondrial particles (-M2, -M4 and -M8 subtypes) and -M2-immunoreactive epitopes in patients with chronic hepatitis C and AMA titers > 1:160 facilitates the diagnosis of primary biliary cirrhosis, and establishes a contraindication for treatment with interferon-alfa despite the presence of HCV infection.

  8. Effects of exercise on fatigue, sleep, and performance: a randomized trial.

    Science.gov (United States)

    Coleman, Elizabeth Ann; Goodwin, Julia A; Kennedy, Robert; Coon, Sharon K; Richards, Kathy; Enderlin, Carol; Stewart, Carol B; McNatt, Paula; Lockhart, Kim; Anaissie, Elias J

    2012-09-01

    To compare usual care with a home-based individualized exercise program (HBIEP) in patients receiving intensive treatment for multiple myeloma (MM)and epoetin alfa therapy. Randomized trial with repeated measures of two groups (one experimental and one control) and an approximate 15-week experimental period. Outpatient setting of the Myeloma Institute for Research and Therapy at the Rockfellow Cancer Center at the University of Arkansas for Medical Sciences. 187 patients with newly diagnosed MM enrolled in a separate study evaluating effectiveness of the Total Therapy regimen, with or without thalidomide. Measurements included the Profile of Mood States fatigue scale, Functional Assessment of Cancer Therapy-Fatigue, ActiGraph® recordings, 6-Minute Walk Test, and hemoglobin levels at baseline and before and after stem cell collection. Descriptive statistics were used to compare demographics and treatment effects, and repeated measures analysis of variance was used to determine effects of HBIEP. Fatigue, nighttime sleep, performance (aerobic capacity) as dependent or outcome measures, and HBIEP combining strength building and aerobic exercise as the independent variable. Both groups were equivalent for age, gender, race, receipt of thalidomide, hemoglobin levels, and type of treatment regimen for MM. No statistically significant differences existed among the experimental and control groups for fatigue, sleep, or performance (aerobic capacity). Statistically significant differences (p sleep and performance (aerobic capacity). The effect of exercise seemed to be minimal on decreasing fatigue, improving sleep, and improving performance (aerobic capacity). Exercise is safe and has physiologic benefits for patients undergoing MM treatment; exercise combined with epoetin alfa helped alleviate anemia.

  9. Níveis de interleucina-6 e fator de necrose tumoral-alfa no liquor de recém-nascidos a termo com encefalopatia hipóxico-isquêmica

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    Silveira Rita de Cássia

    2003-01-01

    Full Text Available OBJETIVO: avaliar os níveis liquóricos de IL-6 e TNF-alfa em recém-nascidos a termo com encefalopatia hipóxico-isquêmica (EHI, comparando-os com os de recém-nascidos controles. METODOLOGIA: estudo caso-controle realizado no período de julho de 1999 a outubro de 2001, incluindo dois grupos de recém-nascidos a termo: controle, com 20 recém-nascidos sem sepse e/ou meningite e com escore de Apgar > 9 no primeiro e quinto minutos de vida; e casos, com 15 recém-nascidos asfixiados, caracterizados pelo escore de Apgar 3,0 mmol/l e necessidade de ventilação com pressão positiva pelo menos durante 2 minutos após o nascimento. Foram coletadas amostras de liquor nas primeiras 48 horas de vida, para determinação dos níveis de IL-6 e TNF-alfa pelo método de enzimoimunoensaio. RESULTADOS: os grupos não diferiram quanto ao peso de nascimento, idade gestacional, classificação quanto ao peso e idade gestacional, tipo de parto e tempo médio de obtenção do liquor; seus exames foram obtidos em média com 17 horas de vida. Nos recém-nascidos asfixiados, as medianas dos níveis liquóricos foram: 157,5 pg/ml para IL-6 e 14,7 pg/ml para TNF-alfa, significativamente mais elevadas que nos controles (IL-6: 4,1 pg/ml e TNF-alfa: 0,16 pg/ml. CONCLUSÕES: recém-nascidos a termo com EHI apresentaram níveis liquóricos de IL-6 e TNF-alfa mais elevados que controles, possivelmente devido à produção local cerebral dessas citocinas, especialmente o TNF-alfa. Estes achados estimulam estudos futuros, utilizando bloqueadores cerebrais das ações dessas citocinas como estratégia de neuroproteção.

  10. TARTIŞMAYI SONLANDIRMAK: CRONBACH'IN ALFA KATSAYISI, İKİ DEĞERLİ [0,1] ÖLÇÜMLENMİŞ MADDELER İLE KULLANILABİLİR

    OpenAIRE

    Bademci, Vahit

    2010-01-01

    ÖzetÖlçümlerin güvenirliğini kestirmek için değişik yöntemler vardır. Bunlardan biriside Cronbach'ın alfa katsayısı yöntemidir. Cronbach'ın alfa katsayısı ile ilgili olarak da, bukatsayının sadece ağırlıklı ölçümlenmiş (Örneğin, 1,2,3,4,5 gibi) maddelerlekullanılabileceği şeklinde bir görüş vardır. Ancak, bazı bilim adamlarınca ileri sürülen bugörüş doğru değildir. Çünkü, Cronbach'...

  11. Short-term Treatment With Interferon Alfa Diminishes Expression of HIV-1 and Reduces CD4+ T-Cell Activation in Patients Coinfected With HIV and Hepatitis C Virus and Receiving Antiretroviral Therapy.

    Science.gov (United States)

    Morón-López, Sara; Gómez-Mora, Elisabet; Salgado, Maria; Ouchi, Dan; Puertas, Maria C; Urrea, Víctor; Navarro, Jordi; Jou, Antoni; Pérez, Mercedes; Tural, Cristina; Clotet, Bonaventura; Montaner, Luis J; Blanco, Julià; Crespo, Manuel; Martinez-Picado, Javier

    2016-03-15

    Long-term treatment with interferon (IFN) alfa plus ribavirin decreases the proviral human immunodeficiency virus type 1 (HIV) DNA level. However, the short-term impact of IFN alfa on persistent HIV and its effects on immune activation after antiretroviral therapy remain unknown. Our study showed that the cell-associated HIV RNA level and CD4(+) T-cell activation decreased in the IFN group (n = 10). No changes were detected in levels of residual plasma viremia, replication-competent reservoirs, proviral DNA, or 2-long-terminal repeat circles, although APOBEC3G, TRIM5α, BST2, and TRIM22 were upregulated in the IFN group. These data suggest that short-term treatment with IFN alfa combined with RBV decreases HIV expression, in part through inhibition of HIV transcription by TRIM22 and decrease in T-cell activation. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin ± amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial.

    Science.gov (United States)

    Pessôa, Mario G; Cheinquer, Hugo; Almeida, Paulo R L; Silva, Giovanni F; Lima, Maria Patelli J S; Paraná, Raymundo; Lacerda, Marco A; Parise, Edison R; Pernambuco, José R B; Pedrosa, Suelene S; Teixeira, Rosângela; Sette, Hoel; Tatsch, Fernando

    2012-01-01

    A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care(pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after ≥ 24 weeks of treatment with conventional interferon plus ribavirin. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (40KD) 180 µg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.

  13. Duchenne muscular dystrophy: alpha-dystroglycan immunoexpression in skeletal muscle and cognitive performance Distrofia muscular de Duchenne: imunoexpressão da alfa-distroglicana em musculatura esquelética e performance cognitiva

    Directory of Open Access Journals (Sweden)

    Conceição Campanario da Silva Pereira

    2005-12-01

    Full Text Available The Duchenne muscular systrophy (DMD is a muscular dystrophy with cognitive impairment present in 20-30% of the cases. In the present study, in order to study the relationship between the alpha-dystroglycan (alpha-DG immunostaining in skeletal muscle and cognitive performance in DMD patients, 19 were assessed. Twelve patients performed the intelligence quotient (IQ below the average. Among the 19 patients, two were assessed by the Stanford-Binet test and 17 by Wechsler Intelligence Scale for Children-III (WISC-III. Nine patients performed a verbal IQ below the average, only three patients performed an average verbal IQ. The muscle biopsies immunostained with antibodies to alpha-DG showed that 17 patients presented a low expression, below 25% of the total fibers. Two patients presented alpha-DG immunostaining above 40% and an IQ within the average. No significant statistical relationship was demonstrated among total IQ, verbal IQ and execution IQ and alpha-DG immunostaining at these patients muscle samples.A distrofia muscular de Duchenne (DMD é uma distrofia muscular com comprometimento cognitivo presente em 20-30% dos casos. No presente estudo, com a finalidade de estudar a relação entre a imunoexpressão da alfa-distroglicana (alfa-DG em musculatura esquelética e a performance cognitiva em pacientes com DMD, foram avaliadas 19 crianças. Doze pacientes apresentaram o quociente de inteligência (QI abaixo da média. Entre os 19 pacientes, dois foram avaliados pelo teste de Stanford-Binet e 17 pelo Wechsler Intelligence Scale para crianças-III (WISC-III. Nove apresentaram QI verbal abaixo da média, e apenas três QI verbal na média. As biopsias musculares com os anticorpos para alfa-DG mostraram que 17 pacientes apresentaram baixa expressão, abaixo de 25% do total de fibras. Dois pacientes apresentaram a imunoexpressão da alfa-DG acima de 40% e QI dentro da média. Não foi demonstrada relação estatisticamente significante entre o QI

  14. Quantitative serum HBsAg and HBeAg are strong predictors of sustained HBeAg seroconversion to pegylated interferon alfa-2b in HBeAg-positive patients.

    Science.gov (United States)

    Ma, Hui; Yang, Rui-Feng; Wei, Lai

    2010-09-01

    To evaluate the usefulness of quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for predicting HBeAg seroconversion in chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or PegIFN alfa-2b. Fifty-eight patients were enrolled; 29 for the training group and 29 for the validating group. Quantification of HBsAg and HBeAg was carried out at baseline, week 12, week 24, and then again at 12 and 24 weeks follow up, respectively, for two groups. Sixteen patients in the training group were followed up for 5 years. The cutoff of 1500 IU/mL in serum HBsAg at week 12 had a positive predictive value (PPV) of 33% and a negative predictive value (NPV) of 91%, and 2890 IU/mL at week 24 had a PPV of 43% and an NPV of 95% for HBeAg seroconversion at week 48. The cutoff of 17.55 Paul Ehrlich Institute units/mL (PEI-U/mL) in serum HBeAg at week 12 had a PPV of 38% and an NPV of 95%, and 8.52 PEI-U/mL at week 24 had a PPV of 44% and a NPV of 100% for HBeAg seroconversion at week 48. Moreover the HBsAg and HBeAg levels of PegIFN alfa-2b group were lower than those of the conventional IFN alfa-2b group. During follow up, patients with HBeAg seroconversion remained HBeAg negative and none of them progressed to cirrhosis, but among the patients with non-HBeAg seroconversion, two progressed to cirrhosis. Two additional patients with negative HBeAg were observed. On-treatment serum HBsAg and HBeAg had high predictive values to predict sustained HBeAg seroconversion by PegIFN alfa-2b. Patients who cleared HBeAg had better survival free of hepatic complications during long-term follow-up study.

  15. Níveis de alfa-tocoferol no soro e leite materno de puérperas atendidas em maternidade pública de Natal, Rio Grande do Norte Levels of alpha-tocopherol in the serum and breast-milk of child-bearing women attending a public maternity hospital in the city of Natal , in the Brazilian State of Rio Grande do Norte

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    Lígia Rejane Siqueira Garcia

    2009-12-01

    analyzed using High-Efficiency Liquid Chromatography. The nutritional adequacy of the breast-milk in terms of vitamin E content was calculated by multiplying the estimated volume of milk ingested by the infant by the concen tration of α-tocopherol in the breast-milk and comparing this directly with the gold standard for intake of this nutrient (4 mg/day. RESULTS: alfa-tocopherol in the blood were 29 ± 0.9 µmol/L (mean ± standard error and in the colostrum and transition milk were 28.7 ± 4,7 µmol/L and 7.8 ± 1.0 µmol/L, respectively. The estimated consumption of colostrum provided 241% the recommended dietary intake and the transition milk provided 66%. CONCLUSIONS: the group of women under study had nutritionally adequate levels of vitamin E, and these levels are reflected in their breast-milk, especially in the colostrum, which contained more than double the nutritional requirement of the infant.

  16. Efeitos do levosimendan sobre TNF-alfa, PNB e MMP-1 em pacientes com insuficiência cardíaca com anemia Effects of levosimendan on TNF-alpha, BNP and MMP-1 in patients with heart failure with anemia

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    Mutlu Büyüklü

    2012-07-01

    Full Text Available FUNDAMENTO: O levosimendan é conhecido pelo seu efeito bilateral de fortalecimento contração das miofibrilas sem aumentar a demanda de oxigênio no miocárdio. A anemia é uma deterioração que causa aumento da dosagem de fármacos em pacientes com insuficiência cardíaca. OBJETIVO: No presente estudo comparamos a eficácia do tratamento com levosimendan em pacientes com insuficiência cardíaca descompensada com ou sem anemia. MÉTODOS: Foram incluídos no estudo 23 pacientes anêmicos com insuficiência cardíaca classe 3 ou 4, segundo a New York Heart Association (NYHA e fração de ejeção abaixo de 35%. Outros 23 pacientes com o mesmo diagnóstico cardíaco, mas sem anemia, serviu como grupo controle. Ao tratamento da insuficiência cardíaca tradicional desses pacientes foi acrescido um tratamento de 24 horas de levosimendan. Amostras foram tomadas para dosar os níveis séricos do fator de necrose tumoral alfa sérico (TNF-alfa, peptídeo natriurético cerebral aminoterminal (NT-proPNB e metaloproteinase da matriz 1 (MMP-1, antes e após a administração. RESULTADOS: Não houve diferença significativa entre os níveis séricos de TNF-alfa e MMP-1, antes e depois do tratamento (p > 0,05. Embora o nível de NT-proBNP tenha diminuído em ambos os grupos após o tratamento, não foi estatisticamente significativo (p = 0,531 e p = 0,913 para os grupos de anemia e de controle, respectivamente. Uma restauração significativa da capacidade funcional foi observada em ambos os grupos avaliados, de acordo com a NYHA (p BACKGROUND: Levosimendan is known with its two-sided effects of strengthening myofibril contraction without increasing myocardial oxygen demand. Anemia is a deteriorating situation that causes increase of drug dosing in patients with heart failure. OBJECTIVES: In this study, we compared the effectiveness of levosimendan treatment in decompensated heart failure patients with or without anemia. METHODS: Twenty-three anemic

  17. Autoantibodies before, during and after administration of recombinant interferon-alpha for chronic viral hepatitis Estudo dos auto-anticorpos nas Hepatites virais crônicas B e C antes, durante e após tratamento com Interferon-alfa

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    Edmundo P.A. Lopes

    1995-10-01

    Full Text Available This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8% of the total patient group had autoantibodies at the beginning of the study (two in each group. During the follow-up period no patient in the control group developed antibodies compared with 3 (11% patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-alfa (IFN-alfa, assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C, que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C, que receberam IFN-alfa durante 6 meses. Anticorpos antinúcleo, antimúsculo liso

  18. Effect of age and acetato DL-alfa-tocoferol supplementation on the vitamin E sera levels and on the proteinogram of calve Efeito da idade e da suplementação oral com o acetato de DL-alfa-tocoferol sobre os níveis séricos de vitamina E e sobre o proteinograma de bezerros

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    Joselito Nunes Costa

    2007-10-01

    Full Text Available The aim of this report was the evaluation of age and oral DL-alfa- tocopherol acetate supplemental effects on the vitamin E sera levels, and on the proteinogram of Jersey calves from birth to 45 days of age. Fourteen calves were divided in two groups of seven animals each. One group received daily 2g of oral DL-alfa-tocopherol acetate, until 45 days of life and the control group did not receive any oral supplementation. Serum blood samples were collected at birth, 5, 10, 20, 30 and 45 days old. Serum vitamin E determination and serum protein detection were evaluated. The highest concentrations of globulins were observed after colostrum ingestion, with a small reduction at 30 days and increasing again afterwards. For the albumin fraction, a small increase was observed from birth to 45 days old. The occurrence of the immune passive transfer fail was observed in a single animal (7.3% which was diagnosed by the low serum protein concentration < 5.0 g/dL after colostrum ingestion. It was an animal from treatment group, and it was well recovery after 20 days old when it presented the serum protein concentration according to its age which suggested a vitamin E beneficial action. It was concluded that the oral 2g/d/VO supplementation with DL-alfa-tocopherol acetate, from birth to 45 days old increased the serum vitamin E levels significantly in calves.Este trabalho teve por objetivo avaliar o efeito da idade e da suplementação oral com acetato de DL-alfa-tocoferol sobre os níveis séricos de vitamina E e sobre o proteinograma de bezerros da raça Jersey do nascimento aos 45 dias de idade. Foram utilizados 14 bezerros divididos em dois grupos de sete animais cada. O grupo tratamento recebeu 2g de acetato de DL-alfa-tocoferol, por via oral, diariamente, até os 45 dias de vida e o controle não recebeu nenhum tipo de suplementação para esta vitamina. Foram colhidas amostras de soro sanguíneo ao nascimento, aos cinco, 10, 20, 30 e 45 dias de idade

  19. Valutare la qualità dei corsi di lifelong learning in America Latina Alcune riflessioni teoriche e metodologiche sul disegno valutativo utilizzato nel progetto AlfaIII Trall

    Directory of Open Access Journals (Sweden)

    Maurizio Betti

    2014-04-01

    Full Text Available The article presents the structure of the evaluation design used in the project of international cooperation between Europe and Latin America called AlfaIII -Trall (Transatlantic Lifelong Learning. Rebalancing Relations. The design implemented meets the need to evaluate the quality of lifelong learning courses promoted by 14 Latin American universities, partners of the project, and aims to trigger virtuous circles of progressive improvement in the efficiency and effectiveness of the various training courses realized. Starting from the analysis of the theoretical and methodological framework that currently characterizes the field of educational evaluation research, the evaluation design of the Trall courses has gradually defined itself as a systemic "model", which aims to connect – from an ecological perspective - multiple indicators of the quality: input, in context, in the process, output. The evaluation design – built through discussion and sharing of many partners in the project – is also proposed as a system of formative and democratic evaluation, where the analysis of gathered information is an opportunity, within each university context, to achieve collective moments of intersubjective interpretation of data among the different training 'actors', to identify potential improvements  and to make democratic decisions about the redesign of the courses.

  20. Platelet sparing effect of COX II inhibition used with pegylated interferon alfa-2a for the treatment of chronic hepatitis C: a short term pilot study.

    Science.gov (United States)

    George, Magdalene M; Li, S David; Mindikoglu, Ayse L; Baluch, Mehdi H; Dhillon, Sonu; Farr, Deborah; Van Thiel, David H

    2004-09-21

    The role of a cyclooxygenase (COX) II inhibitor in reducing microvascular inflammation and the platelet count associated with interferon (IFN) plus ribavirin therapy of chronic hepatitis C (HCV) was assessed. Three plasma mediators (biomarkers) associated with platelet activation, inflammation and fibrosis were measured. Eighteen IFN naïve patients were studied. Nine were treated with pegylated IFN alfa-2a (PEG-IFN alpha-2a) plus ribavirin and rofecoxib; nine were treated with PEG-IFN alpha-2a plus ribavirin. A complete blood count, liver panel and HCV-RNA were assayed weekly. Human soluble P-selectin (hs-P-selectin), human interleukin-8 (IL-8), human interleukin-13 (IL-13) and human thrombopoietin (TPO) were assayed at 4 week intervals. The COX II inhibitor reduced the platelet reduction experienced with PEG-IFN alpha-2a treatment of HCV despite a reduction in the plasma TPO level. Hs-P-selectin was increased in both groups. In contrast, human IL-8 levels declined to undetectable levels in virologic responders. Similarly, human IL-13 levels declined with therapy (P < 0.001). These data suggest that: (1) a COX II inhibition is associated with an increase in the platelet count despite a reduction in the TPO level; (2) human IL-8 and human IL-13 but not hs-P-selectin levels decline in those who experience an early virologic response.

  1. Measurement of the total cross section in proton proton collisions at $\\mathbf{\\sqrt{s}=7}$ TeV with the ALFA sub-detector of ATLAS

    CERN Document Server

    Adamczyk, Leszek; The ATLAS collaboration

    2015-01-01

    Measurement of the total pp cross section at the LHC at $\\sqrt{s} = 7$ TeV is presented. In a special run with high-$\\beta^*$ beam optics, an integrated luminosity of 80 $\\mu$b$^{−1}$ was accumulated in order to measure the differential elastic cross section as a function of the Mandelstam momentum transfer variable $t$. The measurement is performed with the ALFA sub-detector of ATLAS. Using a fit to the differential elastic cross section in the $|t|$ range from 0.01 GeV$^2$ to 0.1 GeV$^2$ to extrapolate to $|t|\\rightarrow 0$, the total cross section, $\\sigma_{tot}(pp \\rightarrow X)$, is measured via the optical theorem to be: $\\sigma_{tot}(pp \\rightarrow X) = 95.35 \\pm 0.38$ (stat.) $\\pm 1.25 $ (exp.) $\\pm 0.37$ (extr.) mb , where the first error is statistical, the second accounts for all experimental systematic uncertainties and the last is related to uncertainties in the extrapolation to $|t|\\rightarrow 0$ . In addition, the slope of the elastic cross section at small $t$ is determined to be $B = 19.73 ...

  2. CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study.

    Directory of Open Access Journals (Sweden)

    I-Cheng Lee

    Full Text Available There is lack of a practical biomarker to predict sustained virological response (SVR in chronic hepatitis B (CHB patients undergoing peginterferon alfa-2a (PEG-IFN. The aim of this pilot study was to identify immunological features associated with SVR.Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg-positive or 48 weeks (for HBeAg-negative PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg, CXCL9, IFN-γ-inducible protein 10 (IP-10, interferon-gamma (IFN-γ and transforming growth factor beta (TGF-β were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load 80 pg/mL, HBV DNA 10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 10(7 IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%.Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.

  3. Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.

    Science.gov (United States)

    Han, Hwalih; Noureddin, Mazen; Witthaus, Michael; Park, Yoon J; Hoofnagle, Jay H; Liang, T Jake; Rotman, Yaron

    2013-11-01

    Interferon treatment for chronic hepatitis C is associated with non-specific symptoms including fever. We aimed to determine the association of temperature changes with interferon antiviral activity. 60 treatment-naïve patients with chronic hepatitis C (67% genotype 1/4/6, 33% genotype 2/3) were admitted to start peginterferon alfa-2a and ribavirin in a clinical trial. Temperature was measured at baseline and 3 times daily for the first 24h and the maximal increase from baseline during that time (ΔTmax) was determined. Serum HCV-RNA, interferon-gamma-inducible protein-10 (IP-10) and expression of interferon-stimulated genes (ISGs - CD274, ISG15, RSAD2, IRF7, CXCL10) in peripheral blood mononuclear cells (PBMCs) were measured at very early time points, and response kinetics calculated. The IL28B single nucleotide polymorphism, rs12979860, was genotyped. Temperatures rose by 1.2±0.8°C, peaking after 12.5h. ΔTmax was strongly associated with 1st phase virological decline (r=0.59, pTemperature rise following peginterferon injection is closely associated with virological response and is modulated by IL28B polymorphism, reflecting host interferon-responsiveness. Published by Elsevier B.V.

  4. Use of drotrecorgin alfa--recombinant activated human protein C in treatment of septic shock in the course of therapy for nephrolithiasis.

    Science.gov (United States)

    Biernacka, Jadwiga; Wośko, Jarosław; Dabrowski, Wojciech; Nestorowicz, Andrzej

    2003-05-01

    Septic shock is the most dangerous complication of nephrolithiasis management utilizing percutaneous methods. The patient, D.M., aged 60 was subjected to scheduled percutaneous nephrolithotomy due to coral calculosis of the pyelocalyceal system. As pyuria was noted intraoperatively, nephrostomy was left after the procedure. Over ten hours after the surgery the patient developed the symptoms of severe septic shock with progressive respiratory distress, renal failure, intravascular coagulation syndrome and impaired consciousness. Nephrectomy was performed, antibiotic treatment and high doses of norepinephrine instituted. Hemodynamic stabilization was obtained, without, however, marked improvement of the patient's condition. Because of persistent coagulation disorders and multiorgan dysfunction, recombinant activated protein C preparation--drotrecorgin alfa (Xigris Eli Lilly) was added to the therapeutic regimen. From the second day of infusion, systematic improvement of the coagulation system parameters was observed, making it possible to reduce the doses of catecholamines, oxygen concentration in the gas mixture used for ventilation, as well as stabilization of the function of the preserved kidney. The patient was weaned off the respirator on the 8th day of treatment and on the 13th day referred to the Urology Department, from which she was soon discharged home. 1. Surgical resection of the infection source and cause of the septic shock is the prerequisite for successful pharmacological treatment. 2. Administration of rh-APC to a patient meeting the PROWESS criteria may be an effective and safe method of treatment in the complex management of septic shock.

  5. Plasma levels of tumor necrosis factor-alpha in patients with visceral leishmaniasis (Kala-Azar. Association with activity of the disease and clinical remisson following antimonial therapy Níveis plasmáticos do fator de necrose tumoral-alfa (TNF-alfa em pacientes com leishmaniose visceral (Calazar. Associação com atividade da doença e remissão clínica com terapia antimonial

    Directory of Open Access Journals (Sweden)

    Reinaldo Salomão

    1996-04-01

    Full Text Available Evaluation of TNF-alpha in patients with Kala-azar has drawn increasing interest due to its regulatory role on the immune system, in addition to its cachetizing activity. The objective of this study was to examine the association between plasma levels of TNF-alpha, measured by immunore-activity (ELISA and bioactivity (cytotoxicity assay with L-929 cells, and clinical manifestations of visceral leishmaniasis. Plasma samples from 19 patients with Kala-azar were obtained before, during and at the end of antimonial therapy. TNF-alpha determinations was done by using the cytotoxicity assay (all patients and the enzyme-linked immunoassay (ELISA - 14 patients. A discrepancy between results obtained by ELISA and cytotoxicity assay was observed. Levels of circulating TNF-alpha, assessed by ELISA, were higher in patients than in healthy controls, and declined significantly with improvement in clinical and laboratory parameters. Plasma levels before treatment were 124.7 ± 93.3 pg/ml (mean ± SD and were higher than at the end of therapy 13.9 ± 25.1 pg/ml (mean ± SD (p = 0.001. In contrast, plasma levels of TNF-alpha evaluated by cytotoxicity assay did not follow a predicted course during follow-up. Lysis, in this case, might be not totally attributed to TNF-alpha. The discrepancy might be attributed to the presence of factor(s known to influence the release and activity of TNF-alpha.Avaliação de TNF-alfa em pacientes com calazar tem despertado grande interesse devido ao seu papel no sistema imunológico e à sua atividade caquetizante. O objetivo deste estudo foi examinar a associação entre os níveis plasmáticos de TNF-alfa, medidos através de sua imunorreatividade (ELISA e bioatividade (ensaio citotóxico sobre as células L-929, e as manifestações clínicas da leishmaniose visceral. Amostras de 19 pacientes foram obtidas para determinação do TNF-alfa antes, durante e após a terapia antimonial, utilizando o ensaio de citotoxicidade (todos

  6. Concentração de alfa-tocoferol no soro e colostro materno de adolescentes e adultas Levels of alpha-tocopherol in maternal serum and colostrum of adolescents and adults

    Directory of Open Access Journals (Sweden)

    Roberto Dimenstein

    2010-06-01

    Full Text Available OBJETIVOS: avaliar a concentração de alfa-tocoferol no soro e colostro materno de puérperas adolescentes e adultas e verificar a adequação nutricional de vitamina E do colostro oferecido ao lactente. MÉTODOS: participaram do estudo 72 puérperas, sendo 25 adolescentes e 47 adultas. Foram coletados 5 mL de sangue e 2 mL de colostro em condição de jejum para análise dos níveis de alfa-tocoferol. As amostras foram analisadas por cromatografia líquida de alta eficiência. A adequação nutricional do colostro para a vitamina E foi calculada pelo produto do volume estimado de ingestão de leite com a concentração de alfa-tocoferol no colostro e por comparação direta desse produto com o valor de referência para ingestão do nutriente (4 mg/dia. RESULTADOS: os níveis de alfa-tocoferol no soro de puérperas adolescentes e adultas foram, respectivamente, 30,8±9,8 e 34,1±9,5 µmol/L (média±DP. No colostro, as adolescentes apresentaram concentração de alfa-tocoferol de 32,9±15,8 µmol/L e as adultas de 30,4 ± 18,0 µmol/L, não sendo encontrada diferença significativa entre as concentrações séricas, assim como no colostro dos grupos estudados. CONCLUSÕES: Tanto as puérperas adolescentes quanto as adultas apresentaram um estado nutricional satisfatório de vitamina E refletido no colostro cujos valores foram capazes de suprir o requerimento nutricional do lactente, sugerindo que a idade materna não influencia os níveis de alfa-tocoferol do colostro humano.PURPOSE: to assess the alpha-tocopherol concentration in the serum and colostrum of adolescent and adult mothers and to determine the nutritional adequacy of vitamin E in the colostrum offered to infants. METHODS: in total, 72 pregnant women participated in the study, 25 adolescents and 47 adults. An amount of 5 mL of blood and 2 mL of colostrum were collected under fasting conditions for the analysis of alpha-tocopherol levels. The samples were analyzed by means of high

  7. El receptor de estrógenos alfa como mediador del efecto proliferativo de progestágenos en cáncer de mama

    Directory of Open Access Journals (Sweden)

    Sebastián Giulianelli

    2012-08-01

    Full Text Available En carcinomas mamarios murinos (C4-HD y en células de cáncer de mama humano (T47D observamos que el progestágeno sintético, acetato de medroxiprogesterona (MPA, induce la activación del receptor de estrógenos alfa (REa y su asociación nuclear con el receptor de progesterona (RP. En este trabajo postulamos que dicha interacción a nivel genómico sería fundamental para desarrollar respuestas proliferativas mediadas por progestágenos. Demostramos que el antiestrógeno fulvestrant (FUL, ICI182.780 indujo la regresión completa de tumores C4-HD creciendo con MPA. El progestágeno indujo la expresión temprana de CCND1 y MYC en células T47D y este efecto fue revertido al bloquear el REa. En células tratadas con MPA utilizamos ensayos de inmunoprecipitación de la cromatina (ChIP y corroboramos la colocalización nuclear de RP/REa en los mismos sitios de los promotores de CCND1 y MYC. El ICI no afectó la unión de RP a ambas secuencias regulatorias, pero sí inhibió la unión del REa. Confirmamos la interacción nuclear entre REa y RP en muestras de cáncer de mama humano. Los resultados demuestran que la presencia del REa, interactuando con el RP, en promotores de CCND1 y MYC es fundamental para la transcripción génica y la proliferación celular inducida por el progestágeno.

  8. Antimicrobial efficacy of tobramycin polymeric nanoparticles for Pseudomonas aeruginosa infections in cystic fibrosis: formulation, characterisation and functionalisation with dornase alfa (DNase).

    Science.gov (United States)

    Deacon, Jill; Abdelghany, Sharif M; Quinn, Derek J; Schmid, Daniela; Megaw, Julianne; Donnelly, Ryan F; Jones, David S; Kissenpfennig, Adrien; Elborn, J Stuart; Gilmore, Brendan F; Taggart, Clifford C; Scott, Christopher J

    2015-01-28

    Inhaled antibiotics, such as tobramycin, for the treatment of Pseudomonas aeruginosa pulmonary infections are associated with the increase in life expectancy seen in cystic fibrosis (CF) patients over recent years. However, the effectiveness of this aminoglycoside is still limited by its inability to penetrate the thick DNA-rich mucus in the lungs of these patients, leading to low antibiotic exposure to resident bacteria. In this study, we created novel polymeric nanoparticle (NP) delivery vehicles for tobramycin. Using isothermal titration calorimetry, we showed that tobramycin binds with alginate polymer and, by exploiting this interaction, optimised the production of tobramycin alginate/chitosan NPs. It was established that NP antimicrobial activity against P. aeruginosa PA01 was equivalent to unencapsulated tobramycin (minimum inhibitory concentration 0.625mg/L). Galleria mellonella was employed as an in vivo model for P. aeruginosa infection. Survival rates of 90% were observed following injection of NPs, inferring low NP toxicity. After infection with P. aeruginosa, we showed that a lethal inoculum was effectively cleared by tobramycin NPs in a dose dependent manner. Crucially, a treatment with NPs prior to infection provided a longer window of antibiotic protection, doubling survival rates from 40% with free tobramycin to 80% with NP treatment. Tobramycin NPs were then functionalised with dornase alfa (recombinant human deoxyribonuclease I, DNase), demonstrating DNA degradation and improved NP penetration of CF sputum. Following incubation with CF sputum, tobramycin NPs both with and without DNase functionalisation, exhibited anti-pseudomonal effects. Overall, this work demonstrates the production of effective antimicrobial NPs, which may have clinical utility as mucus-penetrating tobramycin delivery vehicles, combining two widely used CF therapeutics into a single NP formulation. This nano-antibiotic represents a strategy to overcome the mucus barrier

  9. Efeitos do alfa-tocoferol nas lesões de isquemia-reperfusão induzidas em pata direita de ratos

    Directory of Open Access Journals (Sweden)

    Bitu-Moreno José

    2001-01-01

    Full Text Available Recentes estudos demonstraram que os radicais livres de oxigênio parecem desempenhar papel importante nas lesões de isquemia-reperfusão. O alfa-tocoferol(AT age in vivo como um anti-oxidante. Nosso objetivo foi o de verificar se o AT atenuava as lesões de isquemia-reperfusão em pata direita de ratos. Os animais, randomizados, foram divididos nos seguintes grupos(G: G1-controle sem isquemia; G2 e G3 - quatro horas isquemia e duas reperfusão. Os animais do G2 foram tratados com salina e os do G3 com AT, 50mg/kg. Como parâmetros examinamos as alterações de volume e circunferência do pé direito ao longo do experimento, assim como a captação de 99mTc-pirofosfato e a microscopia eletrônica de transmissão do músculo soleus direito. Os aumentos de volume e circunferência do pé dos animais do G2 foram estatisticamente maiores quando comparados com o G1. As medidas do G3 não diferiram do G1. A captação de 99mTc-pirofosfato foi bem aumentada nos G2 e G3, quando comparados ao G1, porém sem diferenças entre os grupos isquêmicos. As lesões ao MET foram menos intensas em três animais do G3, quando comparados ao G2. Conclusão: O tratamento com AT diminuiu a formação do edema mas só protegeu parcialmente as células musculares contra as lesões de isquemia-reperfusão.

  10. Effect of treatment with Omega-3 fatty acids on C-reactive protein and tumor necrosis factor-alfa in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Hamid Tayyebi-Khosroshahi

    2012-01-01

    Full Text Available C-reactive protein (CRP, a strong independent risk marker of cardiovascular disease (CVD, and tumor necrosis factor-alfa (TNF-α, a known pro-inflammatory cytokine, are elevated and have damaging effects in patients with chronic renal failure (CRF. Omega-3 fatty acids play an important modulatory role in inflammatory responses. The aim of this study is to review the alterations in serum levels of TNF-α, CRP and other parameters caused by omega-3 supplementation in dialysis patients. The clinical trial was performed in 37 patients with end-stage renal disease undergoing dialysis in hemodialysis centers of three university hospitals in Tabriz. Blood samples were obtained from the study patients for hemoglobin, albumin, ferritin, triglyceride, total cholesterol, low-density lipoprotein (LDL and high-density lipoprotein (HDL-cholesterol, TNF-α and high specific-CRP (hs-CRP measurement. The patients received 3 g omega-3 per day for 2 months. The side-effects noticed were nausea, diarrhea and dyspepsia and undesired drug smell. The difference noted in hemoglobin, albumin, ferritin, CRP, triglyceride, total, LDL and HDL-cholesterol before and after supplementation with omega-3 fatty acid was not statistically significant (P > 0.05. However, the use of omega-3 decreased the serum levels of TNF-α significantly. We conclude that the use of 3 g of omega-3 per day caused significant decrease in serum levels of TNF-α in the dialysis population, and its use is recommended in such patients.

  11. Influência da vitamina D associada ao interferon alfa-peguilado e ribavirina na resposta virológica sustentada na hepatite C crônica

    Directory of Open Access Journals (Sweden)

    Luiza Vitelo ANDRIGHETTO

    2016-09-01

    Full Text Available O objetivo deste trabalho foi avaliar a influência da vitamina D no tratamento de hepatite C com interferon-alfa peguilado e ribavirina. Foram utilizados artigos científicos relevantes publicados entre os anos de 2000 e 2015. Em diversos estudos foi observado que níveis mais elevados de vitamina D estavam associados à rápida resposta ao tratamento e à maior taxa de RVS, sugerindo que a deficiência de vitamina D pode estar ligada a uma falta de resposta ao tratamento antiviral. A influência do polimorfismo do gene IL28B em associação com a vitamina D também foi avaliada. Os estudos levaram à conclusão que a vitamina D e o polimorfismo do gene IL28B são indicadores que agem de forma independente para o alcance da RVS. Quando avaliados, a suplementação de vitamina D levou à maior taxa de RVS em pacientes que receberam suplementação, comparados com os pacientes que só utilizaram a terapia convencional, demonstrando que a vitamina D pode ter um impacto positivo na eficácia do tratamento tanto em pacientes com genótipo de difícil resposta como nos genótipos de melhor prognóstico. Entretanto, os mecanismos de ação pelos quais a vitamina D e seus metabólitos aumentam a eficácia da terapia anti HCV e a RVS ainda não estão completamente claros. A alta prevalência de deficiência de vitamina D associada à baixa resposta ao tratamento e à alta RVS em pacientes que apresentam níveis séricos mais elevados de vitamina D mostram que a vitamina D é um indicador independente fortemente associado à RVS.

  12. Acute inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alfa-2a in a patient with chronic hepatitis C virus infection: a case report

    Directory of Open Access Journals (Sweden)

    Lahbabi Mounia

    2012-09-01

    Full Text Available Abstract Introduction The combination of polyethylene glycol (PEGylated interferon (pegylated interferon and ribavirin has been shown to be an effective treatment for chronic hepatitis C virus. In general, common side effects related to this combination therapy are mild and are well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to PEG-interferon α2a (pegylated interferon alfa-2a is extremely rare. In the literature, only one case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a has been published previously. Case presentation To the best of our knowledge we present only the second case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a, occurring in a 63-year-old Caucasian man. He developed tingling, numbness, and weakness of his upper and lower extremities with acute neurological deficits after five weeks of a combination therapy with PEG-interferon α2a and ribavirin for chronic hepatitis C virus infection. His clinical course, neurological findings, and his electromyogram results were all consistent with acute inflammatory demyelinating polyneuropathy. Our patient recovered completely after interferon was stopped and symptomatic treatment and a further electromyogram showed a disappearance of neuropathy. Four weeks later, PEG-interferon α2a was reintroduced with a gradually increasing dose without any reappearance of neurological symptoms allowing hepatitis C seroconversion. Conclusions Recognition of this rare yet possible presentation is important for early and accurate diagnosis and treatment. This case report also suggests that the reintroduction of PEGylated interferon in patients who had presented with acute inflammatory demyelinating polyneuropathy related to interferon α may be safe, but this must be confirmed by further studies.

  13. Efficacy and safety of peg-IFN alfa-2a with ribavirin for the treatment of HCV/HIV coinfected patients who failed previous IFN based therapy.

    Science.gov (United States)

    Rodríguez-Torres, Maribel; Rodríguez-Orengo, José F; Ríos-Bedoya, Carlos F; Fernández-Carbia, Alberto; González-Lassalle, Elsa; Salgado-Mercado, Rosa; Marxuach-Cuétara, Acisclo M

    2007-01-01

    Interferon (IFN) regimens for HCV treatment are less effective in HCV/HIV-coinfected patients. There are no effective treatments for patients who fail IFN therapies. We examined the safety and efficacy of peginterferon alfa-2a (peg-IFNalpha-2a) plus ribavirin (RBV) in 41HCV/HIV-coinfected patients non-responsive to prior IFN treatment. Patients received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks (n=41). At week 24, patients with non-detectable HCV RNA or > or =2-log decrease from baseline, received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks further. Patients not responding to treatment at week 24 were discontinued. Intent to treat (ITT) sustained viral response (SVR) was 21.9%. Patients who received at least 24 weeks of peg-IFNalpha-2a plus RBV treatment (n=35), SVR rates were 25.7%. SVR was associated with significant improvements in liver histology grade (p=0.02), stage (p=0.02), and fibrosis progression rate (FPR) (p=0.03). Patients that failed to achieve SVR had statistically significant decreases in grade (p=0.09) and FPR (p=0.01). peg-IFNalpha-2a plus RBV is effective and safe to achieve SVR in HCV/HIV coinfected patients non-responsive to prior IFN treatment. Patients that achieve SVR have significant improvements in liver histology parameters. In patients that do not achieve SVR there are histological benefits beyond virological response that suggest that peg-IFNalpha-2a+RBV therapy may decrease risk of progression to end stage liver disease.

  14. Tumor necrosis factor-alpha and the cytokine network in psoriasis Fator de necrose tumoral-alfa e a rede de citocinas na psoriase

    Directory of Open Access Journals (Sweden)

    Arles Martins Brotas

    2012-10-01

    Full Text Available New molecular methods of research have greatly expanded the knowledge about the role of cytokines in several diseases, including psoriasis. The work orchestrated by these peptides is essential for the communication between resident inflammatory cells (keratinocytes and endothelial cells and infiltrating cells (neutrophils, lymphocytes, Langerhans cells. This is a complex network due to redundancy, synergism and, sometimes, the antagonism of cytokines, which prevents full understanding of the pathogenesis of the disease. Currently, it seems premature to try to establish a main actor, but TNFalpha participates in all stages of psoriatic plaque development, as we shall see.A introdução de novos métodos moleculares de investigação ampliou muito o conhecimento sobre o papel das citocinas em diversas doenças, entre elas a psoríase. O trabalho orquestrado desses polipeptídeos é fundamental na comunicação entre as células inflamatórias residentes (queratinócitos e células endoteliais e infiltrantes (neutrófilos, linfócitos, células de Langerhans. Trata-se de uma rede complexa devido à redundância, ao sinergismo e, por vezes, ao antagonismo das citocinas, o que dificulta a compreensão da fisiopatogenia da doença a partir de um mecanismo linear. No momento atual, parece precoce tentar estabelecer um regente, mas o TNF-alfa se destaca em todos os passos do desenvolvimento da placa psoriásica, como veremos a seguir.

  15. Hospital Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — Hospital Compare has information about the quality of care at over 4,000 Medicare-certified hospitals across the country. You can use Hospital Compare to find...

  16. Determinación de isótopos de uranio y torio en muestras ambientales por espectrometría alfa; solución de problemas metodológicos y aplicaciones medioambientales

    OpenAIRE

    Lehritani Hamine, Mouloud

    2012-01-01

    Concluimos esta tesis doctoral procediendo a realizar un resumen general de los aspectos más relevantes de todo el trabajo llevado a cabo, así como las conclusiones más importantes obtenidas. 1. Hemos realizado en primer lugar una descripción detallada del sistema de espectrometría alfa con detectores PIPS, que se ha mostrado que es la técnica radiométrica más apropiada para la determinación de las concentraciones de actividad de los isótopos de uranio y de los isótopos de torio y el 210Po en...

  17. Diseño, construcción e implementación de un prototipo de estimulación audiovisual para el análisis de las ondas alfa

    OpenAIRE

    Méndez Alvarado, Daniela Alexandra; Lema Condo, Efrén Leandro

    2013-01-01

    El equipo de estimulación audiovisual que contiene luz estroboscópica y sonido binaural conduce a las personas a un estado alfa que representa reposo físico y mental permitiendo a así un mayor grado de concentración y se encuentra comprendida en un rango de frecuencia de 8 a 12 Hz. The visual stimulation equipment containing strobe light and binaural sound drives people to an alpha state representing physical and mental rest and allowing greater concentration and is included in a frequency...

  18. Experiencia con las reacciones adversas asociadas con el interferón alfa 2b recombinante en hematología Experience with the adverse reactions associated with recombinant alpha 2b interferon in hematology

    Directory of Open Access Journals (Sweden)

    Idalmis Brito Pascual

    2005-08-01

    Full Text Available El interferón alfa 2b es una citoquina con actividad antiviral, antiproliferativa e inmunomoduladora que ha demostrado ser eficaz para el tratamiento de enfermedades virales y neoplásicas. El presente trabajo se realizó con el propósito de describir la frecuencia de las reacciones adversas asociada con la administración de Heberon alfa R (interferón alfa 2b recombinante en enfermedades hematológicas. Se analizaron las características de base de los pacientes, así como la frecuencia, intensidad y relación de causalidad de los eventos reportados. Los eventos adversos más frecuentes fueron las manifestaciones del síndrome gripal que incluyó fiebre, escalofrío, astenia, mialgias, anorexia y cefalea. Estas manifestaciones son transitorias y responden al tratamiento con antiinflamatorios no esteroideos. La mayoría de los eventos fueron de intensidad leve a moderada y no requirieron la suspensión del tratamiento. En conclusión, el Heberon alfa R es un fármaco relativamente seguro para el tratamiento de trastornos hematológicosAlpha 2b interferon is a cytokine with antiviral, antiproliferative and immunomodulator activity that has proved to be efficient for the treatment of viral and neoplastic diseases, This paper is aimed at describing the frequency of adverse reactions associated with the administration of alpha R Heberon (recombinant alpha 2b interferon in hematological diseases. The basic characteristics of the patients, as well as the frequency, intensity and causality relation of the reported events were analyzed. The most common adverse effects were the manifestations of the gripal syndrome that included fever, chills, astenia, myalgia, anorexia and headache. These manifestations are transitory and respond to the treatment with non-steroideal antiinflammatory drugs. Most of the events were from mild to moderate intensity and did not require the suspension of the treatment. To conclude, alpha R Heberon is a relatively safe drug

  19. Avaliação da eficácia clínica do uso de laser de baixa potência, vitamina E (alfa-tocoferol) e protocolo farmacológico no manejo da mucosite oral radioinduzida

    OpenAIRE

    Kizzy Santos Fernandes

    2012-01-01

    A mucosite oral é o efeito colateral agudo mais importante decorrente do tratamento radioterápico em região de cabeça e pescoço. O objetivo do presente estudo foi avaliar a eficácia clínica do laser de baixa potência, da Vitamina E (alfa-tocoferol) e do protocolo farmacológico (nistatina, tetraciclina, hidrocortisona e vitamina E) como formas de tratamento para a mucosite oral em graus 2 e 3. Este estudo consiste em um ensaio clínico randomizado realizado com 41 pacientes tratados no período ...

  20. Erythropoiesis stimulating agents and techniques: a challenge for doping analysts.

    Science.gov (United States)

    Jelkmann, W

    2009-01-01

    Recombinant human erythropoietin (rHuEPO) engineered in Chinese hamster ovary (CHO) cell cultures (Epoetin alfa and Epoetin beta) and its hyperglycosylated analogue Darbepoetin alfa are known to be misused by athletes. The drugs can be detected by isoelectric focusing (IEF) and immunoblotting of urine samples, because "EPO" is in reality a mixture of isoforms and the N-glycans of the recombinant products differ from those of the endogenous hormone. However, there is a plethora of novel erythropoiesis stimulating agents (ESAs). Since the originator Epoetins alfa and beta are no longer protected by patent in the European Union, rHuEPO biosimilars have entered the market. In addition, several companies in Asia, Africa and Latin America produce copied rHuEPOs for clinical purposes. While the amino acid sequence of all Epoetins is identical, the structure of their glycans differs depending on the mode of production. Some products contain more acidic and others more basic EPO isoforms. Epoetin delta is special, as it was engineered by homologous recombination in human fibrosarcoma cells (HT-1080), thus lacking N-glycolylneuraminic acid like native human EPO. ESAs under development include EPO fusion proteins, synthetic erythropoiesis stimulating protein (SEP) and peptidic (Hematide(), CNTO 528) as well as non-peptidic EPO mimetics. Furthermore, preclinical respectively clinical trials have been performed with small orally active drugs that stimulate endogenous EPO production by activating the EPO promoter ("GATA-inhibitors": diazepane derivatives) or enhancer ("HIF-stabilizers": 2-oxoglutarate analogues). The prohibited direct EPO gene transfer may become a problem in sports only in the future.

  1. Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept Talidomida, peginterferón alfa-2b y ribavirina en el tratamiento de pacientes no respondedores con hepatitis crónica C genotipo 1: estudio piloto

    Directory of Open Access Journals (Sweden)

    Benjamín Pardo-Yules

    2011-12-01

    Full Text Available Background: fewer than half of patients infected with hepatitis C virus (HCV achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV therapy. Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC patients, who had failed to respond to the (Peg-IFN/RBV, with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study. Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.Antecedentes: menos de la mitad de los pacientes con hepatitis C logra eliminar el virus de manera sostenida después de la terapia con peginterferón alfa y ribavirina (Peg-IFN/RBV. Objetivos: la talidomida posee propiedades antiinflamatorias e inmunomoduladoras a través de la inhibición del TNF-α y al efecto estimulador sobre las células T CD8+. Métodos: se inició un estudio prospectivo y abierto de re-tratamiento de pacientes con hepatitis crónica C genotipo 1, no respondedores al tratamiento con Peg-IFN/RBV, mediante triple terapia añadiendo a los mismos antivirales 200 mg/día de talidomida. Resultados: ninguno de los once pacientes que fueron incluidos en

  2. Análise de crédito por meio de modelos de previsão de insolvência: um estudo de caso na Empresa Cerâmica Alfa S.A. = Credit analysis through models for the forcasting of insolvency of the company Cerâmica Alfa S.A.

    Directory of Open Access Journals (Sweden)

    Paula Bez Birolo

    2011-07-01

    Full Text Available O objetivo deste artigo é avaliar os benefícios da utilização de modelos de previsão de insolvência para a análise de crédito em uma empresa do setor cerâmico. É descritivo, de caráter quantitativo, realizado por meio de um estudo de caso na empresa Cerâmica ALFA S.A. Para execução da pesquisa selecionou-se intencionalmente seis clientes, de acordo com os seguintes dados: a informações creditícias disponíveis no sistema gerencial de crédito/cobrança e b demonstrações contábeis divulgadas nos sites dos respectivos clientes. Os resultados apontam que os modelos de Elizabetsky e Kanitz demonstram fragilidades em identificar a situação financeira dos clientes. O modelo de previsão de insolvência desenvolvido por Matias apresenta melhor desempenho, em relação aos anteriores, para a análise de crédito. Conclui-se que é vantajoso utilizar o modelo de Matias para a análise de crédito, pois ele é adequado às necessidades da empresa e serve como um instrumento para auxílio na concessão de crédito e tomada de decisão. The objective of this article is to assess the benefits of using insolvency forecasting models for the credit analysis of a company in the ceramic sector. This study is descriptive of a quantitative nature through a case study in Cerâmica ALFA S.A. Six clients with the following data were intentionally selected for the execution of the research: a credit information available in the credit/collection management system and b account statements divulged in the sites of the respective clients. The results show that the Elizabetsky and Kanitz models demonstrated fragility in identifying the financial situation of the clients. The insolvency forecasting model developed by Matias showed better performance in relation to the previous ones for credit analysis. It was concludrd that it is advantageous to use the Matias model for credit analysis, because it is suitable for the company’s requirements and serves

  3. Comparison of the effectiveness of equal doses of short and long-acting erythrocyte stimulating agents for managing anemia in chronic kidney disease adult patients

    Directory of Open Access Journals (Sweden)

    Abdulmalik Alkatheri

    2016-12-01

    Full Text Available Anemia is the most common side effect in patients with chronic kidney disease (CKD mainly due to lower levels of erythropoietin (EPO hormone. The aim of the present study is to compare the efficacy of equivalent doses of erythropoiesis stimulating agents (ESAs: short acting (Eprex®; Epoetin alfa and long acting (Darbepoetin alfa: DA in the treatment of anemia of CKD adult patients treated from September 2013 to January 2015. A total of fifty five patients were included; 22 patients were treated with Eprex®® (Epoetin alfa and 33 patients received DA. Different blood indices were assessed in the initial 8 weeks. The equality of the doses was based on the conversion formula (1 µg of DA = 300 IU Eprex®. Treatment with lower dose of DA (0.64±0.07 µg/kg QW induced a significant increase in hemoglobin (Hb from week 4 through week 8, while red blood corpuscles (RBCs and hematocrit (Hct were significantly elevated in week 8. A significant increase in Hb and Hct were observed starting from week 2 through week 8 parallel with a significant rise in RBCs count, starting from week 3 through week 8 after treatment with DA (0.8±0.06 µg/kg QW, while a significant increment of Hb and Hct were noticed after treatment with DA (1.215±0.11 µg/kg QW from week 3 to week 7. Administration of higher dose DA (1.37±0.22 µg/kg QW led to a significant rise of RBCs in week 3, 6 and 7 while Hb and Hct in week 6 and 7. Treatment with equal doses of Eprex® (170.85±16.4 IU/kg and 238±25 .9 IU/kg induced only a mild increase in RBCs in week 7 and 6 respectively, while higher dose of Eprex® (413±40.8 IU/kg elevated RBCs significantly at week 8 and Hct in week 6 and 8. Administration of DA QW is more effective than Eprex® QTIW in terms of target anemia parameters: RBCs, Hb and Hct during the first 8 weeks of administration.

  4. Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas.

    Science.gov (United States)

    Jakacki, Regina I; Dombi, Eva; Steinberg, Seth M; Goldman, Stewart; Kieran, Mark W; Ullrich, Nicole J; Pollack, Ian F; Goodwin, Anne; Manley, Peter E; Fangusaro, Jason; Allen, Rudy; Widemann, Brigitte C

    2017-02-01

    There is no proven medical therapy for plexiform neurofibromas (PNs). We undertook a phase II trial of pegylated interferon (PI) to evaluate response and time to progression (TTP). PI was administered as a subcutaneous injection to patients with neurofibromatosis type 1‒related PN, stratified by the presence of symptoms (asymptomatic: stratum 1, symptomatic: stratum 2) or documented imaging progression (stratum 3). Patients in strata 1 and 2 received PI for up to one year if stable, 2 years for those with clinical (stratum 2) or imaging response (≥20% decrease in volume). Patients on stratum 3 continued PI until progression. PI was considered active in stratum 3 if TTP doubled compared with the placebo arm of a previous randomized trial using tipifarnib. Enrolled were 82 evaluable patients (median age 10 y; range 1.6 to 21.4). Fatigue and/or worsening of behavioral issues were the most common toxicities requiring dose modification. Across all strata, imaging responses were seen in 4 patients (5%). Three of 26 symptomatic patients on stratum 2 met the criteria for clinical response without corresponding imaging changes. In stratum 3, median TTP was 29.4 months versus 11.8 for the placebo arm of the previous trial (P=.031). The slope of tumor growth on PI slowed significantly compared with the slope before starting PI (P=.044). In patients with active PN, PI results in more than doubling of the TTP compared with placebo. Imaging changes in symptomatic patients were not associated with changes in clinical status.

  5. Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats.

    Science.gov (United States)

    Abdel-Hamid, Nabil Mohie; Wahid, Ahmed; Nazmy, Maiiada Hassan; Eisa, Marwa Abdel-Moniem

    2016-01-01

    Complementary and alternative medicine has been highly appreciated as a supportive regimen for classical treatment strategies. Here we offer a nutrition-based adjuvant therapy for liver fibrosis, a major risk factor for cirrhosis and hepatocellular carcinoma. To evaluate the possible hepatoprotective effects of Jerusalem artichoke tubers (JAT) in combination with interferon and ribavirin. Twelve groups of rats were administered JAT, interferon and ribavirin either separately or in combination from day one of CCL4 administration until the end of the study. Animals were killed after 8 weeks of CCL4- induced hepatotoxicity. Hepatocytes from rats treated with triple combination of interferon, ribavirin, and JAT showed more less normal architecture compared to CCL4- treated rats. We also detected significantly higher hepatic protein expression levels of p53, BAX and transforming growth factor-β (TGF-β) in the CCl4- intoxicated group compared to normal controls, as evidenced by immunohistochemical staining and western blotting analyses. Addition of JAT as a supportive regimen improved response to ribavirin and interferon and effectively participated in retaining normal histopathological and biochemical criteria and significantly lowered protein expression of p53, BAX, and TGF-β. We suggest that addition of JAT as a supportive regimen to interferon and ribavirin effectively potentiates their anti-fibrotic effects.

  6. Comparative Genomics

    Indian Academy of Sciences (India)

    tory motifs and other non-coding DNA motifs, and genome flux and dynamics. Finally the article describes how the information one can extract from a comparative analysis of genomes depends to a large extent, on the specific aspect of the genomes that is being compared and the phylogenetic distances of the organisms ...

  7. Therapeutic Effects of Rivastigmine and Alfa-Lipoic Acid Combination in the Charles Bonnet Syndrome: Electroencephalography Correlates.

    Science.gov (United States)

    Hanoglu, Lutfu; Yildiz, Sultan; Polat, Burcu; Demirci, Sema; Tavli, Ahmet Mithat; Yilmaz, Nesrin; Yulug, Burak

    2016-01-01

    Charles Bonnet Syndrome (CBS) is a rare clinical condition which is characterized by complex hallucinations in visually impaired patients. The pathophysiology of this disorder remains largely unknown, and there is still no proven treatment for this disease. In our study, we aimed to investigate the neural activity through Electroencephalography (EEG) power and evaluate the effect of rivastigmine in combination with alpha-lipoic acid on hallucination in two CBS patients with diabetic retinopathy. EEG data was recorded with standard routine EEG protocols for both patients in our electrophysiological research laboratory (REMER Clinical Electrophysiology and Neuromodulation Research and Application Laboratory) with Brain Vision Recorder (Brainproduct, Munich, Germany). All spectral analyses were processed by BrainVision Analyzer 2 (Brainproduct, Munich, Germany, 2.0.4 Version) in 128 Hz sample rates and the EEG recording and analysis was performed before the administration of rivastigmine (4.5 mg/daily and five patch daily for the first and second patients, respectively) in combination with alpha-lipoic acid (600 mg/daily) for both patients while they were not hallucinated during the time period recordings. Based on our measurement protocol, we have compared the patients in the study group with the three control subjects who were found to be normal except of visual disturbances secondary to significant diabetic retinopathy. Highest theta power values were found in right occipital and left temporo-parietal regions for first and second CBS patients, respectively. Additionally, power spectra were lower in two cases as compared to their control groups in the alpha band for all electrodes. We have also shown that acid rivastigmine in combination with alpha-lipoic exerted significant anti-hallucinatory efficiency. Our present findings could support the hypothesis that increased activation of specific areas in the source monitoring system plays an important role in the

  8. Avaliação dos níveis séricos de 17-alfa-OH progesterona e androstenediona durante o ciclo estral em marrãs (Sus Scrofa Domestica - Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Gilson Hélio Toniollo

    1998-01-01

    Full Text Available No presente trabalho, foram utilizadas 21 fêmeas suínas, virgens, sexualmente aptas, criadas e mantidas sob condições industriais, para observação dos perfis hormonais séricos de 17-alfa-OH progesterona e androstenediona, durante o ciclo estral. As colheitas de sangue foram efetuadas sempre no mesmo intervalo, entre 8 e 10 horas. Cada animal foi submetido a 14 punções venosas, distribuídas nos dias zero, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 21, 22 e 23 do ciclo estral. Considerou-se o dia zero como o primeiro dia da fase estral, e o 23º dia como o primeiro do estro subseqüente. Os ensaios para dosagens hormonais foram executados utilizando-se a técnica de radioimunoensaio (RIE em fase sólida e para isso foi empregado conjunto de reagentes comerciais (Coat-A-Count®. Para o hormônio 17-alfa-OH progesterona, foram encontrados valores médios que variaram entre 0,18 e 2,7 ng/ml e para o hormônio androstenediona esses valores oscilaram entre 0,08 e 0,24 ng/ml.

  9. Determination of the total cross section in proton-proton collisions at the LHC at √(s) = 8 from elastic scattering using the ALFA sub-detector of ATLAS

    Energy Technology Data Exchange (ETDEWEB)

    Heinz, Christian; Stenzel, Hasko; Dueren, Michael [2. Physikalisches Institut, Universitaet Giessen (Germany)

    2016-07-01

    The ALFA (Absolute Luminosity for ATLAS) Roman Pot detector system is part of the forward instrumentation of ATLAS located about 240 m away from the interaction point in the LHC tunnel in both directions. ALFA consists of a scintillating fibre tracker housed in vertical Roman Pots which enables the measurement of elastic proton-proton scattering at small scattering angles. In 2012 data were recorded at a centre-of-mass energy of √(s) = 8 TeV during a fill with special beam optics of the LHC with β* = 90 m and parallel-to-point focusing. The four-momentum transfer t is measured for elastically scattered protons and used to extract the differential elastic cross section. In this talk a preliminary determination of the total cross section and of the slope of the elastic cross section at small vertical stroke t vertical stroke obtained from a fit to the differential cross section using the optical theorem is reported. In addition a second run at √(s) = 8 TeV with a special beam optics of β* = 1 km, providing access to the Coulomb-nuclear interference region, is being analysed. Preliminary analysis results from this run are presented as well.

  10. Uso de los interferones en Dermatología: experiencia con el alfa-interferon en la micosis fungoide Use of interferons in Dermatology: experience with alpha-interferon in mycosis fungoides

    Directory of Open Access Journals (Sweden)

    Edelisa Moredo Romo

    2004-08-01

    Full Text Available Se revisó la literatura y se constató la amplia utilización de los interferones (INFs en Dermatología. Se presenta un estudio retrospectivo de 7 pacientes con diagnóstico de micosis fungoides tratados con alfa-interferón recombinante (alfa-INFR y se concluye su efectividad en el tratamiento de esta enfermedad y su disponibilidad en el tratamiento en Cuba. Los efectos adversos observados a las dosis utilizadas fueron fundamentalmente fiebre, escalofríos y malestar general que cedieron con tratamiento analgésico. No se encontraron efectos adversos hematológicos.Literature was reviewed and the wide use of interferons (INFs in Dermatology was proved. A retrospective study of 7 patients that were diagnosed mycosis fungoides and treated with recombinant alpha-interferon (alpha-INFR was presented It effectiveness in the treatment of this disease and its availability in Cuba were demonstrated. The adverse effects observed in the used doses were mainly fever, chills and malaise that improved with analgesic treatment. No hematological adverse effects were observed.

  11. Purificação e caracterização de alfa-galactosidases de sementes de Platymiscium pubescens Micheli Purification and characterization of alpha-galactosidases from Platymiscium pubescens Micheli seeds

    Directory of Open Access Journals (Sweden)

    Giordani de Oliveira

    2005-08-01

    Full Text Available Este trabalho objetivou foi determinar a composição bioquímica de sementes de espécies florestais e caracterizar a enzima alfa-galactosidase de sementes germinadas de Platymiscium pubescens. Os maiores teores de lipídios foram determinados em sementes de Chorisia speciosa, Caesalpinia peltophoroides, Tabebuia serratifolia e Tabebuia velanedae, enquanto sementes de Enterolobium contortisiliquum, Schizolobium parahyba e Cassia grandis apresentaram os maiores teores protéicos. A alfa-galactosidase catalisa a hidrólise dos oligossacarídeos de rafinose, em sementes de leguminosas, durante a germinação. A maior atividade da alfa-galactosidase foi detectada em sementes de Platymiscium pubescens após 72 h de embebição. Duas formas de alfa-galactosidases, C1 e C2, foram purificadas de sementes germinadas de P. pubescens, usando-se fracionamento com sulfato de amônio e cromatografias de filtração em gel e de afinidade. Essas enzimas apresentaram atividade máxima em pH 5,5 e a 50-55 ºC. Os valores de Km ap das formas C1 e C2, para o substrato ro-nitrofenil-alfa-D-galactopiranosídeo, foram de 0,54 mM e 0,78 mM, e para a rafinose, de 4,64 mM e 5,09 mM, respectivamente. Essas enzimas exibiram estabilidade térmica moderada, mantendo 70% da atividade original após 3 h de incubação a 45 ºC. A atividade enzimática da C1 e C2 foi totalmente perdida na presença de CuSO4 e dodecil sulfato de sódio (SDS. Tais enzimas também hidrolisaram melibiose, rafinose e estaquiose, indicando potencial para aplicações biotecnológicas.The objective of this work was to determine seed biochemical composition of forest species and to characterize alpha-galactosidase enzyme of germinated seeds of Platymiscium pubescens. The highest lipid levels were found in seeds of Chorisia speciosa, Caesalpinia peltophoroides, Tabebuia serratifolia and Tabebuia velanedae, whereas seeds of Enterolobium contortisiliquum, Schizolobium parahyba and Cassia grandis showed

  12. Atividade inflamatória em mucosa de reservatório ileal na polipose adenomatosa familiar e retocolite ulcerativa inespecífica: avaliação da expressão de TNF-alfa e IL-1beta, e da ativação NF- kapaB Inflammatory activity in pelvic ileal pouches for familial adenomatous polyposis and ulcerative colitis: expression of TNF-alpha, IL-1beta and the activation of NF- kappaB

    Directory of Open Access Journals (Sweden)

    Raquel Franco Leal

    2006-12-01

    Full Text Available A ileíte do reservatório pós retocolectomia total constitui uma das complicações mais comuns nos doentes com RCUI, apresentando pequena freqüência nos doentes com PAF. OBJETIVO: Avaliar a atividade inflamatória em mucosa de reservatórios ileais endoscopicamente normais, através da expressão de TNF-alfa, NF-kapaB e IL-1beta. CASUÍSTICA E MÉTODOS: Selecionaram-se 20 doentes submetidos à retocolectomia total com reservatório ileal em "J" pelo Grupo de Coloproctologia da UNICAMP, sendo 10 doentes com RCUI e 10 com PAF. O grupo controle foi constituído por íleo terminal de intestino normal. Realizadas biópsias da mucosa do reservatório ileal e do íleo terminal normal, e congeladas em nitrogênio líquido. A expressão de TNF-alfa e IL-1beta foi analisada por extrato total e de NF-kB por meio de imunoprecipitado. A separação protéica foi feita por eletroforese em gel de poliacrilamida. RESULTADOS: Expressão de TNF-alfa e IL-1beta apresentaram níveis maiores nos doentes com RCUI, quando comparados àqueles com PAF (p0.1 e IL-1beta (p > 0.05 sem diferença estatística em relação aos demais grupos. CONCLUSÃO: Os doentes com RCUI apresentaram maiores níveis de expressão das citocinas estudadas, mesmo sem evidência clínica e endoscópica de ileíte do reservatório, podendo justificar maior suscetibilidade dos doentes com RCUI a esta complicação.Pouchitis after total retocolectomy is one of the most common complication of patients with ulcerative colitis (UC, while its frequency is quite rare in familial adenomatous polyposis (FAP. PURPOSE: To evaluate the inflammatory activity in endoscopicaly normal mucosa of the ileal pouch, by determining the expression of TNF-alpha and IL-1beta, and the activation of NF-kappaB. METHODS AND PATIENTS: Twenty patients with "J" pouch after total retocolectomy were studied, being 10 patients with UC and 10 with FAP. The control group was constituted by biopsies from terminal ileum take

  13. Comparative thanatology.

    Science.gov (United States)

    Anderson, James R

    2016-07-11

    A quick guide on comparative thanatology, the study of death and dying, particular how individuals respond to a conspecific's death, across animal phylogeny. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Physician Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — Physician Compare, which meets Affordable Care Act of 2010 requirements, helps you search for and select physicians and other healthcare professionals enrolled in...

  15. The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil

    Directory of Open Access Journals (Sweden)

    Artico Simara

    2012-12-01

    Full Text Available Abstract Background More than 50% of patients infected with chronic hepatitis C virus (HCV do not respond to treatment with conventional interferon (IFN combined with ribavirin (RBV. The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR. Methods From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR. Virological Response (VR within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. Results The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031. As predictive factors that contribute to improve SVR, were identified the age (p = 0.005, to be relapsers to previous treatment (p = 0.023 and present liver biopsy examination Metavir F0-F2 (p = 0.004. In assessing the safety profile, 51 patients (23.6% discontinued treatment prematurely. Conclusions This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored.

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

    Science.gov (United States)

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

    2017-05-20

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

  17. Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study

    Science.gov (United States)

    Galle, Jan-Christoph; Addison, Janet; Suranyi, Michael G.; Claes, Kathleen; Di Giulio, Salvatore; Guerin, Alain; Herlitz, Hans; Kiss, István; Farouk, Mourad; Manamley, Nick; Wirnsberger, Gerhard; Winearls, Christopher

    2016-01-01

    Background Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Methods Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Results Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Conclusions Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients. PMID

  18. Continuous quality improvement in daily clinical practice: a proof of concept study.

    Directory of Open Access Journals (Sweden)

    Jonathan A Lorch

    Full Text Available Continuous Quality Improvement (CQI is an iterative process of: planning to improve a product or process, plan implementation, analyzing and comparing results against those expected, and corrective action on differences between actual and expected results. It is little used in clinical medicine. Anemia, a complex problem in End Stage Renal Disease patients, served to test the ability of an unique electronic medical record (EMR optimized for daily care to empower CQI in practice. We used data collected during daily care, stored in the EMR, and organized to display temporal relationships between clinical, laboratory, and therapeutic events. Our aims were optimal hemoglobin with minimum epoetin, and maintaining stable hemoglobin and epoetin. The study was done on 250 patients treated by maintenance hemodialysis (HD, receiving epoetin prior to February 1, 2010 and followed to July 31, 2011. Repleting iron, ensuring iron sufficiency, slow epoetin reduction, and decision support tools enabling data display over long periods in patient-centered reports were key elements. Epoetin dose, adjusted 6-8 weekly, was based on current clinical conditions and past responses. Hemoglobin increased by months 1-2; epoetin decreased from month 4. By months 16-18, epoetin had decreased 42% to 9,720 units/week while hemoglobin increased 8% to 123.6 g/L. Hemoglobin and epoetin were stable from month 7 onward. New epoetin orders decreased 83%. Transferrin saturation increased after the study start. Individual patient hemoglobin variation decreased by 23%, range by 27%. Mortality, 11.78 per 100 patient years, was 42% less than United States dialysis patient mortality. Allowable epoetin charges decreased by $15.33 per treatment and were $22.88 less than current Medicare allowance. The study validates the hypothesis that an EMR optimized for daily patient care can empower CQI in clinical medicine and serve to monitor medical care quality and cost.

  19. Expressão local do fator de necrose tumoral alfa na ruptura prematura de membranas Local expression of tumor necrosis factor-alpha on premature rupture of membranes

    Directory of Open Access Journals (Sweden)

    Valquíria Roveran

    2009-05-01

    Full Text Available OBJETIVO: comparar a expressão do fator de necrose tumoral alfa (TNF-α em membranas ovulares com ruptura prematura (RPM e com ruptura oportuna das mesmas; verificar a associação entre a expressão do TNF-α em membranas ovulares e o grau de corioamnionite das mesmas e correlacionar a expressão do TNF-α e o tempo de ruptura das membranas. MÉTODOS: foram analisadas as membranas ovulares de 31 parturientes com RPM, com idade gestacional acima de 34 semanas, e de 14 parturientes com ruptura oportuna das membranas, com idade gestacional igual ou maior de 37 semanas. A detecção da corioamnionite foi feita por meio de estudo histopatológico. A avaliação da expressão do TNF-α foi feita por meio de técnica imunoistoquímica, na qual foi empregado o método streptavidina-biotina-peroxidase (LSAB. RESULTADOS: o tempo médio de ruptura foi de 16,6 horas. A frequência da expressão de TNF-α, nos Grupos Controle e Estudo, não mostrou diferença significante (χ2=6,6; p=0,08. No Grupo Estudo, houve correlação entre o grau de corioamnionite e a intensidade da expressão de TNF-α (coeficiente de Spearman (Rs=0,4; p=0,02. CONCLUSÕES: não houve diferença significante entre as expressões do TNF-α em membranas ovulares com ruptura prematura e com ruptura oportuna das mesmas; no Grupo Estudo, constatou-se associação significante entre a expressão do TNF-α e o grau de corioamnionite e não houve associação entre o tempo de ruptura e a intensidade da expressão do TNF-α.PURPOSE: to compare the expression of tumor necrosis factor-alpha (TNF-α in ovular membranes with premature rupture (MPR and with opportune rupture; to verify the association between the expression of the TNF-α in ovular membranes and the degree of chorioamnionitis, correlating the expression of the TNF-α and the membranes' time of rupture. METHODS: ovular membranes from 31 parturients with MPR, with gestational ages over 34 weeks, and from parturients with opportune

  20. Endotoxemia por lipopolissacarídeo de Escherichia coli, em eqüinos: efeitos de antiinflamatórios nas concentrações sérica e peritoneal do fator de necrose tumoral alfa (TNF-alfa Escherichia coli lipopolisacharide (LPS induced endotoxemia in horses: effects of anti-inflammatory drugs on seric and peritoneal tumor necrosis factor alpha (TNF-alpha concentrations

    Directory of Open Access Journals (Sweden)

    R.C. Campebell

    2007-08-01

    Full Text Available Avaliou-se a inibição da produção do fator de necrose tumoral alfa (TNF-alfa devido ao pré-tratamento com antiinflamatório esteroidal (dexametasona e não esteroidal (diclofenaco sódico em eqüinos com endotoxemia induzida experimentalmente. Foram utilizados 15 cavalos machos não castrados, distribuídos em três grupos de cinco animais: controle (C, diclofenaco sódico (DS e dexametasona (DM. A endotoxemia subletal foi induzida pela infusão intravenosa (IV de 0,1mg/kg/pv de lipopolissacarídeo (LPS de Escherichia coli 055:B5, administrado em 250ml de solução estéril de cloreto de sódio a 0,9%, durante 15min. Os cavalos do grupo-controle foram tratados com solução de cloreto de sódio a 9% IV. Nos animais do grupo DS, administraram-se, por via oral, 2,2mg/kg de diclofenaco sódico e, nos do grupo DM, 1,1mg/kg de dexametasona IV, respectivamente, 60 e 30min antes da infusão da endotoxina. Mensurou-se, por meio de ensaio de toxicidade com células da linhagem L929, a concentração de TNF-alfa no soro e no líquido peritoneal às 0, 1¼, 3 e 6 horas após injeção do LPS. No grupo-controle, observou-se aumento significativo de TNF-alfa sérico, em relação ao valor basal e aos grupos DS e DM, 1,15 horas após a indução da endotoxemia. No líquido peritoneal, as concentrações observadas estavam abaixo daquelas da curva padrão de TNF-alfa, não havendo diferença entre os grupos (P>0,05.The inhibition of tumor necrosis factor alpha (TNF-alpha production due to pre-treatment with steroidal (dexamethazone and non-steroidal (sodium diclofenac anti-inflammatories was studied in horses under experimentally induced endotoxemy. Fifteen stallions were allotted into three groups of five animals each: control (C, sodium diclofenac (SD and dexamethazone (DM. Sublethal endotoxemy was induced with 0.1mg/kg/bw Escherichia coli 055:B5 lipopolysaccharide (LPS, IV, administrated in 250ml of 0.9% sterile sodium chloride, during 15 minutes

  1. Tumor necrosis factor-alfa and interleukin-4 in cerbrospinal fluid and plasma in different clinical forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Obradović Dragana

    2012-01-01

    relapse and remission (p < 0.001. The only significant correlation between cytokine level with either EDSS, or albumin ratio, or IgG index, was found between CSF TNF-alpha levels and albumin ratio in the patients with relapse (R square = 0.431, p < 0.001. Conclusion. According to the obtained data MS relapse was characterized by high concentrations of TNF-alpha in CSF and plasma and low concentrations of IL-4 in CSF. Remission was characterized by high concentrations of IL-4 and low concentrations of TNF-alpha both in CSF and plasma. SPMS was characterized with lower concentrations of TNF-alpha and IL-4 compared to relapse, both in CSF and plasma.

  2. Comparative Advantage

    DEFF Research Database (Denmark)

    Zhang, Jie; Jensen, Camilla

    2007-01-01

    that are typically explained from the supply-side variables, the comparative advantage of the exporting countries. A simple model is proposed and tested. The results render strong support for the relevance of supply-side factors such as natural endowments, technology, and infrastructure in explaining international...

  3. Efeito da suplementação com vitamina E sobre a concentração de alfa-tocoferol no colostro humano Effect of vitamin E supplementation on alpha-tocopherol levels in human colostrum

    Directory of Open Access Journals (Sweden)

    Roberto Dimenstein

    2011-06-01

    Full Text Available OBJETIVO: Avaliar a concentração de alfa-tocoferol no colostro humano em condições de suplementação com cápsulas de vitamina A acrescidas de vitamina E sintética. MÉTODOS: Foram recrutadas para o estudo 30 parturientes saudáveis atendidas em uma maternidade pública. Após jejum noturno, foram coletadas amostras de sangue e de colostro (2 mL das parturientes. Após a primeira coleta, as mesmas receberam suplemento na forma de uma cápsula de palmitato de retinila (200000 UI ou 60 mg acrescido de vitamina E sintética (49,4 mg de dl-alfa-tocoferol. Após 24 horas da suplementação, foi realizada nova coleta de 2 mL de colostro, também em jejum. RESULTADOS: A concentração sérica de alfa-tocoferol foi de 1 042,9 ± 319,0 μg/dL. Os teores de alfa-tocoferol no colostro antes da suplementação foram de 1155,4 ± 811,0 μg/dL, vs. 1396,3 ± 862,2 μg/dL 24 horas depois da suplementação (P > 0,05. Foi encontrada correlação entre o alfa-tocoferol do colostro na condição de jejum antes da suplementação e 24 horas após a suplementação (P = 0,001; r = 0,58, mas não entre soro e o colostro em nenhuma das condições acima citadas. CONCLUSÕES: Não houve aumento na concentração de alfa-tocoferol do colostro 24 horas após a suplementação. Isso indica que não é vantajoso suplementar a mãe com vitamina E sintética. Entretanto, os resultados também sugerem que, se o estado nutricional prévio à suplementação estiver adequado, mais tocoferol será encontrado no colostro após a suplementação. Novos estudos devem ser realizados para investigar o efeito da suplementação com a forma natural do alfa-tocoferol.OBJECTIVE: To assess the levels of alpha-tocopherol in human colostrum following supplementation with capsules containing vitamin A plus synthetic vitamin E. METHODS: Thirty healthy women about to give birth were recruited from a public maternity hospital. After overnight fasting, blood samples as well as colostrum

  4. PERCEPCIÓN DEL IMPACTO DE LA APLICACIÓN DE MECANISMOS DE ASEGURAMIENTO DE LA CALIDAD EN LA EDUCACIÓN SUPERIOR EN COSTA RICA: PROYECTO ALFA-CINDA-UNIVERSIDAD DE COSTA RICA (PERCEIVED IMPACT OF QUALITY ASSURANCE MECHANISMS ON COSTA-RICAN HIGHER EDUCATION: THE ALFA-CINDA-UNIVERSIDAD-DE-COSTA-RICA PROJECT

    Directory of Open Access Journals (Sweden)

    Guido Guido, Elsiana

    2012-05-01

    Full Text Available Resumen: En este artículo se presentan las acciones realizadas dentro del Proyecto Alfa Nro. DCl-ALA 2008/42: Aseguramiento de la calidad: políticas públicas y gestión universitaria financiado con fondos de la Unión Europea y coordinado, de manera general, por el Centro Interuniversitario de Desarrollo, CINDA. Participan 16 universidades latinoamericanas y 7 universidades europeas, y el objetivo general del proyecto es mejorar la gestión de la calidad de la Educación Superior, tanto a nivel de los sistemas nacionales como de las instituciones de Educación Superior, y contribuir con la generación de conocimiento y confianzas mutuas acerca de la calidad de la Educación Superior entre los países latinoamericanos y europeos. Como parte de las actividades desarrolladas se llevaron a cabo estudios en 7 países (5 de Latinoamérica y 2 de Europa para evaluar el impacto de los procesos de aseguramiento de la calidad implementados en las universidades. En Costa Rica, el proyecto ha sido coordinado y ejecutado por la Universidad de Costa Rica desde el año 2009 hasta la fecha. El estudio se realizó en dos universidades estatales y dos privadas, durante el período comprendido entre octubre de 2010 y mayo de 2011, se realizaron 26 entrevistas presenciales y 8 sesiones de grupo a las diferentes poblaciones definidas en el estudio, además, se realizaron un total de 652 encuestas a estudiantes activos y a personas egresadas. Los principales resultados obtenidos en Costa Rica se resumen en este artículo, de acuerdo con los niveles y dimensiones de calidad que fueron definidos en el marco referencial del proyecto.Abstract: The article presents actions carried out in Costa Rica, in the frame of the project Alfa Nro. DCl-ALA 2008/42: Quality assurance: public policies and management in universities. This project is funded by the European Commission and its general coordination is in charge of the Inter-university Center for Development (CINDA, in

  5. Severe sepsis: are PROWESS and PROWESS-SHOCK trials comparable? A clinical and statistical heterogeneity analysis.

    Science.gov (United States)

    Kalil, Andre C; Florescu, Diana F

    2013-07-04

    Despite the same manufacturer, the same drotrecogin alfa activated dose, and the same placebo-controlled design, the negative result from the PROWESS-SHOCK trial contradicted the survival benefit observed in the PROWESS trial. We hypothesize that the different results were due to factors other than the experimental therapy and performed an analysis of the clinical heterogeneity (differences related to the trials' clinical aspects) and the statistical heterogeneity (differences related to the trials' statistical aspects) between these trials. Baseline characteristics and co-interventions were analyzed by chi-square testing and mortality was analyzed by random-effects modeling and I2. Our findings show that clinical variables presented significant heterogeneity, and that up to 90% of the mortality differences between both trials were not due to chance. These results demonstrate that PROWESS and PROWESS-SHOCK are not comparable trials due to the highly significant clinical and statistical heterogeneity. We propose a new and pragmatic solution.

  6. Deconstructing a famous Alfa Romeo

    NARCIS (Netherlands)

    Bootsma, H.; Bootsma, J.; Van Dijk, T.

    2008-01-01

    So is this the famous racing car Mussolini liked to show off, the one driven by Achille Varzi and used by Clemar Bucci to impress Evita Perón? Is just has to be, if materials research conducted by TU Delft is anything to go by. It¿s just that the chassis number doesn¿t match. ¿That Bucci guy has

  7. Recombinant factor VIIa (eptacog alfa): a pharmacoeconomic review of its use in haemophilia in patients with inhibitors to clotting factors VIII or IX.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A; Plosker, Greg L

    2007-01-01

    Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment. Prophylactic treatment with recombinant factor VIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery. Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia. In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters. Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients

  8. Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol.

    Directory of Open Access Journals (Sweden)

    Georg Griesinger

    Full Text Available What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS based on the number of growing follicles ≥ 11 mm and/or estradiol (E2 levels?The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2 levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.In comparison to long gonadotropin-releasing hormone (GnRH agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF, while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years IVF population treated in a GnRH-antagonist protocol.From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses.The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH in a gonadotropin-releasing hormone (GnRH-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG, and a combination of both, were determined.The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at

  9. Single-arm, observational study of the ease of use of a redesigned pen device to deliver recombinant human follicle-stimulating hormone (follitropin alfa for assisted reproductive technology treatment

    Directory of Open Access Journals (Sweden)

    Illingworth PJ

    2014-06-01

    Full Text Available Peter J Illingworth,1 Robert Lahoud,1 Frank Quinn,1 Kendal Chidwick,2 Claire Wilkinson,2 Gavin Sacks1 1IVFAustralia, Greenwich, Sydney, NSW, Australia; 2Scientific Affairs, Merck Serono Australia Pty Ltd, Frenchs Forest, Sydney, NSW, Australia Purpose: Evaluation of patients’ ease of use of the redesigned, disposable, ready-to-use ­follitropin alfa pen during controlled ovarian stimulation for assisted reproductive technology. Methods: This single-center, observational, open-label, single-arm study recruited infertile normo-ovulatory women (aged 18–45 years. Nurses trained patients to self-administer recombinant human follicle-stimulating hormone daily using the follitropin alfa pen (300 IU, 450 IU, and 900 IU. Before treatment, patients completed Questionnaire A. Following self-administered treatment, on stimulation days 5–6 and 7–8 (within a day of receiving recombinant human chorionic gonadotropin, patients completed Questionnaire B. Nurses completed an ease-of-learning/teaching questionnaire. The primary endpoint was proportion of patients rating the pen as “easy/very easy” to use (Questionnaire B on the final visit before recombinant human chorionic gonadotropin. Secondary endpoints included: proportion of patients rating the follitropin alfa pen as easy to learn, use, prepare, deliver, and dispose of (Questionnaires A and B. Proportions (95% confidence intervals [CIs] were provided for primary and secondary endpoints. Adverse events were reported descriptively. Results: Eighty-six patients received recombinant human follicle-stimulating hormone. Of the 72 patients who had completed the overall assessment questions, 66 (91.7%; 95% CI =82.7%–96.9% found the pen “easy” to use. Also, 70/86 (81.4% patients “strongly agreed/agreed” that, overall, it was easy to learn how to use the pen; 72/86 (83.7% “strongly agreed/agreed” that easily understandable, verbal information was provided; and 70/86

  10. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial.

    Science.gov (United States)

    Masarova, Lucia; Patel, Keyur P; Newberry, Kate J; Cortes, Jorge; Borthakur, Gautam; Konopleva, Marina; Estrov, Zeev; Kantarjian, Hagop; Verstovsek, Srdan

    2017-04-01

    Pegylated interferon alfa-2a is an immunomodulatory agent used to treat polycythemia vera. The durability of responses and long-term safety of this drug in patients with polycythaemia vera and essential thrombocythaemia have not been reported. Here, we present long-term efficacy and safety data from a single-centre, open-label, phase 2 trial, after a median of 83 months follow up. Patients older than 18 years who were diagnosed with essential thrombocythaemia or polycythaemia vera according to 2001 WHO criteria were eligible to enrol in our study. The initial starting dose of pegylated interferon alfa-2a was 450 μg subcutaneously once per week, but was decreased in a stepwise manner due to toxic effects to a final starting dose of 90 mg per week: three patients were started at a dose of 450 mg per week, three at 360 mg per week, 19 at 270 mg per week, 26 at 180 mg per week, and 32 at 90 mg per week. Treatment was continued for as long as the patients derived clinical benefit with reductions in dose and frequency of administration allowed at the discretion of the treating physician. Haematological responses were assessed every 3-6 months on the basis of blood counts as defined by the European LeukemiaNet critieria. The primary endpoint of the initial study was the proportion of patients with a haematological response. Complete haematological response was defined as normalisation of blood counts (for patients with essential thrombocythaemia, platelets ≤440 × 10 9 per L; for patients with polycythaemia vera, haemoglobin interferon alfa-2a induced haematological (66 [80%] of 83 patients) and molecular responses (35 [63%] of 55 patients) in 40 patients with essential thrombocythaemia and 43 patients with polycythaemia vera, with median durations of 66 months (IQR 35-83) and 53 months (24-70), respectively. 26 (39%) of 66 haematological responders and 25 (71%) of 35 molecular responders (with the JAK2 Val617Phe mutation) have maintained some response during

  11. Níveis de cortisol salivar e sérico, alfa-amilase e fluxo de saliva total não estimulada em gestantes e não gestantes

    OpenAIRE

    Abrão, Aline Lauria Pires; Leal, Soraya Coelho; Falcão, Denise Pinheiro

    2014-01-01

    OBJETIVO: Comparar os níveis de cortisol sérico e salivar, alfa-amilase salivar (sAA) e fluxo de saliva não estimulada (UWS) em gestantes e não gestantes. MÉTODOS: Trata-se de um estudo longitudinal realizado no centro de promoção da saúde de um hospital universitário. Nove gestantes e 12 não gestantes participaram do estudo. Foram coletados e analisados soro e UWS nos três trimestres gestacionais e duas vezes por mês durante o ciclo menstrual. A análise do cortisol salivar e sérico foi reali...

  12. New digital ink for the obtention of innovating ceramics effects to obtain new possibilities and tendencies for the future; Este trabajo ha sido premiado con el Alfa de Oro en la Feria Internacional de Ceramica de Valencia CEVISAMA 2012

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    This technical note contains the most significant aspects of the work New digital inks for the production of innovative ceramic effects which generate new possibilities and future trends in which the Group Torrecid won the Alfa de Oro 2012 given by the Spanish Society of Ceramics and Glass. To achieve the stated objectives to work in different fields of activity for each specific ink has been necessary, comprising, among other, aspects such as the development of special frits, selecting the most suitable solvents or optimizing the compositions to ensure that the inks have appropriate behaviour in the printing process and met all the requirements of stability and quality that the ceramic industry demand. (Author)

  13. MODIFICACIÓN FÍSICA DEL ALMIDÓN DE YUCA Y EVALUACIÓN DE LA SUSCEPTIBILIDAD A LA HIDRÓLISIS ENZIMÁTICA POR UNA ALFA AMILASA

    OpenAIRE

    Jenny Martín; Elizabeth López

    2010-01-01

    Almidón de yuca comercial (variedad MTAI 8) se sometió a modificación física por sinéresis, extrusión, gelatinización y secado por rodillos. Al almidón nativo y a los almidones modificados se les determinó su morfología, cristalinidad, distribución molecular y susceptibilidad a la hidrólisis enzimática con una alfa amilasa porcina pancreática. En los almidones modificados físicamente se incrementó el grado de hidrólisis, en comparación con el almidón nativo. Sin embargo no se observaron difer...

  14. Establecimiento y validación de un ensayo inmunoenzimático tipo ELISA, empleado en el control de calidad del Interferón alfa 2b humano recombinante

    OpenAIRE

    Susset Valderrama; Eliana Pérez; Yurisleydis Aldama; Lourdes Costa; Marisel Quintana; Gudelia Pérez; Gerardo García

    2009-01-01

    Se estableció y validó un ELISA para la cuantificación del Interferón alfa 2b humano recombinante en el Ingrediente Farmacéutico Activo, definiéndose los criterios de validez del ensayo y basado en el cumplimiento de las Buenas Prácticas de Laboratorio. Se evaluaron los parámetros de: linealidad, especificidad, exactitud, rango, precisión y robustez. El ensayo establecido resultó específico, con una exactitud entre 84,3% y 102,4%, se demostró un ajuste cuadrático y un rango de trabajo entre 1...

  15. Normal bone density in male pseudohermaphroditism due to 5alpha- reductase 2 deficiency Pseudohermafroditas masculinos por deficiência de 5alfa-redutase 2 apresentam densidade óssea normal

    Directory of Open Access Journals (Sweden)

    Elaine Maria Frade Costa

    2001-10-01

    Full Text Available Bone is an androgen-dependent tissue, but it is not clear whether the androgen action in bone depends on testosterone or on dihydrotestosterone. Patients with 5alpha-reductase 2 deficiency present normal levels of testosterone and low levels of dihydrotestosterone, providing an in vivo human model for the analysis of the effect of testosterone on bone. OBJECTIVE: To analyze bone mineral density in 4 adult patients with male pseudohermaphroditism due to 5alpha-reductase 2 deficiency. RESULTS: Three patients presented normal bone mineral density of the lumbar column (L1-L4 and femur neck, and the other patient presented a slight osteopenia in the lumbar column. CONCLUSION: Patients with dihydrotestosterone deficiency present normal bone mineral density, suggesting that dihydrotestosterone is not the main androgen acting in bone.O tecido ósseo é um tecido andrógeno-dependente porém não está claro se a ação androgênica depende da testosterona ou da diidrotestosterona. Os pacientes portadores de deficiência de 5alfa-redutase tipo 2, constituem um modelo natural para avaliar o efeito isolado da testosterona sobre a massa óssea. OBJETIVO: Avaliar a densidade mineral óssea em quatro pacientes adultos portadores de pseudohermafroditismo masculino por deficiência da 5alfa-redutase tipo 2. RESULTADOS: Três pacientes apresentaram densidade mineral óssea normal na coluna lombar e fêmur e o quarto paciente apresentou osteopenia leve em coluna lombar. CONCLUSÃO: Pacientes com deficiência de diidrotestosterona apresentam densidade mineral óssea normal sugerindo que a diidrotestosterona não é o andrógeno que age sobre o osso.

  16. Rationale and design of oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN Trial).

    Science.gov (United States)

    Kato, Hideki; Nangaku, Masaomi; Hirakata, Hideki; Wada, Takashi; Hayashi, Terumasa; Sato, Hiroshi; Yamazaki, Yasushi; Masaki, Takao; Kagimura, Tatsuo; Yamamoto, Hiroyasu; Hase, Hiroki; Kamouchi, Masahiro; Imai, Enyu; Mizuno, Kyoichi; Iwasaki, Manabu; Akizawa, Tadao; Tsubakihara, Yoshiharu; Maruyama, Shoichi; Narita, Ichiei

    2017-06-28

    Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified. This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKD patients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index. The subjects consist of CKD patients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated. By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKD patients.

  17. Comparative immunology.

    Science.gov (United States)

    Cooper, Edwin L

    2006-03-01

    As a discipline, comparative immunology enhances zoology and has gained wide acceptance in the biological sciences. It is an offshoot of the parent field, immunology, and is an amalgam of immunology and zoology. All animals from protozoans to humans have solved the threat of extinction by having evolved an immune-defense strategy that ensures the capacity to react against foreign, non-self microorganisms and cancers that disturb the homeostatic self. Invertebrate-type innate immune responses evolved first and they characterize the metazoans. These rapid natural responses act immediately and are often essential for the occurrence of slower, more specific, adaptive vertebrate-type immune responses. As components of the innate immune system, there is an emphasis on several major steps in the evolutionary process: (i) recognition; (ii) the phagocytic cell; and (iii) the natural killer cell. When vertebrates evolved, beginning with fish, thymus-controlled T cells first appeared, as did bone marrow-derived B cells (first found in amphibians with long bones). These were the precursors of the plasma cells that synthesize and secrete antibodies. Confirming the concept of self/non-self, invertebrates possess natural, non-adaptive, innate, non-clonal, non-anticipatory immune responses, whereas vertebrates possess adaptive, acquired, clonal, and anticipatory responses. This symposium concerns: (i) aspects of the immune spectrum in representative groups; (ii) specific findings (in particular models; e.g. earthworms); (iii) clues as to the possible biomedical application of relevant molecules derived from animals, notably invertebrates; and (iv) some views on the more practical applications of understanding immune systems of invertebrates and ectotherms, and their possible role in survival.

  18. A comparative study between cone-beam computed tomography and periapical radiographs in the diagnosis of simulated endodontic complications.

    Science.gov (United States)

    D'Addazio, P S S; Campos, C N; Özcan, M; Teixeira, H G C; Passoni, R M; Carvalho, A C P

    2011-03-01

    To compare cone-beam computed tomography (CBCT) with periapical radiography for the identification of simulated endodontic complications. Sixteen human teeth, in three mandibles, were submitted to the following simulated endodontic complications: G1) fractured endodontic file; G2) root perforation; G3) cast post with deviation; G4) external root resorption. Periapical radiographs were taken of each tooth at three different angles, and CBCT scan was taken. One calibrated examiner who was specialized in dental radiology interpreted the images. The results were analysed using the following scoring system: 0 - unidentified alteration; 1 - alteration identified with inaccurate diagnosis; and 2 - alteration identified with accurate diagnosis. Data were analysed using McNemar and Wilcoxon tests (alfa=0.05). In the overall assessment, CBCT was superior when compared with periapical radiographs (Pperiapical radiographs especially in the detection and assessment of external root resorption. © 2010 International Endodontic Journal.

  19. Beyond anaemia management: evolving role of erythropoietin therapy in neurological disorders, multiple myeloma and tumour hypoxia models.

    Science.gov (United States)

    Boogaerts, Marc; Mittelman, Moshe; Vaupel, Peter

    2005-01-01

    Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results. Copyright 2005 S. Karger AG, Basel.

  20. Czynnik martwicy nowotworów alfa (TNF-α jako potencjalny osoczowy marker przebiegu stwardnienia rozsianego – badania wstępne

    Directory of Open Access Journals (Sweden)

    Magdalena Justyna Kacperska

    2014-07-01

    Full Text Available Stwardnienie rozsiane (łac. sclerosis multiplex, SM zaliczane jest do częstych przewlekłych chorób ośrodkowego układu nerwowego wiążących się z postępującą niepełnosprawnością. Dotyczy zwykle osób pomiędzy 20. a 40.rokiem życia, przy czym dwukrotnie częściej chorują kobiety. Mimo wieloletnich badań nadal bardzo mało wiemy na temat patogenezy tej choroby. Klinicznie można wyróżnić cztery jej postaci, do najczęściej występujących należą postać rzutowo-remisyjna, wtórnie postępująca oraz pierwotnie postępująca. Patogeneza SM jest procesem bardzo skomplikowanym, biorą w nim udział m.in.: uszkodzenie bariery krew–mózg oraz bariery krew – płyn mózgowo-rdzeniowy, wtórny przerost astrogleju, toczący się proces zapalny i szeroko pojęta neurodegeneracja. Szczególną rolę w rozwoju SM, głównie na jego wczesnym etapie, odgrywa proces zapalny, w którym biorą udział różne subpopulacje komórek zapalnych. Dotychczasowe badania wskazują na szczególny udział w tym procesie czynnika martwicy nowotworów alfa (TNF-α zaliczanego do cytokin prozapalnych. Cel badania: Celem niniejszej pracy była analiza stężenia TNF-α w osoczu pacjentów z SM w rzucie i remisji choroby oraz jego korelacja z parametrami klinicznymi przebiegu choroby w celu oceny roli TNF-α jako potencjalnego markera zaawansowania SM. Poszukując najważniejszych producentów TNF-α we krwi chorych z SM, analizowano również związek pomiędzy stężeniem TNF-α w osoczu i liczebnością leukocytów we krwi oraz ich subpopulacji. Materiał i metodyka: W badaniu wzięło udział 37 pacjentów z grup badanych (20 w grupie z rzutem i 17 w grupie z remisją choroby oraz 30 osób z grupy kontrolnej. Od pacjentów pobrano do odpowiednich probówek krew żylną w ilości 4 ml. Wirowano ją (5000 rpm, 20 min, 23ºC, a następnie ostrożnie usuwano górną warstwę z osoczem, zabezpieczano i przechowywano w temperaturze –80ºC do czasu

  1. Análise comparativa do processo de invasão de hepatócitos de rato por Listeria monocytogenes e Salmonella Typhimurium: caracterização morfológica, quantificação da liberação de TNF-alfa e da morte celular por apoptose

    OpenAIRE

    Sânia Alves dos Santos

    2009-01-01

    INTRODUÇÃO: Os hepatócitos apresentam papel potencial em iniciar e amplificar a resposta inflamatória aguda no fígado, através da liberação de citocinas pró-inflamatórias, em papel complementar ao exercido pelas células de Kupffer e endoteliais. A invasão bacteriana da célula hepática é um estímulo para que o hepatócito produza citocinas como o TNF-alfa, capaz de induzir sua própria morte por apoptose. O TNF-alfa pode ser tanto um agente citotóxico (induzindo a morte celular), quanto um agent...

  2. Estudo da coerência do eletrencefalograma para a banda de frequência alfa em indivíduos adultos normais e com provável demência do tipo Alzheimer Alpha band coherence analysis of EEG in healthy adult and Alzheimer's type dementia subjects

    Directory of Open Access Journals (Sweden)

    RENATO ANGHINAH

    2000-06-01

    Full Text Available Estudamos a coerência inter-hemisférica do espectro do eletrencefalograma (EEG obtido pela transformada rápida de Fourier, da região occipital do escalpo (eletrodos O1 e O2 para a banda de frequência alfa (alfa1 - 8,0 a 10,0 Hz e alfa2 -10,1 a 12,5 Hz em indivíduos normais maiores de 50 anos e pacientes com diagnóstico provável de demência do tipo Alzheimer (DTA, no intuíto de observar se há diferenças entre estes parâmetros que contribuam com o diagnóstico desta enfermidade. Encontramos diminuição na coerência inter-hemisférica dos indivíduos com DTA para ambas as sub-bandas do ritmo alfa. Acreditamos que a análise de coerência do EEG possa ser um método de grande auxílio no diagnóstico de DTAWe studied the occiptal inter-hemispheric coherence (IHCoh of EEG (electrodes O1-O2 for alpha band (alpha1 - 8,0 to 10,0 Hz and alpha2 - 10,1 to 12,5 Hz in healthy adults and Alzheimer's type dementia (ATD subjects, to observe if there is any significant difference between these two groups that could help in the early diagnosis of ATD. We found a decrease of occipital IHCoh in ATD group for both alpha sub-bands. We believe that Coh analysis of EEG is a powerful auxiliary method in ATD diagnosis.

  3. Influência do desenvolvimento etário e da suplementação com vitamina E (acetato de DL-alfa-tocoferol no metabolismo oxidativo dos neutrófilos de bovinos da raça Holandesa (Bos taurus

    Directory of Open Access Journals (Sweden)

    Joselito Nunes Costa

    2004-10-01

    Full Text Available O presente trabalho teve por objetivo analisar a influência do desenvolvimento etário e da suplementação com acetato de DL-alfa-tocoferol sobre o metabolismo oxidativo de neutrófilos, em bovinos da raça holandesa, no período do nascimento até os 150 dias de idade. Foram utilizados 20 bezerros divididos em dois grupos de dez animais. Os animais do grupo Tratamento receberam 2000UI de acetato de DL-alfa-tocoferol, por via intramuscular, ao nascimento, aos 15, 30, 60, 90 e 120 dias de idade, sendo o outro o grupo Controle, que não recebeu qualquer suplementação. Em ambos os grupos, o metabolismo oxidativo dos neutrófilos demonstrou pouca atividade durante os primeiros 60 dias de vida, sendo indicativo da ineficiência deste importante mecanismo bactericida. Não foi observado efeito significativo da administração do acetato de DL-alfa-tocoferol sobre o metabolismo oxidativo de neutrófilos.

  4. Eficácia terapêutica do interferon alfa em criança com hemangioma gigante craniofacial: relato de caso Therapeutical effectiveness of interferon alpha in a child with craniofacial giant hemangioma: case report

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    Nilson Lopes da Fonseca Junior

    2008-06-01

    Full Text Available O hemangioma é o tumor benigno mais freqüente da infância. O hemangioma capilar geralmente apresenta-se como uma mancha ou tumoração violácea bem delimitada. O diagnóstico destas lesões é clínico. O hemangioma gigante é rara e extensa variação do hemangioma capilar, que geralmente ocorre em recém-nascidos e lactentes. Várias são as modalidades terapêuticas, como a injeção intralesional de corticóide, laserterapia, injeção intralesional de soluções esclerosantes, corticoterapia sistêmica, cirurgia, radioterapia e embolização. Novas modalidades terapêuticas têm sido desenvolvidas, com o objetivo de se obter melhores resultados e possibilitar o tratamento de lesões de difícil acesso cirúrgico e refratárias às modalidades terapêuticas utilizadas rotineiramente. Os melhores resultados tem sido obtidos com o interferon alfa. Este é um caso de uma paciente com três meses de idade, que apresentava desde o nascimento, tumoração arroxeada e amolecida em pálpebra superior do olho direito, lesões cutâneas planas e arroxeadas em região temporal e parietal direita. Realizada tomografia computadorizada de crânio evidenciando processo expansivo orbitário vascularizado com extensão para fossa média, seio cavernoso e fossa posterior. O tratamento inicial foi a corticoterapia oral durante quarenta dias, com redução progressiva por quatro semanas. Com o quadro praticamente inalterado, foi iniciado o tratamento com interferon alfa, na dose de 3.000.000 U/m², subcutâneo, três vezes por semana. Após 9 meses de tratamento, observa-se apenas uma pequena lesão orbitária residual. Neste caso, o interferon alfa apresentou-se como boa opção no tratamento do hemangioma gigante craniofacial.Hemangiomas are the most commom benign tumors of infancy. Capillary hemangioma generally is presented as a spot or well-defined purple lesion. The diagnosis of these tumors is based on physical examination. Giant hemangioma is a rare

  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. Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C