Sample records for gallium nitrate rituximab

  1. Gallium nitrate ameliorates type II collagen-induced arthritis in mice.

    PubMed

    Choi, Jae-Hyeog; Lee, Jong-Hwan; Roh, Kug-Hwan; Seo, Su-Kil; Choi, Il-Whan; Park, Sae-Gwang; Lim, Jun-Goo; Lee, Won-Jin; Kim, Myoung-Hun; Cho, Kwang-rae; Kim, Young-Jae

    2014-05-01

    Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Gallium nitrate has been reported to reserve immunosuppressive activities. Therefore, we assessed the therapeutic effects of gallium nitrate in the mouse model of developed type II collagen-induced arthritis (CIA). CIA was induced by bovine type II collagen with Complete Freund's adjuvant. CIA mice were intraperitoneally treated from day 36 to day 49 after immunization with 3.5mg/kg/day, 7mg/kg/day gallium nitrate or vehicle. Gallium nitrate ameliorated the progression of mice with CIA. The clinical symptoms of collagen-induced arthritis did not progress after treatment with gallium nitrate. Gallium nitrate inhibited the increase of CD4(+) T cell populations (p<0.05) and also inhibited the type II collagen-specific IgG2a-isotype autoantibodies (p<0.05). Gallium nitrate reduced the serum levels of TNF-α, IL-6 and IFN-γ (p<0.05) and the mRNA expression levels of these cytokine and MMPs (MMP2 and MMP9) in joint tissues. Western blotting of members of the NF-κB signaling pathway revealed that gallium nitrate inhibits the activation of NF-κB by blocking IκB degradation. These data suggest that gallium nitrate is a potential therapeutic agent for autoimmune inflammatory arthritis through its inhibition of the NF-κB pathway, and these results may help to elucidate gallium nitrate-mediated mechanisms of immunosuppression in patients with RA. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Gallium nitrate: effects on cartilage during limb regeneration in the axolotl, Ambystoma mexicanum.

    PubMed

    Tassava, Roy A; Mendenhall, Luciara; Apseloff, Glen; Gerber, Nicholas

    2002-09-01

    Gallium nitrate, a drug shown to have efficacy in Paget's disease of bone, hypercalcemia of malignancy, and a variety of experimental autoimmune diseases, also inhibits the growth of some types of cancer. We examined dose and timing of administration of gallium nitrate on limb regeneration in the Mexican axolotl, Ambystoma mexicanum. Administered by intraperitoneal injection, gallium nitrate inhibited limb regeneration in a dose-dependent manner. Gallium nitrate initially suppressed epithelial wound healing and subsequently distorted both anterior-posterior and proximo-distal chondrogenic patterns. Gallium nitrate given at three days after amputation severely inhibited regeneration at high doses (6.25 mg/axolotl) and altered the normal patterning of the regenerates at low doses (3.75 mg/axolotl). Administration of 6.25 mg of gallium nitrate at four or 14 days prior to amputation also inhibited regeneration. In amputated limbs of gallium-treated axolotls, the chondrocytes were lost from inside the radius/ulna. Limbs that regenerated after gallium treatment was terminated showed blastema formation preferentially over the ulna. New cartilage of the regenerate often attached to the sides of the existing radius/ulna proximally into the stump and less so to the distal cut ends. J. Exp. Zool. 293:384-394, 2002. Copyright 2002 Wiley-Liss, Inc.

  3. Nuclear microprobe imaging of gallium nitrate in cancer cells

    NASA Astrophysics Data System (ADS)

    Ortega, Richard; Suda, Asami; Devès, Guillaume

    2003-09-01

    Gallium nitrate is used in clinical oncology as treatment for hypercalcemia and for cancer that has spread to the bone. Its mechanism of antitumor action has not been fully elucidated yet. The knowledge of the intracellular distribution of anticancer drugs is of particular interest in oncology to better understand their cellular pharmacology. In addition, most metal-based anticancer compounds interact with endogenous trace elements in cells, altering their metabolism. The purpose of this experiment was to examine, by use of nuclear microprobe analysis, the cellular distribution of gallium and endogenous trace elements within cancer cells exposed to gallium nitrate. In a majority of cellular analyses, gallium was found homogeneously distributed in cells following the distribution of carbon. In a smaller number of cells, however, gallium appeared concentrated together with P, Ca and Fe within round structures of about 2-5 μm diameter located in the perinuclear region. These intracellular structures are typical of lysosomial material.

  4. Gallium nitrate induces fibrinogen flocculation: an explanation for its hemostatic effect?

    PubMed

    Bauters, A; Holt, D J; Zerbib, P; Rogosnitzky, M

    2013-12-01

    A novel hemostatic effect of gallium nitrate has recently been discovered. Our aim was to perform a preliminary investigation into its mode of action. Thromboelastography® showed no effect on coagulation but pointed instead to changes in fibrinogen concentration. We measured functional fibrinogen in whole blood after addition of gallium nitrate and nitric acid. We found that gallium nitrate induces fibrinogen precipitation in whole blood to a significantly higher degree than solutions of nitric acid alone. This precipitate is not primarily pH driven, and appears to occur via flocculation. This behavior is in line with the generally observed ability of metals to induce fibrinogen precipitation. Further investigation is required into this novel phenomenon.

  5. In Vitro and In Vivo Biological Activities of Iron Chelators and Gallium Nitrate against Acinetobacter baumannii

    PubMed Central

    Harris, Greg; KuoLee, Rhonda; Chen, Wangxue

    2012-01-01

    We investigated the ability of compounds interfering with iron metabolism to inhibit the growth of Acinetobacter baumannii. Iron restriction with transferrin or 2,2-bipyridyl significantly inhibited A. baumannii growth in vitro. Gallium nitrate alone was moderately effective at reducing A. baumannii growth but became bacteriostatic in the presence of serum or transferrin. More importantly, gallium nitrate treatment reduced lung bacterial burdens in mice. The use of gallium-based therapies shows promise for the control of multidrug-resistant A. baumannii. PMID:22825117

  6. In vitro and in vivo biological activities of iron chelators and gallium nitrate against Acinetobacter baumannii.

    PubMed

    de Léséleuc, Louis; Harris, Greg; KuoLee, Rhonda; Chen, Wangxue

    2012-10-01

    We investigated the ability of compounds interfering with iron metabolism to inhibit the growth of Acinetobacter baumannii. Iron restriction with transferrin or 2,2-bipyridyl significantly inhibited A. baumannii growth in vitro. Gallium nitrate alone was moderately effective at reducing A. baumannii growth but became bacteriostatic in the presence of serum or transferrin. More importantly, gallium nitrate treatment reduced lung bacterial burdens in mice. The use of gallium-based therapies shows promise for the control of multidrug-resistant A. baumannii.

  7. The Inhibition of Escherichia coli Biofilm Formation by Gallium Nitrate-Modified Titanium.

    PubMed

    Zhu, Yuanyuan; Qiu, Yan; Chen, Ruiqi; Liao, Lianming

    2015-08-01

    Periprosthetic infections are notoriously difficult to treat due to biofilm formation. Previously, we reported that gallium-EDTA attached to PVC (polyvinyl chloride) surface could prevent bacterial colonization. Herein we examined the effect of this gallium-EDTA complex on Escherichia coli biofilm formation on titanium. It was clearly demonstrated that gallium nitrate significantly inhibited the growth and auto-aggregation of Escherichia coli. Furthermore, titanium with gallium-EDTA coating resisted bacterial colonization as indicated by crystal violet staining. When the chips were immersed in human serum and incubated at 37 °C, they demonstrated significant antimicrobial activity after more than 28 days of incubation. These findings indicate that gallium-EDTA coating of implants can result in a surface that can resist bacterial colonization. This technology holds great promise for the prevention and treatment of periprosthetic infections.

  8. Thermal Plasma Synthesis of Crystalline Gallium Nitride Nanopowder from Gallium Nitrate Hydrate and Melamine

    PubMed Central

    Kim, Tae-Hee; Choi, Sooseok; Park, Dong-Wha

    2016-01-01

    Gallium nitride (GaN) nanopowder used as a blue fluorescent material was synthesized by using a direct current (DC) non-transferred arc plasma. Gallium nitrate hydrate (Ga(NO3)3∙xH2O) was used as a raw material and NH3 gas was used as a nitridation source. Additionally, melamine (C3H6N6) powder was injected into the plasma flame to prevent the oxidation of gallium to gallium oxide (Ga2O3). Argon thermal plasma was applied to synthesize GaN nanopowder. The synthesized GaN nanopowder by thermal plasma has low crystallinity and purity. It was improved to relatively high crystallinity and purity by annealing. The crystallinity is enhanced by the thermal treatment and the purity was increased by the elimination of residual C3H6N6. The combined process of thermal plasma and annealing was appropriate for synthesizing crystalline GaN nanopowder. The annealing process after the plasma synthesis of GaN nanopowder eliminated residual contamination and enhanced the crystallinity of GaN nanopowder. As a result, crystalline GaN nanopowder which has an average particle size of 30 nm was synthesized by the combination of thermal plasma treatment and annealing. PMID:28344295

  9. Role of Oxidative Stress in the Induction of Metallothionein-2A and Heme Oxygenase-1 Gene Expression by the Antineoplastic Agent Gallium Nitrate in Human Lymphoma Cells

    PubMed Central

    Yang, Meiying; Chitambar, Christopher R.

    2008-01-01

    The mechanisms of action of gallium nitrate, an antineoplastic drug, are only partly understood. Using a DNA microarray to examine genes induced by gallium nitrate in CCRF-CEM cells, we found that gallium increased metallothionein-2A (MT2A) and heme oxygenase-1 (HO-1) gene expression and altered the levels of other stress-related genes. MT2A and HO-1 were increased after 6 and 16 h of incubation with gallium nitrate. An increase in oxidative stress, evidenced by a decrease in cellular GSH and GSH/GSSG ratio, and an increase in dichlorodihydrofluoroscein (DCF) fluorescence, was seen after 1 – 4 h incubation of cells with gallium nitrate. DCF fluorescence was blocked by the mitochondria-targeted antioxidant mitoquinone. N-acetyl-L-cysteine blocked gallium-induced MT2A and HO-1 expression and increased gallium’s cytotoxicity. Studies with a zinc-specific fluoroprobe suggested that gallium produced an expansion of an intracellular labile zinc pool, suggesting an action of gallium on zinc homeostasis. Gallium nitrate increased the phosphorylation of p38 mitogen-activated protein kinase and activated Nrf-2, a regulator of HO-1 gene transcription. Gallium-induced Nrf-2 activation and HO-1 expression were diminished by a p38 MAP kinase inhibitor. We conclude that gallium nitrate induces cellular oxidative stress as an early event which then triggers the expression of HO-1 and MT2A through different pathways. PMID:18586083

  10. Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves.

    PubMed

    Monk, Caroline S; Sweeney, Raymond W; Bernstein, Lawrence R; Fecteau, Marie-Eve

    2016-02-01

    To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves. 8 healthy neonatal calves. Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry. Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN. In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves.

  11. Effects of heat shock, stannous chloride, and gallium nitrate on the rat inflammatory response.

    PubMed

    House, S D; Guidon, P T; Perdrizet, G A; Rewinski, M; Kyriakos, R; Bockman, R S; Mistry, T; Gallagher, R A; Hightower, L E

    2001-04-01

    Heat and a variety of other stressors cause mammalian cells and tissues to acquire cytoprotection. This transient state of altered cellular physiology is nonproliferative and antiapoptotic. In this study, male Wistar rats were stress conditioned with either stannous chloride or gallium nitrate, which have immunosuppressive effects in vivo and in vitro, or heat shock, the most intensively studied inducer of cytoprotection. The early stages of inflammation in response to topical suffusion of mesentery tissue with formyl-methionyl-leucyl-phenylalanine (FMLP) were monitored using intravital microscopy. Microvascular hemodynamics (venular diameter, red blood cell velocity [Vrbc], white blood cell [WBC] flux, and leukocyte-endothelial adhesion [LEA]) were used as indicators of inflammation, and tissue levels of inducible Hsp70, determined using immunoblot assays, provided a marker of cytoprotection. None of the experimental treatments blocked decreases in WBC flux during FMLP suffusion, an indicator of increased low-affinity interactions between leukocytes and vascular endothelium known as rolling adhesion. During FMLP suffusion LEA, an indicator of firm attachment between leukocytes and vascular endothelial cells increased in placebo and gallium nitrate-treated animals but not in heat- and stannous chloride-treated animals, an anti-inflammatory effect. Hsp70 was not detected in aortic tissue from placebo and gallium nitrate-treated animals, indicating that Hsp70-dependent cytoprotection was not present. In contrast, Hsp70 was detected in aortic tissues from heat- and stannous chloride-treated animals, indicating that these tissues were in a cytoprotected state that was also an anti-inflammatory state.

  12. Comparison of the antimicrobial activities of gallium nitrate and gallium maltolate against Mycobacterium avium subsp. paratuberculosis in vitro.

    PubMed

    Fecteau, Marie-Eve; Aceto, Helen W; Bernstein, Lawrence R; Sweeney, Raymond W

    2014-10-01

    Johne's disease (JD) is an enteric infection of cattle and other ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This study compared the antimicrobial activities of gallium nitrate (GaN) and gallium maltolate (GaM) against two field MAP isolates by use of broth culture. The concentrations that resulted in 99% growth inhibition of isolates 1 and 2 were, respectively, 636 µM and 183 µM for GaN, and 251 µM and 142 µM for GaM. For both isolates, time to detection was significantly higher for GaM than GaN. These results suggest that GaM is more efficient than GaN in inhibiting MAP growth in vitro. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Gallium-containing anticancer compounds.

    PubMed

    Chitambar, Christopher R

    2012-06-01

    There is an ever pressing need to develop new drugs for the treatment of cancer. Gallium nitrate, a group IIIa metal salt, inhibits the proliferation of tumor cells in vitro and in vivo and has shown activity against non-Hodgkin's lymphoma and bladder cancer in clinical trials. Gallium can function as an iron mimetic and perturb iron-dependent proliferation and other iron-related processes in tumor cells. Gallium nitrate lacks crossresistance with conventional chemotherapeutic drugs and is not myelosuppressive; it can be used when other drugs have failed or when the blood count is low. Given the therapeutic potential of gallium, newer generations of gallium compounds are now in various phases of preclinical and clinical development. These compounds hold the promise of greater anti-tumor activity against a broader spectrum of cancers. The development of gallium compounds for cancer treatment and their mechanisms of action will be discussed.

  14. Gallium-containing anticancer compounds

    PubMed Central

    Chitambar, Christopher R

    2013-01-01

    There is an ever pressing need to develop new drugs for the treatment of cancer. Gallium nitrate, a group IIIa metal salt, inhibits the proliferation of tumor cells in vitro and in vivo and has shown activity against non-Hodgkin’s lymphoma and bladder cancer in clinical trials. Gallium can function as an iron mimetic and perturb iron-dependent proliferation and other iron-related processes in tumor cells. Gallium nitrate lacks cross resistance with conventional chemotherapeutic drugs and is not myelosuppressive; it can be used when other drugs have failed or when the blood count is low. Given the therapeutic potential of gallium, newer generations of gallium compounds are now in various phases of preclinical and clinical development. These compounds hold the promise of greater anti-tumor activity against a broader spectrum of cancers. The development of gallium compounds for cancer treatment and their mechanisms of action will be discussed. PMID:22800370

  15. Effects of heat shock, stannous chloride, and gallium nitrate on the rat inflammatory response

    PubMed Central

    House, S.D.; Guidon, P.T.; Perdrizet, G.A.; Rewinski, M.; Kyriakos, R.; Bockman, R.S.; Mistry, T.; Gallagher, P.A.; Hightower, L.E.

    2001-01-01

    Heat and a variety of other stressors cause mammalian cells and tissues to acquire cytoprotection. This transient state of altered cellular physiology is nonproliferative and antiapoptotic. In this study, male Wistar rats were stress conditioned with either stannous chloride or gallium nitrate, which have immunosuppressive effects in vivo and in vitro, or heat shock, the most intensively studied inducer of cytoprotection. The early stages of inflammation in response to topical suffusion of mesentery tissue with formyl-methionyl-leucyl-phenylalanine (FMLP) were monitored using intravital microscopy. Microvascular hemodynamics (venular diameter, red blood cell velocity [Vrbc], white blood cell [WBC] flux, and leukocyte-endothelial adhesion [LEA]) were used as indicators of inflammation, and tissue levels of inducible Hsp70, determined using immunoblot assays, provided a marker of cytoprotection. None of the experimental treatments blocked decreases in WBC flux during FMLP suffusion, an indicator of increased low-affinity interactions between leukocytes and vascular endothelium known as rolling adhesion. During FMLP suffusion LEA, an indicator of firm attachment between leukocytes and vascular endothelial cells increased in placebo and gallium nitrate-treated animals but not in heat- and stannous chloride–treated animals, an anti-inflammatory effect. Hsp70 was not detected in aortic tissue from placebo and gallium nitrate–treated animals, indicating that Hsp70-dependent cytoprotection was not present. In contrast, Hsp70 was detected in aortic tissues from heat- and stannous chloride–treated animals, indicating that these tissues were in a cytoprotected state that was also an anti-inflammatory state. PMID:11599578

  16. Ambient temperature deposition of gallium nitride/gallium oxynitride from a deep eutectic electrolyte, under potential control.

    PubMed

    Sarkar, Sujoy; Sampath, S

    2016-05-11

    A ternary, ionically conducting, deep eutectic solvent based on acetamide, urea and gallium nitrate is reported for the electrodeposition of gallium nitride/gallium indium nitride under ambient conditions; blue and white light emitting photoluminescent deposits are obtained under potential control.

  17. Serum resistance, gallium nitrate tolerance and extrapulmonary dissemination are linked to heme consumption in a bacteremic strain of Acinetobacter baumannii.

    PubMed

    de Léséleuc, Louis; Harris, Greg; KuoLee, Rhonda; Xu, H Howard; Chen, Wangxue

    2014-05-01

    Bacteremia caused by Acinetobacter baumannii is a highly lethal complication of hospital-acquired pneumonia. In the present study, we investigated the serum resistance, gallium nitrate tolerance and heme consumption of A. baumannii strain LAC-4 which was recently reported to display high virulence in a mouse pneumonia model with extrapulmonary dissemination leading to fatal bacteremia. This strain showed enhanced growth in mouse and fetal bovine serum that was independent of complement and was not observed with regular growth media. The LAC-4 strain was found to possess a high tolerance to gallium nitrate (GaN), whereas serum synergized with GaN in inhibiting A. baumannii strain ATCC 17978. We found that LAC-4 contains a heme oxygenase gene and expresses a highly efficient heme consumption system. This system can be fully blocked in vitro and in vivo by gallium protoporphyrin IX (GaPPIX). Inhibition of heme consumption by GaPPIX completely abrogated the growth advantage of LAC-4 in serum as well as its tolerance to GaN. More importantly, GaPPIX treatment of mice intranasally infected with LAC-4 prevented extrapulmonary dissemination and death. Thus, we propose that heme provides an additional source of iron for LAC-4 to bypass iron restriction caused by serum transferrin, lactoferrin or free gallium salts. Heme consumption systems in A. baumannii may constitute major virulence factors for lethal bacteremic isolates. Copyright © 2014 Crown Copyright and Elsevier Inc. Published by Elsevier GmbH.. All rights reserved.

  18. Rituximab desensitization in three patients with severe rituximab allergy.

    PubMed

    Öztürk, Erman; Özyiğit, Leyla Pur; Öztürk, Ayşe Bilge; Akay, Meltem Olga; Çetiner, Mustafa; Ferhanoğlu, Burhan

    Rituximab is a chimeric monoclonal antibody that targets CD20 positive B cells and has a positive effect on both overall and progression-free survival in B-cell lymphoid malignancies. Combination rituximab with chemotherapy treatment provide survival improvement. Although rituximab is an important treatment option in hematological malignancies, the risk of allergic reactions is high. These reactions are usually IgE-mediated and can be varied in regard of severity from urticaria to anaphylaxis. It is an option to interrupt the treatment and ommit rituximab therapy who had allergic reactions. Drug desensitization is another option and successful results have been reported by applying desensitization to such reactions. Drug desensitization alters the immune response to induce a state of temporary clinical tolerance to the allergic drug by giving gradual increasing of doses of drug at fixed time intervals. Herein, we present 3 cases successfully treated with rituximab desensitization. The cases were using rituximab with the diagnosis of Burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, respectively. Two cases had grade 2 and 1 case had grade 3 systemic allergic reaction with rituximab. There was no known allergy history in all 3 cases. All patients tolerated the desensitization protocol. The subsequent treatments of the patients were also given by desensitization protocol. A total of 12 desensitizations were administered to 3 cases. No severe or life-threating reactions were observed in subsequent applications. To date applying desensitization protocols ensure rituximab treatment safely. Rituximab desensitization can be performed at trained allergy centers, and it may be an appropriate option for rituximab allergic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Distribution of trace levels of therapeutic gallium in bone as mapped by synchrotron x-ray microscopy.

    PubMed Central

    Bockman, R S; Repo, M A; Warrell, R P; Pounds, J G; Schidlovsky, G; Gordon, B M; Jones, K W

    1990-01-01

    Gallium nitrate, a drug that inhibits calcium release from bone, has been proven a safe and effective treatment for the accelerated bone resorption associated with cancer. Though bone is a target organ for gallium, the kinetics, sites, and effects of gallium accumulation in bone are not known. We have used synchrotron x-ray microscopy to map the distribution of trace levels of gallium in bone. After short-term in vivo administration of gallium nitrate to rats, trace (nanogram) amounts of gallium preferentially localized to the metabolically active regions in the metaphysis as well as the endosteal and periosteal surfaces of diaphyseal bone, regions where new bone formation and modeling were occurring. The amounts measured were well below the levels known to be cytotoxic. Iron and zinc, trace elements normally found in bone, were decreased in amount after in vivo administration of gallium. These studies represent a first step toward understanding the mechanism(s) of action of gallium in bone by suggesting the possible cellular, structural, and elemental "targets" of gallium. Images PMID:2349224

  20. Rituximab biosimilars.

    PubMed

    Vital, Edward M; Kay, Jonathan; Emery, Paul

    2013-07-01

    Rituximab is a monoclonal antibody targeting CD20, used to treat B cell malignancies and B cell-mediated autoimmune diseases. Rituximab has the largest market of any monoclonal antibody therapeutic. Its patent will expire within the next few years and several manufacturers have already produced or are developing rituximab biosimilars that aim to match the innovator rituximab as closely as possible. In this review, we discuss key factors that determine the efficacy of rituximab therapy, potential technical challenges in the manufacture and evaluation of biosimilars, regulatory considerations regarding the review and approval of biosimilars, and the current status of biosimilar rituximab development by various manufacturers. Due to the nature of the topic, literature searches included conference abstracts, regulatory and industry websites as well as peer reviewed literature. Cost is a key limitation of current biologics usage and there is a political impetus to the licensing of biosimilars. Concerns regarding potential dissimilarities of biosimilars are legitimate, but surmountable with techniques for in vitro, in vivo and clinical testing and more clearly defined regulatory requirements. These should provide reassurance to prescribers. However, the cost of manufacturing and licensing a biosimilar remains high and the reduction in cost may be more limited than for a non-biologic small molecule drug and its generic version. This cost reduction will be critical to the impact and use of rituximab biosimilars.

  1. Gallium and its competing roles with iron in biological systems.

    PubMed

    Chitambar, Christopher R

    2016-08-01

    Gallium, a group IIIa metal, shares chemical properties with iron. Studies have shown that gallium-based compounds have potential therapeutic activity against certain cancers and infectious microorganisms. By functioning as an iron mimetic, gallium perturbs iron-dependent proliferation processes in tumor cells. Gallium's action on iron homeostasis leads to disruption of ribonucleotide reductase, mitochondrial function, and the regulation of transferrin receptor and ferritin. In addition, gallium nitrate stimulates an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1. Gallium's anti-infective activity against bacteria and fungi results from disruption of microbial iron utilization through mechanisms which include gallium binding to siderophores and downregulation of bacterial iron uptake. Gallium compounds lack cross-resistance to conventional chemotherapeutic drugs and antibiotics thus making them attractive agents for drug development. This review will focus on the mechanisms of action of gallium with emphasis on its interaction with iron and iron proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Gallium-based anti-infectives: targeting microbial iron-uptake mechanisms.

    PubMed

    Kelson, Andrew B; Carnevali, Maia; Truong-Le, Vu

    2013-10-01

    Microbes have evolved elaborate iron-acquisition systems to sequester iron from the host environment using siderophores and heme uptake systems. Gallium(III) is structurally similar to iron(III), except that it cannot be reduced under physiological conditions, therefore gallium has the potential to serve as an iron analog, and thus an anti-microbial. Because Ga(III) can bind to virtually any complex that binds Fe(III), simple gallium salts as well as more complex siderophores and hemes are potential carriers to deliver Ga(III) to the microbes. These gallium complexes represent a new class of anti-infectives that is different in mechanism of action from conventional antibiotics. Simple gallium salts such as gallium nitrate, maltolate, and simple gallium siderophore complexes such as gallium citrate have shown good antibacterial activities. The most studied complex has been gallium citrate, which exhibits broad activity against many Gram negative bacteria at ∼1-5μg/ml MICs, strong biofilm activity, low drug resistance, and efficacy in vivo. Using the structural features of specific siderophore and heme made by pathogenic bacteria and fungi, researchers have begun to evaluate new gallium complexes to target key pathogens. This review will summarize potential iron-acquisition system targets and recent research on gallium-based anti-infectives. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Iron-targeting antitumor activity of gallium compounds and novel insights into triapine(®)-metal complexes.

    PubMed

    Chitambar, Christopher R; Antholine, William E

    2013-03-10

    Despite advances made in the treatment of cancer, a significant number of patients succumb to this disease every year. Hence, there is a great need to develop new anticancer agents. Emerging data show that malignant cells have a greater requirement for iron than normal cells do and that proteins involved in iron import, export, and storage may be altered in cancer cells. Therefore, strategies to perturb these iron-dependent steps in malignant cells hold promise for the treatment of cancer. Recent studies show that gallium compounds and metal-thiosemicarbazone complexes inhibit tumor cell growth by targeting iron homeostasis, including iron-dependent ribonucleotide reductase. Chemical similarities of gallium(III) with iron(III) enable the former to mimic the latter and interpose itself in critical iron-dependent steps in cellular proliferation. Newer gallium compounds have emerged with additional mechanisms of action. In clinical trials, the first-generation-compound gallium nitrate has exhibited activity against bladder cancer and non-Hodgkin's lymphoma, while the thiosemicarbazone Triapine(®) has demonstrated activity against other tumors. Novel gallium compounds with greater cytotoxicity and a broader spectrum of antineoplastic activity than gallium nitrate should continue to be developed. The antineoplastic activity and toxicity of the existing novel gallium compounds and thiosemicarbazone-metal complexes should be tested in animal tumor models and advanced to Phase I and II clinical trials. Future research should identify biologic markers that predict tumor sensitivity to gallium compounds. This will help direct gallium-based therapy to cancer patients who are most likely to benefit from it.

  4. A hypothesis for anti-nanobacteria effects of gallium with observations from treating kidney disease.

    PubMed

    Eby, George A

    2008-10-01

    Nanobacteria, 100-fold smaller than common bacteria, have been purported to exist in urine, and by precipitating calcium and other minerals into carbonate apatite around themselves, induce the formation of surrounding kidney stones. Nanobacteria-like structures have also been shown in blood, within arteries, aortic aneurysms, and cardiac valves. Gallium has antibiotic properties to iron-dependent bacteria and has potent anti-inflammatory, anticancer and anti-hypercalcemic properties, and it readily reverses osteoporosis. It was hypothesized that gallium nitrate might have benefit in treating kidney stones. Gallium nitrate (120mg gallium) was mixed with water making two liters of a gallium mineral water drink to treat chronic, treatment-resistant kidney stone pain and urinary tract bleeding in a 110 pound woman. On the third day of gallium mineral water treatment, the urine appeared snow white, thick (rope-like) and suggestive of a calcific crystalline nature. After release of the white urine, the urine returned to normal in color, viscosity and pH, kidney pain was no longer present, and there was no further evidence of blood in the urine. There were no treatment side effects or sequela. For a one year observation period thereafter, no kidney stones, white urine, kidney or urinary tract pain or blood in the urine was noted. The hypothetical susceptibility of nanobacteria to gallium treatment also suggests application to atherosclerosis and other diseases. Although some support for gallium in treating kidney stones is presented, this hypothesis is built upon another hypothesis, is extremely speculative, and alternative explanations for the white urine exist. Further research into gallium's effects on kidney disease and other nanobacteria-induced diseases such as cardiovascular diseases is suggested.

  5. Role of Rituximab and Rituximab Biosimilars in Diffuse Large B-Cell Lymphoma.

    PubMed

    Coleman, Morton; Lammers, Philip E; Ciceri, Fabio; Jacobs, Ira A

    2016-04-01

    Diffuse large B-cell lymphoma (DLBCL), an aggressive non-Hodgkin lymphoma (NHL), is the most-common subtype of NHL. DLBCL can be classified into at least 3 major immunologically distinct types, which contributes to considerable variation in disease prognosis and response to treatment. DLBCL potentially is curable, even when diagnosed at advanced stages. The current standard of care for most patients with untreated or relapsed/refractory DLBCL is chemoimmunotherapy containing rituximab, an anti-CD20 monoclonal antibody. With advanced understanding of the molecular mechanisms involved in the pathogenesis of DLBCL and specific signaling pathways that are activated in different subtypes, potential new therapeutic targets have been identified, some of which are at the late stages of clinical development. This review summarizes the critical role of rituximab in the current standard of care treatment for DLBCL and discusses why rituximab is likely to remain an important component of treatment options for DLBCL in the foreseeable future. In addition, current and emerging therapeutic agents, including potential benefits of rituximab biosimilars, for patients with DLBCL are discussed. The advent of rituximab biosimilars may facilitate accessibility of rituximab-based chemotherapies to patients with DLBCL and has potential cost-saving benefits for healthcare systems globally. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Iron-Targeting Antitumor Activity of Gallium Compounds and Novel Insights Into Triapine®-Metal Complexes

    PubMed Central

    Antholine, William E.

    2013-01-01

    Abstract Significance: Despite advances made in the treatment of cancer, a significant number of patients succumb to this disease every year. Hence, there is a great need to develop new anticancer agents. Recent Advances: Emerging data show that malignant cells have a greater requirement for iron than normal cells do and that proteins involved in iron import, export, and storage may be altered in cancer cells. Therefore, strategies to perturb these iron-dependent steps in malignant cells hold promise for the treatment of cancer. Recent studies show that gallium compounds and metal-thiosemicarbazone complexes inhibit tumor cell growth by targeting iron homeostasis, including iron-dependent ribonucleotide reductase. Chemical similarities of gallium(III) with iron(III) enable the former to mimic the latter and interpose itself in critical iron-dependent steps in cellular proliferation. Newer gallium compounds have emerged with additional mechanisms of action. In clinical trials, the first-generation-compound gallium nitrate has exhibited activity against bladder cancer and non-Hodgkin's lymphoma, while the thiosemicarbazone Triapine® has demonstrated activity against other tumors. Critical Issues: Novel gallium compounds with greater cytotoxicity and a broader spectrum of antineoplastic activity than gallium nitrate should continue to be developed. Future Directions: The antineoplastic activity and toxicity of the existing novel gallium compounds and thiosemicarbazone-metal complexes should be tested in animal tumor models and advanced to Phase I and II clinical trials. Future research should identify biologic markers that predict tumor sensitivity to gallium compounds. This will help direct gallium-based therapy to cancer patients who are most likely to benefit from it. Antioxid. Redox Signal. 00, 000–000. PMID:22900955

  7. Rituximab selectively suppresses specific islet antibodies.

    PubMed

    Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

    2011-10-01

    The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P < 0.0001). In the subgroup (n = 6) treated within 50 days of diabetes, IAAs were markedly suppressed by rituximab in all patients for 1 year and for four patients as long as 3 years despite continuing insulin therapy. Independent of rituximab treatment, the mean level of IAAs at study entry was markedly lower (P = 0.035) for patients who maintained C-peptide levels during the first year of follow-up in both rituximab-treated and placebo groups. A single course of rituximab differentially suppresses IAAs, clearly blocking IAAs for >1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific

  8. Rituximab treatment for fibrillary glomerulonephritis.

    PubMed

    Hogan, Jonathan; Restivo, Michaela; Canetta, Pietro A; Herlitz, Leal C; Radhakrishnan, Jai; Appel, Gerald B; Bomback, Andrew S

    2014-10-01

    Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  9. The therapeutic potential of iron-targeting gallium compounds in human disease: From basic research to clinical application.

    PubMed

    Chitambar, Christopher R

    2017-01-01

    Gallium, group IIIa metal, shares certain chemical characteristics with iron which enable it to function as an iron mimetic that can disrupt iron-dependent tumor cell growth. Gallium may also display antimicrobial activity by disrupting iron homeostasis in certain bacteria and fungi. Gallium's action on iron homeostasis leads to inhibition of ribonucleotide reductase, mitochondrial function, and changes in proteins of iron transport and storage. In addition, gallium induces an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1. Early clinical trials evaluated the efficacy of the simple gallium salts, gallium nitrate and gallium chloride. However, newer gallium-ligands such as Tris(8-quinolinolato)gallium(III) (KP46) and gallium maltolate have been developed and are undergoing clinical evaluation. Additional gallium-ligands that demonstrate antitumor activity in preclinical studies have emerged. Their mechanisms of action and their spectrum of antitumor activity may extend beyond the earlier generations of gallium compounds and warrant further investigation. This review will focus on the evolution and potential of gallium-based therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

    PubMed

    Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

    2013-05-01

    Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

  11. Discovery – Development of Rituximab

    Cancer.gov

    NCI funded the development of rituximab, one of the first monoclonal antibody cancer treatments. With the discovery of rituximab, more than 70 percent of patients diagnosed with non-hodgkin lymphoma now live five years past their initial diagnosis.

  12. Gallium

    USGS Publications Warehouse

    Foley, Nora K.; Jaskula, Brian W.; Kimball, Bryn E.; Schulte, Ruth F.; Schulz, Klaus J.; DeYoung,, John H.; Seal, Robert R.; Bradley, Dwight C.

    2017-12-19

    Gallium is a soft, silvery metallic element with an atomic number of 31 and the chemical symbol Ga. Gallium is used in a wide variety of products that have microelectronic components containing either gallium arsenide (GaAs) or gallium nitride (GaN). GaAs is able to change electricity directly into laser light and is used in the manufacture of optoelectronic devices (laser diodes, light-emitting diodes [LEDs], photo detectors, and solar cells), which are important for aerospace and telecommunications applications and industrial and medical equipment. GaAs is also used in the production of highly specialized integrated circuits, semiconductors, and transistors; these are necessary for defense applications and high-performance computers. For example, cell phones with advanced personal computer-like functionality (smartphones) use GaAs-rich semiconductor components. GaN is used principally in the manufacture of LEDs and laser diodes, power electronics, and radio-frequency electronics. Because GaN power transistors operate at higher voltages and with a higher power density than GaAs devices, the uses for advanced GaN-based products are expected to increase in the future. Gallium technologies also have large power-handling capabilities and are used for cable television transmission, commercial wireless infrastructure, power electronics, and satellites. Gallium is also used for such familiar applications as screen backlighting for computer notebooks, flat-screen televisions, and desktop computer monitors.Gallium is dispersed in small amounts in many minerals and rocks where it substitutes for elements of similar size and charge, such as aluminum and zinc. For example, gallium is found in small amounts (about 50 parts per million) in such aluminum-bearing minerals as diaspore-boehmite and gibbsite, which form bauxite deposits, and in the zinc-sulfide mineral sphalerite, which is found in many mineral deposits. At the present time, gallium metal is derived mainly as a

  13. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.

    PubMed

    Seymour, John F; Kipps, Thomas J; Eichhorst, Barbara; Hillmen, Peter; D'Rozario, James; Assouline, Sarit; Owen, Carolyn; Gerecitano, John; Robak, Tadeusz; De la Serna, Javier; Jaeger, Ulrich; Cartron, Guillaume; Montillo, Marco; Humerickhouse, Rod; Punnoose, Elizabeth A; Li, Yan; Boyer, Michelle; Humphrey, Kathryn; Mobasher, Mehrdad; Kater, Arnon P

    2018-03-22

    Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival. After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary

  14. Rituximab for relapsing-remitting multiple sclerosis.

    PubMed

    He, Dian; Guo, Rui; Zhang, Fubo; Zhang, Chao; Dong, Shuai; Zhou, Hongyu

    2013-12-06

    This is an update of the Cochrane review "Rituximab for relapsing-remitting multiple sclerosis" (first published in The Cochrane Library 2011, Issue 12).More than 80% of individuals with multiple sclerosis (MS) experience a relapsing-remitting disease course. Approximately 10 years after disease onset, an estimated 50% of individuals with relapsing-remitting MS (RRMS) convert to secondary progressive MS. MS causes a major socioeconomic burden for the individual patient and for society. Effective treatment that reduces relapse frequency and prevents progression could impact both costs and quality of life and help to reduce the socioeconomic burden of MS. Alternative and more effective MS treatments with new modes of action and good safety are needed to expand the current treatment repertoire. It has been shown that B lymphocytes are involved in the pathophysiology of MS and rituximab lyses B-cells via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Current clinical trials are evaluating the role of rituximab as a B-cell depletion therapy in the treatment of RRMS. The safety and effectiveness of rituximab, as monotherapy or combination therapy, versus placebo or approved disease-modifying drugs (DMDs) (interferon-β (IFN-β), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab) to reduce disease activity for people with RRMS were assessed. The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (9 August 2013). We checked the references in identified trials and manually searched the reports (2004 to August 2013) from neurological associations and MS societies in Europe and America. We also communicated with researchers who were participating in trials on rituximab and contacted Genentech, BiogenIdec and Roche. All randomised, double-blind, controlled parallel group clinical trials with a length

  15. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia.

    PubMed

    Maury, Sébastien; Chevret, Sylvie; Thomas, Xavier; Heim, Dominik; Leguay, Thibaut; Huguet, Françoise; Chevallier, Patrice; Hunault, Mathilde; Boissel, Nicolas; Escoffre-Barbe, Martine; Hess, Urs; Vey, Norbert; Pignon, Jean-Michel; Braun, Thorsten; Marolleau, Jean-Pierre; Cahn, Jean-Yves; Chalandon, Yves; Lhéritier, Véronique; Beldjord, Kheira; Béné, Marie C; Ifrah, Norbert; Dombret, Hervé

    2016-09-15

    Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point. Rituximab was given during all treatment phases, for a total of 16 to 18 infusions. From May 2006 through April 2014, a total of 209 patients were enrolled: 105 in the rituximab group and 104 in the control group. After a median follow-up of 30 months, event-free survival was longer in the rituximab group than in the control group (hazard ratio, 0.66; 95% confidence interval [CI], 0.45 to 0.98; P=0.04); the estimated 2-year event-free survival rates were 65% (95% CI, 56 to 75) and 52% (95% CI, 43 to 63), respectively. Treatment with rituximab remained associated with longer event-free survival in a multivariate analysis. The overall incidence rate of severe adverse events did not differ significantly between the two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group. Adding rituximab to the ALL chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. (Funded by the Regional Clinical Research Office, Paris, and others; ClinicalTrials.gov number, NCT00327678 .).

  16. Rituximab maintenance for relapsed refractory thrombotic thrombocytopenic purpura.

    PubMed

    Bhagirath, Vinai C; Kelton, John G; Moore, Jane; Arnold, Donald M

    2012-12-01

    Rituximab, an anti-CD20 chimeric monoclonal antibody, has been used successfully to treat patients with relapsed or refractory thrombotic thrombocytopenic purpura (TTP); however, the optimal dose and frequency and the role of rituximab maintenance remain uncertain. We describe a 45-year-old woman with chronic relapsing immune thrombocytopenia who responded to rituximab retreatment administered in four doses over the course of 12 months. Previously, she had received four doses of rituximab and sustained a remission for 19 months. During her latest TTP relapse, multiple treatments were administered including rituximab retreatment. After the first dose (375 mg/m2), she developed serum sickness requiring further doses to be deferred. Three subsequent doses were administered at 4-month intervals over the course of 12 months. ADAMTS13 activity was measured by von Willebrand factor (VWF) digestion. ADAMTS13 inhibition was measured by a modification of the VWF digestion assay and anti-ADAMTS13 antibodies were measured by enzyme-linked immunoassay (enzyme-linked immunosorbent assay, American Diagnostica). Clinical and laboratory remission were achieved after one dose of rituximab, with normalization of ADAMTS13 activity and disappearance of ADAMTS13 inhibitor. Three subsequent doses of rituximab were given without incident and the patient remained in remission after 3.5 years of follow-up (2.5 years since her last dose of rituximab). Maintenance dosing of rituximab should be considered in some patients with relapsing TTP. © 2012 American Association of Blood Banks.

  17. Preparation & in vitro evaluation of 90Y-DOTA-rituximab

    PubMed Central

    Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

    2016-01-01

    Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried

  18. Rituximab-related viral infections in lymphoma patients.

    PubMed

    Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Dede, Didem Sener; Dizdar, Omer; Altundag, Kadri; Barista, Ibrahim

    2007-07-01

    Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

  19. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis

    PubMed Central

    Fornoni, Alessia; Sageshima, Junichiro; Wei, Changli; Merscher-Gomez, Sandra; Robier, Aguillon-Prada; Jauregui, Alexandra N.; Li, Jing; Mattiazzi, Adela; Ciancio, Gaetano; Chen, Linda; Zilleruelo, Gaston; Abitbol, Carolyn; Chandar, Jayanthi; Seeherunvong, Wacheree; Ricordi, Camillo; Ikehata, Masami; Rastaldi, Maria Pia; Reiser, Jochen; Burke, George W.

    2013-01-01

    Focal segmental glomerulosclerosis (FSGS) is a prevalent glomerular disease characterized by proteinuria, progression to end stage renal disease and recurrence of proteinuria after kidney transplantation in approximately one third of patients. It has been suggested that rituximab might treat recurrent FSGS through an unknown mechanism. Rituximab recognizes CD20 on B-lymphocytes but might also bind sphingomyelin-phosphodiesterase-acid-like-3b (SMPDL-3b) and regulates acid-sphyngomyelinase (ASMase) activity. We hypothesized that rituximab prevents recurrent FSGS and preserves podocyte SMPDL-3b expression. We studied 41 patients at high risk for recurrent FSGS, 27 of whom were treated with rituximab at time of kidney transplant. Incidence of nephrotic-range proteinuria and change in estimated glomerular filtration rate (ΔeGFR) were analyzed. SMPDL-3b immunostaining was performed in post-reperfusion kidney biopsies. SMPDL-3b protein, ASMase activity, and cytoskeleton remodeling were studied in cultured normal human podocytes that had been exposed to patient sera with or without rituximab. Rituximab treatment was associated with lower incidence of post-transplant proteinuria and decreased ΔeGFR. The number of SMPDL-3b+ podocytes in post-reperfusion biopsies was reduced in patients who developed recurrent FSGS. Rituximab partially prevented SMPDL-3b and ASMase downregulation that was observed in podocytes treated with the sera of patients with recurrent FSGS. Either SMPDL-3b overexpression or treatment with rituximab prevented disruption of the actin cytoskeleton and podocyte apoptosis induced by patient sera. This effect was diminished in cultured podocytes where the gene encoding SMPDL-3b was silenced. Our study suggests that treatment of high-risk patients with rituximab at time of kidney transplant might prevent recurrent FSGS by modulating podocyte function in an SMPDL-3b–dependent manner. PMID:21632984

  20. Desensitization to rituximab in a multidisciplinary setting.

    PubMed

    Amorós-Reboredo, Patrícia; Sánchez-López, Jaime; Bastida-Fernández, Carla; do Pazo-Oubiña, Fernando; Borràs-Maixenchs, Núria; Giné, Eva; Valero, Antonio; Creus-Baró, Natàlia

    2015-10-01

    The need to offer first-line therapy to the increasing number of patients who have suffered an hypersensitivity reaction has stimulated the use of rapid desensitization protocols. To present our experience working as a multidisciplinary team using a rituximab rapid desensitization scheme. Patient demographics, allergic reaction, skin tests to rituximab, number of desensitizations, reactions during the desensitization protocol and actions taken, number of administered and completed cycles, were retrospectively collected in patients who received at least one desensitization to rituximab. Number of desensitizations successfully managed. Between 2012 and June 2013 five patients received a total of 19 desensitizations to rituximab using a 12 step rapid desensitization protocol. All patients received the scheduled chemotherapeutic cycles as inpatients, with no delay in administration dates. Three patients presented a hypersensitivity reaction during the first desensitization and in one patient the event occurred again during the second treatment cycle. All reactions occurred in the last step, when the infusion rate reached the maximum speed. The developed protocol for rapid desensitization was successful in five patients receiving rituximab. Patients could receive the full intended dose.

  1. Rituximab as an immunosuppressant in antineutrophil cytoplasmic antibody-associated vasculitis

    PubMed Central

    McGregor, JulieAnne G.; Hogan, Susan L.; Kotzen, Elizabeth S.; Poulton, Caroline J.; Hu, Yichun; Negrete-Lopez, Roberto; Kidd, Jason M.; Katsanos, Suzanne L.; Bunch, Donna O.; Nachman, Patrick H.; Falk, Ronald J.

    2015-01-01

    Background Rituximab has been used in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) since 2003. Our objective was to describe outcomes and adverse events following rituximab since that time in an inception cohort. Methods Patients with AAV (diagnosed 1991–2012) who received rituximab (n = 120) were evaluated and incidence per person-year (PPY) with 95% confidence interval was calculated for relapse and infections. Time to remission and relapse by number of rituximab infusions given per treatment course (≤2 versus >2) and by ever having been exposed to cyclophosphamide were compared using Kaplan–Meier curves. Rituximab-treated patients were characterized in comparison with AAV patients treated with cyclophosphamide but not exposed to rituximab (n = 351) using Fisher's exact or rank tests. Results Rituximab resulted in 86% achieving remission and 41% having a subsequent relapse in a median of 19 months (range 9–29). Time to remission and relapse were similar between rituximab infusion courses (≤2 versus >2; remission P = 0.86 and relapse P = 0.78, respectively). Incidence of relapse was 0.22 PPY (0.14, 0.31) and of severe infection was 0.12 PPY (0.08, 0.24). Time to relapse was shorter in those never exposed to cyclophosphamide (n = 20): 50% by 8 months versus 50% by 24 and 30 months for those with prior or concurrent exposure to cyclophosphamide (n = 100). Compared with those who never received rituximab, rituximab-treated patients were younger (P < 0.001), more likely to have granulomatosis with polyangiitis (P = 0.001) and had more upper airway (P = 0.01) and less kidney involvement (P = 0.007). Conclusions Rituximab is beneficial when prescribed outside of a trial setting. Response to treatment and relapse is similar regardless of infusion number. Rituximab without cyclophosphamide may result in a shorter time to relapse supporting combination of these therapies. PMID:25805743

  2. Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab.

    PubMed

    Berman, Horacio; Rodríguez-Pintó, Ignasi; Cervera, Ricard; Morel, Nathalie; Costedoat-Chalumeau, Nathalie; Erkan, Doruk; Shoenfeld, Yehuda; Espinosa, Gerard

    2013-09-01

    The catastrophic variant of the antiphospholipid syndrome (APS) is characterized by thrombosis in multiple organs developing over a short period of time. First-line treatment for the catastrophic APS is the combination of anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulin. Despite this regimen, the mortality remains high and new treatment options are needed. By a systematic review of the Catastrophic APS Registry (CAPS Registry), we identified 20 patients treated with rituximab. The purpose of this study is to describe the clinical manifestations, laboratory features, and outcomes of rituximab-treated CAPS patients. In addition, the rationale for using rituximab in catastrophic APS is discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Rituximab in systemic lupus erythematosus and lupus nephritis.

    PubMed

    Beckwith, Hannah; Lightstone, Liz

    2014-01-01

    Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor. It has been used in the treatment of non-Hodgkin's lymphoma for over 30 years and has an excellent safety profile. Recent work has demonstrated a role for B cell depletion therapy in the management of autoimmune disease, and the efficacy of rituximab in many observational studies in SLE and LN has been noted. Unfortunately, two large randomised controlled trials evaluating rituximab for the treatment of renal and non-renal lupus failed to meet their primary endpoints. Reasons for this have been discussed extensively within the medical community with a general consensus that trial design (steroid use, trial size and endpoints used) was the principal reason for the failures. Despite the lack of trial evidence, clinical experience means many physicians firmly believe in the value of rituximab in SLE/LN treatment and have continued to use it in their clinical practice. Recent work has demonstrated the efficacy of rituximab as a steroid-sparing agent and as an alternative therapeutic option for refractory SLE/LN. There are two further rituximab randomised controlled trials planned/started in LN – one using a steroid-minimising regimen with rituximab for induction and one evaluating rituximab for LN refractory to 6 months standard of care treatment. Rituximab remains a problematic drug in lupus and LN – it is a biologically plausible agent with a huge amount of supportive

  4. Detection and quantification of rituximab in the human urine.

    PubMed

    Jacobs, Roland; Langer-Jacobus, Thais; Duong, Michelle; Stahl, Klaus; Haller, Hermann; Schmidt, Reinhold E; Schiffer, Mario

    2017-12-01

    B cell depletion by rituximab treatment might be inefficient in patients suffering from nephrotic syndrome. Due to the impaired glomerular filtration barrier a significant portion of the therapeutic antibody might be lost into the urinary space. In order to determine the amount of rituximab in the urine of such patients, CD20+ Daudi cells were stained with the patients' urine followed by a fluorochrome-labeled secondary antibody. Mean fluorescence intensity of that way labeled Daudi cells was determined by flow cytometry. Control samples with defined rituximab concentrations were used to create standard curves. The analyses revealed that all nephelometric IgG+ urine samples tested also manifested rituximab at concentrations between 100 and 46,707μg/L. The flow cytometry-based approach is an easy and reliable method to assess rituximab in patients' urine samples for monitoring individual rituximab treatment courses in all patients co-presenting impaired renal filtration. Presence of such antibodies in the urine could be considered as criteria to modify the formulation or modality of rituximab delivery in order to prevent the loss of the therapeutic antibodies and thereby ensuring efficacy of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Rituximab Therapy for Rejection in Pediatric Heart Transplant.

    PubMed

    Erdogan, Ilkay; Varan, Birgul; Sezgin, Atilla; Pirat, Arash; Zeyneloglu, Pinar

    2018-04-01

    Humoral rejection is the B-cell-mediated production of immunoglobulin G antibody against the transplanted heart. Antibody-mediated rejection may be resistant to standard immunosuppressive therapy and is associated with high mortality and graft loss. Rituximab can be used to treat antibody-mediated rejection in heart transplant recipients. This retrospective study describes our experience with rituximab treatment in children with heart transplants. We present 7 pediatric patients with antibody-mediated rejection who were treated with plasma exchange and rituximab therapy. Rituximab was given at a dose of 375 mg/m2 by slow infusion in the intensive care unit after 5 days of plasmapheresis, in addition to a conventional regimen consisting of steroids, mycophenolate mofetil, and tacrolimus. The peripheral blood count and sodium, potassium, serum urea nitrogen, creatinine, aspartate aminotransferase, and alanine aminotransferase levels were measured in all patients before and after treatment. Seven patients were treated with plasma exchange and rituximab. We repeated this therapy in 5 patients because of refractoriness or recurrent rejection. After diagnoses of antibody-mediated rejection, 4 patients died within 6 months (mortality rate of 57.1%). We did not observe any adverse effects or complications related to rituximab. Rituximab can be used in humoral rejection after pediatric heart transplant. However, the success of the treatment is controversial, and further study is needed to find an effective treatment for antibody-mediated rejection and steroid-resistant cellular rejection in children.

  6. Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis

    PubMed Central

    Stone, John H.; Merkel, Peter A.; Spiera, Robert; Seo, Philip; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Turkiewicz, Anthony; Tchao, Nadia K.; Webber, Lisa; Ding, Linna; Sejismundo, Lourdes P.; Mieras, Kathleen; Weitzenkamp, David; Ikle, David; Seyfert-Margolis, Vicki; Mueller, Mark; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina A.; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Specks, Ulrich

    2011-01-01

    BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; Clinical

  7. An In Vitro Comparison of PMMA and Calcium Sulfate as Carriers for the Local Delivery of Gallium(III) Nitrate to Staphylococcal Infected Surgical Sites

    PubMed Central

    Garcia, Rebecca A.; Tennent, David J.; Chang, David; Wenke, Joseph C.; Sanchez, Carlos J.

    2016-01-01

    Antibiotic-loaded bone cements, including poly(methyl methacrylate) (PMMA) and calcium sulfate (CaSO4), are often used for treatment of orthopaedic infections involving Staphylococcus spp., although the effectiveness of this treatment modality may be limited due to the emergence of antimicrobial resistance and/or the development of biofilms within surgical sites. Gallium(III) is an iron analog capable of inhibiting essential iron-dependent pathways, exerting broad antimicrobial activity against multiple microorganisms, including Staphylococcus spp. Herein, we evaluated PMMA and CaSO4 as carriers for delivery of gallium(III) nitrate (Ga(NO3)3) to infected surgical sites by assessing the release kinetics subsequent to incorporation and antimicrobial activity against S. aureus and S. epidermidis. PMMA and to a lesser extent CaSO4 were observed to be compatible as carriers for Ga(NO3)3, eluting concentrations with antimicrobial activity against planktonic bacteria, inhibiting bacterial growth, and preventing bacterial colonization of beads, and effective against established bacterial biofilms of S. aureus and S. epidermidis. Collectively, our in vitro results indicate that PMMA is a more suitable carrier compared to CaSO4 for delivery of Ga(NO3)3; moreover they provide evidence for the potential use of Ga(NO3)3 with PMMA as a strategy for the prevention and/or treatment for orthopaedic infections. PMID:26885514

  8. Gallium scan

    MedlinePlus

    ... material called gallium and is a type of nuclear medicine exam. A related test is gallium scan ... Brown ML, Forstrom LA, et al. Society of nuclear medicine procedure guideline for gallium scintigraphy in inflammation. ...

  9. Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder

    PubMed Central

    Nosadini, Margherita; Alper, Gulay; Riney, Catherine J.; Benson, Leslie A.; Mohammad, Shekeeb S.; Ramanathan, Sudarshini; Nolan, Melinda; Appleton, Richard; Leventer, Richard J.; Deiva, Kumaran; Brilot, Fabienne; Gorman, Mark P.; Waldman, Amy T.; Banwell, Brenda

    2016-01-01

    Objective: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. Methods: Multicenter retrospective study of 16 children with NMO/NMOSD receiving ≥2 rituximab courses. According to CD19 counts, events during rituximab were categorized as “repopulation,” “depletion,” or “depletion failure” relapses (repopulation threshold CD19 ≥10 × 106 cells/L). Results: The 16 patients (14 girls; mean age 9.6 years, range 1.8–15.3) had a mean of 6.1 events (range 1–11) during a mean follow-up of 6.1 years (range 1.6–13.6) and received a total of 76 rituximab courses (mean 4.7, range 2–9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 “repopulation,” 3 “depletion,” and 4 “depletion failure” relapses. Of the 13 “repopulation” relapses, 4 had CD19 10–50 × 106 cells/L, 10 had inadequate monitoring (≤1 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. Conclusion: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. Classification of evidence: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation

  10. Preparation & in vitro evaluation of ⁹⁰Y-DOTA-rituximab.

    PubMed

    Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

    2016-01-01

    Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the

  11. Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries

    PubMed Central

    De Cock, Erwin; Kritikou, Persefoni; Sandoval, Mariana; Tao, Sunning; Wiesner, Christof; Carella, Angelo Michele; Ngoh, Charles; Waterboer, Tim

    2016-01-01

    Background Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. Methods This non-interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient’s first year of treatment (11 rituximab sessions). Results Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p <0.0001). By country, relative reduction in time was 27–58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1–5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p <0.0001). By country, relative reduction was 53–91%. Absolute reduction in extrapolated chair time for the first year of treatment was 3.1–5.5 eight-hour days. Conclusions Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. Trial

  12. In vitro and in vivo antimicrobial activities of gallium nitrate against multidrug-resistant Acinetobacter baumannii.

    PubMed

    Antunes, Luísa C S; Imperi, Francesco; Minandri, Fabrizia; Visca, Paolo

    2012-11-01

    Multidrug-resistant Acinetobacter baumannii poses a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumannii chemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO(3))(3), the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58 A. baumannii strains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO(3))(3) delayed the entry of A. baumannii into the exponential phase and drastically reduced bacterial growth rates. Ga(NO(3))(3) activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO(3))(3) also protected Galleria mellonella larvae from lethal A. baumannii infection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO(3))(3) inhibited the growth in human serum of 76% of the multidrug-resistant A. baumannii isolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment of A. baumannii bloodstream infections. Ga(NO(3))(3) also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistant A. baumannii.

  13. In Vitro and In Vivo Antimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

    PubMed Central

    Antunes, Luísa C. S.; Imperi, Francesco; Minandri, Fabrizia

    2012-01-01

    Multidrug-resistant Acinetobacter baumannii poses a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumannii chemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO3)3, the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58 A. baumannii strains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO3)3 delayed the entry of A. baumannii into the exponential phase and drastically reduced bacterial growth rates. Ga(NO3)3 activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO3)3 also protected Galleria mellonella larvae from lethal A. baumannii infection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO3)3 inhibited the growth in human serum of 76% of the multidrug-resistant A. baumannii isolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment of A. baumannii bloodstream infections. Ga(NO3)3 also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistant A. baumannii. PMID:22964249

  14. Effect of gallium nitrate on the expression of osteoprotegerin and receptor activator of nuclear factor‑κB ligand in osteoblasts in vivo and in vitro.

    PubMed

    Li, Jingwu; Wang, Guang-Bin; Feng, Xue; Zhang, Jing; Fu, Qin

    2016-01-01

    Osteoporosis is characterized by the progressive loss of bone mass and the micro‑architectural deterioration of bone tissue, leading to bone fragility and an increased risk of fracture. Gallium has demonstrated efficacy in the treatment of several diverse disorders that are characterized by accelerated bone loss. Osteoblasts orchestrate bone degradation by expressing the receptor activator of NF‑κB ligand (RANKL), however they additionally protect the skeleton by secreting osteoprotegerin (OPG). Therefore, the relative concentration of RANKL and OPG in bone is a key determinant of bone mass and strength. The current study demonstrated that gallium nitrate (GaN) is able to counteract bone loss in an experimental model of established osteoporosis. Ovariectomized (OVX) rats exhibited significantly increased bone mineral density following GaN treatment for 4 and 8 weeks by 19.3 and 37.3%, respectively (P<0.05). The bone volume of the OVX + GaN group was increased by 40.9% (P<0.05) compared with the OVX group. In addition, the current study demonstrated that GaN stimulates the synthesis of OPG however has no effect on the expression of RANKL in osteoblasts, as demonstrated by RT‑qPCR, western blotting and ELISA, resulting in an increase in the OPG/RANKL ratio and a reduction in osteoclast differentiation in vivo and in vitro.

  15. Effect of gallium nitrate on the expression of osteoprotegerin and receptor activator of nuclear factor-κB ligand in osteoblasts in vivo and in vitro

    PubMed Central

    LI, JINGWU; WANG, GUANG-BIN; FENG, XUE; ZHANG, JING; FU, QIN

    2016-01-01

    Osteoporosis is characterized by the progressive loss of bone mass and the micro-architectural deterioration of bone tissue, leading to bone fragility and an increased risk of fracture. Gallium has demonstrated efficacy in the treatment of several diverse disorders that are characterized by accelerated bone loss. Osteoblasts orchestrate bone degradation by expressing the receptor activator of NF-κB ligand (RANKL), however they additionally protect the skeleton by secreting osteoprotegerin (OPG). Therefore, the relative concentration of RANKL and OPG in bone is a key determinant of bone mass and strength. The current study demonstrated that gallium nitrate (GaN) is able to counteract bone loss in an experimental model of established osteoporosis. Ovariectomized (OVX) rats exhibited significantly increased bone mineral density following GaN treatment for 4 and 8 weeks by 19.3 and 37.3%, respectively (P<0.05). The bone volume of the OVX + GaN group was increased by 40.9% (P<0.05) compared with the OVX group. In addition, the current study demonstrated that GaN stimulates the synthesis of OPG however has no effect on the expression of RANKL in osteoblasts, as demonstrated by RT-qPCR, western blotting and ELISA, resulting in an increase in the OPG/RANKL ratio and a reduction in osteoclast differentiation in vivo and in vitro. PMID:26647856

  16. Immunotherapy with Rituximab in Follicular Lymphomas

    PubMed Central

    SAGUNA, Carmen; MUT, Ileana Delia; LUPU, Anca Roxana; TEVET, Mihaela; BUMBEA, Horia; DRAGAN, Cornel

    2011-01-01

    ABSTRACT Background: Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory. The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. Material and method: The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, Bucharest Results and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab. PMID:22205891

  17. Immunotherapy with rituximab in follicular lymphomas.

    PubMed

    Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

    2011-04-01

    Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

  18. Rituximab in treatment of idiopathic glomerulopathy.

    PubMed

    El-Reshaid, Kamel; Sallam, Hossameldin Tawfik; Hakim, Abbass Ali; Al-Attiyah, Rajaa

    2012-09-01

    The aim of our study was to assess the role of rituximab (Mabthera) in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS). A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD) group, 31 of the 32 patients had complete remission (CR) and were off any immunosuppressive therapy and one of the previous non-responders (NR) did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months). Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS), while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG), 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab. The drug is

  19. Rituximab Retreatment for Low-Tumor Burden Follicular Lymphoma

    Cancer.gov

    A summary of results from a randomized clinical trial of patients with low–tumor burden follicular lymphoma that compared maintenance therapy with rituximab versus retreatment with rituximab only when there was evidence of disease progression.

  20. Rituximab

    PubMed Central

    Storz, Ulrich

    2014-01-01

    Because drug development is not a static process, a drug’s market authorisation may change over time. In many cases, the number of indications for which a drug is approved increases. Because this facet of drug development also comes at significant costs, a corresponding patent filing strategy is required to protect these investments. The strategy as applied to rituximab, which is approved for a variety of indications, is discussed in this review. PMID:24866199

  1. Rituximab and chemotherapy in diffuse large B-cell lymphoma.

    PubMed

    Sonet, Anne; Bosly, André

    2009-06-01

    Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

  2. Indium Gallium Nitride/Gallium Nitride (InGaN/GaN) Nanorods Superlattice (SL)

    DTIC Science & Technology

    2006-03-29

    Final Report (Technical) 3. DATES COVERED 29-03-2005 to 29-05-2006 4. TITLE AND SUBTITLE Indium Gallium Nitride/ Gallium Nitride (InGaN/GaN...Institution: Quantum functional Semiconductor Research Center (QSRC), Dongguk University - Title of project: Indium Gallium Nitride/ Gallium Nitride...Accepted with minor revision Indium Gallium Nitride / Gallium Nitride (InGaN/ GaN) Nanorods Superlattice (SL) Abstract The growth condition, electrical

  3. Vulvovaginal pyoderma gangrenosum secondary to rituximab therapy.

    PubMed

    Dixit, Shreya; Selva-Nayagam, Priya; Hamann, Ian; Fischer, Gayle

    2015-01-01

    Rituximab is being used increasingly for the treatment of B-cell malignancies and nonmalignant conditions. Pyoderma gangrenosum is a rare neutrophilic dermatosis, which can be either idiopathic or associated with underlying systemic inflammatory conditions. We present a series of 4 patients who presented with ulcerative pyoderma gangrenosum in the vulvovaginal area after treatment with rituximab.

  4. Sodium enhances indium-gallium interdiffusion in copper indium gallium diselenide photovoltaic absorbers.

    PubMed

    Colombara, Diego; Werner, Florian; Schwarz, Torsten; Cañero Infante, Ingrid; Fleming, Yves; Valle, Nathalie; Spindler, Conrad; Vacchieri, Erica; Rey, Germain; Guennou, Mael; Bouttemy, Muriel; Manjón, Alba Garzón; Peral Alonso, Inmaculada; Melchiorre, Michele; El Adib, Brahime; Gault, Baptiste; Raabe, Dierk; Dale, Phillip J; Siebentritt, Susanne

    2018-02-26

    Copper indium gallium diselenide-based technology provides the most efficient solar energy conversion among all thin-film photovoltaic devices. This is possible due to engineered gallium depth gradients and alkali extrinsic doping. Sodium is well known to impede interdiffusion of indium and gallium in polycrystalline Cu(In,Ga)Se 2 films, thus influencing the gallium depth distribution. Here, however, sodium is shown to have the opposite effect in monocrystalline gallium-free CuInSe 2 grown on GaAs substrates. Gallium in-diffusion from the substrates is enhanced when sodium is incorporated into the film, leading to Cu(In,Ga)Se 2 and Cu(In,Ga) 3 Se 5 phase formation. These results show that sodium does not decrease per se indium and gallium interdiffusion. Instead, it is suggested that sodium promotes indium and gallium intragrain diffusion, while it hinders intergrain diffusion by segregating at grain boundaries. The deeper understanding of dopant-mediated atomic diffusion mechanisms should lead to more effective chemical and electrical passivation strategies, and more efficient solar cells.

  5. Experimental Studies of Lateral Electron Transport in Gallium Arsenide-Aluminum Gallium Arsenide Heterostructures.

    DTIC Science & Technology

    1982-12-01

    AD-A125 858 EXPERIMENTAL STUDIES OF LATERAL ELECTRON TRANSPORT IN 1/3 GALLIUM ARSENIDE-RL..(U) ILLINOIS UNIV AT URBANA COORDINATED SCIENCE LAB N R...EXPERIMENTAL STUDIES OF LATERALXILECTRON TRANSPORT ,:g IN GALLIUM ARSENIDE -ALUMINUM GALLIUM ARSENIDE- -HETEROSTRUCTURES APRVE O PUBLICRLEAS.DSRBUINULMTE. 2...EXPERIMENTAL STUDIES OF LATERAL ELECTRON TRANSPORT IN GALLIUM ARSENIDE-ALUMINUM GALLIUM ARSENIDE Technical Report R-975 HETEROSTRUCTURES 6. PERFORMING ONG

  6. Current role of rituximab in systemic lupus erythematosus.

    PubMed

    Mok, Chi Chiu

    2015-02-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by periods of flares and remission, resulting in organ damage over time caused by persistent disease activity and treatment-related complications. Conventional therapies are not ideal in terms of efficacy and safety. Novel biological therapies are being developed to enhance therapeutic efficacy, minimize disease exacerbation and reduce toxicities. As dysregulation of B cells is the hallmark of SLE, B-cell targeted therapies are the focus of recent clinical research. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used with success in recalcitrant lupus manifestations. However, randomized controlled trials have failed to reveal its benefit in renal and non-renal SLE when combined with conventional immunosuppressive protocols. Although heterogeneity of SLE manifestations, pitfalls in study design and the limitations of the assessment tools for various clinical end points may have contributed to the discouraging results, rituximab remains an option in patients who are refractory or intolerant to conventional therapies. Recently, a regimen consisting of rituximab and mycophenolate mofetil without oral corticosteroids was reported to be effective in lupus nephritis. While the efficacy of this regimen has to be confirmed, future controlled trials should focus on the efficacy of rituximab in refractory lupus manifestations and its synergistic effect with other immunosuppressive agents such as cyclophosphamide. In short-term randomized controlled trials, a non-significant increase in serious adverse events was observed in SLE patients treated with rituximab. Long-term safety data of rituximab in SLE, in particular the incidence of hypogammaglobulinemia and serious/opportunistic infections, have to be continuously surveyed. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  7. Beneficial effect of tocilizumab in myasthenia gravis refractory to rituximab.

    PubMed

    Jonsson, Dagur Ingi; Pirskanen, Ritva; Piehl, Fredrik

    2017-06-01

    Muscle fatigue associated with myasthenia gravis is caused by autoantibodies interfering with neuromuscular transmission. Immunomodulating treatment is widely used in moderate to severe myasthenia, although the use of newer biological drugs except rituximab is rare. We describe the effect of tocilizumab, a blocker of interleukin-6 signalling, in two female myasthenia patients with high titres of serum acetylcholine receptor antibodies and insufficient response to rituximab. The first patient had been treated with high dose immunoglobulins regularly for several years and the second patient had been treated both with different oral immune suppressants and immunoglobulins before testing a low dose of rituximab without significant clinical effect. Subsequent treatment with tocilizumab resulted in clinical improvement within a few months. The first patient was switched back to rituximab, which resulted in worsening until tocilizumab was restarted. Tocilizumab can be a therapeutic option in cases not responding to rituximab. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

    PubMed

    Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

    2012-05-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

  9. Refractory pemphigus vulgaris treated with rituximab and mycophenolate mofetil*

    PubMed Central

    Biot, Stephanie Del Rio Navarrete; Franco, Joanna Pimenta de Araujo; Lima, Ricardo Barbosa; Pereira, Henrique Novo Costa; Marques, Luiz Paulo José; Martins, Carlos José

    2014-01-01

    The main treatment for pemphigus vulgaris are systemic corticosteroids and immunosuppressive agents, but due to adverse reactions and therapeutic failure, new drugs such as rituximab and mycophenolate mofetil have been used. In this case report are described two cases of severe pemphigus vulgaris refractory to various treatments, with resolution after use of rituximab and mycophenolate mofetil, associated with corticosteroids. A higher-than-usual dose of rituximab was employed, without the occurrence of serious adverse reactions. Mycophenolate mofetil was added as adjunctive therapy due to lack of response to azathioprine. PMID:25387507

  10. A retrospective study on the management of patients with rituximab refractory follicular lymphoma.

    PubMed

    Solal-Céligny, Philippe; Leconte, Pierre; Bardet, Aurélie; Hernandez, Juana; Troussard, Xavier

    2018-01-01

    Given that there are currently no clear recommendations regarding therapeutic options for rituximab refractory/relapsed follicular lymphoma patients, this study aimed to describe the real-life management of patients with refractory follicular lymphoma after systemic rituximab-containing regimens (rFL), and rFL patient characteristics. In this retrospective, national, multicentre study, descriptive analyses were mainly performed according to rituximab-containing regimen at rFL diagnosis [rituximab monotherapy (R-MONO), rituximab + chemotherapy (R-COMBO), and ongoing rituximab maintenance (R-MAINTAIN)]. The 459 analysed patients experienced rituximab-refractoriness between October 2013 and September 2015: R-MONO: 58 (13%), R-COMBO: 197 (43%), R-MAINTAIN: 204 (44%). Post-refractoriness strategies were heterogeneous: idelalisib ± rituximab (22%), without anti-lymphoma treatment (21%), rituximab-chemotherapy (21%) and stem cell transplantation (18%). Rituximab was continued in combination in 41% of cases. Chosen strategies varied according to patient age (without anti-lymphoma treatment: 28% of patients if ≥65 years vs. 12% if <65 years old; stem-cell transplantation: 4% vs. 38%), treatment line at rFL, FL International Prognostic Index score and prior treatment. This French retrospective study, the first one conducted in a large cohort of rFL patients, showed that further strategies were highly heterogeneous, depending notably on patient characteristics and previous treatment. These data are the basis for a better understanding of rFL management and for the design of clinical trials in these patients. © 2017 John Wiley & Sons Ltd.

  11. Comparative clinical evaluation of gallium-aluminum-arsenide diode laser and potassium nitrate in treating dentinal hypersensitivity.

    PubMed

    Tevatia, Siddharth; Khatri, Vivek; Sharma, Nikhil; Dodwad, Vidya

    2017-01-01

    Dentinal hypersensitivity (DH) is a chronic disorder in which patients report sharp and acute pain to a variety of stimuli. Till date, a standardized procedure to treat DH is missing, though several alternative treatment strategies have been designed, including laser therapies. The aim of the study was to treat DH with minimum chemical concentration and least laser energy level with longer follow-up period. One hundred and twenty patients were randomly divided into four groups: (i) Group 1-5% potassium nitrate (KNO 3 ); (ii) Group 2 - gallium-aluminum-arsenide diode laser (62.2 J/cm 2 , wavelength - 980 nm, noncontact pulse mode, and power wattage - 0.5 W); (iii) Group 3 - combined 5% KNO 3 and the diode laser; and (iv) Group 4 - placebo (control). The visual analog scale (VAS) scores were recorded, analyzed, and compared to tactile stimuli, cold water, and air blast tests at different intervals for 6 weeks. Synergistic use of 5% KNO 3 and diode laser (Group 3) significantly reduced the DH pain, which was almost negligible after 6 th week (97%-99% of the pain was reported to be relieved) and showed promising results than any other studied groups. Further, the diode laser (Group 2) showed better results than 5% KNO 3 (Group 1). One-way ANOVA and Bonferroni correction post hoc test revealed the combination of groups with significant differences in the mean VAS scores at the different interval of time ( P < 0.01). Convincingly, the combined application of 5% KNO 3 with the diode laser can be recommended for treating DH patients.

  12. Rituximab-based treatment, HCV replication, and hepatic flares.

    PubMed

    Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

    2012-01-01

    Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

  13. Gallium nitride optoelectronic devices

    NASA Technical Reports Server (NTRS)

    Chu, T. L.; Chu, S. S.

    1972-01-01

    The growth of bulk gallium nitride crystals was achieved by the ammonolysis of gallium monochloride. Gallium nitride single crystals up to 2.5 x 0.5 cm in size were produced. The crystals are suitable as substrates for the epitaxial growth of gallium nitride. The epitaxial growth of gallium nitride on sapphire substrates with main faces of (0001) and (1T02) orientations was achieved by the ammonolysis of gallium monochloride in a gas flow system. The grown layers had electron concentrations in the range of 1 to 3 x 10 to the 19th power/cu cm and Hall mobilities in the range of 50 to 100 sq cm/v/sec at room temperature.

  14. The Effect of Rituximab on Vaccine Responses in Patients with Immune Thrombocytopenia

    PubMed Central

    Nazi, Ishac; Kelton, John G.; Larché, Mark; Snider, Denis P.; Heddle, Nancy M.; Crowther, Mark A.; Cook, Richard J.; Tinmouth, Alan T.; Mangel, Joy; Arnold, Donald M.

    2013-01-01

    B-cell depletion therapy may impair vaccine responses and increase infection risk in patients with immune thrombocytopenia (ITP). Capitalizing on a multicenter randomized placebo-controlled trial, we investigated the effects of rituximab on the antibody and cellular responses to Streptococcus pneumoniae polysaccharide vaccine and Haemophilus influenzae type b (Hib) conjugate vaccine in ITP patients. Of 60 patients in the main trial, 24 patients received both vaccines 6 months after rituximab (n=17) or placebo (n=7). Among 20 evaluable patients, 3/14 (21%) in the rituximab group and 4/6 (67%) in the placebo group achieved a 4-fold increase in anti-pneumococcal antibodies (p=0.12). For anti-Hib antibodies, 4/14 (29%) and 5/6 (83%), respectively, achieved a 4-fold increase (p<0.05). Fewer patients in the rituximab group demonstrated functional Hib killing (2/14 [14%] versus 5/6 [83%], p<0.05). Three of 14 rituximab-treated patients failed to respond to vaccines by any criteria. After vaccinations, pre-plasma cell blasts and interferon-γ secreting T-cells were reduced in rituximab-treated patients. We found that antibody responses were impaired for at least 6 months after rituximab. Cellular immunity was reduced in parallel with the depleted B-cell pool. These findings have implications for the timing of vaccinations and the mechanism of infection after rituximab in patients with ITP. PMID:23851398

  15. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function.

    PubMed

    Pescovitz, Mark D; Greenbaum, Carla J; Krause-Steinrauf, Heidi; Becker, Dorothy J; Gitelman, Stephen E; Goland, Robin; Gottlieb, Peter A; Marks, Jennifer B; McGee, Paula F; Moran, Antoinette M; Raskin, Philip; Rodriguez, Henry; Schatz, Desmond A; Wherrett, Diane; Wilson, Darrell M; Lachin, John M; Skyler, Jay S

    2009-11-26

    The immunopathogenesis of type 1 diabetes mellitus is associated with T-lymphocyte autoimmunity. However, there is growing evidence that B lymphocytes play a role in many T-lymphocyte-mediated diseases. It is possible to achieve selective depletion of B lymphocytes with rituximab, an anti-CD20 monoclonal antibody. This phase 2 study evaluated the role of B-lymphocyte depletion in patients with type 1 diabetes. We conducted a randomized, double-blind study in which 87 patients between 8 and 40 years of age who had newly diagnosed type 1 diabetes were assigned to receive infusions of rituximab or placebo on days 1, 8, 15, and 22 of the study. The primary outcome, assessed 1 year after the first infusion, was the geometric mean area under the curve (AUC) for the serum C-peptide level during the first 2 hours of a mixed-meal tolerance test. Secondary outcomes included safety and changes in the glycated hemoglobin level and insulin dose. At 1 year, the mean AUC for the level of C peptide was significantly higher in the rituximab group than in the placebo group. The rituximab group also had significantly lower levels of glycated hemoglobin and required less insulin. Between 3 months and 12 months, the rate of decline in C-peptide levels in the rituximab group was significantly less than that in the placebo group. CD19+ B lymphocytes were depleted in patients in the rituximab group, but levels increased to 69% of baseline values at 12 months. More patients in the rituximab group than in the placebo group had adverse events, mostly grade 1 or grade 2, after the first infusion. The reactions appeared to be minimal with subsequent infusions. There was no increase in infections or neutropenia with rituximab. A four-dose course of rituximab partially preserved beta-cell function over a period of 1 year in patients with type 1 diabetes. The finding that B lymphocytes contribute to the pathogenesis of type 1 diabetes may open a new pathway for exploration in the treatment of

  16. Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma.

    PubMed

    Le Gouill, Steven; Thieblemont, Catherine; Oberic, Lucie; Moreau, Anne; Bouabdallah, Krimo; Dartigeas, Caroline; Damaj, Gandhi; Gastinne, Thomas; Ribrag, Vincent; Feugier, Pierre; Casasnovas, Olivier; Zerazhi, Hacène; Haioun, Corinne; Maisonneuve, Hervé; Houot, Roch; Jardin, Fabrice; Van Den Neste, Eric; Tournilhac, Olivier; Le Dû, Katell; Morschhauser, Franck; Cartron, Guillaume; Fornecker, Luc-Matthieu; Canioni, Danielle; Callanan, Mary; Béné, Marie C; Salles, Gilles; Tilly, Hervé; Lamy, Thierry; Gressin, Remy; Hermine, Olivier

    2017-09-28

    Mantle-cell lymphoma is generally incurable. Despite high rates of complete response after initial immunochemotherapy followed by autologous stem-cell transplantation, patients have relapses. We investigated whether rituximab maintenance therapy at a dose of 375 mg per square meter of body-surface area administered every 2 months for 3 years after transplantation would prolong the duration of response. In a phase 3 trial involving 299 patients who were younger than 66 years of age at diagnosis, we randomly assigned 240 patients to receive rituximab maintenance therapy or to undergo observation after autologous stem-cell transplantation (120 patients per group); 59 patients did not undergo randomization. The primary end point was event-free survival (with an event defined as disease progression, relapse, death, allergy to rituximab, or severe infection) after transplantation among patients who underwent randomization. After four courses of immunochemotherapy induction (rituximab, dexamethasone, cytarabine, and a platinum derivative [R-DHAP]), the overall response rate was 89%, and the complete response rate 77%. Transplantation was performed in 257 patients. The median follow-up from randomization after transplantation was 50.2 months (range, 46.4 to 54.2). Starting from randomization, the rate of event-free survival at 4 years was 79% (95% confidence interval [CI], 70 to 86) in the rituximab group versus 61% (95% CI, 51 to 70) in the observation group (P=0.001). The rate of progression-free survival at 4 years was 83% (95% CI, 73 to 88) in the rituximab group versus 64% (95% CI, 55 to 73) in the observation group (P<0.001). The rate of overall survival was 89% (95% CI, 81 to 94) in the rituximab group versus 80% (95% CI, 72 to 88) in the observation group (P=0.04). According to a Cox regression unadjusted analysis, the rate of overall survival at 4 years was higher in the rituximab group than in the observation group (hazard ratio for death, 0.50; 95% CI, 0.26 to 0

  17. Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

    PubMed Central

    Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

    2012-01-01

    Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

  18. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy

    PubMed Central

    Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

    2018-01-01

    We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN. PMID:29582832

  19. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

    PubMed

    Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

    2018-04-01

    We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  20. Rituximab in anti-GBM disease: A retrospective study of 8 patients.

    PubMed

    Touzot, Maxime; Poisson, Johanne; Faguer, Stanislas; Ribes, David; Cohen, Pascal; Geffray, Loic; Anguel, Nadia; François, Helene; Karras, Alexandre; Cacoub, Patrice; Durrbach, Antoine; Saadoun, David

    2015-06-01

    Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Low Temperature Flux Growth of 2H-SiC and Beta-Gallium Oxide

    NASA Technical Reports Server (NTRS)

    Singh, N. B.; Choa, Fow-Sen; Su, Ching-Hua; Arnold, Bradley; Kelly, Lisa

    2016-01-01

    We present brief overview of our study on the low temperature flux growth of two very important novel wide bandgap materials 2H-SiC and Beta-gallium oxide (Beta-Ga2O3). We have synthesized and grown 5 millimeter to 1 centimeter size single crystals of Beta-gallium oxide (Beta-Ga2O3). We used a flux and semi wet method to grow transparent good quality crystals. In the semi-wet method Ga2O3 was synthesized with starting gallium nitrate solution and urea as a nucleation agent. In the flux method we used tin and other metallic flux. This crystal was placed in an alumina crucible and temperature was raised above 1050 degrees Centigrade. After a time period of thirty hours, we observed prismatic and needle shaped crystals of gallium oxide. Scanning electron microscopic studies showed step growth morphology. Crystal was polished to measure the properties. Bandgap was measured 4.7electronvolts using the optical absorption curve. Another wide bandgap hexagonal 2H-SiC was grown by using Si-Al eutectic flux in the graphite crucible. We used slight AlN also as the impurity in the flux. The temperature was raised up to 1050 degrees Centigrade and slowly cooled to 850 degrees Centigrade. Preliminary characterization results of this material are also reported.

  2. Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

    PubMed

    Klepfish, A; Rachmilevitch, E; Schattner, A

    2006-11-01

    A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

  3. Rituximab in highly sensitized kidney transplant recipients.

    PubMed

    Munoz, A S; Rioveros, A A; Cabanayan-Casasola, C B; Danguilan, R A; Ona, E T

    2008-09-01

    Rituximab, an anti-CD20 monoclonal antibody therapy, depletes B cells and suppresses antibody production. This study sought to describe the efficacy and safety of rituximab among seven highly sensitized kidney transplant patients. A highly sensitized patient was defined as panel-reactive antibody (PRA) >30%, more than three pregnancies, or history of positive tissue crossmatch. Demographics, immunological risk profile, and immunosuppression were collected on all highly sensitized patients transplanted from March to July 2007 and given rituximab. We noted graft function as well as clinical events posttransplantation. The seven patients included in the study showed a mean age of 39 years (range = 17-60) and a mean follow-up of 3 months (range = 1.5-5). Their average PRA was 62% with mean HLA mismatches of three. Five patients (71%) were retransplantations; one had a history of a positive crossmatch, and two had multiple pregnancies. Two had donor-specific antibody, but negative tissue crossmatches. All had living donors. Six patients received a single dose of rituximab (375 mg/m2) 1 day prior to transplantation and one received two doses after 19 sessions of plasmapheresis. All were given tacrolimus, mycophenolate, and steroids combined with induction therapy using 30 mg alemtuzumab in 33%; two doses of 20 mg basiliximab in 33%; and seven doses of 1 mg/kg/dose of daclizumab in 14%. Mean shown creatinine levels were 1.1 and 1.2 mg/dL at 1 and 6 months posttransplantation. Two recipients experienced acute humoral rejections within 1 month after transplantation. Both were given steroid pulsing, one of whom was steroid-resistant necessitating alemtuzumab therapy and plasmapheresis. Graft function of both improved with creatinine values of 1.3 mg/dL on discharge. No episodes of infection were noted. Rituximab can be safely administered and may be effective to improve outcomes among highly sensitized kidney transplant patients.

  4. Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review.

    PubMed

    Thiebaut, Mathilde; Launay, David; Rivière, Sébastien; Mahévas, Thibault; Bellakhal, Syrine; Hachulla, Eric; Fain, Olivier; Mekinian, Arsène

    2018-06-01

    To describe safety and efficacy of rituximab in patients with systemic sclerosis. We included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones. Thirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [-4; 4] vs loss of -7 [-19; 0]; p=0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [-16.8; 2.5], (p=0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p=0.007), 13 [8; 18] at M12 (p=0.008) and 10 [4; 16] at the last follow-up (p=0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p=0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p=0.04). Our personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium

    PubMed Central

    Runci, Federica; Bonchi, Carlo; Frangipani, Emanuela; Visaggio, Daniela

    2016-01-01

    ABSTRACT Biofilm-associated infections caused by Acinetobacter baumannii are extremely recalcitrant to antibiotic treatment. We report that A. baumannii develops a mature biofilm when grown in complement-free human serum (HS). We demonstrate that 16 μM gallium nitrate (GaN) drastically reduces A. baumannii growth and biofilm formation in HS, whereas 64 μM GaN causes massive disruption of preformed A. baumannii biofilm. These findings pave the way to the repurposing of GaN as an antibiofilm agent for A. baumannii. PMID:27799219

  6. Gallium--A smart metal

    USGS Publications Warehouse

    Foley, Nora; Jaskula, Brian W.

    2013-01-01

    Gallium is a soft, silvery metallic element with an atomic number of 31 and the chemical symbol Ga. The French chemist Paul-Emile Lecoq de Boisbaudran discovered gallium in sphalerite (a zinc-sulfide mineral) in 1875 using spectroscopy. He named the element "gallia" after his native land of France (formerly Gaul; in Latin, Gallia). The existence of gallium had been predicted in 1871 by Dmitri Mendeleev, the Russian chemist who published the first periodic table of the elements. Mendeleev noted a gap in his table and named the missing element "eka-aluminum" because he determined that its location was one place away from aluminum in the table. Mendeleev thought that the missing element (gallium) would be very much like aluminum in its chemical properties, and he was right. Solid gallium has a low melting temperature (~29 degrees Celsius, or °C) and an unusually high boiling point (~2,204 °C). Because of these properties, the earliest uses of gallium were in high-temperature thermometers and in designing metal alloys that melt easily. The development of a gallium-based direct band-gap semiconductor in the 1960s led to what is now one of the most well-known applications for gallium-based products--the manufacture of smartphones and data-centric networks.

  7. REACTIVATION OF LATENT VIRUSES IN INDIVIDUALS RECEIVING RITUXIMAB FOR NEW ONSET TYPE 1 DIABETES

    PubMed Central

    Kroll, Jing Lu; Beam, Craig; Li, Shaobing; Viscidi, Raphael; Dighero, Bonnie; Cho, Alice; Boulware, David; Pescovitz, Mark; Weinberg, Adriana

    2013-01-01

    Background Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. Objectives To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. Study Design Subjects received 4 weekly doses of rituximab (N=57) or placebo (N=30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. Results EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p<0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p<0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. Conclusions Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses. PMID:23422292

  8. Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes.

    PubMed

    Kroll, Jing Lu; Beam, Craig; Li, Shaobing; Viscidi, Raphael; Dighero, Bonnie; Cho, Alice; Boulware, David; Pescovitz, Mark; Weinberg, Adriana

    2013-06-01

    Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. Subjects received 4 weekly doses of rituximab (N = 57) or placebo (N = 30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p < 0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p < 0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome.

    PubMed

    Stahl, Klaus; Duong, Michelle; Schwarz, Anke; Wagner, A D; Haller, Hermann; Schiffer, Mario; Jacobs, Roland

    2017-01-01

    Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

  10. Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

    PubMed

    Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

    2018-02-01

    Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p < 0.0001). Five patients in the relapsed group also had a total of 10 relapses after B-cell recovery; their median time from B-cell recovery to initial relapse was significantly shorter than in the non-relapsed group (31 vs. 161 days, p = 0.014). Number of relapses before rituximab, history of steroid resistance, onset age, previous treatment, time to ceasing steroids after rituximab, and duration of B-cell depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

  11. Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study

    PubMed Central

    Michallet, Anne-Sophie; Aktan, Melih; Hiddemann, Wolfgang; Ilhan, Osman; Johansson, Peter; Laribi, Kamel; Meddeb, Balkis; Moreno, Carol; Raposo, João; Schuh, Anna; Ünal, Ali; Widenius, Tom; Bernhardt, Alf; Kellershohn, Kerstin; Messeri, Dimitri; Osborne, Stuart; Leblond, Véronique

    2018-01-01

    MABLE investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rituximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (rituximab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall survival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus bendamustine than rituximab plus chlorambucil (66% vs. 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia. PMID:29419437

  12. Comparative clinical evaluation of gallium-aluminum-arsenide diode laser and potassium nitrate in treating dentinal hypersensitivity

    PubMed Central

    Tevatia, Siddharth; Khatri, Vivek; Sharma, Nikhil; Dodwad, Vidya

    2017-01-01

    Context: Dentinal hypersensitivity (DH) is a chronic disorder in which patients report sharp and acute pain to a variety of stimuli. Till date, a standardized procedure to treat DH is missing, though several alternative treatment strategies have been designed, including laser therapies. Aim: The aim of the study was to treat DH with minimum chemical concentration and least laser energy level with longer follow-up period. Materials and Methods: One hundred and twenty patients were randomly divided into four groups: (i) Group 1-5% potassium nitrate (KNO3); (ii) Group 2 - gallium-aluminum-arsenide diode laser (62.2 J/cm2, wavelength - 980 nm, noncontact pulse mode, and power wattage - 0.5 W); (iii) Group 3 - combined 5% KNO3 and the diode laser; and (iv) Group 4 - placebo (control). The visual analog scale (VAS) scores were recorded, analyzed, and compared to tactile stimuli, cold water, and air blast tests at different intervals for 6 weeks. Results: Synergistic use of 5% KNO3 and diode laser (Group 3) significantly reduced the DH pain, which was almost negligible after 6th week (97%–99% of the pain was reported to be relieved) and showed promising results than any other studied groups. Further, the diode laser (Group 2) showed better results than 5% KNO3 (Group 1). One-way ANOVA and Bonferroni correction post hoc test revealed the combination of groups with significant differences in the mean VAS scores at the different interval of time (P < 0.01). Conclusions: Convincingly, the combined application of 5% KNO3 with the diode laser can be recommended for treating DH patients. PMID:29491586

  13. Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

    PubMed

    Zara, Gabriella; Zambello, Renato; Ermani, M

    2011-12-01

    Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. Idiopathic orbital inflammatory disease successfully treated with rituximab.

    PubMed

    Schafranski, Marcelo Derbli

    2009-02-01

    We report a case of a 66-year-old Caucasian female with a diagnosis of idiopathic orbital inflammatory disease (OID) refractory to azathioprine therapy. The coexistence of diabetes mellitus represented a relative contraindication to chronic prednisone use. After two infusions of rituximab, a chimeric anti-CD20+ antibody, ophthalmic signs and symptoms remarkably improved. To our knowledge, this is the first case of idiopathic OID successfully treated with rituximab.

  15. Eficiency of different doses of rituximab in rheumatoid arthritis.

    PubMed

    Mena-Vázquez, Natalia; Manrique-Arija, Sara; Ureña-Garnica, Inmaculada; Romero-Barco, Carmen M; Jiménez-Núñez, Francisco G; Coret, Virginia; Irigoyen-Oyarzábal, María Victoria; Fernández-Nebro, Antonio

    2016-01-01

    Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium.

    PubMed

    Runci, Federica; Bonchi, Carlo; Frangipani, Emanuela; Visaggio, Daniela; Visca, Paolo

    2017-01-01

    Biofilm-associated infections caused by Acinetobacter baumannii are extremely recalcitrant to antibiotic treatment. We report that A. baumannii develops a mature biofilm when grown in complement-free human serum (HS). We demonstrate that 16 μM gallium nitrate (GaN) drastically reduces A. baumannii growth and biofilm formation in HS, whereas 64 μM GaN causes massive disruption of preformed A. baumannii biofilm. These findings pave the way to the repurposing of GaN as an antibiofilm agent for A. baumannii. Copyright © 2016 American Society for Microbiology.

  17. B-lymphocyte depletion with rituximab and β-cell function: two-year results.

    PubMed

    Pescovitz, Mark D; Greenbaum, Carla J; Bundy, Brian; Becker, Dorothy J; Gitelman, Stephen E; Goland, Robin; Gottlieb, Peter A; Marks, Jennifer B; Moran, Antoinette; Raskin, Philip; Rodriguez, Henry; Schatz, Desmond A; Wherrett, Diane K; Wilson, Darrell M; Krischer, Jeffrey P; Skyler, Jay S

    2014-02-01

    We previously reported that selective depletion of B-lymphocytes with rituximab, an anti-CD20 monoclonal antibody, slowed decline of β-cell function in recent-onset type 1 diabetes mellitus (T1DM) at 1 year. Subjects were followed further to determine whether there was persistence of effect. Eighty-seven subjects (aged 8-40 years) were randomly assigned to, and 81 received, infusions of rituximab or placebo on days 1, 8, 15, and 22. The primary outcome-baseline-adjusted mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 1 year-showed higher C-peptide AUC with rituximab versus placebo. Subjects were further followed with additional MMTTs every 6 months. The rate of decline of C-peptide was parallel between groups but shifted by 8.2 months in rituximab-treated subjects. Over 30 months, AUC, insulin dose, and HbA1c were similar for rituximab and placebo. However, in evaluating change in C-peptide over the entire follow-up period, the rituximab group means were significantly larger as compared within assessment times with the placebo group means using a global test (P = 0.03). Odds ratio for loss of C-peptide to <0.2 nmol/L following rituximab was 0.565 (P = 0.064). B-lymphocytes recovered to baseline values by 18 months. Serum IgG levels were maintained in the normal range but IgM levels were depressed. Like several other immunotherapeutic approaches tested, in recent-onset T1DM, rituximab delays the fall in C-peptide but does not appear to fundamentally alter the underlying pathophysiology of the disease.

  18. Effect of Rituximab in Patients With Leucine-Rich, Glioma-Inactivated 1 Antibody–Associated Encephalopathy

    PubMed Central

    Irani, Sarosh R.; Gelfand, Jeffrey M.; Bettcher, Brianne M.; Singhal, Neel S.; Geschwind, Michael D.

    2015-01-01

    IMPORTANCE This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)–complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody–associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases. OBSERVATIONS This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48–73 years) treated with rituximab. Median time from symptom onset to rituximab initiation was 414 days (range, 312–851 days). One patient showed a rapid clinical improvement after treatment with rituximab alone and experienced a rituximab-responsive clinical relapse. Another showed possible improvement on neuropsychometric memory indexes after rituximab therapy. In contrast, all patients showed robust responses to treatment with glucocorticoids, intravenous immunoglobulins, and/or plasma exchange at some point in their illness. Treatment with glucocorticoids—less so with intravenous immunoglobulins and plasma exchange—was associated with the most marked reductions in VGKC-complex antibodies. The only patient who did not receive glucocorticoids showed the poorest clinical and serologic responses. CONCLUSIONS AND RELEVANCE Rituximab was well tolerated in this predominantly older adult patient population and may be an effective option for some patients with LGI1 antibody–associated encephalopathy. Glucocorticoid therapy appears particularly efficacious. Earlier rituximab administration and randomized trials are required to formally assess efficacy. PMID:24842754

  19. Rituximab-associated infections.

    PubMed

    Gea-Banacloche, Juan C

    2010-04-01

    After more than 10 years of use, rituximab has proven to be remarkably safe. However, accumulated evidence now suggests that under some circumstances it may significantly increase the risk of infections. This risk is difficult to quantify because of confounding factors (namely, concomitant use of immunosuppressive or chemotherapeutic agents and underlying conditions), as well as under-reporting. Increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by human immunodeficiency virus (HIV) infection or immunosuppressive agents like fludarabine. From the practical standpoint, the most important infection is hepatitis B reactivation, which may be delayed and result in fulminant liver failure and death. Special care should be placed on screening for hepatitis B virus (HBV) and preemptive antiviral treatment. Some investigators have reported an increase in Pneumocystis pneumonia. Finally, there is increasing evidence of a possible association with progressive multifocal leukoencephalopathy (PML), a lethal encephalitis caused by the polyomavirus JC. This review enumerates the described infectious complications, summarizes the possible underlying mechanisms of the increased risk, and makes recommendations regarding prevention, diagnosis and management.

  20. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up

    PubMed Central

    Debiec, Hanna; Plaisier, Emmanuelle; Cachanado, Marine; Rousseau, Alexandra; Wakselman, Laura; Michel, Pierre-Antoine; Mihout, Fabrice; Dussol, Bertrand; Matignon, Marie; Mousson, Christiane; Simon, Tabassome

    2017-01-01

    Randomized trials of rituximab in primary membranous nephropathy (PMN) have not been conducted. We undertook a multicenter, randomized, controlled trial at 31 French hospitals (NCT01508468). Patients with biopsy-proven PMN and nephrotic syndrome after 6 months of nonimmunosuppressive antiproteinuric treatment (NIAT) were randomly assigned to 6-month therapy with NIAT and 375 mg/m2 intravenous rituximab on days 1 and 8 (n=37) or NIAT alone (n=38). Median times to last follow-up were 17.0 (interquartile range, 12.5–24.0) months and 17.0 (interquartile range, 13.0–23.0) months in NIAT-rituximab and NIAT groups, respectively. Primary outcome was a combined end point of complete or partial remission of proteinuria at 6 months. At month 6, 13 (35.1%; 95% confidence interval [95% CI], 19.7 to 50.5) patients in the NIAT-rituximab group and eight (21.1%; 95% CI, 8.1 to 34.0) patients in the NIAT group achieved remission (P=0.21). Rates of antiphospholipase A2 receptor antibody (anti–PLA2R-Ab) depletion in NIAT-rituximab and NIAT groups were 14 of 25 (56%) and one of 23 (4.3%) patients at month 3 (P<0.001) and 13 of 26 (50%) and three of 25 (12%) patients at month 6 (P=0.004), respectively. Eight serious adverse events occurred in each group. During the observational phase, remission rates before change of assigned treatment were 24 of 37 (64.9%) and 13 of 38 (34.2%) patients in NIAT-rituximab and NIAT groups, respectively (P<0.01). Positive effect of rituximab on proteinuria remission occurred after 6 months. These data suggest that PLA2R-Ab levels are early markers of rituximab effect and that addition of rituximab to NIAT does not affect safety. PMID:27352623

  1. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

    PubMed

    Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

    2016-06-01

    To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Rituximab used in three cases with relapsed non-Hodgkin’s lymphoma

    PubMed Central

    ELLI, MURAT; YILMAZ, SEMA; AYDIN, RAMAZAN; MURAT, SADRIYE; BILGICI, MELTEM CEYHAN; DAGDEMIR, AYHAN

    2013-01-01

    Relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL) patients have a poor prognosis. New treatment modalities have been used to improve survival rates in children with relapsed or refractory B-NHL. CD20 is expressed in >98% of childhood B-NHL and a chimeric anti-CD20 monoclonal antibody, rituximab, is increasingly being used at relapse. The aim of the present study was to determine the efficacy of rituximab on relapsed B-NHL. Three B-NHL cases were treated successfully with a combination of intensive chemotherapy protocol plus rituximab. PMID:24649209

  3. Socioeconomic inequality in the use of rituximab therapy among non-Hodgkin lymphoma patients in Chinese public hospitals.

    PubMed

    Yu-Wen, Huang; Mei-Bian, Zhang; Xiang, Xu; Xiao-Hua, Xu; Quan, Zhou; Le, Jian

    2014-03-01

    Rituximab is a patient-paid effective monoclonal-antibody drug for non-Hodgkin lymphoma (NHL). Little is known in China, a country with unequal distribution of wealth and medical insurance systems, about the impact of socioeconomic status (SES) on selecting rituximab therapy in NHL patients. A total of 328 NHL inpatients in 2 public hospitals in Hangzhou were recruited and divided into 2 equal groups: with rituximab therapy and with no rituximab therapy group. Selection and frequency of rituximab therapy increased with duration of education and in urban citizens (P < .01). Officers and businessmen were more likely to use rituximab therapy compared with farmers (P < .01). Patients covered by Urban Employee Basic Medical Insurance were more likely to select rituximab therapy than those insured with Urban-Rural Residents Basic Medical Insurance (P < .01). There was an inequality in provision of rituximab therapy among Chinese NHL patients, and this was associated with differences in SES status. Effective measures are suggested to ameliorate the inequality issue.

  4. Rituximab in refractory myasthenia gravis: extended prospective study results.

    PubMed

    Beecher, Grayson; Anderson, Dustin; Siddiqi, Zaeem A

    2018-05-09

    Rituximab appears beneficial in treatment-refractory myasthenia gravis (MG), however, prospective, long-term durability data is lacking. In this prospective, open-label study of rituximab in refractory MG, 22 patients (10 AChR, 9 MuSK, 3 seronegative) received rituximab at baseline, with repeat cycles driven by clinical worsening. Manual muscle testing (MMT) scores and CD19/CD20+ B cell counts were serially monitored. At mean follow-up of 28.8 ± 19.0 months (range=6-66 months), mean MMT scores declined from 10.6 ± 5.4 to 3.3 ± 3.1 (p<0.0001). Mean prednisone dose declined from 25.2 ± 15.1 mg/d to 7.3 ± 7.1 mg/d (p=0.002). Ten relapses occurred, with average time to first relapse of 17.1 ± 5.5 months (range=9-23 months). CD19/CD20+ count recovery did not predict relapse. Three patients experienced prolonged B cell depletion (range=24-45 months) after one cycle. Sustained clinical improvement was associated with rituximab after one cycle, with prolonged time to relapse and reduction in steroid dose. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  5. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

    PubMed

    Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepanski, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

    2010-09-01

    This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

  6. Relapsed chronic lymphocytic leukemia retreated with rituximab: interim results of the PERLE study.

    PubMed

    Chaoui, Driss; Choquet, Sylvain; Sanhes, Laurence; Mahé, Béatrice; Hacini, Maya; Fitoussi, Olivier; Arkam, Yazid; Orfeuvre, Hubert; Dilhuydy, Marie-Sarah; Barry, Marly; Jourdan, Eric; Dreyfus, Brigitte; Tempescul, Adrian; Leprêtre, Stéphane; Bardet, Aurélie; Leconte, Pierre; Maynadié, Marc; Delmer, Alain

    2017-06-01

    This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%). The overall response rate (ORR) was 74.6%, in favor of R-purine analogs (90%), R-bendamustine (75%), and R-alkylating agents (69%). Lower ORR in Del 17p patients (43%) and third time rituximab (31%). Most frequent adverse events were hematological (23% patients) including neutropenia (11%) and infections (12%); grade 3/4 AEs (23% patients), mainly hematological (18%); death during induction treatment (7%). This first large study focusing on relapsed/refractory CLL patients retreated with rituximab-based regimens is still ongoing.

  7. Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia.

    PubMed

    Dretzke, J; Barton, P; Kaambwa, B; Connock, M; Uthman, O; Bayliss, S; Meads, C

    2010-10-01

    This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators' data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer's model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer's base-case incremental cost-effectiveness ratio (ICER) changed from 15,593 pounds to between 40,000 pounds and 42,000 pounds per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the

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

    PubMed Central

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

    2016-01-01

    Abstract Objective. To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. Methods. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Results. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19 + B cells and CD68 + macrophages in responders. Conclusion. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. PMID:27215813

  9. Fundamental studies of the metallurgical, electrical, and optical properties of gallium phosphide and gallium phosphide alloys

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Abstracts, bibliographic data, oral presentations, and published papers on (1) Diffusion of Sulfur in Gallium Phosphide and Gallium Arsenide, and (2) Properties of Gallium Phosphide Schottky Barrier Rectifiers for Use at High Temperature are presented.

  10. Renal amyloidosis. Evaluation by gallium imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, V.W.; Skinner, M.; Cohen, A.S.

    1986-09-01

    A study has been performed to evaluate the efficacy of gallium imaging in the detection of renal amyloidosis. Ten of the 11 patients who had biopsy-proven renal amyloidosis demonstrated marked uptake in both kidneys. One patient revealed moderate gallium uptake in his kidneys. None of the patients had underlying renal or extrarenal pathology other than amyloidosis, which could account for renal gallium uptake (renal infection, neoplasm, hepatic failure or frequent blood transfusions). Four patients also had extrarenal foci of abnormal gallium uptake, suggesting other sites of amyloid deposits. Our data strongly suggest that gallium imaging has a high sensitivity formore » detection of renal amyloidosis. Its specificity is enhanced significantly by careful review of the clinical history to exclude other known causes of renal gallium uptake. Potentially, gallium imaging may be used to monitor the progress of patients under experimental therapy.« less

  11. Use of Rituximab for Refractory Cytopenias Associated with Autoimmune Lymphoproliferative Syndrome (ALPS)

    PubMed Central

    Rao, V. Koneti; Price, Susan; Perkins, Katie; Aldridge, Patricia; Tretler, Jean; Davis, Joie; Dale, Janet K.; Gill, Fred; Hartman, Kip R.; Stork, Linda C.; Gnarra, David J.; Krishnamurti, Lakshmanan; Newburger, Peter E.; Puck, Jennifer; Fleisher, Thomas

    2009-01-01

    Background ALPS is a disorder of apoptosis resulting in accumulation of autoreactive lymphocytes, leading to marked lymphadenopathy, hepatosplenomegaly and multilineage cytopenias due to splenic sequestration and/or autoimmune destruction often presenting in childhood. We summarize our experience of rituximab use during the last 8 years in twelve patients, 9 children and 3 adults, out of 259 individuals with ALPS, belonging to 166 families currently enrolled in studies at the National Institutes of Health. Methods Refractory immune thrombocytopenia (platelet count <20,000) in 9 patients and autoimmune hemolytic anemia (AIHA) in 3 patients led to treatment with rituximab. Among them, 7 patients had undergone prior surgical splenectomy; 3 had significant splenomegaly; and 2 had no palpable spleen. Results In 7 out of 9 patients with ALPS and thrombocytopenia, rituximab therapy led to median response duration of 21months (range 14–36 months). In contrast, none of the 3 children treated with rituximab for AIHA responded. Noted toxicities included profound and prolonged hypogammaglobulinemia in 3 patients requiring replacement IVIG, total absence of antibody response to polysaccharide vaccines lasting up to 4 years after rituximab infusions in 1 patient and prolonged neutropenia in 1 patient. Conclusion Toxicities including hypogammaglobulinemia and neutropenia constitute an additional infection risk burden, especially in asplenic individuals, and may warrant avoidance of rituximab until other immunosuppressive medication options are exhausted. Long term follow up of ALPS patients with cytopenias after any treatment is necessary to determine relative risks and benefits. PMID:19214977

  12. Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

    PubMed

    Aguirre-Valencia, David; Posso-Osorio, Iván; Bravo, Juan-Carlos; Bonilla-Abadía, Fabio; Tobón, Gabriel J; Cañas, Carlos A

    2017-09-01

    Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

  13. Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

    PubMed

    Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

    2014-10-15

    Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial.

    PubMed

    Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin; Busch, Raymonde; Kovacs, Gabor; Maurer, Christian; Lange, Elisabeth; Köppler, Hubert; Kiehl, Michael; Sökler, Martin; Schlag, Rudolf; Vehling-Kaiser, Ursula; Köchling, Georg; Plöger, Christoph; Gregor, Michael; Plesner, Torben; Trneny, Marek; Fischer, Kirsten; Döhner, Harmut; Kneba, Michael; Wendtner, Clemens-Martin; Klapper, Wolfram; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Böttcher, Sebastian; Hallek, Michael

    2016-07-01

    Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab. Treatment-naive fit patients with chronic lymphocytic leukaemia (aged 33-81 years) without del(17p) were enrolled after undergoing a central screening process. Patients were randomly assigned (1:1) with a computer-generated randomisation list using randomly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage. Patients were allocated to receive six cycles of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days or to intravenous bendamustine (90 mg/m(2) per day) for the first 2 days of each cycle. Rituximab 375 mg/m(2) was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m(2) during the next five cycles on day 1. The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the standard therapy. We aimed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67·5% or less with a corresponding non-inferiority margin of 1·388 for the hazard ratio (HR) based on the 90·4% CI. The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included in the intention-to-treat population: 282 patients in the fludarabine, cyclophosphamide, and rituximab group and 279 in the bendamustine and rituximab group. After a median observation time of 37·1 months (IQR 31·0

  15. Long-chain amine-templated synthesis of gallium sulfide and gallium selenide nanotubes

    NASA Astrophysics Data System (ADS)

    Seral-Ascaso, A.; Metel, S.; Pokle, A.; Backes, C.; Zhang, C. J.; Nerl, H. C.; Rode, K.; Berner, N. C.; Downing, C.; McEvoy, N.; Muñoz, E.; Harvey, A.; Gholamvand, Z.; Duesberg, G. S.; Coleman, J. N.; Nicolosi, V.

    2016-06-01

    We describe the soft chemistry synthesis of amine-templated gallium chalcogenide nanotubes through the reaction of gallium(iii) acetylacetonate and the chalcogen (sulfur, selenium) using a mixture of long-chain amines (hexadecylamine and dodecylamine) as a solvent. Beyond their role as solvent, the amines also act as a template, directing the growth of discrete units with a one-dimensional multilayer tubular nanostructure. These new materials, which broaden the family of amine-stabilized gallium chalcogenides, can be tentatively classified as direct large band gap semiconductors. Their preliminary performance as active material for electrodes in lithium ion batteries has also been tested, demonstrating great potential in energy storage field even without optimization.We describe the soft chemistry synthesis of amine-templated gallium chalcogenide nanotubes through the reaction of gallium(iii) acetylacetonate and the chalcogen (sulfur, selenium) using a mixture of long-chain amines (hexadecylamine and dodecylamine) as a solvent. Beyond their role as solvent, the amines also act as a template, directing the growth of discrete units with a one-dimensional multilayer tubular nanostructure. These new materials, which broaden the family of amine-stabilized gallium chalcogenides, can be tentatively classified as direct large band gap semiconductors. Their preliminary performance as active material for electrodes in lithium ion batteries has also been tested, demonstrating great potential in energy storage field even without optimization. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01663d

  16. 49 CFR 173.162 - Gallium.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Gallium. 173.162 Section 173.162 Transportation... PACKAGINGS Non-bulk Packaging for Hazardous Materials Other Than Class 1 and Class 7 § 173.162 Gallium. (a) Except when packaged in cylinders or steel flasks, gallium must be packaged in packagings which meet the...

  17. 49 CFR 173.162 - Gallium.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Gallium. 173.162 Section 173.162 Transportation... PACKAGINGS Non-bulk Packaging for Hazardous Materials Other Than Class 1 and Class 7 § 173.162 Gallium. (a) Except when packaged in cylinders or steel flasks, gallium must be packaged in packagings which meet the...

  18. 49 CFR 173.162 - Gallium.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Gallium. 173.162 Section 173.162 Transportation... PACKAGINGS Non-bulk Packaging for Hazardous Materials Other Than Class 1 and Class 7 § 173.162 Gallium. (a) Except when packaged in cylinders or steel flasks, gallium must be packaged in packagings which meet the...

  19. Efficacy of rituximab (anti‐CD20) for refractory systemic lupus erythematosus involving the central nervous system

    PubMed Central

    Tokunaga, Mikiko; Saito, Kazuyoshi; Kawabata, Daisuke; Imura, Yoshitaka; Fujii, Takao; Nakayamada, Shingo; Tsujimura, Shizuyo; Nawata, Masao; Iwata, Shigeru; Azuma, Taeko; Mimori, Tsuneyo; Tanaka, Yoshiya

    2007-01-01

    Aim Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious treatment‐resistant phenotype of systemic lupus erythematosus. A standard treatment for NPSLE is not available. This report describes the clinical and laboratory tests of 10 patients with NPSLE before and after rituximab treatment, including changes in lymphocyte phenotypes. Methods Rituximab was administered at different doses in 10 patients with refractory NPSLE, despite intensive treatment. Results Treatment with rituximab resulted in rapid improvement of central nervous system‐related manifestations, particularly acute confusional state. Rituximab also improved cognitive dysfunction, psychosis and seizure, and reduced the SLE Disease Activity Index Score at day 28 in all 10 patients. These effects lasted for >1 year in five patients. Flow cytometric analysis showed that rituximab down regulated CD40 and CD80 on B cells and CD40L, CD69 and inducible costimulator on CD4+ T cells. Conclusions Rituximab rapidly improved refractory NPSLE, as evident by resolution of various clinical signs and symptoms and improvement of radiographic findings. The down regulation of functional molecules on B and T cells suggests that rituximab modulates the interaction of activated B and T cells through costimulatory molecules. These results warrant further analysis of rituximab as treatment for NPSLE. PMID:17107983

  20. [Rituximab: a new therapeutic alternative in Grave's disease].

    PubMed

    Tello-Winniczuk, Nina; Díaz-Jouanen, Efraín

    2011-01-01

    Graves' disease is the most frequent cause of hyperthyroidism, affecting mainly young aged women, with an etiology of autoimmune basis. One of its manifestations, Graves' ophthalmopathy whose pathophysiology is unknown, represents one of the greatest therapeutic challenges in these patients, because they require aggressive treatment with steroids and multiple subsequent reconstructive surgeries in certain cases. It also represents a high burden to the health system. Drugs targeting B cells have been very effective for many autoimmune diseases. Rituximab is a murine humanized monoclonal antibody against CD20 + cells currently being studied in various autoimmune diseases including Graves' disease. The objective of this paper is to expose possible mechanisms by which rituximab could act in both hyperthyroidism and ophthalmopathy of Graves' disease, as well as the experience with its use acquired so far. The employment of rituximab in recently diagnosed patients or with mild ophthalmopathy is questionable with the evidence available today however, we think that it may have a role in refractory cases or those who have a contraindication for steroid use.

  1. Mineral resource of the month: gallium

    USGS Publications Warehouse

    Jaskula, Brian W.

    2009-01-01

    The metal element gallium occurs in very small concentrations in rocks and ores of other metals — native gallium is not known. As society gets more and more high-tech, gallium becomes more useful. Gallium is one of only five metals that are liquid at or close to room temperature. It has one of the longest liquid ranges of any metal (29.8 degrees Celsius to 2204 degrees Celsius) and has a low vapor pressure even at high temperatures. Ultra-pure gallium has a brilliant silvery appearance, and the solid metal exhibits conchoidal fracture similar to glass.

  2. Controlled Electrochemical Deformation of Liquid-Phase Gallium.

    PubMed

    Chrimes, Adam F; Berean, Kyle J; Mitchell, Arnan; Rosengarten, Gary; Kalantar-zadeh, Kourosh

    2016-02-17

    Pure gallium is a soft metal with a low temperature melting point of 29.8 °C. This low melting temperature can potentially be employed for creating optical components with changeable configurations on demand by manipulating gallium in its liquid state. Gallium is a smooth and highly reflective metal that can be readily maneuvered using electric fields. These features allow gallium to be used as a reconfigurable optical reflector. This work demonstrates the use of gallium for creating reconfigurable optical reflectors manipulated through the use of electric fields when gallium is in a liquid state. The use of gallium allows the formed structures to be frozen and preserved as long as the temperature of the metal remains below its melting temperature. The lens can be readily reshaped by raising the temperature above the melting point and reapplying an electric field to produce a different curvature of the gallium reflector.

  3. Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab.

    PubMed

    Hamaki, T; Kami, M; Kusumi, E; Ueyama, J; Miyakoshi, S; Morinaga, S; Mutou, Y

    2001-12-01

    A 53-year-old man who had a history of fluminant hepatitis caused by precore mutant hepatitis B virus (HBV) was admitted to our hospital for the treatment of relapsed non-Hodgkin's lymphoma in July 2000. At admission, serum levels of aspartate aminotransferase and alanine aminotransferase were normal, but he tested positive for HBs antigen. The titer was 64-fold by radioimmunoassay. We initiated lamivudine at a daily dose of 75 mg to prevent HBV proliferation during chemotherapy. By September 2000, he had received six courses of rituximab at 375 mg/m(2) and four courses of fludarabine and mitoxantrone. No hepatic damage was observed from the initiation of treatment until March 2001. At present, four months after the completion of chemotherapy, he continues lamivudine, and the titer of HBs antigen is low at 4-fold. Rituximab is usually associated with mild toxicity, usually limited to infusion periods. The drug is not generally associated with increased incidence of opportunistic infections. However, some case reports have been recently published on severe viral infections following administration of rituximab. These include fluminant hepatitis caused by HBV, pure red cell aplasia due to parvovirus B19 and fatal varicella-zoster infection. While it remains unknown whether rituximab can be safely administered in patients with chronic HBV infection, this case report suggested that prophylactic administration of lamivudine is beneficial for suppressing reactivation of HBV during chemotherapy including rituximab. Rituximab should be used cautiously for patients with HBV infection, but prophylactic administration of lamivudine may be beneficial for preventing reactivation of HBV. Copyright 2001 Wiley-Liss, Inc.

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

    PubMed

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

    2016-09-01

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

  5. Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era

    PubMed Central

    Gisselbrecht, Christian; Glass, Bertram; Mounier, Nicolas; Singh Gill, Devinder; Linch, David C.; Trneny, Marek; Bosly, Andre; Ketterer, Nicolas; Shpilberg, Ofer; Hagberg, Hans; Ma, David; Brière, Josette; Moskowitz, Craig H.; Schmitz, Norbert

    2010-01-01

    Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001). Conclusion In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP. PMID:20660832

  6. Rituximab-Related Late-Onset Neutropenia in Kidney Transplant Recipients Treated for Antibody-Mediated Acute Rejection.

    PubMed

    Ahmadi, Fatemeh; Dashti-Khavidaki, Simin; Khatami, Mohammad-Reza; Lessan-Pezeshki, Mahboob; Khalili, Hossein; Khosravi, Malihe

    2017-08-01

    Kidney transplant is a new area for use of rituximab, which is being used to treat acute antibody-mediated rejection or as an induction agent in ABO- or HLA-incompatible grafts. We report on late-onset neutropenia in rituximab-treated kidney transplant recipients with antibody-mediated rejection. This observational prospective study was performed on kidney transplant recipients with clinically suspicious or biopsy-proven antibody-mediated rejection treated with plasmapheresis plus intravenous immunoglobulin with (cases) or without (controls) rituximab. Compared with none of the controls, 4 of 6 patients (66.7%) in the rituximab-treated group experienced late-onset neutropenia 35 to 93 days after the last dose of rituximab. The course of neutropenia was complicated by endocarditis in 1 patient, resulting in his death just because of a lack of valvular surgery. Increased use of rituximab to treat antibody-mediated rejection among kidney transplant recipients requires attention to its late-onset adverse event, neutropenia. Although asymptomatic in some patients, kidney transplant recipients treated concomitantly with plasmapheresis and mycophenolate mofetil are predisposed to hypogammaglobulinemia, and monitoring of patients for infections is required.

  7. [Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

    PubMed

    Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

    2016-06-01

    Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE))

    PubMed Central

    Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepański, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

    2010-01-01

    Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Methods Patients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. Results At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Conclusions Rituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses. PMID:20488885

  9. Synchrotron X-Ray Fluorescence Microscopy of Gallium in Bladder Tissue following Gallium Maltolate Administration during Urinary Tract Infection

    PubMed Central

    Sampieri, Francesca; Chirino, Manuel; Hamilton, Don L.; Blyth, Robert I. R.; Sham, Tsun-Kong; Dowling, Patricia M.; Thompson, Julie

    2013-01-01

    A mouse model of cystitis caused by uropathogenic Escherichia coli was used to study the distribution of gallium in bladder tissue following oral administration of gallium maltolate during urinary tract infection. The median concentration of gallium in homogenized bladder tissue from infected mice was 1.93 μg/g after daily administration of gallium maltolate for 5 days. Synchrotron X-ray fluorescence imaging and X-ray absorption spectroscopy of bladder sections confirmed that gallium arrived at the transitional epithelium, a potential site of uropathogenic E. coli infection. Gallium and iron were similarly but not identically distributed in the tissues, suggesting that at least some distribution mechanisms are not common between the two elements. The results of this study indicate that gallium maltolate may be a suitable candidate for further development as a novel antimicrobial therapy for urinary tract infections caused by uropathogenic E. coli. PMID:23877680

  10. Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies

    PubMed Central

    2017-01-01

    Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed. PMID:28573137

  11. Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review.

    PubMed

    Hehir, Michael K; Hobson-Webb, Lisa D; Benatar, Michael; Barnett, Carolina; Silvestri, Nicholas J; Howard, James F; Howard, Diantha; Visser, Amy; Crum, Brian A; Nowak, Richard; Beekman, Rachel; Kumar, Aditya; Ruzhansky, Katherine; Chen, I-Hweii Amy; Pulley, Michael T; LaBoy, Shannon M; Fellman, Melissa A; Greene, Shane M; Pasnoor, Mamatha; Burns, Ted M

    2017-09-05

    To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls ( p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) ( p = 0.001 and p = 0.005). This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome. © 2017 American Academy of Neurology.

  12. Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.

    PubMed

    Egawa, H; Teramukai, S; Haga, H; Tanabe, M; Mori, A; Ikegami, T; Kawagishi, N; Ohdan, H; Kasahara, M; Umeshita, K

    2014-01-01

    We evaluated the effects of rituximab prophylaxis on outcomes of ABO-blood-type-incompatible living donor liver transplantation (ABO-I LDLT) in 381 adult patients in the Japanese registry of ABO-I LDLT. Patients underwent dual or triple immunosuppression with or without B cell desensitization therapies such as plasmapheresis, splenectomy, local infusion, intravenous immunoglobulin and rituximab. Era before 2005, intensive care unit-bound status, high Model for End-Stage Liver Disease score and absence of rituximab prophylaxis were significant risk factors for overall survival and antibody-mediated rejection (AMR) in the univariate analysis. After adjustment for era effects in the multivariate analysis, only absence of rituximab prophylaxis was a significant risk factor for AMR, and there were no significant risk factors for survival. Rituximab prophylaxis significantly decreased the incidence of AMR, especially hepatic necrosis (p < 0.001). In the rituximab group, other B cell desensitization therapies had no add-on effects. Multiple or large rituximab doses significantly increased the incidence of infection, and early administration had no advantage. In conclusion, outcomes in adult ABO-I LDLT have significantly improved in the latest era coincident with the introduction of rituximab. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial.

    PubMed

    Rummel, Mathias J; Niederle, Norbert; Maschmeyer, Georg; Banat, G Andre; von Grünhagen, Ulrich; Losem, Christoph; Kofahl-Krause, Dorothea; Heil, Gerhard; Welslau, Manfred; Balser, Christina; Kaiser, Ulrich; Weidmann, Eckhart; Dürk, Heinz; Ballo, Harald; Stauch, Martina; Roller, Fritz; Barth, Juergen; Hoelzer, Dieter; Hinke, Axel; Brugger, Wolfram

    2013-04-06

    Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas. We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m(2) on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m(2) on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335. 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69.5 months [26.1 to not yet reached] vs 31.2 months [15.2-65.7]; hazard ratio 0.58, 95% CI 0.44-0.74; p

  14. The Preparation and Structural Characterization of Three Structural Types of Gallium Compounds Derived from Gallium (II) Chloride

    NASA Technical Reports Server (NTRS)

    Gordon, Edward M.; Hepp, Aloysius F.; Duraj. Stan A.; Habash, Tuhfeh S.; Fanwick, Phillip E.; Schupp, John D.; Eckles, William E.; Long, Shawn

    1997-01-01

    The three compounds Ga2Cl4(4-mepy)2 (1),[GaCl2(4-mepy)4]GaCl4x1/2(4-mepy); (2) and GaCl2(4-mepy)2(S2CNEt2); (3) (4-mepy= 4-methylpyridine) have been prepared from reactions of gallium (II) chloride in 4-methylpyridine and characterized by single-crystal X-ray analysis. Small variations in the reaction conditions for gallium(II) chloride can produce crystals with substantially different structural properties. The three compounds described here encompass a neutral gallium(II) dimer in which each gallium is four-coordinate, an ionic compound containing both anionic and cationic gallium complex ions with different coordination numbers and a neutral six-coordinate heteroleptic

  15. Construction of Gallium Point at NMIJ

    NASA Astrophysics Data System (ADS)

    Widiatmo, J. V.; Saito, I.; Yamazawa, K.

    2017-03-01

    Two open-type gallium point cells were fabricated using ingots whose nominal purities are 7N. Measurement systems for the realization of the melting point of gallium using these cells were built. The melting point of gallium is repeatedly realized by means of the measurement systems for evaluating the repeatability. Measurements for evaluating the effect of hydrostatic pressure coming from the molten gallium existing during the melting process and the effect of gas pressure that fills the cell were also performed. Direct cell comparisons between those cells were conducted. This comparison was aimed to evaluate the consistency of each cell, especially related to the nominal purity. Direct cell comparison between the open-type and the sealed-type gallium point cell was also conducted. Chemical analysis was conducted using samples extracted from ingots used in both the newly built open-type gallium point cells, from which the effect of impurities in the ingot was evaluated.

  16. Rituximab treatment in primary angiitis of the central nervous system.

    PubMed

    Patel, Shreeya; Ross, Laura; Oon, Shereen; Nikpour, Mandana

    2018-06-01

    Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis affecting the brain and spinal cord. Treatment with biological agents has revolutionised the treatment of many rheumatic conditions but there is scant literature regarding the use of biological agents in PACNS. We present three cases of PACNS treated with rituximab, including two cases of relapsed disease, and a literature review suggesting a role for rituximab in this condition. © 2018 Royal Australasian College of Physicians.

  17. Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience.

    PubMed

    Salles, Gilles; Barrett, Martin; Foà, Robin; Maurer, Joerg; O'Brien, Susan; Valente, Nancy; Wenger, Michael; Maloney, David G

    2017-10-01

    Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue. F. Hoffmann-La Roche Ltd., Basel, Switzerland.

  18. P-type gallium nitride

    DOEpatents

    Rubin, M.; Newman, N.; Fu, T.; Ross, J.; Chan, J.

    1997-08-12

    Several methods have been found to make p-type gallium nitride. P-type gallium nitride has long been sought for electronic devices. N-type gallium nitride is readily available. Discovery of p-type gallium nitride and the methods for making it will enable its use in ultraviolet and blue light-emitting diodes and lasers. pGaN will further enable blue photocathode elements to be made. Molecular beam epitaxy on substrates held at the proper temperatures, assisted by a nitrogen beam of the proper energy produced several types of p-type GaN with hole concentrations of about 5{times}10{sup 11} /cm{sup 3} and hole mobilities of about 500 cm{sup 2} /V-sec, measured at 250 K. P-type GaN can be formed of unintentionally-doped material or can be doped with magnesium by diffusion, ion implantation, or co-evaporation. When applicable, the nitrogen can be substituted with other group III elements such as Al. 9 figs.

  19. P-type gallium nitride

    DOEpatents

    Rubin, Michael; Newman, Nathan; Fu, Tracy; Ross, Jennifer; Chan, James

    1997-01-01

    Several methods have been found to make p-type gallium nitride. P-type gallium nitride has long been sought for electronic devices. N-type gallium nitride is readily available. Discovery of p-type gallium nitride and the methods for making it will enable its use in ultraviolet and blue light-emitting diodes and lasers. pGaN will further enable blue photocathode elements to be made. Molecular beam epitaxy on substrates held at the proper temperatures, assisted by a nitrogen beam of the proper energy produced several types of p-type GaN with hole concentrations of about 5.times.10.sup.11 /cm.sup.3 and hole mobilities of about 500 cm.sup.2 /V-sec, measured at 250.degree. K. P-type GaN can be formed of unintentionally-doped material or can be doped with magnesium by diffusion, ion implantation, or co-evaporation. When applicable, the nitrogen can be substituted with other group III elements such as Al.

  20. Development of a Multi-layer Anti-reflective Coating for Gallium Arsenide/Aluminum Gallium Arsenide Solar Cells

    DTIC Science & Technology

    2015-07-01

    optical loss mechanism, which limits the efficiency of the PV device.1 Photon absorption needs to occur inside the solar cell active region (near the...Aluminum Gallium Arsenide Solar Cells by Kimberley A Olver Approved for public release; distribution unlimited...Development of a Multi-layer Anti-reflective Coating for Gallium Arsenide/Aluminum Gallium Arsenide Solar Cells by Kimberley A Olver

  1. Hepatitis B reactivation and rituximab: a new boxed warning and considerations for solid organ transplantation.

    PubMed

    Martin, S T; Cardwell, S M; Nailor, M D; Gabardi, S

    2014-04-01

    Use of rituximab, a chimeric monoclonal antibody directed at the CD20 antigen, continues to increase in solid organ transplantation (SOT) for several off-label uses. In September 2013, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication to oncology, rheumatology and pharmacy communities outlining a new Boxed Warning for rituximab. Citing 109 cases of fatal hepatitis B virus (HBV) reactivation in persons receiving rituximab therapy with previous or chronic HBV infection documented in their Adverse Event Reporting System (AERS), the FDA recommends screening for HBV serologies in all patients planned to receive rituximab and antiviral prophylaxis in any patient with a positive history of HBV infection. There is a lack of data pertaining to this topic in the SOT population despite an increase in off-label indications. Previous reports suggest patients receiving rituximab, on average, were administered six doses prior to HBV reactivation. Recommendations on prophylaxis, treatment and re-challenging patients with therapy after resolution of reactivation remain unclear. Based on data from the FDA AERS and multiple analyses in oncology, SOT providers utilizing rituximab should adhere to the FDA warnings and recommendations regarding HBV reactivation until further data are available in the SOT population. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Population pharmacokinetics of rituximab in patients with diffuse large B-cell lymphoma and association with clinical outcome.

    PubMed

    Rozman, Samo; Grabnar, Iztok; Novaković, Srdjan; Mrhar, Ales; Jezeršek Novaković, Barbara

    2017-08-01

    Pharmacokinetic (PK) studies suggest that there is a room for improvement in clinical use of rituximab through more individualized treatment. The objective of this study was to characterize rituximab PK in 29 newly diagnosed patients with diffuse large B-cell lymphoma treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every 3 weeks. We also evaluated the association of rituximab PK with clinical outcome. Rituximab serum levels were determined by enzyme-linked immunosorbent assay and evaluated by a population PK analysis applying nonlinear mixed effects modelling. The data were best described by a two-compartment model comprising linear nonspecific clearance of 0.252 [95% confidence interval (CI): 0.227-0.279] l day -1 and time-varying specific clearance of 0.278 (95% CI: 0.181-0.390) l day -1 , corresponding to target-mediated drug disposition of rituximab. Nonspecific clearance was lower in older patients and those with lower body weight. Additionally, volume of the central compartment was higher in males. A clear association of clinical response with rituximab PK has been observed. Rate constant of specific clearance decay was 0.143 day -1 (95% CI: 0.0478-0.418) in patients with no disease progression, while in patients with disease progression it was 82.2% lower (95% CI: 33.4-95.0). This finding indicates that time-changes in clearance could serve as a predictive marker of response to rituximab. Our report demonstrates the rationale for studies evaluating higher doses of rituximab in selected patients. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  3. Generator for gallium-68 and compositions obtained therefrom

    DOEpatents

    Neirinckx, Rudi D.; Davis, Michael A.

    1981-01-01

    A generator for obtaining radioactive gallium-68 from germanium-68 bound in a resin containing unsubstituted phenolic hydroxyl groups. The germanium-68 is loaded into the resin from an aqueous solution of the germanium-68. A physiologically acceptable solution of gallium-68 having an activity of 0.1 to 50 millicuries per milliliter of gallium-68 solution is obtained. The solution is obtained from the bound germanium-68 which forms gallium-68 in situ by eluting the column with a hydrochloric acid solution to form an acidic solution of gallium-68. The acidic solution of gallium-68 can be neutralized.

  4. Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product

    PubMed Central

    Lee, Kyoung Hoon; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Jung, Soon Kwan; Chang, Shin Jae

    2018-01-01

    ABSTRACT CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and

  5. Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product.

    PubMed

    Lee, Kyoung Hoon; Lee, Jihun; Bae, Jin Soo; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Lee, Jung Woo; Jung, Soon Kwan; Chang, Shin Jae

    2018-04-01

    CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for

  6. Antitumor effect of novel gallium compounds and efficacy of nanoparticle-mediated gallium delivery in lung cancer.

    PubMed

    Wehrung, Daniel; Oyewumi, Moses O

    2012-02-01

    The widespread application of gallium (Ga) in cancer therapy has been greatly hampered by lack of specificity resulting in poor tumor accumulation and retention. To address the challenge, two lipophilic gallium (III) compounds (gallium hexanedione; GaH and gallium acetylacetonate; GaAcAc) were synthesized and antitumor studies were conducted in human lung adenocarcinoma (A549) cells. Nanoparticles (NPs) containing various concentrations of the Ga compounds were prepared using a binary mixture of Gelucire 44/14 and cetyl alcohol as matrix materials. NPs were characterized based on size, morphology, stability and biocompatibility. Antitumor effects of free or NP-loaded Ga compounds were investigated based on cell viability, production of reactive oxygen species and reduction of mitochondrial potential. Compared to free Ga compounds, cytotoxicity of NP-loaded Ga (5-150 microg/ml) was less dependent on concentration and incubation time (exposure) with A549 cells. NP-mediated delivery (5-150 microg Ga/ml) enhanced antitumor effects of Ga compounds and the effect was pronounced at: (i) shorter incubation times; and (ii) at low concentrations of gallium (approximately 50 microg/ml) (p < 0.0006). Additional studies showed that NP-mediated Ga delivery was not dependent on transferrin receptor uptake mechanism (p > 0.13) suggesting the potential in overcoming gallium resistance in some tumors. In general, preparation of stable and biocompatible NPs that facilitated Ga tumor uptake and antitumor effects could be effective in gallium-based cancer therapy.

  7. Subcutaneous Rituximab for the Treatment of B-Cell Hematologic Malignancies: A Review of the Scientific Rationale and Clinical Development.

    PubMed

    Davies, Andrew; Berge, Claude; Boehnke, Axel; Dadabhoy, Anjum; Lugtenburg, Pieternella; Rule, Simon; Rummel, Mathias; McIntyre, Christine; Smith, Rodney; Badoux, Xavier

    2017-10-01

    Rituximab (MabThera ® /Rituxan ® ), a chimeric murine/human monoclonal antibody that binds specifically to the transmembrane antigen CD20, was the first therapeutic antibody to enter clinical practice for the treatment of cancer. As monotherapy and in combination with chemotherapy, rituximab has been shown to prolong progression-free survival and, in some indications overall survival, in patients with various B-cell malignancies, while having a well-established and manageable safety profile and a wide therapeutic window. As a result, rituximab is considered to have revolutionized treatment practices for patients with B-cell malignancies. A subcutaneous (SC) formulation of rituximab has been developed, comprising the same monoclonal antibody as the originally marketed formulation [rituximab concentrate for solution for intravenous (IV) infusion], and has undergone a detailed, sequential clinical development program. This program demonstrated that, at fixed doses, rituximab SC achieves non-inferior serum trough concentrations in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia, with comparable efficacy and safety relative to the IV formulation. The added benefit of rituximab SC was demonstrated in dedicated studies showing that rituximab SC allows for simplified and shortened drug preparation and administration times resulting in a reduced treatment burden for patients as well as improved resource utilization (efficiency) at the treatment facility. The improved efficiency of delivering rituximab's benefit to patients may broaden patient access to rituximab therapy in areas with low levels of healthcare resources, including IV-chair capacity constraints. This article is a companion paper to G. Salles, et al., which is also published in this issue. F. Hoffmann-La Roche Ltd.

  8. Survival in advanced diffuse large B-cell lymphoma in pre- and post-rituximab Eras in the United States.

    PubMed

    Shah, Binay Kumar; Bista, Amir; Shafii, Bahman

    2014-09-01

    Rituximab was approved by the United States Food and Drug Administration (FDA) as a first-line agent for treatment of advanced diffuse large B-cell lymphoma (DLBCL) in February 2006. We conducted this population-based study to determine if the results from the clinical trials have translated into survival benefit in the general population. We selected patients with advanced diffuse large B-cell lymphoma from the Surveillance, Epidemiology, and End RESULTS (SEER) 18 database, and calculated relative survival rates for patients diagnosed from 2002-2005 (pre-rituximab) and 2006-2009 (post-rituximab). We used the Z-test in the SEER*Stat to compare relative survival rates of patients categorized by race (White, Black, or Others), gender (male, female), and age groups (<60, 60+ years). One-year relative survival in Whites and Others improved significantly in the post-rituximab era compared to the pre-rituximab era (64.80±0.6% vs. 61.3±0.6%; p=0.0002 and 64.5±1.9% vs. 54.9±2.2%; p=0.0011, respectively). The 3-year relative survival improved significantly in Whites and Others in the post-rituximab era compared to the pre-rituximab era (53.7±0.7% vs. 50.3±0.7%; p=0.0001 and 52.0±2.3% vs. 40.8±2.3%; p=0.0002, respectively). However, no significant improvements were observed in 1-year and 3-year relative survival in Blacks, and in young males during the post-rituximab era compared to the pre-rituximab era. The relative survival rates among young males and 'Black' patients with advanced diffuse large B-cell lymphoma have not improved during the post-rituximab era. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Gallium-67 activity in bronchoalveolar lavage fluid in sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trauth, H.A.; Heimes, K.; Schubotz, R.

    1986-01-01

    Roentgenograms and gallium-67 scans and gallium-67 counts of BAL fluid samples, together with differential cell counts, have proved to be useful in assessing activity and lung involvement in sarcoidosis. In active pulmonary sarcoidosis gallium-67 scans are usually positive. Quantitation of gallium-67 uptake in lung scans, however, may be difficult. Because gallium-67 uptake and cell counts in BAL fluid may be correlated, we set out to investigate gallium-67 activity in BAL fluid recovered from patient of different groups. Sixteen patients with recently diagnosed and untreated sarcoidosis, nine patients with healthy lungs, and five patients with CFA were studied. Gallium-67 uptake ofmore » the lung, gallium-67 activity in the lavage fluid, SACE and LACE levels, and alpha 1-AT activity were measured. Significantly more gallium-67 activity was found in BAL fluid from sarcoidosis patients than in that from CFA patients (alpha = .001) or patients with healthy lungs (alpha = .001). Gallium-67 activity in BAL fluid could be well correlated with the number of lymphocytes in BAL fluid, but poorly with the number of macrophages. Subjects with increased levels of SACE or serum alpha 1-AT showed higher lavage gallium-67 activity than did normals, but no correlation could be established. High gallium-67 activity in lavage fluid may be correlated with acute sarcoidosis or physiological deterioration; low activity denotes change for the better. The results show that gallium-67 counts in BAL fluid reflects the intensity of gallium-67 uptake and thus of activity of pulmonary sarcoidosis.« less

  10. Effect of rituximab on human in vivo antibody immune responses.

    PubMed

    Pescovitz, Mark D; Torgerson, Troy R; Ochs, Hans D; Ocheltree, Elizabeth; McGee, Paula; Krause-Steinrauf, Heidi; Lachin, John M; Canniff, Jennifer; Greenbaum, Carla; Herold, Kevan C; Skyler, Jay S; Weinberg, Adriana

    2011-12-01

    B-lymphocyte depletion with rituximab has been shown to benefit patients with various autoimmune diseases. We have previously demonstrated that this benefit is also apparent in patients with newly diagnosed type 1 diabetes. The effect of rituximab on in vivo antibody responses, particularly during the period of B-lymphocyte depletion, is incompletely determined. This study was designed to assess this knowledge void. In patients with recent-onset type 1 diabetes treated with rituximab (n = 46) or placebo (n = 29), antibody responses to neoantigen phiX174 during B-lymphocyte depletion and with hepatitis A (as a second neoantigen) and tetanus/diphtheria (as recall antigens) after B-lymphocyte recovery were studied. Anti- tetanus, diphtheria, mumps, measles, and rubella titers were measured before and after treatment by means of ELISA. Antibody titers and percentage IgM versus percentage IgG to phiX174 were measured by means of phage neutralization. B-lymphocyte subsets were determined by means of flow cytometry. No change occurred in preexisting antibody titers. Tetanus/diphtheria and hepatitis A immunization responses were protective in the rituximab-treated subjects, although significantly blunted compared with those seen in the controls subjects, when immunized at the time of B-lymphocyte recovery. Anti-phiX174 responses were severely reduced during the period of B-lymphocyte depletion, but with B-lymphocyte recovery, anti-phiX174 responses were within the normal range. During the time of B-lymphocyte depletion, rituximab recipients had a decreased antibody response to neoantigens and significantly lower titers after recall immunization with diphtheria and tetanus toxoid. With recovery, immune responses return toward normal. Immunization during the time of B-lymphocyte depletion, although ineffective, does not preclude a subsequent response to the antigen. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights

  11. Rituximab is not a "magic drug" in post-transplant recurrence of nephrotic syndrome.

    PubMed

    Grenda, Ryszard; Jarmużek, Wioletta; Rubik, Jacek; Piątosa, Barbara; Prokurat, Sylwester

    2016-09-01

    Pediatric patients with end-stage renal failure due to severe drug-resistant nephrotic syndrome are at risk of rapid recurrence after renal transplantation. Treatment options include plasmapheresis, high-dose of cyclosporine A/methylprednisolone and more recently-rituximab (anti-B CD20 monoclonal depleting antibody). We report five patients with immediate (1-2 days) post-transplant recurrence of nephrotic syndrome, treated with this kind of combined therapy including 2-4 weekly doses of 375 mg/m(2) of rituximab. Only two (of five) patients have showed full long-term remission, while the partial remission was seen in two cases, and no clinical effect at all was achieved in one patient. The correlation between B CD19 cells depletion and clinical effect was present in two cases only. Severe adverse events were present in two patients, including one fatal rituximab-related acute lung injury. The anti-CD20 monoclonal antibody may be not effective in all pediatric cases of rapid post-transplant recurrence of nephrotic syndrome, and benefit/risk ratio must be carefully balanced on individual basis before taking the decision to use this protocol. • nephrotic syndrome may recur immediately after renal transplantation • plasmapheresis combined with pharmacotherapy is used as rescue management • rituximab was reported as effective drug both in primary and post-transplant nephrotic syndrome What is New: • rituximab may not be effective is several cases of post-transplant nephrotic syndrome due to variety of underlying mechanisms of the disease, which may be or not be responsive to this drug • there may be no correlation between drug-induced depletion of specific B cells and clinical effect; this might suggest B-cell independent manner of rituximab action.

  12. ‘Les liaisons dangereuses’: Hepatitis C, Rituximab and B-cell non-Hodgkin’s lymphomas

    PubMed Central

    Marignani, Massimo; Fonzo, Michela di; Begini, Paola; Gigante, Elia; Deli, Ilaria; Pellicelli, Adriano M; Gallina, Sara; de Santis, Emanuela; Fave, Gianfranco Delle; Cox, M Christina

    2012-01-01

    Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin’s lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy. PMID:22577616

  13. Carbon nanothermometer containing gallium.

    PubMed

    Gao, Yihua; Bando, Yoshio

    2002-02-07

    Many applications have been found for carbon nanotubes, and we can now add a role as a 'nanothermometer' to this list. We describe how the height of a continuous, unidimensional column of liquid gallium inside a carbon nanotube (up to about 10 micrometres long and about 75 nanometres in diameter) varies linearly and reproducibly in the temperature range 50-500 degrees C, with an expansion coefficient that is the same as for gallium in the macroscopic state. We chose gallium as our thermal indicator because it has one of the greatest liquid ranges of any metal (29.78-2,403 degrees C) and a low vapour pressure even at high temperatures. This nanothermometer should be suitable for use in a wide variety of microenvironments.

  14. Gallium Electromagnetic (GEM) Thrustor Concept and Design

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.; Markusic, Thomas E.

    2006-01-01

    We describe the design of a new type of two-stage pulsed electromagnetic accelerator, the gallium electromagnetic (GEM) thruster. A schematic illustration of the GEM thruster concept is given in Fig. 1. In this concept, liquid gallium propellant is pumped into the first stage through a porous metal electrode using an electromagneticpump[l]. At a designated time, a pulsed discharge (approx.10-50 J) is initiated in the first stage, ablating the liquid gallium from the porous electrode surface and ejecting a dense thermal gallium plasma into the second state. The presence of the gallium plasma in the second stage serves to trigger the high-energy (approx.500 I), send-stage puke which provides the primary electromagnetic (j x B) acceleration.

  15. Rituximab in the treatment of follicular lymphoma: the future of biosimilars in the evolving therapeutic landscape

    PubMed Central

    Subramanian, Janakiraman; Cavenagh, Jamie; Desai, Bhardwaj; Jacobs, Ira

    2017-01-01

    Follicular lymphoma (FL) is the second most common type of non-Hodgkin’s lymphoma. FL is an incurable disease with treatment options ranging from a “watch-and-wait” approach to localized therapy with radiation or systemic therapy with rituximab in combination with chemotherapy regimens. This review summarizes the role of rituximab across the spectrum of FL treatment and the evolving therapeutic landscape with the emergence of novel agents currently in clinical development. Despite the prospect of new agents on the horizon, it is widely accepted that rituximab will remain as the cornerstone of therapy because of its established long-term efficacy. Many biologics, including rituximab, have lost exclusivity of composition-of-matter patent or will do so in the next few years, which is a concern for patients and physicians alike. Moreover, access to rituximab is challenging, particularly in countries with restricted resources. Together, these concerns have fueled the development of safe and effective biosimilars. The term “biosimilar” refers to a biologic product that is highly similar to an approved reference (or originator) product, notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences in purity, potency, or safety. Biosimilars are developed to treat the same condition(s) using the same treatment regimens as an approved reference biologic, and have the potential to increase access to more affordable treatment of FL. Herein, we also discuss the potential benefits of eagerly awaited rituximab biosimilars, which may mitigate the impact of the lack of access to rituximab. PMID:28479860

  16. Gallium poisoning: a rare case report.

    PubMed

    Ivanoff, Chris S; Ivanoff, Athena E; Hottel, Timothy L

    2012-02-01

    The authors present a case of a college student who suffered acute gallium poisoning as a result of accidental exposure to gallium halide complexes. This is extremely rare and has never been reported in the literature. Acute symptoms after the incident, which initially presented as dermatitis and appeared relatively not life-threatening, rapidly progressed to dangerous episodes of tachycardia, tremors, dyspnea, vertigo, and unexpected black-outs. Had there been effective emergency medical care protocols, diagnostic testing, treatment and antidotes, the latent manifestations of irreversible cardiomyopathy may have been prevented. Given how quickly exposure led to morbidity, this article aims to raise an awareness of the toxic potential of gallium. This has particular relevance for workers involved in the production of semiconductors where there is a potential for accidental exposure to gallium by-products during device processing. It may also have implications for dentists who use gallium alloys to replace mercury containing amalgam. In the absence of threshold limit values and exposure limits for humans, as well as emergency medical guidelines for treatment of poisoning, the case calls on the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration to establish guidelines and medical management protocols specific for gallium. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab.

    PubMed

    Knight, Tyler; Bond, T Christopher; Popelar, Breanna; Wang, Li; Niewoehner, John W; Anastassopoulos, Kathryn; Philbin, Michael

    2017-01-01

    Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P =0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P =0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P <0.001), and PPPM physician office visits (2.01 vs 2.33; P =0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P <0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P <0.001) and less PPPM HOPD visits (0.53 vs 1.26; P <0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%-75% lower for RCI compared to IVIg ($2,126 vs $3,964; P <0.001), rituximab ($2,008 vs $2,607; P =0.018), and IVIg+rituximab ($1,234 vs $4,858; P <0.001). Patients treated with RCI had less PPPM non-medication MRU and costs

  18. Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab

    PubMed Central

    Knight, Tyler; Bond, T Christopher; Popelar, Breanna; Wang, Li; Niewoehner, John W; Anastassopoulos, Kathryn; Philbin, Michael

    2017-01-01

    Background Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. Methods Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. Results One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P<0.001), and PPPM physician office visits (2.01 vs 2.33; P=0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001) and less PPPM HOPD visits (0.53 vs 1.26; P<0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%–75% lower for RCI compared to IVIg ($2,126 vs $3,964; P<0.001), rituximab ($2,008 vs $2,607; P=0.018), and IVIg+rituximab ($1,234 vs $4,858; P<0.001). Conclusion Patients treated with RCI had less PPPM

  19. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction

    PubMed Central

    Lafayette, Richard A.; Canetta, Pietro A.; Rovin, Brad H.; Appel, Gerald B.; Novak, Jan; Nath, Karl A.; Sethi, Sanjeev; Tumlin, James A.; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A.; Leung, Nelson; Enders, Felicity T.; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy

    2017-01-01

    IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody–producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy–proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin–converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8–2.4) mg/dl, and proteinuria was 2.1 (0.6–5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose–deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. PMID:27821627

  20. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

    PubMed

    Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

    2017-04-01

    IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

  1. Rituximab in the treatment of shrinking lung syndrome in systemic lupus erythematosus.

    PubMed

    Peñacoba Toribio, Patricia; Córica Albani, María Emilia; Mayos Pérez, Mercedes; Rodríguez de la Serna, Arturo

    2014-01-01

    Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  2. Nocardiosis in a patient with rheumatoid athritis treated with rituximab and a summary of reported cases

    PubMed Central

    Ngiu, C S; Said, M S Mohamed; Periyasamy, P; Low, S F

    2010-01-01

    Rituximab is a B-cell-depleting monoclonal anti-CD20 antibody. It is widely used in haematology and rheumatology. However, usage of rituximab in immunosupressed patient has been associated with various opportunistic infections. The authors reported a case of refractory rheumatoid arthritis treated with rituximab, which later presented with non-resolving pneumonia with pulmonary nodule. Percutaneous computer tomogram guided lung biopsy was arranged to confirm the suspicion of tuberculosis, but did not yield conclusive results. Later, she presented left-chest abscess and underwent incision and drainage. The pus culture and sensitivity confirmed pulmonary nocardiosis with chest wall dissemination. She was treated with 2-week course of trimethoprim sulfamethoxazole and responded. The authors also reviewed published cases of nocardiosis post-rituximab. PMID:22778377

  3. Achieving a satisfactory clinical and biochemical response in antiphospholipid syndrome and severe thrombocytopenia with rituximab: two case reports.

    PubMed

    Gamoudi, Donia; Cutajar, Melanie; Gamoudi, Nadia; Camilleri, David James; Gatt, Alex

    2017-06-01

    In AP syndrome (APS) with severe thrombocytopenia, rituximab represents a unique drug which can balance the effect of bleeding and thrombosis. By reducing the production of autoantibodies, rituximab can simultaneously raise the platelets and reduce the chance of thrombosis by suppressing APL antibodies. Rituximab can supersede splenectomy as second-line therapy in similar patients.

  4. Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.

    PubMed

    Uchida, Junji; Iwai, Tomoaki; Nishide, Shunji; Kabei, Kazuya; Kuwabara, Nobuyuki; Yamasaki, Takeshi; Naganuma, Toshihide; Kumada, Norihiko; Takemoto, Yoshiaki; Nakatani, Tatsuya

    2017-07-25

    BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.

  5. Cytomegalovirus retinitis complicating combination therapy with rituximab and fludarabine.

    PubMed

    Chan, Thomas S Y; Cheung, Carol Y M; Yeung, Ian Y L; Hwang, Yu-Yan; Gill, Harinder; Wong, Ian Y; Kwong, Yok-Lam

    2015-06-01

    Cytomegalovirus (CMV) retinitis is exceptionally rare outside the clinical context of acquired immunodeficiency syndrome and organ allografting. In a population where seropositivity for past CMV infection exceeded 90 %, CMV retinitis was observed in five of 138 patients (3.6 %) receiving fludarabine-containing regimens together with rituximab, which was significantly more frequent than in 141 patients receiving fludarabine-containing regimens alone, where no case was observed (P = 0.029). Treatment of CMV retinitis comprised both intravitreal and systemic ganciclovir/foscarnet. Upon recovery, secondary retinal atrophy occurred in all patients, leading to blindness in 86 % of affected eyes. CMV retinitis is an important complication in patients receiving concomitant rituximab and fludarabine-containing regimens.

  6. Use of rituximab as a treatment for systemic lupus erythematosus: retrospective review

    PubMed Central

    Machado, Roberta Ismael Lacerda; Scheinberg, Morton Aaron; de Queiroz, Maria Yvone Carlos Formiga; de Brito, Danielle Christinne Soares Egypto; Guimarães, Maria Fernanda Brandao de Resende; Giovelli, Raquel Altoé; Freire, Eutilia Andrade Medeiros

    2014-01-01

    ABSTRACT Objective: To report the experience in three Brazilian institutions with the use of rituximab in patients with different clinical forms of lupus erythematosus systemic in activity. Methods: The study consisted of a sample of 17 patients with LES, who were already being treated, but that at some stage of the disease showed refractory symptoms. The patients were subdivided into groups according to the clinical manifestation, and the responses for the use of rituximab were rated as complete, partial or no response. Data were collected through a spreadsheet, and used specific parameters for each group. The treatment was carried on by using therapeutic dose of 1g, and repeating the infusion within an interval of 15 days. Results: The clinical responses to rituximab of the group only hematological and of the group only osteoarticular were complete in all cases. In the renal group there was a clinical complete response, two partial and one absent. In the renal and hematological group complete response, there was one death and a missing response. The pulmonary group presented a complete response and two partial. Conclusion: The present study demonstrated that rituximab can bring benefits to patients with lupus erythematosus systemic, with good tolerability and mild side effects; it presented, however, variable response according to the system affected. PMID:24728244

  7. Correction: Ambient temperature deposition of gallium nitride/gallium oxynitride from a deep eutectic electrolyte, under potential control.

    PubMed

    Sarkar, Sujoy; Sampath, S

    2016-05-28

    Correction for 'Ambient temperature deposition of gallium nitride/gallium oxynitride from a deep eutectic electrolyte, under potential control' by Sujoy Sarkar et al., Chem. Commun., 2016, 52, 6407-6410.

  8. Off-label use of rituximab in autoimmune disease in the Top End of the Northern Territory, 2008-2016.

    PubMed

    Wongseelashote, Sarah; Tayal, Vipin; Bourke, Peter Francis

    2018-02-01

    Rituximab, an anti-CD20 B-cell depleting monoclonal antibody, is increasingly prescribed off-label for a range of autoimmune diseases. There has not previously been an audit of off-label rituximab use in the Northern Territory, where the majority of patients are Aboriginal. To evaluate retrospectively off-label rituximab use in autoimmune diseases in the Top End of the Northern Territory. We performed a retrospective audit of 8 years of off-label rituximab use at the Royal Darwin Hospital, the sole tertiary referral centre for the Darwin, Katherine and East Arnhem regions. Electronic and paper records were reviewed for demographic information, diagnosis/indication for rituximab, doses, previous/concomitant immunosuppression, clinical outcomes and specific adverse events. Rituximab was prescribed off-label to 66 patients for 24 autoimmune diseases. The majority of patients (62.1%) were Aboriginal and 60.6% female. The most common indications were refractory/relapsing disease despite standard therapies (68.7%) or severe disease with rituximab incorporated into an induction immunosuppressive regimen (19.4%). Systemic lupus erythematosus was the underlying diagnosis in 28.8% of cases. A clinically significant response was demonstrated in 74.2% of cases overall. There were 18 clinically significant infections; however, 13 were in patients receiving concurrent immunosuppressive therapy. There was a total of nine deaths from any cause. Rituximab has been used off-label for a range of autoimmune diseases in this population with a high proportion of Aboriginal patients successfully and safely in the majority of cases. © 2017 Royal Australasian College of Physicians.

  9. Revised neutrino-gallium cross section and prospects of BEST in resolving the gallium anomaly

    NASA Astrophysics Data System (ADS)

    Barinov, Vladislav; Cleveland, Bruce; Gavrin, Vladimir; Gorbunov, Dmitry; Ibragimova, Tatiana

    2018-04-01

    O (1 )eV sterile neutrino can be responsible for a number of anomalous results of neutrino oscillation experiments. This hypothesis may be tested at short base line neutrino oscillation experiments, several of which are either ongoing or under construction. Here, we concentrate on the so-called gallium anomaly, found by SAGE and GALLEX experiments, and its foreseeable future tests with BEST experiment at Baksan Neutrino Observatory. We start with a revision of the neutrino-gallium cross section that is performed by utilizing the recent measurements of the nuclear final state spectra. We accordingly correct the parameters of gallium anomaly and refine the BEST prospects in testing it and searching for sterile neutrinos. We further evolve the previously proposed idea to investigate the anomaly with 65Zn artificial neutrino source as a next option available at BEST and estimate its sensitivity to the sterile neutrino model parameters following the Bayesian approach. We show that after the two stages of operation BEST will make 5 σ discovery of the sterile neutrinos, if they are behind the gallium anomaly.

  10. Structure of dental gallium alloys.

    PubMed

    Herø, H; Simensen, C J; Jørgensen, R B

    1996-07-01

    The interest in gallium alloys as a replacement for amalgam has increased in recent years due to the risk of environmental pollution from amalgam. Alloy powders with compositions close to those for alloys of amalgam are mixed with a liquid gallium alloy. The mix is condensed into a prepared cavity in much the same way as for amalgam. The aim of the present work was to study the structure of: (1) two commercial alloy powders containing mainly silver, tin and copper, and (2) the phases formed by mixing these powders with a liquid alloy of gallium, indium and tin. One of the alloy powders contained 9 wt% palladium. Cross-sections of cylindrical specimens made by these gallium mixes were investigated by scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Discrete grains of the following phases were found to be present in both gallium alloys: hexagonal Ag2Ga, tetragonal Cu(Pd)Ga2, cubic Ag9In4 and tetragonal beta-Sn. Indications of hexagonal or orthorhombic Ag2Sn were found in the remaining, unreacted alloy particles. In the palladium-containing alloy the X-ray reflections indicate a minor fraction of cubic Cu9Ga4 in addition to the Cu(Pd)Ga2 phase. Particles of beta-Sn are probably precipitated because Sn-Ga phases cannot be formed according to the binary phase diagram.

  11. Efficacy and safety of rituximab in pemphigus: experience of the German Registry of Autoimmune Diseases.

    PubMed

    Kasperkiewicz, Michael; Eming, Rüdiger; Behzad, Melika; Hunzelmann, Nicolas; Meurer, Michael; Schulze-Koops, Hendrik; von Wussow, Peter; Hertl, Michael; Zillikens, Detlef; Freivogel, Klaus; Dörner, Thomas; Schmidt, Enno

    2012-10-01

    Rituximab has been reported to be effective in various small case series of patients with severe and/or refractory pemphigus. However, no systematic evaluation is available to corroborate this observation. The aim of this study was to systematically determine efficacy and safety of rituximab in treatment-resistant pemphigus. Multicenter retrospective, observational study of 36 patients with severe pemphigus vulgaris (n = 33) and pemphigus foliaceus (n = 3) treated with rituximab before August 31(st) , 2008 and enrolled in a national observational registery between December 2008 and June 2009. Within a mean period of observation of 11 (1-37) months, 21 (58 %) pemphigus patients showed complete, 13 (36 %) partial, and 2 (6 %) no response to rituximab treatment. This correlates with a mean improvement of the visual analog scale for well-being of 34 (20-60) at baseline to 75 (40-95) at the last control visit. In 4 (11 %) patients, severe adverse events were recorded including 1 (3 %) serious infection. Data collected in this systematic registry indicate that rituximab is an effective and relatively safe adjuvant treatment option for refractory pemphigus. To further extend our knowledge on efficacy and safety of this drug, controlled prospective trials are required. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  12. Structure and luminescence of nanocrystalline gallium nitride synthesized by a novel polymer pyrolysis route

    NASA Astrophysics Data System (ADS)

    Garcia, Rafael; Hirata, Gustavo A.; Thomas, Alan C.; Ponce, Fernando A.

    2006-10-01

    Thermal decomposition in a horizontal quartz tube reactor of a polymer [-(CH 6N 4O) 3Ga(NO 3) 3-] in a nitrogen atmosphere, yield directly nano-structured gallium nitride (GaN) powder. The polymer was obtained by the reaction between high purity gallium nitrate (Ga(NO 3) 3) dissolved in toluene and carbohydrazide as an azotic ligand. The powder synthesized by this method showed a yellow color and elemental analysis suggested that the color is due to some carbon and oxygen impurities in the as-synthesized powder. Electron microscopy showed that the as-synthesized powders consist of a mixture of various porous particles containing nanowires and nano-sized platelets. The size of the crystallites can be controlled by annealing processes under ammonia. Photoluminescence analysis at 10 K on as-synthesized powders showed a broad red luminescence around 668 nm under UV laser excitation (He-Cd laser, 325 nm). However after annealing process the red luminescence disappears and the typical band edge emission of GaN around 357 nm (3.47 eV) and the UV band were the dominant emissions in the PL spectra.

  13. Preventing Supercooling Of Gallium

    NASA Technical Reports Server (NTRS)

    Massucco, Arthur A.; Wenghoefer, Hans M.; Wilkins, Ronnie

    1994-01-01

    Principle of heterogeneous nucleation exploited to prevent gallium from supercooling, enabling its use as heat-storage material that crystallizes reproducibly at its freezing or melting temperature of 29 to 30 degrees C. In original intended application, gallium used as heat-storage material in gloves of space suits. Terrestrial application lies in preparation of freezing-temperature reference samples for laboratories. Principle of heterogeneous nucleation also exploited similarly in heat pipes filled with sodium.

  14. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial.

    PubMed

    Tak, P P; Rigby, W F; Rubbert-Roth, A; Peterfy, C G; van Vollenhoven, R F; Stohl, W; Hessey, E; Chen, A; Tyrrell, H; Shaw, T M

    2011-01-01

    Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment with MTX. In this double-blind randomised controlled phase III study, 755 MTX-naïve patients with active RA were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX. The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score. 249, 249 and 250 patients were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX, respectively. At week 52, treatment with rituximab 2×1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage (mean change in total modified Sharp score 0.359 vs 1.079; p=0.0004) and an improvement in clinical outcomes (ACR50 65% vs 42%; p<0.0001); rituximab 2×500 mg + MTX improved clinical outcomes (ACR50 59% vs 42%; p<0.0001) compared with MTX alone but did not significantly reduce the progression of joint damage. Safety outcomes were similar between treatment groups. Treatment with rituximab 2×1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA. ClinicalTrials.gov identifier NCT00299104.

  15. A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

    PubMed

    Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

    2016-10-01

    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Repurposing of gallium-based drugs for antibacterial therapy.

    PubMed

    Bonchi, Carlo; Imperi, Francesco; Minandri, Fabrizia; Visca, Paolo; Frangipani, Emanuela

    2014-01-01

    While the occurrence and spread of antibiotic resistance in bacterial pathogens is vanishing current anti-infective therapies, the antibiotic discovery pipeline is drying up. In the last years, the repurposing of existing drugs for new clinical applications has become a major research area in drug discovery, also in the field of anti-infectives. This review discusses the potential of repurposing previously approved gallium formulations in antibacterial chemotherapy. Gallium has no proven function in biological systems, but it can act as an iron-mimetic in both prokaryotic and eukaryotic cells. The activity of gallium mostly relies on its ability to replace iron in redox enzymes, thus impairing their function and ultimately hampering cell growth. Cancer cells and bacteria are preferential gallium targets due to their active metabolism and fast growth. The wealth of knowledge on the pharmacological properties of gallium has opened the door to the repurposing of gallium-based drugs for the treatment of infections sustained by antibiotic-resistant bacterial pathogens, such as Acinetobacter baumannii or Pseudomonas aeruginosa, and for suppression of Mycobacterium tuberculosis growth. The promising antibacterial activity of gallium both in vitro and in different animal models of infection raises the hope that gallium will confirm its efficacy in clinical trials, and will become a valuable therapeutic option to cure otherwise untreatable bacterial infections. © 2014 International Union of Biochemistry and Molecular Biology.

  17. NIM Realization of the Gallium Triple Point

    NASA Astrophysics Data System (ADS)

    Xiaoke, Yan; Ping, Qiu; Yuning, Duan; Yongmei, Qu

    2003-09-01

    In the last three years (1999 to 2001), the gallium triple-point cell has been successfully developed, and much corresponding research has been carried out at the National Institute of Metrology (NIM), Beijing, China. This paper presents the cell design, apparatus and procedure for realizing the gallium triple point, and presents studies on the different freezing methods. The reproducibility is 0.03 mK, and the expanded uncertainty of realization of the gallium triple point is evaluated to be 0.17 mK (p=0.99, k=2.9). Also, the reproducibility of the gallium triple point was compared with that of the triple point of water.

  18. B-lymphoma cells escape rituximab-triggered elimination by NK cells through increased HLA class I expression.

    PubMed

    Borgerding, Andrea; Hasenkamp, Justin; Engelke, Michael; Burkhart, Nina; Trümper, Lorenz; Wienands, Jürgen; Glass, Bertram

    2010-03-01

    Antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells is a major effector mechanism of the monoclonal anti-CD20 antibody rituximab in eliminating B-cell lymphomas. Resistance to this treatment occurs, although CD20 antigen is expressed on the tumor cells. A model of ADCC was established by stimulating human bulk NK cells and inhibitory killer immunoglobulin receptor (KIR)-defined NK cells from human leukocyte antigen (HLA)-typed donors. NK-cell activation was triggered via stimulation of the Fc receptor with immunoglobulin G aggregates, rituximab-labeled HLA-defined CD20-positive B-lymphoblast cell lines or CD20-positive B-lymphoma cell lines. The effect of KIR ligation by anti-KIR antibodies and HLA, the HLA expression density and rituximab concentrations on the efficacy of ADCC were analyzed in granzyme B ELISPOT measuring NK-cell activation and fluorescein-activated cell sorting cytotoxicity assay. HLA, but not CD20 expression density correlated with NK-cell activity against rituximab-labeled targets. ADCC was increased or decreased following HLA shielding or KIR activation by anti-KIR antibodies, respectively. Herein we show that rituximab-induced ADCC is attenuated upon ligation of KIR by HLA molecules expressed on human B-lymphoma target cells. Moreover, anti-KIR antibodies do not only block KIR/HLA interactions, but display agonistic effects at the KIR, which has to be considered for therapeutical applications. KIR activation and HLA expression density are critical determinants for the efficacy of rituximab treatment. An explanation for the failure of rituximab treatment may be the protection of the tumor cells from ADCC by inhibiting NK-cell function with their surface HLA. Copyright 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  19. The surface tension of liquid gallium

    NASA Technical Reports Server (NTRS)

    Hardy, S. C.

    1985-01-01

    The surface tension of liquid gallium has been measured using the sessile drop technique in an Auger spectrometer. The experimental method is described. The surface tension in mJ/sq m is found to decrease linearly with increasing temperature and may be represented as 708-0.66(T-29.8), where T is the temperature in centigrade. This result is of interest because gallium has been suggested as a model fluid for Marangoni flow experiments. In addition, the surface tension is of technological significance in the processing of compound semiconductors involving gallium.

  20. 40 CFR 721.10391 - Copper gallium indium selenide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Copper gallium indium selenide. 721... Substances § 721.10391 Copper gallium indium selenide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as copper gallium indium selenide (PMN P-10...

  1. 40 CFR 721.10391 - Copper gallium indium selenide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Copper gallium indium selenide. 721... Substances § 721.10391 Copper gallium indium selenide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as copper gallium indium selenide (PMN P-10...

  2. 40 CFR 721.10391 - Copper gallium indium selenide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Copper gallium indium selenide. 721... Substances § 721.10391 Copper gallium indium selenide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as copper gallium indium selenide (PMN P-10...

  3. Epitaxial Deposition Of Germanium Doped With Gallium

    NASA Technical Reports Server (NTRS)

    Huffman, James E.

    1994-01-01

    Epitaxial layers of germanium doped with gallium made by chemical vapor deposition. Method involves combination of techniques and materials used in chemical vapor deposition with GeH4 or GeCl4 as source of germanium and GaCl3 as source of gallium. Resulting epitaxial layers of germanium doped with gallium expected to be highly pure, with high crystalline quality. High-quality material useful in infrared sensors.

  4. Automated realization of the gallium melting and triple points

    NASA Astrophysics Data System (ADS)

    Yan, X.; Duan, Y.; Zhang, J. T.; Wang, W.

    2013-09-01

    In order to improve the automation and convenience of the process involved in realizing the gallium fixed points, an automated apparatus, based on thermoelectric and heat pipe technologies, was designed and developed. This paper describes the apparatus design and procedures for freezing gallium mantles and realizing gallium melting and triple points. Also, investigations on the melting behavior of a gallium melting point cell and of gallium triple point cells were carried out while controlling the temperature outside the gallium point cells at 30 °C, 30.5 °C, 31 °C, and 31.5 °C. The obtained melting plateau curves show dentate temperature oscillations on the melting plateaus for the gallium point cells when thermal couplings occurred between the outer and inner liquid-solid interfaces. The maximum amplitude of the temperature fluctuations was about 1.5 mK. Therefore, the temperature oscillations can be used to indicate the ending of the equilibrium phase transitions. The duration and amplitude of such temperature oscillations depend on the temperature difference between the setting temperature and the gallium point temperature; the smaller the temperature difference, the longer the duration of both the melting plateaus and the temperature fluctuations.

  5. Gallium-mediated growth of multiwall carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Pan, Zheng Wei; Dai, Sheng; Beach, David B.; Evans, Neal D.; Lowndes, Douglas H.

    2003-03-01

    Liquid gallium was used as a viable and effective solvent and template for high-yield growth of multiwall carbon nanotubes. The gallium-mediated nanotubes thus obtained differ morphologically from nanotubes obtained by using transition metals as catalysts. The nanotubes have a pin-like morphology, generally composed of an oval-shaped tip filled with liquid gallium and a tapered hollow body. The inner diameter of the tube is so large that the inner/outer diameter ratio is usually larger than 0.9. The tubes are naturally opened at both ends. These gallium-filled nanotubes may be used as a nanothermometer in the temperature range of 30 to 550 °C. This study opens an interesting route for carbon nanotube synthesis.

  6. Radiochemical separation of gallium by amalgam exchange

    USGS Publications Warehouse

    Ruch, R.R.

    1969-01-01

    An amalgam-exchange separation of radioactive gallium from a number of interfering radioisotopes has been developed. A dilute (ca. 0.3%) gallium amalgam is agitated with a slightly acidic solution of 72Ga3+ containing concentrations of sodium thiocyanate and either perchlorate or chloride. The amalgam is then removed and the radioactive gallium stripped by agitation with dilute nitric acid. The combined exchange yield of the perchlorate-thiocyanate system is 90??4% and that of the chloride-thiocyanate system is 75??4%. Decontamination yields of most of the 11 interfering isotopes studied were less than 0.02%. The technique is applicable for use with activation analysis for the determination of trace amounts of gallium. ?? 1969.

  7. Methotrexate-cytarabine-dexamethasone combination chemotherapy with or without rituximab in patients with primary central nervous system lymphoma.

    PubMed

    Sun, Xuefei; Liu, Jing; Wang, Yaming; Bai, Xueyan; Chen, Yuedan; Qian, Jun; Zhu, Hong; Liu, Fusheng; Qiu, Xiaoguang; Sun, Shengjun; Ji, Nan; Liu, Yuanbo

    2017-07-25

    High-dose methotrexate based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because of its large size, which limits its penetration of the blood-brain barrier. In this study, we investigated the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen). The patients treated with RMAD had a complete remission rate of 66.7% after induction chemotherapy; this rate was only 33.3% in patients treated with MAD alone (p = .011). The most common grade 1-3 adverse events were similar and included hematologic toxicity, increased aminotransferase levels, and gastrointestinal reactions. Multivariate analysis revealed that rituximab treatment was associated with longer progression-free survival (PFS, p = .005) but not overall survival (OS). Additionally, we observed that elevated serum lactate dehydrogenase was associated with shorter OS and PFS. We retrospectively analyzed 60 immunocompetent patients with newly diagnosed PCNSL at Beijing Tiantan Hospital, Capital Medical University from January 2010 to June 2016. Twenty-four patients received 3-6 courses of 3.5 g/m2 methotrexate on day 1; 0.5-1 g/m2 cytarabine on day 2; and 5-10 mg dexamethasone on days 1, 2 and 3. Thirty-six patients received the same combination plus rituximab 375 mg/m2 on day 0. All patients repeated the treatment every 3 weeks. High-dose methotrexate based chemotherapy with rituximab yields a higher complete remission rate and does not increase serious toxicities. PFS benefits from the addition of rituximab. OS has an increasing trend in patients treated with rituximab without statistical significance.

  8. Rituximab as maintenance therapy for ANCA associated vasculitis: how, when and why?

    PubMed

    Alba, Marco A; Flores-Suárez, Luis Felipe

    2016-01-01

    ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders.

    PubMed

    Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe; Stenner, Rachel

    2006-08-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells which has proven to be effective in the therapy of CD-20 positive lymphomas. Its B-cell cytotoxic action has also been exploited in many non-malignant autoimmune disorders in which it has been used with the aim of interfering with the production of pathologic antibodies. The present knowledge regarding the use of rituximab in antibody-associated disorders of hemostasis (i.e. idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, acquired hemophilia A, congenital hemophilia with inhibitors, acquired inhibitors against coagulation factors) is presented briefly in this review. The results suggest that rituximab can be useful in the treatment of disorders of hemostasis associated with inhibitor formation. Although collectively the number of patients treated is now quite substantial, most of the data are drawn from isolated case reports or descriptions of small, uncontrolled series. Large, prospective, randomized trials are, therefore, needed to confirm the positive, preliminary results.

  10. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis

    PubMed Central

    Buch, Maya H; Smolen, Josef S; Betteridge, Neil; Breedveld, Ferdinand C; Burmester, Gerd; Dörner, Thomas; Ferraccioli, Gianfranco; Gottenberg, Jacques-Eric; Isaacs, John; Kvien, Tore K; Mariette, Xavier; Martin-Mola, Emilio; Pavelka, Karel; Tak, Paul P; van der Heijde, Desiree; van Vollenhoven, Ronald F; Emery, Paul

    2011-01-01

    Background Since initial approval for the treatment of rheumatoid arthritis (RA), rituximab has been evaluated in clinical trials involving various populations with RA. Information has also been gathered from registries. This report therefore updates the 2007 consensus document on the use of rituximab in the treatment of RA. Methods Preparation of this new document involved many international experts experienced in the treatment of RA. Following a meeting to agree upon the core agenda, a systematic literature review was undertaken to identify all relevant data. Data were then interrogated by a drafting committee, with subsequent review and discussion by a wider expert committee leading to the formulation of an updated consensus statement. These committees also included patients with RA. Results The new statement covers wide-ranging issues including the use of rituximab in earlier RA and impact on structural progression, and aspects particularly pertinent to rituximab such as co-medication, optimal dosage regimens, repeat treatment cycles and how to manage non-response. Biological therapy following rituximab usage is also addressed, and safety concerns including appropriate screening for hepatitis, immunoglobulin levels and infection risk. This consensus statement will support clinicians and inform patients when using B-cell depletion in the management of RA, providing up-to-date information and highlighting areas for further research. Conclusion New therapeutic strategies and treatment options for RA, a chronic destructive and disabling disease, have expanded over recent years. These have been summarised in general strategic suggestions and specific management recommendations, emphasising the importance of expedient disease-modifying antirheumatic drug implementation and tight disease control. This consensus statement is in line with these fundamental principles of management. PMID:21378402

  11. In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dahle, Jostein, E-mail: jostein.dahle@rr-research.n; Krogh, Cecilie; Melhus, Katrine B.

    2009-11-01

    Purpose: To determine whether the low-dose-rate alpha-particle-emitting radioimmunoconjugate {sup 227}Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with {sup 227}Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with {sup 227}Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established tomore » estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the {sup 227}Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with {sup 227}Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL {sup 227}Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 10{sup 5} to 10{sup 7} cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy alpha-particle radiation from {sup 227}Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate {sup 227}Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.« less

  12. Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab.

    PubMed

    López De Padilla, Consuelo M; Crowson, Cynthia S; Hein, Molly S; Strausbauch, Michael A; Aggarwal, Rohit; Levesque, Marc C; Ascherman, Dana P; Oddis, Chester V; Reed, Ann M

    2015-01-01

    The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

  13. Novel use of rituximab in a case of Riedel's thyroiditis refractory to glucocorticoids and tamoxifen.

    PubMed

    Soh, Shui-Boon; Pham, Alan; O'Hehir, Robyn E; Cherk, Martin; Topliss, Duncan J

    2013-09-01

    A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of i.v. rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study.

  14. Impact of inadequate doses of rituximab in the treatment of diffuse large B cell lymphoma in Malaysian patients.

    PubMed

    Gan, Gin Gin; Subramaniam, Rajaletchumy; Bee, Ping Chong; Chin, Edmund Fui Min; Abdul-Halim, Habibah; Tai, Mei Chee

    2014-01-01

    The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL. The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome. A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001). The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.

  15. Shock wave experiments on gallium

    NASA Astrophysics Data System (ADS)

    Jensen, Brian; Branch, Brittany; Cherne, Frank

    2017-06-01

    Gallium exhibits a complex phase diagram with multiple solid phases, an anomalous melt boundary, and a low-temperature melt transition making it a suitable material for shock wave studies focused on multiphase properties including kinetics and strength. Apart from high-pressure shock wave data that exists for the liquid phase, there is a clear lack of data in the low-pressure regime where much of the complexity in the phase diagram exists. In this work, a series of shock wave experiments were performed to begin examining the low-pressure region of the phase diagram. Additional data on a gallium alloy, which remains liquid at room temperature, will be presented and compared to data available for pure gallium (LA-UR-17-21449).

  16. Rituximab is effective in severe treatment-resistant neurological Behçet's syndrome.

    PubMed

    Kidd, D P

    2015-12-01

    The objective of this study is to describe a case of severe and treatment-resistant neurological Behçet's syndrome responsive to a novel therapy. This case report describes the patient who failed to respond to conventional therapy but the brain stem lesion resolved with the anti-CD20 biological agent rituximab. Neurological complications are uncommon in Behçet's syndrome; 80% involve a meningoencephalitis which can be severe and relapsing. This is the first report of effectiveness of rituximab in this uncommon disease.

  17. Method of fabricating germanium and gallium arsenide devices

    NASA Technical Reports Server (NTRS)

    Jhabvala, Murzban (Inventor)

    1990-01-01

    A method of semiconductor diode fabrication is disclosed which relies on the epitaxial growth of a precisely doped thickness layer of gallium arsenide or germanium on a semi-insulating or intrinsic substrate, respectively, of gallium arsenide or germanium by either molecular beam epitaxy (MBE) or by metal-organic chemical vapor deposition (MOCVD). The method involves: depositing a layer of doped or undoped silicon dioxide on a germanium or gallium arsenide wafer or substrate, selectively removing the silicon dioxide layer to define one or more surface regions for a device to be fabricated thereon, growing a matched epitaxial layer of doped germanium or gallium arsenide of an appropriate thickness using MBE or MOCVD techniques on both the silicon dioxide layer and the defined one or more regions; and etching the silicon dioxide and the epitaxial material on top of the silicon dioxide to leave a matched epitaxial layer of germanium or gallium arsenide on the germanium or gallium arsenide substrate, respectively, and upon which a field effect device can thereafter be formed.

  18. Antibacterial effect of gallium and silver on Pseudomonas aeruginosa treated with gallium-silver-phosphate-based glasses.

    PubMed

    Valappil, Sabeel P; Higham, Susan M

    2014-01-01

    Gallium and silver incorporated phosphate-based glasses were evaluated for antibacterial effect on the growth of Pseudomonas aeruginosa, which is a leading cause of opportunistic infections. The glasses were produced by conventional melt quenching methods at 1100°C for 1 h. Glass degradation studies were conducted by weight loss method. Disc diffusion assay and cell viability assay displayed statistically significant (p ≤ 0.0005) effect on P. aeruginosa growth which increased with decreasing calcium content in the glasses. The gallium ion release rates (1.83, 0.69 and 0.48 ppm·h(-1)) and silver ion release rates (2.97, 2.84 and 2.47 ppm·h(-1)) were found to account for this variation. Constant depth film fermentor was used to evaluate the anti-biofilm properties of the glasses. Both gallium and silver in the glass contributed to biofilm growth inhibitory effect on P. aeruginosa (up to 2.68 reduction in log 10 values of the viable counts compared with controls). The glasses were found to deliver gallium and silver in a controlled way and exerted cumulative antibacterial action on planktonic and biofilm growth of P. aeruginosa. The antibacterial, especially anti-biofilm, properties of the gallium and silver incorporated phosphate-based glasses make them a potential candidate to combat infections caused by P. aeruginosa.

  19. Rituximab: 13 open questions after 20years of clinical use.

    PubMed

    Pavanello, Francesca; Zucca, Emanuele; Ghielmini, Michele

    2017-02-01

    Rituximab improved the prognosis of all B-cell derived lymphoproliferative diseases, but despite 20years of intensive use, it remains a drug with a number of still obscure characteristics and unanswered questions. These include the mechanism of action and of resistance, the optimal schedule, the interaction with chemotherapy, as well as predictive factors for response rate and duration. Despite being very well tolerated, the question of its long term side effects and the risks of the administration near to a pregnancy have only recently been addressed. Also the indications are still not all clear: rituximab induces remissions as a single agent and improves the effect of chemotherapy, but its use as maintenance or as a substitute for watch and wait is still debated. Also, it is still unclear if its efficacy derives at least partly by reducing the risk of histological transformation in indolent NHL and reducing the risk of CNS relapse in aggressive NHL. Finally, despite of 20years of research, it is still unclear if rituximab can be efficiently substituted by biosimilars or new anti-CD20 antibodies. In this review we address all these questions and analyze the literature addressing these aspects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Impact of rituximab therapy on response to tetanus toxoid vaccination in kidney-transplant patients.

    PubMed

    Puissant-Lubrano, Benedicte; Rostaing, Lionel; Kamar, Nassim; Abbal, Michel; Fort, Marylise; Blancher, Antoine

    2010-03-01

    Rituximab is used after kidney transplant to prevention or treat kidney-allograft rejection. However, the impact of rituximab on the ability of patients to respond to tetanus toxoid vaccination has not yet been studied. The response to tetanus toxoid vaccination was analyzed in 39 kidney transplant recipients immunosuppressed by corticoids, antiproliferative agents, and/or calcineurin inhibitors. Thirteen patients had previously received rituximab (group 1), 26 patients had not (group 2). Response to control bacterial antigens and immunologic parameters (lymphocyte count, B-cell subsets, serum immunoglobulin level) were analyzed before and at 1 month after vaccination. Thirty healthy blood donors were used as controls for the before-vaccination immunologic parameters. Before vaccination, neither patient group differed from controls in serum levels of immunoglobulins and antibodies against bacterial antigens, but they did display lower levels of CD4 T cells and B cells compared with controls. Responders to the tetanus toxoid vaccination were slightly fewer in group 1 (4/13) than in group 2 (16/26), but the intensity of the anti-tetanus toxoid response was not significantly different between these 2 groups. None of the parameters studied at the time of vaccination (anti-tetanus toxoid level, peripheral B or CD4 T-cell count, memory B-cell subsets, treatment with rituximab, time since transplant) were associated with an ability to respond to vaccination. The ability to respond to vaccination and graft outcomes were not correlated in each patient group. Rituximab impaired the secondary immune response after tetanus toxoid vaccination, but did not abolish it in all patients.

  1. Nonlinear behaviour of reflectivity of gallium - Silica interface & its applications

    NASA Astrophysics Data System (ADS)

    Naruka, Preeti; Bissa, Shivangi

    2018-05-01

    In this paper Optical properties and nonlinear behaviour of Gallium-Silica Interface is studied. Change in reflectivity of gallium film is explained as a function of thickness of metallic layer and intensity of incident light by using non-thermal mechanism. Here variation of dielectric constant of gallium with temperature is also explained on considering Binary nanoshell model of gallium nanoparticles of spherical shape. In the present paper application of structural phase transformation of gallium is explained as a Grating assisted coupler.

  2. Radiation Dosimetry Study of [89Zr]rituximab Tracer for Clinical Translation of B cell NHL Imaging using Positron Emission Tomography

    PubMed Central

    Natarajan, Arutselvan; Gambhir, Sanjiv Sam

    2015-01-01

    Purpose We evaluated the dosimetry of [89Zr]rituximab, an anti-CD20 immunoPET tracer to image B cell non-Hodgkin’s lymphoma (NHL) using a humanized transgenic mouse model that expresses human CD20 transgenic mice (huCD20TM). Procedures Rituximab was conjugated to desferrioxamine (Df) for radiolabeling of Zirconium-89. [89Zr]rituximab (2.8±0.2 MBq) was tail vein-injected into huCD20T mice. Positron emission tomography (PET)/CT imaging was performed on the two groups of mice (blocking=2 mg/kg pre-dose of rituximab and non-blocking; n=5) at eight time points (1, 4, 24, 48, 72, 96, 120, and 168 h) post injection. Results The novel [89Zr]rituximab PET tracer had good immunoreactivity, was stable in human serum, and was able to specifically target human CD20 in mice. The human equivalents of highest dose (mean±SD) organs with and without pre-dose are liver (345±284 μSv/MBq) and spleen (1165±149 μSv/MBq), respectively. Conclusions Dosimetry of the human patient whole-body dose was found to be 145 MBq per annum, and the patient dose-limiting organ will be the liver (with rituximab pre-dose blocking) and spleen for non-blocking. The [89Zr]rituximab (t½=78.4 h) imaging of B cell NHL patients could permit the observation of targeting lesions in NHL patients over an extended period due to longer half-life as compared to the [64Cu] rituximab (t½=12.7 h). PMID:25500766

  3. Acute adverse reactions of rapid Rituximab infusion among adult patients with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia.

    PubMed

    Lang, Dora; George, Cobie

    Rapid Rituximab infusion has become increasingly popular globally. Although pharmaceutical manufacturers recommend second and subsequent infusions to run over 2-3 hours, many cancer centres have changed their clinical practice based on their own research and the results from other primary studies. Such research studies claim that it is safe to administer Rituximab rapidly among cancer patients especially in Non Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). In addition, the studies suggest that the rapid infusion of Rituximab also results in benefits of cost saving and better resource utilisation. However, these studies have not been critically appraised for their validity and application to the global population. No previous systematic reviews on this topic have been identified.Objective The objective of this review was to critically appraise, synthesise and present the best available evidence related to the safety of rapid Rituximab infusion among adult patients with NHL and CLL. The participants of interest were adults aged 18 years old and above who had a diagnosis of NHL or CLL at any stage, have had prior exposure to Rituximab and received Rituximab with or without combination of any chemotherapy.The intervention of interest was rapid Rituximab infusion to be completed in 120 minutes or less.The studies of interest were both experimental and non-experimental studies.The primary outcomes of interest were the presence of acute adverse reactions and their severity. The secondary outcomes of interest were the management of the acute adverse reactions and patient mortality rate resulting from adverse reactions.Search strategy The search sought to identify published and unpublished studies from 1997 till 2010. A three-step search strategy was used for electronic databases, grey literature and reference lists.Methodological quality Two independent reviewers used the standard critical appraisal tool from JBI-MAStARI to assess the methodological

  4. [Cost-per-responder analysis comparing romiplostim to rituximab in the treatment of adult primary immune thrombocytopenia in Spain].

    PubMed

    López, M Fernanda; Mingot, María Eva; Valcárcel, David; Vicente García, Vicente; Perrin, Allison; Campos Tapias, Ignasi

    2015-05-08

    Romiplostim, a thrombopoietin-receptor agonist, is approved for second-line use in idiopathic thrombocytopenic purpura (ITP) patients where surgery is contraindicated. Anti-CD20 rituximab, an immunosuppressant, is currently used off-label. This analysis compared the cost per responder for romiplostim versus rituximab in Spain. A decision analytic model was constructed to estimate the 6-month cost per responding patient (achieving a platelet count≥50×10(9)/l) according to the most robust published data. A systematic literature review was performed to extract response rates from phase 3 randomized controlled trials. Romiplostim patients received weekly injections; rituximab patients received 4 weekly intravenous infusions. Medical resource costs were obtained from Spanish reimbursement lists. Treatment non-responders incurred bleeding-related event (BRE) management costs as reported in clinical trials. Medical resource utilization and clinical practice were based on Spanish treatment guidelines and validated by local clinical experts. The literature review identified phase 3 romiplostim trials with a response rate of 83%. Due to a lack of phase 3 controlled rituximab trials, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. The mean cost per patient for romiplostim was €16,289 and €13,459 for rituximab. Rituximab resulted in a 10% higher cost per responder (€21,535 versus €19,625 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related costs compared to rituximab. Due to its high level of efficacy leading to lower BRE costs, romiplostim represents an efficient use of resources for adult ITP patients in the Spanish Healthcare System. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  5. Development and biological studies of ¹⁷⁷Lu-DOTA-rituximab for the treatment of Non-Hodgkin's lymphoma.

    PubMed

    Massicano, Adriana V F; Pujatti, Priscilla B; Alcarde, Lais F; Suzuki, Miriam F; Spencer, Patrick J; Araújo, Elaine B

    2016-01-01

    The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.

  6. Behavior of pure gallium in water and various saline solutions.

    PubMed

    Horasawa, N; Nakajima, H; Takahashi, S; Okabe, T

    1997-12-01

    This study investigated the chemical stability of pure gallium in water and saline solutions in order to obtain fundamental knowledge about the corrosion mechanism of gallium-based alloys. A pure gallium plate (99.999%) was suspended in 50 mL of deionized water, 0.01%, 0.1% or 1% NaCl solution at 24 +/- 2 degrees C for 1, 7, or 28 days. The amounts of gallium released into the solutions were determined by atomic absorption spectrophotometry. The surfaces of the specimens were examined after immersion by x-ray diffractometry (XRD) and x-ray photoelectron spectroscopy (XPS). In the solutions containing 0.1% or more NaCl, the release of gallium ions into the solution was lowered when compared to deionized water after 28-day immersion. Gallium oxide monohydroxide was found by XRD on the specimens immersed in deionized water after 28-day immersion. XPS indicated the formation of gallium oxide/hydroxide on the specimens immersed in water or 0.01% NaCl solution. The chemical stability of pure solid gallium was strongly affected by the presence of Cl- ions in the aqueous solution.

  7. Role of rituximab in treatment of patients with primary central nervous system lymphoma: a retrospective analysis of the Czech lymphoma study group registry.

    PubMed

    Mocikova, Heidi; Pytlik, Robert; Sykorova, Alice; Janikova, Andrea; Prochazka, Vit; Vokurka, Samuel; Berkova, Adela; Belada, David; Campr, Vit; Buresova, Lucie; Trneny, Marek

    2016-12-01

    We have investigated whether the addition of rituximab to methotrexate, procarbazine, vincristine, radiotherapy and cytarabine was associated with improved outcome of primary central nervous system lymphomas (PCNSL). Of 164 patients, 49 received rituximab. Median age was 63 years, median Karnofsky performance score (KPS) was 60 and median follow-up of living patients was 59.5 months. 1- and 2-year PFS were 49.7 and 37.9%, 1- and 2-year OS were 57.0 and 45.3%. Median progression-free survival (PFS), but not overall survival (OS) was significantly better for patients treated with rituximab (22.9 vs. 10.9 months, p = 0.037). In multivariate analysis, age ≤70 years and KPS ≥90 were predictive for PFS and OS, rituximab was an independent prognostic factor for PFS only. In landmark analyses, rituximab was not found beneficial for long-term survivors and no group particularly benefited from rituximab. In conclusion, addition of rituximab was associated with improved PFS, but not OS in this unselected cohort of PCNSL patients.

  8. Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody.

    PubMed

    Winkler, Mark T; Bushey, Ryan T; Gottlin, Elizabeth B; Campa, Michael J; Guadalupe, Eross S; Volkheimer, Alicia D; Weinberg, J Brice; Patz, Edward F

    2017-01-01

    Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH). We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody. CDC of rituximab non-responsive malignant B cells from CLL patients could in some cases be augmented by the CFH monoclonal antibody. Antibody-mediated cytotoxicity of cells was dependent upon functional complement. In one case where B-CLL cells were refractory to CDC by the combination of rituximab plus CFH monoclonal antibody, additionally neutralizing the membrane complement regulatory protein CD59 allowed CDC to occur. Inhibiting CDC regulatory proteins such as CFH holds promise for overcoming resistance to rituximab therapy in B-CLL.

  9. Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome

    PubMed Central

    Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

    2016-01-01

    Abstract Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab. A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established. He received Rituximab 375 mg/m2 (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm3. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39). Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion. PMID:27684863

  10. Rituximab does not reset defective early B cell tolerance checkpoints

    PubMed Central

    Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

    2015-01-01

    Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

  11. Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus

    PubMed Central

    Md Yusof, Md Yuzaiful; Shaw, Daniel; El-Sherbiny, Yasser M; Dunn, Emma; Rawstron, Andy C; Emery, Paul; Vital, Edward M

    2017-01-01

    Objective To assess factors associated with primary and secondary non-response to rituximab in systemic lupus erythematosus (SLE) and evaluate management of secondary non-depletion non-response (2NDNR). Methods 125 patients with SLE treated with rituximab over 12 years were studied prospectively. A major clinical response was defined as improvement of all active British Isles Lupus Assessment Group (BILAG)-2004 domains to grade C/better and no A/B flare. Partial responders were defined by one persistent BILAG B. B-cell subsets were measured using highly sensitive flow cytometry. Patients with 2NDNR, defined by infusion reaction and defective depletion, were treated with ocrelizumab or ofatumumab. Results 117 patients had evaluable data. In cycle 1 (C1), 96/117 (82%) achieved BILAG response (major=50%, partial=32%). In multivariable analysis, younger age (OR 0.97, 95% CI 0.94 to 1.00) and B-cell depletion at 6 weeks (OR 3.22, 95% CI 1.24 to 8.33) increased the odds of major response. Complete depletion was predicted by normal complement and lower pre-rituximab plasmablasts and was not associated with increased serious infection post-rituximab. Seventy-seven (with data on 72) C1 responders were retreated on clinical relapse. Of these, 61/72 (85%) responded in cycle 2 (C2). Of the 11 C2 non-responders, nine met 2NDNR criteria (incidence=12%) and tested positive for anti-rituximab antibodies. Lack of concomitant immunosuppressant and higher pre-rituximab plasmablasts predicted 2NDNR. Five were switched to ocrelizumab/ofatumumab, and all depleted and responded. Conclusion Treatment with anti-CD20 agents can be guided by B-cell monitoring and should aim to achieve complete depletion. 2NDNR is associated with anti-rituximab antibodies, and switching to humanised agents restores depletion and response. In SLE, alternative anti-CD20 antibodies may be more consistently effective. PMID:28684557

  12. Using health-system-wide data to understand hepatitis B virus prophylaxis and reactivation outcomes in patients receiving rituximab.

    PubMed

    Schmajuk, Gabriela; Tonner, Chris; Trupin, Laura; Li, Jing; Sarkar, Urmimala; Ludwig, Dana; Shiboski, Stephen; Sirota, Marina; Dudley, R Adams; Murray, Sara; Yazdany, Jinoos

    2017-03-01

    Hepatitis B virus (HBV) reactivation in the setting of rituximab use is a potentially fatal but preventable safety event. The rate of HBV screening and proportion of patients at risk who receive antiviral prophylaxis in patients initiating rituximab is unknown.We analyzed electronic health record (EHR) data from 2 health systems, a university center and a safety net health system, including diagnosis grouper codes, problem lists, medications, laboratory results, procedures codes, clinical encounter notes, and scanned documents. We identified all patients who received rituximab between 6/1/2012 and 1/1/2016. We calculated the proportion of rituximab users with inadequate screening for HBV according to the Centers for Disease Control guidelines for detecting latent HBV infection before their first rituximab infusion during the study period. We also assessed the proportion of patients with positive hepatitis B screening tests who were prescribed antiviral prophylaxis. Finally, we characterized safety failures and adverse events.We included 926 patients from the university and 132 patients from the safety net health system. Sixty-one percent of patients from the university had adequate screening for HBV compared with 90% from the safety net. Among patients at risk for reactivation based on results of HBV testing, 66% and 92% received antiviral prophylaxis at the university and safety net, respectively.We found wide variations in hepatitis B screening practices among patients receiving rituximab, resulting in unnecessary risks to patients. Interventions should be developed to improve patient safety procedures in this high-risk patient population.

  13. Treatment of Rheumatoid Arthritis with Biologic DMARDS (Rituximab and Etanercept)

    PubMed Central

    Gashi, Afrim A.; Rexhepi, Sylejman; Berisha, Idriz; Kryeziu, Avni; Ismaili, Jehona; Krasniqi, Gezim

    2014-01-01

    ABSTRACT Goal: To determine efficacy and safety of treatment with Rituximab and Etanercept plus Methotrexate in patients with active Rheumatoid Arthritis (RA), who had an inadequate response to nonbiologic DMARDS therapies and to explore the pharmacogenetics and pharmacodynamics of Rituximab and Etanercept in our populations. Study was done at Rheumatology Clinic of University Clinical Centre in Prishtina during 2009-2011 years. Methods: We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the study of long term efficacy of Rituximab and Etanercept. Patients with active Rheumatoid Arthritis and an inadequate response to 1 or more non biologic DMARDS were randomized to receive intravenous Rituximab (1 course consisting of 2 infusions of 1.000 mg each –one group, and Etanercept 25 mg twice weekly –second group, but both groups with background MTX. The primary efficacy end point was a response on the ACR 20%, improvement criteria at 24 weeks, Secondary end points were responses on the ACR 50 and ACR 70, improvement criteria, the DAS 28, and EULAR response criteria at 24 weeks. Results: During our investigations we treated 20 patients, 15 females and 5 males, in the treated group with RTX and 13 patients 8 females and 5 males in the treated group with ETN. Patients of group 1 and group 2 were of ages 37-69 years old and 19-69 years old (average 47-44) Most of the patients belong in 2nd and 3 rd functional stage according to Steinbrocker. All ACR response parameters were significantly improved in RTX treated patients who also had clinically meaningful improvement in fatigue, disability and quality of life. Patients showed a trend less progression in radiographic end points. Most adverse events occurred with the first RTX infusion and were mild to moderate severity. Conclusion: At 24 weeks, a single course of RTX and ETN provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who

  14. Treatment of rheumatoid arthritis with biologic DMARDS (Rituximab and Etanercept).

    PubMed

    Gashi, Afrim A; Rexhepi, Sylejman; Berisha, Idriz; Kryeziu, Avni; Ismaili, Jehona; Krasniqi, Gezim

    2014-01-01

    To determine efficacy and safety of treatment with Rituximab and Etanercept plus Methotrexate in patients with active Rheumatoid Arthritis (RA), who had an inadequate response to nonbiologic DMARDS therapies and to explore the pharmacogenetics and pharmacodynamics of Rituximab and Etanercept in our populations. Study was done at Rheumatology Clinic of University Clinical Centre in Prishtina during 2009-2011 years. We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the study of long-term efficacy of Rituximab and Etanercept. Patients with active Rheumatoid Arthritis and an inadequate response to 1 or more non biologic DMARDS were randomized to receive intravenous Rituximab (1 course consisting of 2 infusions of 1.000 mg each -one group, and Etanercept 25 mg twice weekly -second group, but both groups with background MTX. The primary efficacy end point was a response on the ACR 20%, improvement criteria at 24 weeks, Secondary end points were responses on the ACR 50 and ACR 70, improvement criteria, the DAS 28, and EULAR response criteria at 24 weeks. During our investigations we treated 20 patients, 15 females and 5 males, in the treated group with RTX and 13 patients 8 females and 5 males in the treated group with ETN. Patients of group 1 and group 2 were of ages 37-69 years old and 19-69 years old (average 47-44) Most of the patients belong in 2nd and 3rd functional stage according to Steinbrocker. All ACR response parameters were significantly improved in RTX treated patients who also had clinically meaningful improvement in fatigue, disability and quality of life. Patients showed a trend less progression in radiographic end points. Most adverse events occurred with the first RTX infusion and were mild to moderate severity. At 24 weeks, a single course of RTX and ETN provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more

  15. Surface photovoltage spectroscopy applied to gallium arsenide surfaces

    NASA Technical Reports Server (NTRS)

    Bynik, C. E.

    1975-01-01

    The experimental and theoretical basis for surface photovoltage spectroscopy is outlined. Results of this technique applied to gallium arsenide surfaces, are reviewed and discussed. The results suggest that in gallium arsenide the surface voltage may be due to deep bulk impurity acceptor states that are pinned at the Fermi level at the surface. Establishment of the validity of this model will indicate the direction to proceed to increase the efficiency of gallium arsenide solar cells.

  16. A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

    PubMed

    Fervenza, Fernando C; Canetta, Pietro A; Barbour, Sean J; Lafayette, Richard A; Rovin, Brad H; Aslam, Nabeel; Hladunewich, Michelle A; Irazabal, Maria V; Sethi, Sanjeev; Gipson, Debbie S; Reich, Heather N; Brenchley, Paul; Kretzler, Matthias; Radhakrishnan, Jai; Hebert, Lee A; Gipson, Patrick E; Thomas, Leslie F; McCarthy, Ellen T; Appel, Gerald B; Jefferson, J Ashley; Eirin, Alfonso; Lieske, John C; Hogan, Marie C; Greene, Eddie L; Dillon, John J; Leung, Nelson; Sedor, John R; Rizk, Dana V; Blumenthal, Samuel S; Lasic, Lada B; Juncos, Luis A; Green, Dollie F; Simon, James; Sussman, Amy N; Philibert, David; Cattran, Daniel C

    2015-01-01

    Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic

  17. Nitrate and periplasmic nitrate reductases

    PubMed Central

    Sparacino-Watkins, Courtney; Stolz, John F.; Basu, Partha

    2014-01-01

    The nitrate anion is a simple, abundant and relatively stable species, yet plays a significant role in global cycling of nitrogen, global climate change, and human health. Although it has been known for quite some time that nitrate is an important species environmentally, recent studies have identified potential medical applications. In this respect the nitrate anion remains an enigmatic species that promises to offer exciting science in years to come. Many bacteria readily reduce nitrate to nitrite via nitrate reductases. Classified into three distinct types – periplasmic nitrate reductase (Nap), respiratory nitrate reductase (Nar) and assimilatory nitrate reductase (Nas), they are defined by their cellular location, operon organization and active site structure. Of these, Nap proteins are the focus of this review. Despite similarities in the catalytic and spectroscopic properties Nap from different Proteobacteria are phylogenetically distinct. This review has two major sections: in the first section, nitrate in the nitrogen cycle and human health, taxonomy of nitrate reductases, assimilatory and dissimilatory nitrate reduction, cellular locations of nitrate reductases, structural and redox chemistry are discussed. The second section focuses on the features of periplasmic nitrate reductase where the catalytic subunit of the Nap and its kinetic properties, auxiliary Nap proteins, operon structure and phylogenetic relationships are discussed. PMID:24141308

  18. A FETISH for gallium arsenide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barron, A.R.

    1996-12-31

    An overview of the development of a new dielectric material, cubic-GaS, from the synthesis of new organometallic compounds to the fabrication of a new class of gallium arsenide based transistor is presented as a representative example of the possibility that inorganic chemistry can directly effect the development of new semiconductor devices. The gallium sulfido compound [({sup t}Bu)GaS]{sub 4}, readily prepared from tri-tert-butyl gallium, may be used as a precursor for the growth of GaS thin films by metal organic chemical vapor deposition (MOCVD). Photoluminescence and electronic measurements indicate that this material provides a passivation coating for GaAs. Furthermore, the insulatingmore » properties of cubic-GaS make it suitable as the insulating gate layer in a new class of GaAs transistor: a field effect transistor with a sulfide heterojunction (FETISH).« less

  19. Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

    PubMed

    Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

    2016-08-01

    Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

  20. Fatal Eastern Equine Encephalitis in a Patient on Maintenance Rituximab: A Case Report.

    PubMed

    Solomon, Isaac H; Ciarlini, Pedro D S C; Santagata, Sandro; Ahmed, Asim A; De Girolami, Umberto; Prasad, Sashank; Mukerji, Shibani S

    2017-01-01

    A 63-year-old woman on rituximab maintenance for follicular lymphoma presented with headaches, vomiting, and fever, and was diagnosed with eastern equine encephalomyelitis by cerebrospinal fluid polymerase chain reaction. Eastern equine encephalomyelitis immunoglobulin (Ig)G/IgM remained negative due to rituximab treatment, and magnetic resonance imaging showed minimal abnormalities, making this a diagnostically challenging case. Despite therapy with intravenous Ig, the patient rapidly declined and died on hospital day 12. Autopsy revealed perivascular and parenchymal chronic inflammation, with an absence of B lymphocytes, and virally infected neurons throughout the central nervous system.

  1. Rituximab therapy in steroid-resistant severe hypothyroid Grave's ophthalmopathy

    PubMed Central

    Pandit, Aditi; Gundgurthi, Abhay; Kharb, Sandeep; Brar, Karninder S.; Garg, M. K.

    2013-01-01

    Association of Grave's ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave's ophthalmopathy successfully treated with rituximab. PMID:23776919

  2. Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

    PubMed

    Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

    2015-01-01

    Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

  3. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project

    PubMed Central

    Carson, Kenneth R.; Evens, Andrew M.; Richey, Elizabeth A.; Habermann, Thomas M.; Focosi, Daniele; Seymour, John F.; Laubach, Jacob; Bawn, Susie D.; Gordon, Leo I.; Winter, Jane N.; Furman, Richard R.; Vose, Julie M.; Zelenetz, Andrew D.; Mamtani, Ronac; Raisch, Dennis W.; Dorshimer, Gary W.; Rosen, Steven T.; Muro, Kenji; Gottardi-Littell, Numa R.; Talley, Robert L.; Sartor, Oliver; Green, David; Major, Eugene O.

    2009-01-01

    Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons. PMID:19264918

  4. P-n junctions formed in gallium antimonide

    NASA Technical Reports Server (NTRS)

    Clough, R.; Richman, D.; Tietjen, J.

    1970-01-01

    Vapor phase deposition process forms a heavily doped n-region on a melt-grown p-type gallium antimonide substrate. HCl transports gallium to the reaction zone, where it combines with antimony hydride and the dopant carrier, hydrogen telluride. Temperatures as low as 400 degrees C are required.

  5. Pre-emptive rituximab for Epstein-Barr virus reactivation after haplo-hematopoietic stem cell transplantation.

    PubMed

    Kobayashi, Shogo; Sano, Hideki; Mochizuki, Kazuhiro; Ohara, Yoshihiro; Takahashi, Nobuhisa; Ohto, Hitoshi; Kikuta, Atsushi

    2017-09-01

    Epstein-Barr virus-related post-transplantation lymphoproliferative disease (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with pre-emptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was measured when suspected EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/10 6 peripheral blood mononuclear cells (PBMC), patients were pre-emptively treated with rituximab (375 mg/m 2 /dose). A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17-270 days). The median viral load at initiation of therapy was 2,900 copies/10 6 PBMC (range, 1,000-650 000). Pre-emptive therapy was started after a median of 2 days (range, 0-7 days). The median number of weekly treatment cycles was 2 (range, 1-3). None of the patients developed PTLD or other EBV-associated diseases. Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG. © 2017 Japan Pediatric Society.

  6. Gallium 67 scintigraphy in glomerular disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bakir, A.A.; Lopez-Majano, V.; Levy, P.S.

    1988-12-01

    To evaluate the diagnostic usefulness of gallium 67 scintigraphy in glomerular disease, 45 patients with various glomerulopathies, excluding lupus nephritis and renal vasculitis, were studied. Persistent renal visualization 48 hours after the gallium injection, a positive scintigram, was graded as + (less than), ++ (equal to), and +++ (greater than) the hepatic uptake. Positive scintigrams were seen in ten of 16 cases of focal segmental glomerulosclerosis, six of 11 cases of proliferative glomerulonephritis, and one case of minimal change, and one of two cases of membranous nephropathy; also in three of six cases of sickle glomerulopathy, two cases of diabeticmore » neuropathy, one of two cases of amyloidosis, and one case of mild chronic allograft rejection. The 25 patients with positive scans were younger than the 20 with negative scans (31 +/- 12 v 42 +/- 17 years; P less than 0.01), and exhibited greater proteinuria (8.19 +/- 7.96 v 2.9 +/- 2.3 S/d; P less than 0.01) and lower serum creatinine values (2 +/- 2 v 4.1 +/- 2.8 mg/dL; P less than 0.01). The amount of proteinuria correlated directly with the intensity grade of the gallium image (P less than 0.02), but there was no correlation between the biopsy diagnosis and the outcome of the gallium scan. It was concluded that gallium scintigraphy is not useful in the differential diagnosis of the glomerular diseases under discussion. Younger patients with good renal function and heavy proteinuria are likely to have a positive renal scintigram regardless of the underlying glomerulopathy.« less

  7. Assessment of gallium-67 scanning in pulmonary and extrapulmonary sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Israel, H.L.; Gushue, G.F.; Park, C.H.

    1986-01-01

    Gallium-67 scans have been widely employed in patients with sarcoidosis as a means of indicating alveolitis and the need for corticosteroid therapy. Observation of 32 patients followed 3 or more years after gallium scans showed no correlation between findings and later course: of 10 patients with pulmonary uptake, 7 recovered with minor residuals; of 18 patients with mediastinal of extrathoracic uptake, 10 had persistent or progressive disease; of 4 patients with negative initial scans, 2 had later progression. The value of gallium-67 scans as an aid to diagnosis was studied in 40 patients with extrapulmonary sarcoidosis. In 12 patients, abnormalmore » lacrimal, nodal, or pulmonary uptake aided in selection of biopsy sites. Gallium-67 scans and serum ACE levels were compared in 97 patients as indices of clinical activity. Abnormal gallium-67 uptake was observed in 96.3% of the tests in active disease, and ACE level elevation occurred in 56.3%. In 24 patients with inactive or recovered disease, abnormal gallium-67 uptake occurred in 62.5% and ACE level elevation in 37.5%. Gallium-67 scans have a limited but valuable role in the diagnosis and management of sarcoidosis.« less

  8. Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma.

    PubMed

    Einhorn, L H; Roth, B J; Ansari, R; Dreicer, R; Gonin, R; Loehrer, P J

    1994-11-01

    Phase II trial in metastatic urothelial carcinoma using a novel combination chemotherapy regimen consisting of vinblastine, ifosfamide, and gallium nitrate (VIG). Twenty-seven patients were entered onto this phase II study. Dosages were vinblastine 0.11 mg/kg days 1 and 2, ifosfamide 1.2 gm/m2 days 1 through 5 (with mesna), and gallium 300 mg/m2 as a 24-hour infusion days 1 through 5, with calcitriol (1,25-dihydroxycholecalciferol) 0.5 microgram/d orally starting 3 days before each course (except the first) and continuing throughout gallium administration, plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) 5 micrograms/kg/d days 7 through 16. Courses were repeated every 21 days for a maximum of six cycles. The major toxicity was granulocytopenia. Fifteen patients (55.6%) had grade 3 or 4 granulocytopenia, including eight patients with granulocytopenic fevers. Eleven patients had grade 3 or 4 anemia and four had grade 3 or 4 nephrotoxicity, which was reversible. Other grade 3 to 4 toxicities included hypocalcemia (three patients), thrombocytopenia (two), encephalopathy (one), and temporary blindness (one). There was one treatment-related mortality. Toxicity was more severe in patients older than 70 years and those with prior pelvic irradiation, prior cisplatin adjuvant therapy, or prior nephrectomy. We now decrease VIG by 20% in this patient population. Eighteen patients (67%) achieved an objective response, including 11 (41%) who attained a disease-free status (five with VIG alone and six with subsequent surgery). Median duration of remission was 20 weeks, with five patients still in remission at 22+ to 56+ weeks. VIG combination chemotherapy is very active in patients with metastatic urothelial carcinoma. Toxicity was significant but manageable.

  9. Gallium-67 uptake by the thyroid associated with progressive systemic sclerosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sjoberg, R.J.; Blue, P.W.; Kidd, G.S.

    1989-01-01

    Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patientsmore » with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake.« less

  10. Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

    PubMed

    Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

    2014-03-01

    There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P < 0.001). No toxicity-related death was reported. The use of anti-cancer systemic therapy is safe and efficient in gastric MALT lymphoma. In this retrospective study, the combination of rituximab plus chlorambucil seems more efficient than rituximab or alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

  11. Combating rituximab resistance by inducing ceramide/lysosome-involved cell death through initiation of CD20-TNFR1 co-localization

    PubMed Central

    Zhang, Fan; Yang, Junlan; Li, Huafei; Liu, Moyan; Zhang, Jie; Zhao, Lichao; Wang, Lingxiong; LingHu, RuiXia; Feng, Fan; Gao, Xudong; Dong, Biqin; Liu, Xiaohan; Zi, Jian; Zhang, Weijing; Hu, Yi; Pan, Jingkun; Tian, Lei; Hu, Yazuo; Han, Zhitao; Zhang, Honghong; Wang, Xiaoning; Zhao, Lei

    2016-01-01

    ABSTRACT Despite the success of CD20 antibody rituximab in immunotherapy, acquired resistance is one of the prime obstacles for the successful treatment of B-cell malignancies. There is an urgent need to intensify efforts against resistance in cancer treatment. Growing evidence indicated that lysosomes may form an “Achilles heel” for cancer cells by sensitizing them to death pathways. Here, we uncover an important role of CD20 in initiation of ceramide/lysosomal membrane permeabilization (LMP)-mediated cell death, showing that colocalization of CD20-TNFR1 after type II CD20 antibody ligation can stimulate de novo ceramide synthesis by ceramide synthase and consequently induce remarkable lysosomal permeabilization (LMP) and lysosome-mediated cell death. Further studies show that the potent lysosome-mediated cell death induced by CD20 antibodies exhibits a profound killing effect against both rituximab-sensitive and -resistant (RR) lymphoma. Furthermore, engineering of rituximab by introducing a point mutation endows it with the ability to induce potent ceramide/LMP-mediated cell death in both RR lymphoma and primary B-cell malignancies from patients with rituximab-refractory, suggesting the potential clinical application to combat rituximab resistance. PMID:27467962

  12. Construction of an electrode modified with gallium(III) for voltammetric detection of ovalbumin.

    PubMed

    Sugawara, Kazuharu; Okusawa, Makoto; Takano, Yusaku; Kadoya, Toshihiko

    2014-01-01

    Electrodes modified with gallium(III) complexes were constructed to detect ovalbumin (OVA). For immobilization of a gallium(III)-nitrilotriacetate (NTA) complex, the electrode was first covered with collagen film. After the amino groups of the film had reacted with isothiocyanobenzyl-NTA, the gallium(III) was then able to combine with the NTA moieties. Another design featured an electrode cast with a gallium(III)-acetylacetonate (AA) complex. The amount of gallium(III) in the NTA complex was equivalent to one-quarter of the gallium(III) that could be utilized from an AA complex. However, the calibration curves of OVA using gallium(III)-NTA and gallium(III)-AA complexes were linear in the ranges of 7.0 × 10(-11) - 3.0 × 10(-9) M and 5.0 × 10(-10) - 8.0 × 10(-9) M, respectively. The gallium(III) on the electrode with NTA complex had high flexibility due to the existence of a spacer between the NTA and the collagen film, and, therefore, the reactivity of the gallium(III) to OVA was superior to that of the gallium(III)-AA complex with no spacer.

  13. Sensitizing effects of gallium citrate on hyperthermic cell killing in vitro.

    PubMed

    Miyazaki, N; Nakano, H; Kawakami, N; Kugotani, M; Nishihara, K; Aoki, Y; Shinohara, K

    2000-01-01

    The lethal effects of gallium citrate in combination with heat were studied using four cell lines, L5178Y, FM3A, P388 and HeLa. Cells were incubated with different concentrations (0.2 2 mM) of gallium citrate at 37 degrees C for 24 h and heated at a range of temperatures from 40-44 degrees C for various time periods up to 6 h in the absence of gallium citrate. Survival and cell viability were determined by clonogenic assay and the dye-exclusion test, respectively. All of the cell lines tested were insensitive to heat below 41 degrees C, but were very sensitive to heat above 43 degrees C. Gallium citrate was cytotoxic to these cell lines at different levels: P388 and HeLa were far more sensitive than L5178Y and FM3A. The killing effects of heat at 41 degrees C were greatly enhanced by gallium citrate in L5178Y and P388 cells. The Arrhenius analysis for the lethal effect of heat, determined by clonogenic assay, in L5178Y cells showed that the transition temperature was remarkably decreased for the gallium-treated cells from approximately 43 degrees C to 41 degrees C. The mechanism for this decrease in the transition temperature may be attributable to the additional effects of gallium citrate on energy metabolism. Preincubation with 0.05 mM gallium citrate at 37 degrees C for 7 days also enhanced heat sensitization at 41 degrees C in L5178Y. This preincubation condition may correspond to the condition for the continuous infusion of gallium that is clinically used for cancer treatment. In contrast, treatment with gallium did not greatly enhance the sensitivity of FM3A or HeLa cells to heat at 41 degrees C, but the effects of gallium were significant.

  14. Seed/Catalyst-Free Growth of Gallium-Based Compound Materials on Graphene on Insulator by Electrochemical Deposition at Room Temperature.

    PubMed

    Rashiddy Wong, Freddawati; Ahmed Ali, Amgad; Yasui, Kanji; Hashim, Abdul Manaf

    2015-12-01

    We report the growth of gallium-based compounds, i.e., gallium oxynitride (GaON) and gallium oxide (Ga2O3) on multilayer graphene (MLG) on insulator using a mixture of ammonium nitrate (NH4NO3) and gallium nitrate (Ga(NO3)3) by electrochemical deposition (ECD) method at room temperature (RT) for the first time. The controlling parameters of current density and electrolyte molarity were found to greatly influence the properties of the grown structures. The thicknesses of the deposited structures increase with the current density since it increases the chemical reaction rates. The layers grown at low molarities of both solutions basically show grain-like layer with cracking structures and dominated by both Ga2O3 and GaON. Such cracking structures seem to diminish with the increases of molarities of one of the solutions. It is speculated that the increase of current density and ions in the solutions helps to promote the growth at the area with uneven thicknesses of graphene. When the molarity of Ga(NO3)3 is increased while keeping the molarity of NH4NO3 at the lowest value of 2.5 M, the grown structures are basically dominated by the Ga2O3 structure. On the other hand, when the molarity of NH4NO3 is increased while keeping the molarity of Ga(NO3)3 at the lowest value of 0.8 M, the GaON structure seems to dominate where their cubic and hexagonal arrangements are coexisting. It was found that when the molarities of Ga(NO3)3 are at the high level of 7.5 M, the grown structures tend to be dominated by Ga2O3 even though the molarity of NH4NO3 is made equal or higher than the molarity of Ga(NO3)3. When the grown structure is dominated by the Ga2O3 structure, the deposition process became slow or unstable, resulting to the formation of thin layer. When the molarity of Ga(NO3)3 is increased to 15 M, the nanocluster-like structures were formed instead of continuous thin film structure. This study seems to successfully provide the conditions in growing either GaON-dominated or

  15. Direct determination of gallium on polyurethane foam by X-ray fluorescence.

    PubMed

    Carvalho, M S; Medeiros, J A; Nóbrega, A W; Mantovano, J L; Rocha, V P

    1995-01-01

    Gallium chloride is easily extracted from 6M HCl by comminuted polyether-type polyurethane foam. After the extraction step, the gallium absorbed by the PU foam can be quantitatively determined by X-ray fluorescence. A procedure for the direct determination of gallium absorbed by PU foam by XRFS is thus described. Gallium is determined at levels as low as 60 ng/ml (C(L)), with a calibration sensitivity of 424 cps ml/mug, within a linear range 0.1-2.30 mug/ml. The procedure investigated was successfully applied to determination of gallium in aluminum alloys, bauxite and industrial residue samples.

  16. Challenges for critical raw material recovery from WEEE - The case study of gallium.

    PubMed

    Ueberschaar, Maximilian; Otto, Sarah Julie; Rotter, Vera Susanne

    2017-02-01

    Gallium and gallium compounds are more frequently used in future oriented technologies such as photovoltaics, light diodes and semiconductor technology. In the long term the supply risk is estimated to be critical. Germany is one of the major primary gallium producer, recycler of gallium from new scrap and GaAs wafer producer. Therefore, new concepts for a resource saving handling of gallium and appropriate recycling strategies have to be designed. This study focus on options for a possible recycling of gallium from waste electric and electronic equipment. To identify first starting points, a substance flow analysis was carried out for gallium applied in integrated circuits applied on printed circuit boards and for LEDs used for background lighting in Germany in 2012. Moreover, integrated circuits (radio amplifier chips) were investigated in detail to deduce first approaches for a recycling of such components. An analysis of recycling barriers was carried out in order to investigate general opportunities and risks for the recycling of gallium from chips and LEDs. Results show, that significant gallium losses arose in primary production and in waste management. 93±11%, equivalent to 43,000±4700kg of the total gallium potential was lost over the whole primary production process until applied in electronic goods. The largest share of 14,000±2300kggallium was lost in the production process of primary raw materials. The subsequent refining process was related to additional 6900±3700kg and the chip and wafer production to 21,700±3200kg lost gallium. Results for the waste management revealed only low collection rates for related end-of-life devices. Not collected devices held 300 ± 200 kg gallium. Due to the fact, that current waste management processes do not recover gallium, further 80 ± 10 kg gallium were lost. A thermal pre-treatment of the chips, followed by a manual separation allowed an isolation of gallium rich fractions, with gallium mass fractions up to

  17. Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

    PubMed

    Thompson, Grace; Pepperell, Dominic; Lawrence, Ian; McGettigan, Benjamin David

    2017-02-22

    We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication. 2017 BMJ Publishing Group Ltd.

  18. Imaging B Cells in a Mouse Model of Multiple Sclerosis Using 64Cu-Rituximab PET.

    PubMed

    James, Michelle L; Hoehne, Aileen; Mayer, Aaron T; Lechtenberg, Kendra; Moreno, Monica; Gowrishankar, Gayatri; Ilovich, Ohad; Natarajan, Arutselvan; Johnson, Emily M; Nguyen, Joujou; Quach, Lisa; Han, May; Buckwalter, Marion; Chandra, Sudeep; Gambhir, Sanjiv S

    2017-11-01

    B lymphocytes are a key pathologic feature of multiple sclerosis (MS) and are becoming an important therapeutic target for this condition. Currently, there is no approved technique to noninvasively visualize B cells in the central nervous system (CNS) to monitor MS disease progression and response to therapies. Here, we evaluated 64 Cu-rituximab, a radiolabeled antibody specifically targeting the human B cell marker CD20, for its ability to image B cells in a mouse model of MS using PET. Methods: To model CNS infiltration by B cells, experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice that express human CD20 on B cells. EAE mice were given subcutaneous injections of myelin oligodendrocyte glycoprotein fragment 1-125 emulsified in complete Freund adjuvant. Control mice received complete Freund adjuvant alone. PET imaging of EAE and control mice was performed 1, 4, and 19 h after 64 Cu-rituximab administration. Mice were perfused and sacrificed after the final PET scan, and radioactivity in dissected tissues was measured with a γ-counter. CNS tissues from these mice were immunostained to quantify B cells or were further analyzed via digital autoradiography. Results: Lumbar spinal cord PET signal was significantly higher in EAE mice than in controls at all evaluated time points (e.g., 1 h after injection: 5.44 ± 0.37 vs. 3.33 ± 0.20 percentage injected dose [%ID]/g, P < 0.05). 64 Cu-rituximab PET signal in brain regions ranged between 1.74 ± 0.11 and 2.93 ± 0.15 %ID/g for EAE mice, compared with 1.25 ± 0.08 and 2.24 ± 0.11 %ID/g for controls ( P < 0.05 for all regions except striatum and thalamus at 1 h after injection). Similarly, ex vivo biodistribution results revealed notably higher 64 Cu-rituximab uptake in the brain and spinal cord of huCD20tg EAE, and B220 immunostaining verified that increased 64 Cu-rituximab uptake in CNS tissues corresponded with elevated B cells. Conclusion: B cells can be detected in the CNS of EAE mice

  19. Gallium uptake by transferrin and interaction with receptor 1.

    PubMed

    Chikh, Zohra; Ha-Duong, Nguyêt-Thanh; Miquel, Geneviève; El Hage Chahine, Jean-Michel

    2007-01-01

    The kinetics and thermodynamics of Ga(III) exchange between gallium mononitrilotriacetate and human serum transferrin as well as those of the interaction between gallium-loaded transferrin and the transferrin receptor 1 were investigated in neutral media. Gallium is exchanged between the chelate and the C-site of human serum apotransferrin in interaction with bicarbonate in about 50 s to yield an intermediate complex with an equilibrium constant K (1) = (3.9 +/- 1.2) x 10(-2), a direct second-order rate constant k (1) = 425 +/- 50 M(-1) s(-1) and a reverse second-order rate constant k (-1) = (1.1 +/- 3) x 10(4) M(-1) s(-1). The intermediate complex loses a single proton with proton dissociation constant K (1a) = 80 +/- 40 nM to yield a first kinetic product. This product then undergoes a modification in its conformation which lasts about 500 s to produce a second kinetic intermediate, which in turn undergoes a final extremely slow (several hours) modification in its conformation to yield the gallium-saturated transferrin in its final state. The mechanism of gallium uptake differs from that of iron and does not involve the same transitions in conformation reported during iron uptake. The interaction of gallium-loaded transferrin with the transferrin receptor occurs in a single very fast kinetic step with a dissociation constant K (d) = 1.10 +/- 0.12 microM and a second-order rate constant k (d) = (1.15 +/- 0.3) x 10(10) M(-1) s(-1). This mechanism is different from that observed with the ferric holotransferrin and suggests that the interaction between the receptor and gallium-loaded transferrin probably takes place on the helical domain of the receptor which is specific for the C-site of transferrin and HFE. The relevance of gallium incorporation by the transferrin receptor-mediated iron-acquisition pathway is discussed.

  20. The gallium melting-point standard: a determination of the liquid-solid equilibrium temperature of pure gallium on the International Practical Temperature Scale of 1968.

    PubMed

    Thornton, D D

    1977-01-01

    The sharpness and reproducibility of the gallium melting point were studied and the melting temperature of gallium in terms of IPTS-68 was determined. Small melting-point cells designed for use with thermistors are described. Nine gallium cells including three levels of purity were used in 68 separate determinations fo the melting point. The melting point of 99.99999% pure gallium in terms of IPTS-68 is found to be 29.771(4) +/- 0.001(4) degree C; the melting range is less than 0.0005 degree C and is reproducible to +/- 0.0004 degree C.

  1. Composition of the core from gallium metal–silicate partitioning experiments

    DOE PAGES

    Blanchard, I.; Badro, J.; Siebert, J.; ...

    2015-07-24

    We present gallium concentration (normalized to CI chondrites) in the mantle is at the same level as that of lithophile elements with similar volatility, implying that there must be little to no gallium in Earth's core. Metal-silicate partitioning experiments, however, have shown that gallium is a moderately siderophile element and should be therefore depleted in the mantle by core formation. Moreover, gallium concentrations in the mantle (4 ppm) are too high to be only brought by the late veneer; and neither pressure, nor temperature, nor silicate composition has a large enough effect on gallium partitioning to make it lithophile. Wemore » therefore systematically investigated the effect of core composition (light element content) on the partitioning of gallium by carrying out metal–silicate partitioning experiments in a piston–cylinder press at 2 GPa between 1673 K and 2073 K. Four light elements (Si, O, S, C) were considered, and their effect was found to be sufficiently strong to make gallium lithophile. The partitioning of gallium was then modeled and parameterized as a function of pressure, temperature, redox and core composition. A continuous core formation model was used to track the evolution of gallium partitioning during core formation, for various magma ocean depths, geotherms, core light element contents, and magma ocean composition (redox) during accretion. The only model for which the final gallium concentration in the silicate Earth matched the observed value is the one involving a light-element rich core equilibrating in a FeO-rich deep magma ocean (>1300 km) with a final pressure of at least 50 GPa. More specifically, the incorporation of S and C in the core provided successful models only for concentrations that lie far beyond their allowable cosmochemical or geophysical limits, whereas realistic O and Si amounts (less than 5 wt.%) in the core provided successful models for magma oceans deeper that 1300 km. In conclusion, these results

  2. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era.

    PubMed

    Ziepert, Marita; Hasenclever, Dirk; Kuhnt, Evelyn; Glass, Bertram; Schmitz, Norbert; Pfreundschuh, Michael; Loeffler, Markus

    2010-05-10

    The International Prognostic Index (IPI) is widely used for risk stratification of patients with aggressive B-cell lymphoma. The introduction of rituximab has markedly improved outcome, and R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone) has become the standard treatment for CD20(+) diffuse large B-cell lymphoma. To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP, we analyzed the prognostic relevance of IPI in three prospective clinical trials. In total, 1,062 patients treated with rituximab were included (MabThera International Trial [MInT], 380 patients; dose-escalated regimen of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (MegaCHOEP) trial, 72 patients; CHOP + rituximab for patients older than age 60 years [RICOVER-60] trial, 610 patients). A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free, progression-free, and overall survival. IPI score was significant for all three end points. Rituximab significantly improved treatment outcome within each IPI group resulting in a quenching of the Kaplan-Meier estimators. However, IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid. The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP. The effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy. These results demonstrate that the IPI is still valid in the R-CHOP era.

  3. Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

    PubMed

    Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

    2016-07-01

    Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

  4. Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia.

    PubMed

    Paludo, Jonas; Abeykoon, Jithma P; Shreders, Amanda; Ansell, Stephen M; Kumar, Shaji; Ailawadhi, Sikander; King, Rebecca L; Koehler, Amber B; Reeder, Craig B; Buadi, Francis K; Dispenzieri, Angela; Lacy, Martha Q; Dingli, David; Witzig, Thomas E; Go, Ronald S; Gonsalves, Wilson I; Kourelis, Taxiarchis; Warsame, Rahma; Leung, Nelson; Habermann, Thomas M; Hayman, Suzanne; Lin, Yi; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A; Kapoor, Prashant

    2018-04-03

    The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients' MYD88 L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p = 0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p = 0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p = 0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p = 0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p = 0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥ 3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients' MYD88 mutation status.

  5. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

    PubMed

    Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

    2016-02-01

    Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression

  6. Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

    PubMed

    Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

    2008-11-01

    Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

  7. Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy.

    PubMed

    Freise, Kevin J; Jones, Aksana K; Menon, Rajeev M; Verdugo, Maria E; Humerickhouse, Rod A; Awni, Walid M; Salem, Ahmed Hamed

    2017-12-01

    Venetoclax is indicated at a dosage of 400 mg daily (QD) for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. Ongoing trials are evaluating venetoclax in combination with CD20 targeting monoclonal antibodies, such as rituximab. The objective of this research was to characterize the relationship between venetoclax exposures and progression-free survival (PFS) and to evaluate the effect of rituximab coadministration on PFS in patients with relapsed or refractory (R/R) CLL/small lymphocytic lymphoma (SLL). A total of 323 patients from 3 clinical studies of venetoclax, with and without rituximab coadministration, were pooled for the analyses. A time-variant relative risk survival model was used to relate plasma venetoclax concentrations and rituximab administration to PFS. Demographics and baseline disease characteristics were evaluated for their effect on PFS. A concentration-dependent effect of venetoclax on PFS and a prolonged synergistic effect of 6 cycles of concomitant rituximab were identified. The 17p deletion chromosomal aberration was not identified to affect the PFS of patients treated with venetoclax. A venetoclax dose of 400 mg daily QD was estimated to result in a substantial median PFS of 1.8 years (95% confidence interval [CI], 1.7-2.1), whereas the addition of 6 cycles of rituximab was estimated to increase the median PFS to 3.9 years (95% CI, 2.8-5.6). The analysis demonstrates a concentration-dependent effect of venetoclax on PFS and also a synergistic effect with rituximab. Combining venetoclax with the CD20 targeting monoclonal antibody rituximab in R/R CLL/SLL patients provides substantial synergistic benefit compared with increasing the venetoclax monotherapy dose. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Two chain gallium fluorodiphosphates: synthesis, structure solution, and their transient presence during the hydrothermal crystallisation of a microporous gallium fluorophosphate.

    PubMed

    Millange, Franck; Walton, Richard I; Guillou, Nathalie; Loiseau, Thierry; O'Hare, Dermot; Férey, Gérard

    2002-04-21

    Two novel gallium fluorodiphosphates have been isolated and their structures solved ab initio from powder X-ray diffraction data; the materials readily interconvert under hydrothermal conditions, and are metastable with respect to an open-framework zeolitic gallium fluorophosphate, during the synthesis of which they are present as transient intermediates.

  9. Treatment by rituximab on six Grave's ophthalmopathies resistant to corticosteroids.

    PubMed

    Précausta, Flavien; Arsène, Sophie; Renoult-Pierre, Peggy; Laure, Boris; Crinière, Lise; Pisella, Pierre-Jean

    2017-02-01

    Graves' ophthalmopathy occurs in 50% of Graves' disease cases. Treatment is based on smoking cessation, and control of the euthyroidism and ocular repercussions associated with the disease. The active orbital forms are treated with glucocorticoids. Non-validated therapies have also been recently tested. Rituximab has been effectively used several times to treat corticosteroid-resistant Graves' ophthalmopathy associated with an optic neuropathy, but its use could be proposed only in inflammatory ophthalmopathies after failure of the corticosteroids. We present six cases treated since early 2012 at the University Hospital Center of Tours, France. Six patients were treated at the University Hospital Center of Tours, France, between September 2012 and April 2014. The patients had a Mourits' score greater than three after treatment with corticosteroids and/or a severe NOSPECS score and/or orbital inflammation resistant to maximal treatment with intravenous injections of methylprednisolone and an optic neuropathy. They twice received one gram of rituximab by slow intravenous injection two weeks apart. Efficacy was assessed by a decrease of the orbital inflammatory clinical Mourits' score, and visual acuity and visual field testing. The inflammatory score of patients improved and treatment helped to stop the progression of the sequelae due to neuropathy. The orbital inflammatory clinical score, and the visual acuity and visual field improved but orbital decompression was necessary to complete the treatment. Rituximab has been used for the treatment of active corticosteroid-resistant Graves' ophthalmopathies. We also had positive results on patients with visual threat and optic neuropathy, when combined with surgical decompression. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Gallium induces the production of virulence factors in Pseudomonas aeruginosa.

    PubMed

    García-Contreras, Rodolfo; Pérez-Eretza, Berenice; Lira-Silva, Elizabeth; Jasso-Chávez, Ricardo; Coria-Jiménez, Rafael; Rangel-Vega, Adrián; Maeda, Toshinari; Wood, Thomas K

    2014-02-01

    The novel antimicrobial gallium is a nonredox iron III analogue with bacteriostatic and bactericidal properties, effective for the treatment of Pseudomonas aeruginosa in vitro and in vivo in mouse and rabbit infection models. It interferes with iron metabolism, transport, and presumably its homeostasis. As gallium exerts its antimicrobial effects by competing with iron, we hypothesized that it ultimately will lead cells to an iron deficiency status. As iron deficiency promotes the expression of virulence factors in vitro and promotes the pathogenicity of P. aeruginosa in animal models, it is anticipated that treatment with gallium will also promote the production of virulence factors. To test this hypothesis, the reference strain PA14 and two clinical isolates from patients with cystic fibrosis were exposed to gallium, and their production of pyocyanin, rhamnolipids, elastase, alkaline protease, alginate, pyoverdine, and biofilm was determined. Gallium treatment induced the production of all the virulence factors tested in the three strains except for pyoverdine. In addition, as the Ga-induced virulence factors are quorum sensing controlled, co-administration of Ga and the quorum quencher brominated furanone C-30 was assayed, and it was found that C-30 alleviated growth inhibition from gallium. Hence, adding both C-30 and gallium may be more effective in the treatment of P. aeruginosa infections. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  11. Control of Gallium Oxide Growth on Liquid Metal Eutectic Gallium/Indium Nanoparticles via Thiolation.

    PubMed

    Farrell, Zachary J; Tabor, Christopher

    2018-01-09

    Eutectic gallium-indium alloy (EGaIn, a room-temperature liquid metal) nanoparticles are of interest for their unique potential uses in self-healing and flexible electronic devices. One reason for their interest is due to a passivating oxide skin that develops spontaneously on exposure to ambient atmosphere which resists deformation and rupture of the resultant liquid particles. It is then of interest to develop methods for control of this oxide growth process. It is hypothesized here that functionalization of EGaIn nanoparticles with thiolated molecules could moderate oxide growth based on insights from the Cabrera-Mott oxidation model. To test this, the oxidation dynamics of several thiolated nanoparticle systems were tracked over time with X-ray photoelectron spectroscopy. These results demonstrate the ability to suppress gallium oxide growth by up to 30%. The oxide progressively matures over a 28 day period, terminating in different final thicknesses as a function of thiol selection. These results indicate not only that thiols moderate gallium oxide growth via competition with oxygen for surface sites but also that different thiols alter the thermodynamics of oxide growth through modification of the EGaIn work function.

  12. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial.

    PubMed

    Oddis, Chester V; Reed, Ann M; Aggarwal, Rohit; Rider, Lisa G; Ascherman, Dana P; Levesque, Marc C; Barohn, Richard J; Feldman, Brian M; Harris-Love, Michael O; Koontz, Diane C; Fertig, Noreen; Kelley, Stephanie S; Pryber, Sherrie L; Miller, Frederick W; Rockette, Howard E

    2013-02-01

    To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients. Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures (CSMs) for adults. Juvenile DM patients required ≥3 abnormal CSMs, with or without muscle weakness. Patients were randomized to receive either rituximab early or rituximab late, and glucocorticoid or immunosuppressive therapy was allowed at study entry. The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement (DOI) between the 2 groups. The secondary end points were the time to achieve ≥20% improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8. Among 200 randomized patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no difference in the time to achieving the DOI between the rituximab late (n = 102) and rituximab early (n = 93) groups (P = 0.74 by log rank test), with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary end points also did not significantly differ between the 2 treatment groups. However, 161 (83%) of the randomized patients met the DOI, and individual CSMs improved in both groups throughout the 44-week trial. Although there were no significant differences in the 2 treatment arms for the primary and secondary end points, 83% of adult and juvenile myositis patients with refractory disease met the DOI. The role of B cell-depleting therapies in myositis warrants further study, with consideration for a different trial design. Copyright © 2013 by the American College of Rheumatology.

  13. Gallium Electromagnetic (GEM) Thruster Performance Measurements

    NASA Technical Reports Server (NTRS)

    Thomas, Robert E.; Burton, Rodney L.; Polzin, K. A.

    2009-01-01

    Discharge current, terminal voltage, and mass bit measurements are performed on a coaxial gallium electromagnetic thruster at discharge currents in the range of 7-23 kA. It is found that the mass bit varies quadratically with the discharge current which yields a constant exhaust velocity of 20 km/s. Increasing the electrode radius ratio of the thruster from to 2.6 to 3.4 increases the thruster efficiency from 21% to 30%. When operating with a central gallium anode, macroparticles are ejected at all energy levels tested. A central gallium cathode ejects macroparticles when the current density exceeds 3.7 10(exp 8) A/square m . A spatially and temporally broad spectroscopic survey in the 220-520 nm range is used to determine which species are present in the plasma. The spectra show that neutral, singly, and doubly ionized gallium species are present in the discharge, as well as annular electrode species at higher energy levels. Axial Langmuir triple probe measurements yield electron temperatures in the range of 0.8-3.8 eV and electron densities in the range of 8 x 10(exp )20 to 1.6 x 10(exp 21) m(exp -3) . Triple probe measurements suggest an exhaust plume with a divergence angle of 9 , and a completely doubly ionized plasma at the ablating thruster cathode.

  14. Bragg Reflector-Induced Increased Nonradiative Lifetime in Gallium Arsenide (GaAs)/Aluminum Gallium Arsenide (AlGaAs) Double Heterostructures

    DTIC Science & Technology

    2015-09-01

    ARL-TR-7473 ● SEP 2015 US Army Research Laboratory Bragg Reflector-Induced Increased Nonradiative Lifetime in Gallium Arsenide...return it to the originator. ARL-TR-7473 ● SEP 2015 US Army Research Laboratory Bragg Reflector-Induced Increased Nonradiative ...3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Bragg Reflector-Induced Increased Nonradiative Lifetime in Gallium Arsenide (GaAs)/Aluminum

  15. Extremely-efficient, miniaturized, long-lived alpha-voltaic power source using liquid gallium

    NASA Technical Reports Server (NTRS)

    Snyder, G. Jeffrey (Inventor); Patel, Jagdishbhai (Inventor); Fleurial, Jean-Pierre (Inventor)

    2004-01-01

    A power source converts .alpha.-particle energy to electricity for use in electrical systems. Liquid gallium or other liquid medium is subjected to .alpha.-particle emissions. Electrons are freed by collision from neutral gallium atoms to provide gallium ions. The electrons migrate to a cathode while the gallium ions migrate to an anode. A current and/or voltage difference then arises between the cathode and anode because of the work function difference of the cathode and anode. Gallium atoms are regenerated by the receiving of electrons from the anode enabling the generation of additional electrons from additional .alpha.-particle collisions.

  16. Anisotropy of the magnetic susceptibility of gallium

    USGS Publications Warehouse

    Pankey, T.

    1960-01-01

    The bulk magnetic susceptibilities of single gallium crystals and polycrystalline gallium spheres were measured at 25??C. The following anisotropic diamagnetic susceptibilities were found: a axis (-0.119??0. 001)??10-6 emu/g, b axis (-0.416??0.002)??10 -6 emu/g, and c axis (-0.229??0.001) emu/g. The susceptibility of the polycrystalline spheres, assumed to be the average value for the bulk susceptibility of gallium, was (-0.257??0.003)??10-6 emu/g at 25??C, and (-0.299??0.003)??10-6 emu/g at -196??C. The susceptibility of liquid gallium was (0.0031??0.001) ??10-6 emu/g at 30??C and 100??C. Rotational diagrams of the susceptibilities in the three orthogonal planes of the unit cell were not sinusoidal. The anisotropy in the single crystals was presumably caused by the partial overlap of Brillouin zone boundaries by the Fermi-energy surface. The large change in susceptibility associated with the change in state was attributed to the absence of effective mass influence in the liquid state. ?? 1960 The American Institute of Physics.

  17. Gallium-containing phospho-silicate glasses: synthesis and in vitro bioactivity.

    PubMed

    Franchini, Mirco; Lusvardi, Gigliola; Malavasi, Gianluca; Menabue, Ledi

    2012-08-01

    A series of Ga-containing phospho-silicate glasses based on Bioglass 45S5, having molar formula 46.2SiO2·24.3Na2O·26.9CaO·2.6P2O5·xGa2O3 (x=1.0, 1.6, 3.5), were prepared by fusion method. The reference Bioglass 45S5 without gallium was also prepared. The synthesized glasses were immersed in simulated body fluid (SBF) for 30 days in order to observe ion release and hydroxyapatite (HA) formation. All Ga-containing glasses maintain the ability of HA formation as indicated by main X-ray diffractometric peaks and/or electronic scanning microscopy results. HA layer was formed after 1 day of SBF soaking in 45S5 glass containing up to 1.6% Ga2O3 content. Moreover, gallium released by the glasses was found to be partially precipitated on the glass surface as gallium phosphate. Further increase in gallium content reduced the ion release in SBF. The maximum of Ga(3+) concentration measured in solution is ~6 ppm determined for 3.5% Ga2O3 content. This amount is about half of the toxic level (14 ppm) of gallium and the glasses release gallium till 30 days of immersion in SBF. Considering the above results, the studied materials can be proposed as bioactive glasses with additional antimicrobial effect of gallium having no toxic outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Optical and Electrical Characterization of Bulk Grown Indium-Gallium-Arsenide Alloys

    DTIC Science & Technology

    2010-03-01

    OPTICAL AND ELECTRICAL CHARACTERIZATION OF BULK GROWN INDIUM- GALLIUM -ARSENIDE ALLOYS THESIS...Government. AFIT/GAP/ENP/10-M02 OPTICAL AND ELECTRICAL CHARACTERIZATION OF BULK GROWN INDIUM- GALLIUM -ARSENIDE ALLOYS THESIS Presented to...ELECTRICAL CHARACTERIZATION OF BULK GROWN INDIUM- GALLIUM -ARSENIDE ALLOYS Austin C Bergstrom, BS 2 nd Lieutenant, USAF

  19. IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

    PubMed Central

    Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

    2010-01-01

    Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

  20. Response to rituximab and timeframe to relapse in rheumatoid arthritis patients: association with B-cell markers.

    PubMed

    Pyrpasopoulou, Athina; Douma, Stella; Triantafyllou, Areti; Simoulidou, Elisavet; Samara, Magda; Parapanisiou, Efthymia; Aslanidis, Spyros

    2010-02-01

    Rituximab is used to deplete B cells and control disease activity, mainly in patients with rheumatoid arthritis (RA) who have not responded to anti-tumor necrosis factor (TNF) therapy. Response rates and time to relapse vary significantly among treated individuals. The objective of this study was to monitor the response of seropositive and seronegative RA patients to rituximab and correlate relapse with B-cell markers in the two groups. Seventeen RA patients (eight seropositive for rheumatoid factor [RF+] and nine seronegative [RF-]) were treated with two cycles of rituximab. After treatment, all patients were re-evaluated at the outpatient clinic, and rituximab was readministered when disease relapse was confirmed by clinical-laboratory measures (Disease Activity Score [DAS]-28). CD20+ cells and CD20 receptor expression levels were estimated at initiation, relapse, and re-evaluation timepoints, and were compared between the two groups. Seropositive patients responded favorably to treatment compared with the seronegative group. The mean time to relapse was 337.5 +/- 127.0 days for the RF+ patients versus 233.3 +/- 59.6 days for the RF- patients (p = 0.043), despite more aggressive concomitant treatment in the seronegative group. The DAS28 decrease 3 months after treatment was 1.695 +/- 1.076 in seropositive patients versus 0.94 +/- 1.62 in seronegative patients. At relapse, CD20 receptor expression (molecules/cell) was higher in RF+ patients than in their RF- counterparts, despite a significantly lower percentage of CD20+ cells. Rituximab treatment is efficient in both seropositive and seronegative RA. However, seropositive RA patients tend to respond favorably compared with seronegative patients. The differential CD20 receptor expression in the two groups at relapse potentially suggests a different pathogenetic mechanism of relapse and merits further investigation.

  1. Cost-Effectiveness of Administering Rituximab for Steroid-Dependent Nephrotic Syndrome and Frequently Relapsing Nephrotic Syndrome: A Preliminary Study in Japan

    PubMed Central

    Takura, Tomoyuki; Takei, Takashi; Nitta, Kosaku

    2017-01-01

    With regard to the use of rituximab for patients with steroid-dependent nephrotic syndrome and frequently relapsing nephrotic syndrome, not only has the regimen not been clinically verified but also there is a lack of health economics evidence. Therefore, we conducted a prospective clinical study on 30 patients before (with steroids and immunosuppressants) and after introducing rituximab therapy. Relapse rates and total invoiced medical expenses were selected as the primary endpoints for treatment effectiveness and treatment costs, respectively. As secondary endpoints, cost-effectiveness was compared before and after administering rituximab in relation to previous pharmacotherapy. The observation period was 24 months before and after the initiation of rituximab. We showed that there was a statistically significant improvement in the relapse rate from a mean of 4.30 events before administration to a mean of 0.27 events after administration and that there was a significantly better prognosis in the cumulative avoidance of relapse rate by Kaplan–Meier analysis (p < 0.01). Finally, the total medical costs decreased from 2,923 USD to 1,280 USD per month, and the pre–post cost-effectiveness was confirmed as dominant. We, therefore, conclude that treatment with rituximab was possibly superior to previous pharmacological treatments from a health economics perspective. PMID:28387313

  2. MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study.

    PubMed

    Peterfy, Charles; Emery, Paul; Tak, Paul P; Østergaard, Mikkel; DiCarlo, Julie; Otsa, Kati; Navarro Sarabia, Federico; Pavelka, Karel; Bagnard, Marie-Agnes; Gylvin, Lykke Hinsch; Bernasconi, Corrado; Gabriele, Annarita

    2016-01-01

    To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (-0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. NCT00578305. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Controlled delivery of antimicrobial gallium ions from phosphate-based glasses.

    PubMed

    Valappil, S P; Ready, D; Abou Neel, E A; Pickup, D M; O'Dell, L A; Chrzanowski, W; Pratten, J; Newport, R J; Smith, M E; Wilson, M; Knowles, J C

    2009-05-01

    Gallium-doped phosphate-based glasses (PBGs) have been recently shown to have antibacterial activity. However, the delivery of gallium ions from these glasses can be improved by altering the calcium ion concentration to control the degradation rate of the glasses. In the present study, the effect of increasing calcium content in novel gallium (Ga2O3)-doped PBGs on the susceptibility of Pseudomonas aeruginosa is examined. The lack of new antibiotics in development makes gallium-doped PBG potentially a highly promising new therapeutic agent. The results show that an increase in calcium content (14, 15 and 16 mol.% CaO) cause a decrease in degradation rate (17.6, 13.5 and 7.3 microg mm(-2) h(-1)), gallium ion release and antimicrobial activity against planktonic P. aeruginosa. The most potent glass composition (containing 14 mol.% CaO) was then evaluated for its ability to prevent the growth of biofilms of P. aeruginosa. Gallium release was found to reduce biofilm growth of P. aeruginosa with a maximum effect (0.86 log(10) CFU reduction compared to Ga2O3-free glasses) after 48 h. Analysis of the biofilms by confocal microscopy confirmed the anti-biofilm effect of these glasses as it showed both viable and non-viable bacteria on the glass surface. Results of the solubility and ion release studies show that this glass system is suitable for controlled delivery of Ga3+. 71Ga NMR and Ga K-edge XANES measurements indicate that the gallium is octahedrally coordinated by oxygen atoms in all samples. The results presented here suggest that PBGs may be useful in controlled drug delivery applications, to deliver gallium ions in order to prevent infections due to P. aeruginosa biofilms.

  4. Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nosal, A.; Schleissner, L.A.; Mishkin, F.S.

    1979-03-01

    Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. Itmore » was concluded that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis.« less

  5. Preliminary Spectroscopic Measurements for a Gallium Electromagnetic (GEM) Thruster

    NASA Technical Reports Server (NTRS)

    Thomas, Robert E.; Burton, Rodney L.; Glumac, Nick G.; Polzin, Kurt A.

    2007-01-01

    As a propellant option for electromagnetic thrusters, liquid ,gallium appears to have several advantages relative to other propellants. The merits of using gallium in an electromagnetic thruster (EMT) are discussed and estimates of discharge current levels and mass flow rates yielding efficient operation are given. The gallium atomic weight of 70 predicts high efficiency in the 1500-2000 s specific impulse range, making it ideal for higher-thrust, near-Earth missions. A spatially and temporally broad spectroscopic survey in the 220-520 nm range is used to determine which species are present in the plasma and estimate electron temperature. The spectra show that neutral, singly, and doubly ionized gallium species are present in a 20 J, 1.8 kA (peak) are discharge. With graphite present on the insulator to facilitate breakdown, singly and doubly ionized carbon atoms are also present, and emission is observed from molecular carbon (CZ) radicals. A determination of the electron temperature was attempted using relative emission line data, and while the spatially and temporally averaged, spectra don't fit well to single temperatures, the data and presence of doubly ionized gallium are consistent with distributions in the 1-3 eV range.

  6. 33 CFR 126.28 - Ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. 126.28 Section 126..., ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. (a) When any item of ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

  7. 33 CFR 126.28 - Ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. 126.28 Section 126..., ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. (a) When any item of ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

  8. 33 CFR 126.28 - Ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. 126.28 Section 126..., ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. (a) When any item of ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

  9. 33 CFR 126.28 - Ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. 126.28 Section 126..., ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. (a) When any item of ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

  10. 33 CFR 126.28 - Ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. 126.28 Section 126..., ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate; general provisions. (a) When any item of ammonium nitrate, ammonium nitrate fertilizers, fertilizer mixtures, or nitro carbo nitrate...

  11. Preparation and evaluation of APTES-PEG coated iron oxide nanoparticles conjugated to rhenium-188 labeled rituximab.

    PubMed

    Azadbakht, Bakhtiar; Afarideh, Hossein; Ghannadi-Maragheh, Mohammad; Bahrami-Samani, Ali; Asgari, Mehdi

    2017-05-01

    Radioimmuno-conjugated (Rhenium-188 labeled Rituximab), 3-aminopropyltriethoxysilane (APTES)-polyethylene glycol (PEG) coated iron oxide nanoparticles were synthesized and then characterized. Therapeutic effect and targeting efficacy of complex were evaluated in CD20 express B cell lines and tumor bearing Balb/c mice respectively. To reach these purposes, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using coprecipitation method and then their surface was treated with APTES for increasing retention time of SPIONs in blood circulation and amine group creation. In the next step, N-hydroxysuccinimide (NHS) ester of polyethylene glycol maleimide (NHS-PEG-Mal) was conjugated to the APTES-treated SPIONs. After radiolabeling of Rituximab antibody with Rhenium-188 (T 1/2 =16.9h) using synthesized N 2 S 4 chelator, it was attached to the APTES-PEG-MAL-SPIONs surface through thiol-maleimide coupling reaction. In vitro evaluation of the 188 ReN 2 S 4 -Rituximab-SPION-complex thus obtained revealed that at 24 and 48h post-treatment effective cancer cell killing had been achieved. Bio-distribution study in tumor bearing mice showed capability of this complex for targeted cancer therapy. Active and passive tumor targeting strategies were applied through incorporated anti-CD20 (Rituximab) antibody and also enhanced permeability and retention (EPR) effect of solid tumors for nanoparticles respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Recovery of Gallium from Secondary V-Recycling Slag by Alkali Fusion

    NASA Astrophysics Data System (ADS)

    Gao, Lei; Shi, Zhe; Zhang, Gui-fang

    Secondary V-recycling slag, an industrial waste containing high gallium is being dumped continuously, which causes the loss of gallium. Thus, the alkali fusion process was employed to recover gallium from this slag. The effects factors on extraction of gallium such as roasting temperature, roasting time, alkali fusion agent concentration and CaO concentration were investigated in the paper. The experimental results indicated that excessive roasting temperature and roasting time is unfavorable to the recovery rate of gallium. The appropriate roasting temperature and duration are 1000°C and 2 hours, respectively; The appropriate proportioning of Na2CO3: NaOH is 2:1 when the concentration of alkali fusion agent weighs 0.4 times the mass of the slag; In order to remove SiO2 from the leaching liquor, CaO should be used as an additive in the roasting process. The appropriate concentration of CaO should weigh 0.2 times the mass of the slag. Employing these optimal alkali fusion conditions in the roasting process, gallium recovery is above 90%.

  13. Aminoethyl nitrate – the novel super nitrate?

    PubMed Central

    Bauersachs, Johann

    2009-01-01

    Long-term use of most organic nitrates is limited by development of tolerance, induction of oxidative stress and endothelial dysfunction. In this issue of the BJP, Schuhmacher et al. characterized a novel class of organic nitrates with amino moieties (aminoalkyl nitrates). Aminoethyl nitrate was identified as a novel organic mononitrate with high potency but devoid of induction of mitochondrial oxidative stress. Cross-tolerance to nitroglycerin or the endothelium-dependent agonist acetylcholine after in vivo treatment was not observed. Like all nitrates, aminoethyl nitrate induced vasorelaxation by activation of soluble guanylate cyclase. Thus, in contrast to the prevailing view, high potency in an organic nitrate is not necessarily accompanied by induction of oxidative stress or endothelial dysfunction. This work from Daiber's group is an important step forward in the understanding of nitrate bioactivation, tolerance phenomena and towards the development of better organic nitrates for clinical use. PMID:19732062

  14. Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

    PubMed

    Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

    2014-08-12

    Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

  15. Gallium alloy films investigated for use as boundary lubricants

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Gallium alloyed with other low melting point metals has excellent lubricant properties of fluidity and low vapor pressure for high temperature or vacuum environments. The addition of other soft metals reduces the corrosivity and formation of undesirable alloys normally found with gallium.

  16. Clinical review: Serious adverse events associated with the use of rituximab - a critical care perspective

    PubMed Central

    2012-01-01

    The advent of biologic agents has provided a more specific and targeted approach to the treatment of various hematological malignancies and other autoimmune disorders. Such biologic agents have been relatively well tolerated with fewer adverse events reported as compared with many other chemotherapeutic agents. Rituximab is a monoclonal antibody to the B-cell marker CD20 and is a common biologic agent widely used for the treatment of B-cell lymphoma, lymphoproliferative disorders, and inflammatory conditions that are refractory to conventional treatment, including rheumatoid arthritis and some vasculitides. However, through randomized controlled trials and post-marketing surveillance, an increasing number of serious adverse events are being associated with the use of rituximab, often leading to or complicating an intensive care unit admission. The purpose of this review is to focus on the severe complications that are associated with the use of rituximab and that require critical care. Management and prevention strategies for the most common complications along with some examples of its uses within the critical care setting are also discussed. PMID:22967460

  17. Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and rituximab.

    PubMed

    Vo, Ashley A; Petrozzino, Jeffrey; Yeung, Kai; Sinha, Aditi; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Mackowiak, John; Jordan, Stanley C

    2013-03-27

    Transplantation rates are very low for the broadly sensitized patient (panel reactive antibody [PRA]>80%; HS). Here, we examine the efficacy, outcomes, and cost-effectiveness of desensitization using high-dose intravenous immunoglobulin (IVIG) and rituximab to improve transplantation rates in HS patients. From July 2006 to December 2011, 207 HS (56 living donors/151 deceased donors) patients (donor-specific antibody positive, PRA>80%) were desensitized using IVIG and rituximab. After desensitization, responsive patients proceeded to transplantation with an acceptable crossmatch. Cost and outcomes of desensitization were compared with dialysis. Of the 207 treated patients, 146 (71%) were transplanted. At 48 months, patient and graft survival by Kaplan-Meier were 95% and 87.5%, respectively. The total 3-year cost for patients treated in the desensitization arm was $219,914 per patient compared with $238,667 per patient treated in the dialysis arm. Thus, each patient treated with desensitization is estimated to save the U.S. healthcare system $18,753 in 2011 USD. Overall, estimated patient survival at the end of 3 years was 96.6% for patients in the desensitization arm of the model (based on Cedars-Sinai survival rate) compared with 79.0% for an age, end-stage renal disease etiology, and PRA matched group of patients remaining on dialysis during the study period. We conclude that desensitization with IVIG+rituximab is clinically and cost-effective, with both financial savings and an estimated 17.6% greater probability of 3-year survival associated with desensitization versus dialysis alone. However, the benefits of desensitization and transplantation are limited by organ availability and allocation policies.

  18. High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a (177)Lu-based CD22-specific radioimmunoconjugate and rituximab.

    PubMed

    Weber, Tobias; Bötticher, Benedikt; Mier, Walter; Sauter, Max; Krämer, Susanne; Leotta, Karin; Keller, Armin; Schlegelmilch, Anne; Grosse-Hovest, Ludger; Jäger, Dirk; Haberkorn, Uwe; Arndt, Michaela A E; Krauss, Jürgen

    2016-03-01

    Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter (177)Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A″-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of (177)Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1 (null) ) interleukin-2 receptor common gamma chain (IL2rγ (null) ) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. (177)Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A"-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the (177)Lu-labelled anti-CD22 IgG than of (177)Lu-labelled rituximab. Treatment with (177)Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with (177)Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with (177)Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for refractory B-NHL.

  19. Microfluidic platforms for gallium-based liquid metal alloy

    NASA Astrophysics Data System (ADS)

    Kim, Daeyoung

    As an alternative to toxic mercury, non-toxic gallium-based liquid metal alloy has been gaining popularity due to its higher thermal and electrical conductivities, and low toxicity along with liquid property. However, it is difficult to handle as the alloy becomes readily oxidized in atmospheric air environment. This instant oxidation causes the gallium-based liquid metal alloy to wet almost any solid surface. Therefore, it has been primarily limited to applications which rely only on its deformability, not on its mobility. In this research, various approaches to mobilize gallium-based liquid metal alloy were investigated. Multi-scale surface patterned with polydimethylsiloxane (PDMS) micro pillar array showed super-lyophobic property against gallium-based liquid metal alloy by minimizing the contact area between the solid surface and the liquid metal, and it was expanded to a three-dimensional tunnel shaped microfluidic channel. Vertically-aligned carbon nanotube forest leads to another promising super-lyophobic surface due to its hierarchical micro/nano scale combined structures and chemical inertness. When the carbon nanotubes were transferred onto flexible PDMS by imprinting, the super-lyophobic property was still maintained even under the mechanical deformation such as stretching and bending. Alternatively, the gallium-based liquid metal can be manipulated by modifying the surface of liquid metal itself. With chemical reaction with HCl 'vapor', the oxidized surface (mainly Ga2O3/Ga2O) of gallium-based liquid metal was converted to GaCl3/InCl 3 resulting in the recovery of non-wetting characteristics. Paper which is intrinsically porous is attractive as a super-lyophobic surface and it was found that hydrochloric acid (HCl) impregnation enhanced the anti-wetting property by the chemical reaction. As another alternative method, by coating the viscoelastic oxidized surface of liquid metal with ferromagnetic materials (CoNiMnP or Fe), it showed non

  20. Novel solution-phase structures of gallium-containing pyrogallol[4]arene scaffolds**

    PubMed Central

    Kumari, Harshita; Kline, Steven R.; Wycoff, Wei G.; Paul, Rick L.; Mossine, Andrew V.; Deakyne, Carol A.; Atwood, Jerry L.

    2012-01-01

    The variations in architecture of gallium-seamed (PgC4Ga) and gallium-zinc-seamed (PgC4GaZn) C-butylpyrogallol[4]arene nanoassemblies in solution (SANS/NMR) versus the solid state (XRD) have been investigated. Rearrangement from the solid-state spheroidal to the solution-phase toroidal shape differentiates the gallium-containing pyrogallol[4]arene nanoassemblies from all other PgCnM nanocapsules studied thus far. Different structural arrangements of the metals and arenes of PgC4Ga versus PgC4GaZn have been deduced from the different toroidal dimensions, C–H proton environments and guest encapsulation of the two toroids. PGAA of mixed-metal hexamers reveals a decrease in gallium-to-metal ratio as the second metal varies from cobalt to zinc. Overall, the combined study demonstrates the versatility of gallium in directing the self-assembly of pyrogallol[4]arenes into novel nanoarchitectures. PMID:22511521

  1. Window structure for passivating solar cells based on gallium arsenide

    NASA Technical Reports Server (NTRS)

    Barnett, Allen M. (Inventor)

    1985-01-01

    Passivated gallium arsenide solar photovoltaic cells with high resistance to moisture and oxygen are provided by means of a gallium arsenide phosphide window graded through its thickness from arsenic rich to phosphorus rich.

  2. Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis

    PubMed Central

    Lindgren, Helena

    2015-01-01

    The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacterium Francisella tularensis strain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a ΔfslA mutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a ΔfeoB mutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited >70% of the iron uptake. Addition of gentamicin and/or gallium to infected bone marrow-derived macrophages showed that both 100 μM gallium and 10 μg/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment of F. tularensis-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicin in vitro and in vivo. PMID:26503658

  3. Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis.

    PubMed

    Lindgren, Helena; Sjöstedt, Anders

    2016-01-01

    The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacterium Francisella tularensis strain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a ΔfslA mutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a ΔfeoB mutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited >70% of the iron uptake. Addition of gentamicin and/or gallium to infected bone marrow-derived macrophages showed that both 100 μM gallium and 10 μg/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment of F. tularensis-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicin in vitro and in vivo. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Internalization of Rituximab and the Efficiency of B Cell Depletion in Rheumatoid Arthritis and Systemic Lupus Erythematosus

    PubMed Central

    Cambridge, Geraldine; Isenberg, David A.; Glennie, Martin J.; Cragg, Mark S.; Leandro, Maria

    2015-01-01

    Objective Rituximab, a type I anti‐CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. Methods We used an in vitro whole blood B cell–depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence–quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t‐test or Mann‐Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. Results We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2‐fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell–depletion assays. The lowest levels of internalization were seen in IgD– B cells, including postswitched (IgD–CD27+) memory cells. Internalization of type I anti‐CD20 mAb was also partially inhibited by anti‐IgM stimulation. Conclusion Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower‐internalizing type II mAb should be considered as alternative B cell–depleting agents for the treatment of RA and SLE. PMID:25916583

  5. Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

    PubMed

    Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

  6. Multiple scaling power in liquid gallium under pressure conditions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Renfeng; Wang, Luhong; Li, Liangliang

    Generally, a single scaling exponent, Df, can characterize the fractal structures of metallic glasses according to the scaling power law. However, when the scaling power law is applied to liquid gallium upon compression, the results show multiple scaling exponents and the values are beyond 3 within the first four coordination spheres in real space, indicating that the power law fails to describe the fractal feature in liquid gallium. The increase in the first coordination number with pressure leads to the fact that first coordination spheres at different pressures are not similar to each other in a geometrical sense. This multiplemore » scaling power behavior is confined within a correlation length of ξ ≈ 14–15 Å at applied pressure according to decay of G(r) in liquid gallium. Beyond this length the liquid gallium system could roughly be viewed as homogeneous, as indicated by the scaling exponent, Ds, which is close to 3 beyond the first four coordination spheres.« less

  7. Gallium(iii) and iron(iii) complexes of quinolone antimicrobials.

    PubMed

    Mjos, Katja Dralle; Cawthray, Jacqueline F; Polishchuk, Elena; Abrams, Michael J; Orvig, Chris

    2016-08-16

    Iron is an essential nutrient for many microbes. According to the "Trojan Horse Hypothesis", biological systems have difficulties distinguishing between Fe(3+) and Ga(3+), which constitutes the antimicrobial efficacy of the gallium(iii) ion. Nine novel tris(quinolono)gallium(iii) complexes and their corresponding iron(iii) analogs have been synthesized and fully characterized. Quinolone antimicrobial agents from three drug generations were used in this study: ciprofloxacin, enoxacin, fleroxacin, levofloxacin, lomefloxacin, nalidixic acid, norfloxacin, oxolinic acid, and pipemidic acid. The antimicrobial efficacy of the tris(quinolono)gallium(iii) complexes was studied against E. faecalis and S. aureus (both Gram-positive), as well as E. coli, K. pneumonia, and P. aeruginosa (all Gram-negative) in direct comparison to the tris(quinolono)iron(iii) complexes and the corresponding free quinolone ligands at various concentrations. For the tris(quinolono)gallium(iii) complexes, no combinational antimicrobial effects between Ga(3+) and the quinolone antimicrobial agents were observed.

  8. Preliminary Experimental Measurements for a Gallium Electromagnetic (GEM) Thruster

    NASA Technical Reports Server (NTRS)

    Thomas, Robert E.; Burton, Rodney L.; Glumac, Nick G.; Polzin, Kurt A.

    2007-01-01

    A low-energy gallium plasma source is used to perform a spatially and temporally broad spectroscopic survey in the 220-520 nm range. Neutral, singly, and doubly ionized gallium are present in a 20 J, 1.8 kA (peak) arc discharge operating with a central cathode. When the polarity of the inner electrode is reversed the discharge current and arc voltage waveforms remain similar. Utilizing a central anode configuration, multiple Ga lines are absent in the 270-340 nm range. In addition, neutral and singly ionized Fe spectral lines are present, indicating erosion of the outer electrode. With graphite present on the insulator to facilitate breakdown, line emission from the gallium species is further reduced and while emissions from singly and doubly ionized carbon atoms and molecular carbon (C2) radicals are observed. These data indicate that a significant fraction of energy is shifted from the gallium and deposited into the various carbon species.

  9. Non-LTE gallium abundance in HgMn stars

    NASA Astrophysics Data System (ADS)

    Zboril, M.; Berrington, K. A.

    2001-07-01

    We present, for the first time, the Non-LTE gallium equivalent widths for the most prominent gallium transitions as identified in real spectra and in (hot) mercury-manganese star. The common feature of the departure coefficients is to decrease near the stellar surface, the collision rates are dominant in many cases and the Non-LTE equivalent widths are generally smaller. In particular, the abundance difference as derived from UV and visual lines is reduced. The photoionization cross sections were computed by means of standard R-matrix formalism. The gallium cross-sections are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/373/987

  10. Potential use of gallium-doped phosphate-based glass material for periodontitis treatment.

    PubMed

    Sahdev, Rohan; Ansari, Tahera I; Higham, Susan M; Valappil, Sabeel P

    2015-07-01

    This study aimed at evaluating the potential effect of gallium-incorporated phosphate-based glasses towards periodontitis-associated bacteria, Porphyromonas gingivalis, and matrix metalloproteinase-13. Periodontitis describes a group of inflammatory diseases of the gingiva and supporting structures of the periodontium. They are initiated by the accumulation of plaque bacteria, such as the putative periodontal pathogen Porphyromonas gingivalis, but the host immune response such as elevated matrix metalloproteinases are the major contributing factor for destruction of periodontal tissues. Antibacterial assays of gallium-incorporated phosphate-based glasses were conducted on Porphyromonas gingivalis ATCC 33277 using disc diffusion assay on fastidious anaerobe agar and liquid broth assay in a modified tryptic soy broth. In vitro study investigated the effect of gallium on purified recombinant human matrix metalloproteinase-13 activity using matrix metalloproteinase assay kit. In vivo biocompatibility of gallium-incorporated phosphate-based glass was evaluated in rats as subcutaneous implants. Antibacterial assay of gallium displayed activity against Porphyromonas gingivalis (inhibition zone of 22 ± 0.5 mm compared with 0 mm for control glass, c-PBG). Gallium in the glass contributed to growth inhibitory effect on Porphyromonas gingivalis (up to 1.30 reductions in log 10 values of the viable counts compared with control) in a modified tryptic soy broth. In vitro study showed gallium-incorporated phosphate-based glasses inhibited matrix metalloproteinase activity significantly (p ≤ 0.01) compared with c-PBG. Evaluation of in vivo biocompatibility of gallium-incorporated phosphate-based glasses in rats showed a non-toxic and foreign body response after 2 weeks of implantation. The results indicate that gallium ions might act on multiple targets of biological mechanisms underlying periodontal disease. Moreover, gallium-incorporated phosphate-based glasses

  11. Hot and solid gallium clusters: too small to melt.

    PubMed

    Breaux, Gary A; Benirschke, Robert C; Sugai, Toshiki; Kinnear, Brian S; Jarrold, Martin F

    2003-11-21

    A novel multicollision induced dissociation scheme is employed to determine the energy content for mass-selected gallium cluster ions as a function of their temperature. Measurements were performed for Ga(+)(n) (n=17 39, and 40) over a 90-720 K temperature range. For Ga+39 and Ga+40 a broad maximum in the heat capacity-a signature of a melting transition for a small cluster-occurs at around 550 K. Thus small gallium clusters melt at substantially above the 302.9 K melting point of bulk gallium, in conflict with expectations that they will remain liquid to below 150 K. No melting transition is observed for Ga+17.

  12. Design and properties of novel gallium-doped injectable apatitic cements.

    PubMed

    Mellier, Charlotte; Fayon, Franck; Boukhechba, Florian; Verron, Elise; LeFerrec, Myriam; Montavon, Gilles; Lesoeur, Julie; Schnitzler, Verena; Massiot, Dominique; Janvier, Pascal; Gauthier, Olivier; Bouler, Jean-Michel; Bujoli, Bruno

    2015-09-01

    Different possible options were investigated to combine an apatitic calcium phosphate cement with gallium ions, known as bone resorption inhibitors. Gallium can be either chemisorbed onto calcium-deficient apatite or inserted in the structure of β-tricalcium phosphate, and addition of these gallium-doped components into the cement formulation did not significantly affect the main properties of the biomaterial, in terms of injectability and setting time. Under in vitro conditions, the amount of gallium released from the resulting cement pellets was found to be low, but increased in the presence of osteoclastic cells. When implanted in rabbit bone critical defects, a remodeling process of the gallium-doped implant started and an excellent bone interface was observed. The integration of drugs and materials is a growing force in the medical industry. The incorporation of pharmaceutical products not only promises to expand the therapeutic scope of biomaterials technology but to design a new generation of true combination products whose therapeutic value stem equally from both the structural attributes of the material and the intrinsic therapy of the drug. In this context, for the first time an injectable calcium phosphate cement containing gallium was designed with properties suitable for practical application as a local delivery system, implantable by minimally invasive surgery. This important and original paper reports the design and in-depth chemical and physical characterization of this groundbreaking technology. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Formation of self-organized nanoporous anodic oxide from metallic gallium.

    PubMed

    Pandey, Bipin; Thapa, Prem S; Higgins, Daniel A; Ito, Takashi

    2012-09-25

    This paper reports the formation of self-organized nanoporous gallium oxide by anodization of solid gallium metal. Because of its low melting point (ca. 30 °C), metallic gallium can be shaped into flexible structures, permitting the fabrication of nanoporous anodic oxide monoliths within confined spaces like the inside of a microchannel. Here, solid gallium films prepared on planar substrates were employed to investigate the effects of anodization voltage (1, 5, 10, 15 V) and H(2)SO(4) concentration (1, 2, 4, 6 M) on anodic oxide morphology. Self-organized nanopores aligned perpendicular to the film surface were obtained upon anodization of gallium films in ice-cooled 4 and 6 M aqueous H(2)SO(4) at 10 and 15 V. Nanopore formation could be recognized by an increase in anodic current after a current decrease reflecting barrier oxide formation. The average pore diameter was in the range of 18-40 nm with a narrow diameter distribution (relative standard deviation ca. 10-20%), and was larger at lower H(2)SO(4) concentration and higher applied voltage. The maximum thickness of nanoporous anodic oxide was ca. 2 μm. In addition, anodic formation of self-organized nanopores was demonstrated for a solid gallium monolith incorporated at the end of a glass capillary. Nanoporous anodic oxide monoliths formed from a fusible metal will lead to future development of unique devices for chemical sensing and catalysis.

  14. Predicting optimal response to B-cell depletion with rituximab in multiple sclerosis using CXCL13 index, magnetic resonance imaging and clinical measures

    PubMed Central

    Alvarez, Enrique; Piccio, Laura; Mikesell, Robert J; Trinkaus, Kathryn; Parks, Becky J; Naismith, Robert T

    2015-01-01

    Background B-cell depleting drugs show promise for treating multiple sclerosis. Objective We sought predictors of optimal response to rituximab, a B-cell depleting antibody, to help guide therapy selection. Methods We performed a post hoc study of 30 relapsing multiple sclerosis patients with breakthrough disease while on beta-interferon or glatiramer acetate who were treated with add-on rituximab. Standardized neurologic examinations, brain magnetic resonance imaging, and cerebrospinal fluid were obtained before and after rituximab. Tissue biomarkers were measured. Optimal responders were defined as having no evidence of disease activity. Results At baseline, optimal responders with no evidence of disease activity had higher IgG indices (P = 0.041), and higher CXCL13 indices ((cerebrospinal fluid CXCL13/serum CXCL13)/albumin index; P = 0.024), more contrast enhancing lesions (P = 0.002), better 25 foot timed walk (P = 0.001), and Expanded Disability Status Scale (P = 0.002). Rituximab treatment led to reduced cerebrospinal fluid biomarkers of tissue destruction: myelin basic protein (P = 0.046), neurofilament light chain (P < 0.001), and of inflammation (CXCL13 index; P = 0.042). Conclusions Multiple sclerosis patients with optimal response to rituximab had higher cerebrospinal fluid IgG and CXCL13 indices, more gadolinium-enhancing lesions, and less disability at baseline. Rituximab treatment led to decreased markers of inflammation and tissue damage. If validated, these results will help identify multiple sclerosis patients who will respond optimally to B-cell depletion. PMID:28607711

  15. Realization of the Gallium Triple Point at NMIJ/AIST

    NASA Astrophysics Data System (ADS)

    Nakano, T.; Tamura, O.; Sakurai, H.

    2008-02-01

    The triple point of gallium has been realized by a calorimetric method using capsule-type standard platinum resistance thermometers (CSPRTs) and a small glass cell containing about 97 mmol (6.8 g) of gallium with a nominal purity of 99.99999%. The melting curve shows a very flat and relatively linear dependence on 1/ F in the region from 1/ F = 1 to 1/ F = 20 with a narrow width of the melting curve within 0.1 mK. Also, a large gallium triple-point cell was fabricated for the calibration of client-owned CSPRTs. The gallium triple-point cell consists of a PTFE crucible and a PTFE cap with a re-entrant well and a small vent. The PTFE cell contains 780 g of gallium from the same source as used for the small glass cell. The PTFE cell is completely covered by a stainless-steel jacket with a valve to enable evacuation of the cell. The melting curve of the large cell shows a flat plateau that remains within 0.03 mK over 10 days and that is reproducible within 0.05 mK over 8 months. The calibrated value of a CSPRT obtained using the large cell agrees with that obtained using the small glass cell within the uncertainties of the calibrations.

  16. Tin-gallium-oxide-based UV-C detectors

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Partha; Toporkov, Mykyta; Schoenfeld, Winston V.

    2018-02-01

    The emergence of conductive gallium oxide single crystal substrates offers the potential for vertical Schottky detectors operating in the UV-C spectral region. We report here on our recent work in the development of Tin Gallium oxide (TGO) thin film metal-semiconductor-metal (MSM) and Schottky detectors using plasma-assisted molecular beam epitaxy on c plane sapphire and bulk Ga2O3 substrates. Tin alloying of gallium oxide thin films was found to systematically reduce the optical band gap of the compound, providing tunability in the UV-C spectral region. Tin concentration in the TGO epilayers was found to be highly dependent on growth conditions, and Ga flux in particular. First attempts to demonstrate vertical Schottky photodetectors using TGO epilayers on bulk n-type Ga2O3 substrates were successful. Resultant devices showed strong photoresponse to UV-C light with peak responsivities clearly red shifted in comparison to Ga2O3 homoepitaxial Schottky detectors due to TGO alloying.

  17. Cutaneous gallium uptake in patients with AIDS with mycobacterium avium-intracellulare septicemia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Allwright, S.J.; Chapman, P.R.; Antico, V.F.

    1988-07-01

    Gallium imaging is increasingly being used for the early detection of complications in patients with AIDS. A 26-year-old homosexual man who was HIV antibody positive underwent gallium imaging for investigation of possible Pneumocystis carinii pneumonia. Widespread cutaneous focal uptake was seen, which was subsequently shown to be due to mycobacterium avium-intracellulare (MAI) septicemia. This case demonstrates the importance of whole body imaging rather than imaging target areas only, the utility of gallium imaging in aiding the early detection of clinically unsuspected disease, and shows a new pattern of gallium uptake in disseminated MAI infection.

  18. Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE.

    PubMed

    Tak, Paul P; Rigby, William; Rubbert-Roth, Andrea; Peterfy, Charles; van Vollenhoven, Ronald F; Stohl, William; Healy, Emma; Hessey, Eva; Reynard, Mark; Shaw, Tim

    2012-03-01

    In the IMAGEstudy, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis. The aim of this study was to assess joint damage progression and clinical outcomes over 2 years. Patients (n=755) were randomised to receive rituximab 2×500 mg+MTX, 2×1000 mg+MTX or placebo+MTX. The placebo-controlled period continued to week 104. Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score (mTSS), total erosion score and joint space narrowing score from baseline to week 104. Clinical efficacy and physical function end points were also assessed. At 2 years, rituximab 2×1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone (mTSS change 0.41 vs 1.95; p<0.0001 (79% inhibition)), and a higher proportion of patients receiving rituximab 2×1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone (57% vs 37%; p<0.0001). Contrary to 1-year results, exploratory analysis of rituximab 2×500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61% versus placebo+MTX (mTSS, exploratory p=0.0041). Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2. Safety profiles were similar between groups. Treatment with rituximab 2×1000 mg+MTX was associated with sustained improvements in radiographic, clinical and functional outcomes over 2 years. Clinical trials.gov identifier NCT00299104.

  19. [IgG4-related disease: patient group characterization and rituximab therapy].

    PubMed

    Sedyshev, S Kh; Vasil'ev, V I; Kovrigina, A M; Logvinenko, O A; Rodionova, E B; Safonova, T N; Gaĭduk, I V; Silin, A Iu; Komov, D V; Nasonov, E L

    2013-01-01

    To characterize a group of patients with IgG4-related disease (IgG4-RD) in a Russian population and to evaluate the efficiency of rituximab therapy. In 2009 to 2011, at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, 30 patients (16 men and 14 women; mean age 44 years) were diagnosed with IgG4-RD that was confirmed by determination of serum IgG4 levels and immunohistochemical study of biopsy samples stained for IgG4-positive plasma cells. Seven patients received rituximab therapy. It was assumed at baseline that there were different types of neoplasias in 12 (40%), non-Hodgkin's and Hodgkin's lymphomas in 10 (33.3%), Sjögren's syndrome in 5 (16.7%), and Wegener's granulomatosis in 3 (10%). When 2 or more locations were involved, the condition was regarded as multifocal fibrosclerosis (33.3%). Localized forms were revealed in 20 (66.7%) patients. Among them, the largest number of patients was those who had orbital pseudotumor, Mikulicz's disease, or retroperitoneal fibrosclerosis. The most common sites of involvement were orbits (66.7%), salivary glands (70%) and lymph nodes (36.7%). Comparison of serum IgG4 levels in 28 patients with IgG4-RD, 22 patients with Sjögren's disease, salivary and lacrimal gland lymphomas, and 10 healthy controls showed that the concentration of IgG4 was significantly higher in Group 1 (median 2.6 g/I; IQR 1.22-4.65 (p < 0.001). Tissue IgG4/IgG ratio varied from 25 to 50% and averaged 38%. A moiré-like pattern of varying fibrosis was noted in 83% of cases. Analysis of laboratory data revealed elevated C-reactive protein concentrations (46.7% with a mean of 39.5 mg/l; normal values < 5.0 mg/l), increased erythrocyte sedimentation rate (60% with a mean of 37.6 mm/h), hypergammaglobulinemia (30% with a mean of 29.4%; normal range 13-22%), and rheumatoid factor (23.3%). After rituximab therapy, all the patients showed a decrease of IgG4 levels to the normal levels and positive changes evidenced by visualization

  20. 21 CFR 181.33 - Sodium nitrate and potassium nitrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium nitrate are subject to prior sanctions issued by the U.S. Department of Agriculture for use as sources of...

  1. 21 CFR 181.33 - Sodium nitrate and potassium nitrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium nitrate are subject to prior sanctions issued by the U.S. Department of Agriculture for use as sources of...

  2. 21 CFR 181.33 - Sodium nitrate and potassium nitrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium nitrate and potassium nitrate. 181.33... nitrate and potassium nitrate. Sodium nitrate and potassium nitrate are subject to prior sanctions issued... potassium nitrite, in the production of cured red meat products and cured poultry products. [48 FR 1705, Jan...

  3. Radiation damage of gallium arsenide production cells

    NASA Technical Reports Server (NTRS)

    Mardesich, N.; Joslin, D.; Garlick, J.; Lillington, D.; Gillanders, M.; Cavicchi, B.; Scott-Monck, J.; Kachare, R.; Anspaugh, B.

    1987-01-01

    High efficiency liquid phase epitaxy (LPE) gallium arsenide cells were irradiated with 1 Mev electrons up to fluences of 1 times 10 to the 16th power cm-2. Measurements of spectral response and dark and illuminated I-V data were made at each fluence and then, using computer codes, the experimental data was fitted to gallium arsenide cell models. In this way it was possible to determine the extent of the damage, and hence damage coefficients in both the emitter and base of the cell.

  4. Pure silver ohmic contacts to N- and P- type gallium arsenide materials

    DOEpatents

    Hogan, Stephen J.

    1986-01-01

    Disclosed is an improved process for manufacturing gallium arsenide semiconductor devices having as its components an n-type gallium arsenide substrate layer and a p-type gallium arsenide diffused layer. The improved process comprises forming a pure silver ohmic contact to both the diffused layer and the substrate layer, wherein the n-type layer comprises a substantially low doping carrier concentration.

  5. Ipso Nitration. Regiospecific Nitration via Ipso Nitration Products.

    DTIC Science & Technology

    1985-05-20

    products of nitration of alkylbenzenes and alkylphenol derivatives. The general pattern envisioned is shown in Scheme 1. In order to realize this...we have also explored solid state nitration of various alkylphenols . This procedure involves adsorbing concentrated nitric acid on alumina, followed

  6. A melting-point-of gallium apparatus for thermometer calibration.

    PubMed

    Sostman, H E; Manley, K A

    1978-08-01

    We have investigated the equilibrium melting point of gallium as a temperature fixed-point at which to calibrate small thermistor thermometers, such as those used to measure temperature in enzyme reaction analysis and other temperature-dependent biological assays. We have determined that the melting temperature of "6N" (99.999% pure) gallium is 29.770 +/- 0.002 degrees C, and that the constant-temperature plateau can be prolonged for several hours. We have designed a simple automated apparatus that exploits this phenomenon and that permits routine calibration verification of thermistor temperature probes throughout the laboratory day. We describe the physics of the gallium melt, and the design and use of the apparatus.

  7. Pyoverdine and Proteases Affect the Response of Pseudomonas aeruginosa to Gallium in Human Serum

    PubMed Central

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco

    2015-01-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

  8. Myopericarditis in acquired immunodeficiency syndrome diagnosed by gallium scintigraphy.

    PubMed Central

    Cregler, L. L.; Sosa, I.; Ducey, S.; Abbey, L.

    1990-01-01

    Myocarditis is among the cardiac complications of acquired immunodeficiency syndrome and, yet, is often not discovered until autopsy. Gallium scintigraphy has been employed in diagnosing this entity, but few data are available about its diagnostic accuracy and value. Here, the authors report two cases of myopericarditis as diagnosed by gallium scan. Images Figure 1 Figure 2 PMID:2398508

  9. Biocompatible nano-gallium/hydroxyapatite nanocomposite with antimicrobial activity.

    PubMed

    Kurtjak, Mario; Vukomanović, Marija; Kramer, Lovro; Suvorov, Danilo

    2016-11-01

    Intensive research in the area of medical nanotechnology, especially to cope with the bacterial resistance against conventional antibiotics, has shown strong antimicrobial action of metallic and metal-oxide nanomaterials towards a wide variety of bacteria. However, the important remaining problem is that nanomaterials with highest antibacterial activity generally express also a high level of cytotoxicity for mammalian cells. Here we present gallium nanoparticles as a new solution to this problem. We developed a nanocomposite from bioactive hydroxyapatite nanorods (84 wt %) and antibacterial nanospheres of elemental gallium (16 wt %) with mode diameter of 22 ± 11 nm. In direct comparison, such nanocomposite with gallium nanoparticles exhibited better antibacterial properties against Pseudomonas aeruginosa and lower in-vitro cytotoxicity for human lung fibroblasts IMR-90 and mouse fibroblasts L929 (efficient antibacterial action and low toxicity from 0.1 to 1 g/L) than the nanocomposite of hydroxyapatite and silver nanoparticles (efficient antibacterial action and low toxicity from 0.2 to 0.25 g/L). This is the first report of a biomaterial composite with gallium nanoparticles. The observed strong antibacterial properties and low cytotoxicity make the investigated material promising for the prevention of implantation-induced infections that are frequently caused by P. aeruginosa.

  10. Indium Gallium Nitride Multijunction Solar Cell Simulation Using Silvaco Atlas

    DTIC Science & Technology

    2007-06-01

    models is of great interest in space applications. By increasing the efficiency of photovoltaics, the number of solar panels is decreased. Therefore...obtained in single-junction solar cells by using Gallium Arsenide. Monocrystalline Gallium Arsenide has a maximum efficiency of approximately 25.1% [10

  11. Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer

    PubMed Central

    Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin

    2016-01-01

    An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20–24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice. PMID:27374088

  12. Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer.

    PubMed

    Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin; Yu, Jin-Ming; Wang, Yong-Sheng

    2016-07-26

    An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20-24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice.

  13. Nitrate biosensors and biological methods for nitrate determination.

    PubMed

    Sohail, Manzar; Adeloju, Samuel B

    2016-06-01

    The inorganic nitrate (NO3‾) anion is present under a variety of both natural and artificial environmental conditions. Nitrate is ubiquitous within the environment, food, industrial and physiological systems and is mostly present as hydrated anion of a corresponding dissolved salt. Due to the significant environmental and toxicological effects of nitrate, its determination and monitoring in environmental and industrial waters are often necessary. A wide range of analytical techniques are available for nitrate determination in various sample matrices. This review discusses biosensors available for nitrate determination using the enzyme nitrate reductase (NaR). We conclude that nitrate determination using biosensors is an excellent non-toxic alternative to all other available analytical methods. Over the last fifteen years biosensing technology for nitrate analysis has progressed very well, however, there is a need to expedite the development of nitrate biosensors as a suitable alternative to non-enzymatic techniques through the use of different polymers, nanostructures, mediators and strategies to overcome oxygen interference. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Byproduct Metal Availability Constrained by Dynamics of Carrier Metal Cycle: The Gallium-Aluminum Example.

    PubMed

    Løvik, Amund N; Restrepo, Eliette; Müller, Daniel B

    2016-08-16

    Future availability of byproduct metals is not limited by geological stocks, but by the rate of primary production of their carrier metals, which in turn depends on the development of their in-use stocks, the product lifetimes, and the recycling rates. This linkage, while recognized conceptually in past studies, has not been adequately taken into account in resource availability estimates. Here, we determine the global supply potential for gallium up to 2050 based on scenarios for the global aluminum cycle, and compare it with scenarios for gallium demand derived from a dynamic model of the gallium cycle. We found that the gallium supply potential is heavily influenced by the development of the in-use stocks and recycling rates of aluminum. With current applications, a shortage of gallium is unlikely by 2050. However, the gallium industry may need to introduce ambitious recycling- and material efficiency strategies to meet its demand. If in-use stocks of aluminum saturate or decline, a shift to other gallium sources such as zinc or coal fly ash may be required.

  15. Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

    PubMed

    Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

    2016-01-01

    A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

  16. Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review.

    PubMed

    Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

    2016-09-01

    Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab.A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established.He received Rituximab 375 mg/m (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39).Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion.

  17. Internalization of rituximab and the efficiency of B Cell depletion in rheumatoid arthritis and systemic lupus erythematosus.

    PubMed

    Reddy, Venkat; Cambridge, Geraldine; Isenberg, David A; Glennie, Martin J; Cragg, Mark S; Leandro, Maria

    2015-05-01

    Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. We used an in vitro whole blood B cell-depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence-quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t-test or Mann-Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2-fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell-depletion assays. The lowest levels of internalization were seen in IgD- B cells, including postswitched (IgD-CD27+) memory cells. Internalization of type I anti-CD20 mAb was also partially inhibited by anti-IgM stimulation. Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower-internalizing type II mAb should be considered as alternative B cell-depleting agents for the treatment of RA and SLE. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  18. What should be impossible: resolution of the mononuclear gallium coordination complex, Tris(benzohydroxamato)gallium(III).

    PubMed

    Brumaghim, Julia L; Raymond, Kenneth N

    2003-10-08

    Complexes of Ga3+, a d10 metal ion which lacks ligand-field-stabilization energy, are considered labile. In fact, hexaaquagallium(III) has a ligand exchange rate of 403 s-1, 2.5 times that of the analagous Fe3+ complex (Hugi-Cleary, D.; Helm, L.; Merbach, A. E. J. Am. Chem. Soc. 1987, 109, 4444-4450). Given this lability, resolution of Ga3+ complexes should be impossible. Despite this, we report the resolution of the Lambda and Delta isomers of tris(benzohydroxamate)gallium (III) (1), the first resolution of a mononuclear gallium complex. Not only is resolution possible, but these resolved complexes show remarkable resistance to racemization in aprotic solvents. The unprecedented stability of Lambda- and Delta-1 is a surprise, and as such, alters our understanding of classical coordination chemistry.

  19. [Efficacy and safety of rituximab in the treatment of primary antiphospholipid syndrome: analysis of 24 cases from the bibliography review].

    PubMed

    Pons, Isaac; Espinosa, Gerard; Cervera, Ricard

    2015-02-02

    Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-β2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m(2) weekly and one (4.2%) 8 doses of 375 mg/m(2) weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement. Copyright © 2013 Elsevier España, S.L.U. All rights

  20. Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

    PubMed Central

    Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

  1. 21 CFR 181.33 - Sodium nitrate and potassium nitrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium... nitrite, with or without sodium or potassium nitrite, in the production of cured red meat products and...

  2. 21 CFR 181.33 - Sodium nitrate and potassium nitrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium... nitrite, with or without sodium or potassium nitrite, in the production of cured red meat products and...

  3. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma.

    PubMed

    Chamberlain, Marc C; Johnston, Sandra K

    2010-07-01

    We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18-93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m(2)/dose; 375 mg/m(2)/dose) for 4-6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m(2)/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4-10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6-10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months.

  4. Abnormal gallium scan patterns of the salivary gland in pulmonary sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mishkin, F.S.; Tanaka, T.T.; Niden, A.H.

    1978-12-01

    The findings of gallium imaging suggest that parotid abnormalities in sarcoidosis are common. Correlation with lung and mediastinal uptake suggests that this represents an early disease state and that it responds to steroid administration. That the findings after therapy do not simply represent suppression of the uptake mechanism for gallium is supported by objective improvement in pulmonary function as well as symptomatic relief. Salivary gland accumulation of gallium citrate occurred in one third of our control group patients--in those who had collagen disease and presumably either were alcoholic or had infectious parotitis. This may also be seen in lymphoma andmore » after radiation therapy. Although the combination of salivary gland, pulmonary, and hilar concentration of gallium is not specific, in the appropriate clinical setting the pattern may be helpful in suggesting the correct diagnosis.« less

  5. Capacitive Behavior of Single Gallium Oxide Nanobelt

    PubMed Central

    Cai, Haitao; Liu, Hang; Zhu, Huichao; Shao, Pai; Hou, Changmin

    2015-01-01

    In this research, monocrystalline gallium oxide (Ga2O3) nanobelts were synthesized through oxidation of metal gallium at high temperature. An electronic device, based on an individual Ga2O3 nanobelt on Pt interdigital electrodes (IDEs), was fabricated to investigate the electrical characteristics of the Ga2O3 nanobelt in a dry atmosphere at room temperature. The current-voltage (I-V) and I/V-t characteristics show the capacitive behavior of the Ga2O3 nanobelt, indicating the existence of capacitive elements in the Pt/Ga2O3/Pt structure. PMID:28793506

  6. Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy

    PubMed Central

    Fisher, Benjamin A; Everett, Colin C; Rout, John; O’Dwyer, John L; Emery, Paul; Pitzalis, Costantino; Ng, Wan-Fai; Carr, Andrew; Pease, Colin T; Price, Elizabeth J; Sutcliffe, Nurhan; Makdissi, Jimmy; Tappuni, Anwar R; Gendi, Nagui S T; Hall, Frances C; Ruddock, Sharon P; Fernandez, Catherine; Hulme, Claire T; Davies, Kevin A; Edwards, Christopher John; Lanyon, Peter C; Moots, Robert J; Roussou, Euthalia; Richards, Andrea; Sharples, Linda D; Bombardieri, Michele; Bowman, Simon J

    2018-01-01

    Objectives To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren’s syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. Methods Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0–11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. Results 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were −1.2 (95% CI −2.1 to −0.3; P=0.0099) and −1.2 (95% CI −2.0 to −0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. Conclusions We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker. Trial registration number 65360827, 2010-021430-64; Results. PMID:29275334

  7. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study.

    PubMed

    Benhamou, Ygal; Paintaud, Gilles; Azoulay, Elie; Poullin, Pascale; Galicier, Lionel; Desvignes, Céline; Baudel, Jean-Luc; Peltier, Julie; Mira, Jean-Paul; Pène, Frédéric; Presne, Claire; Saheb, Samir; Deligny, Christophe; Rousseau, Alexandra; Féger, Frédéric; Veyradier, Agnès; Coppo, Paul

    2016-12-01

    The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg m -2 within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246-1251, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

    PubMed

    Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

    2014-10-04

    Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

  9. Pros and cons of rituximab maintenance in follicular lymphoma.

    PubMed

    Zhang, Lu; Ghielmini, Michele; Cheson, Bruce D; Ujjani, Chaitra

    2017-07-01

    Follicular lymphoma (FL) is the most prevalent indolent non-Hodgkin lymphoma. Most patients present with advanced disease and are incurable with current therapy. The approval of rituximab has revolutionized the treatment of follicular lymphoma when administered in the induction setting for high-tumor burden disease, but the use of rituximab as a maintenance therapy (MR) continues to be a point of controversy. In this article, we review the main data and arguments in favor and against MR in FL. In summary, most studies have demonstrated a significant benefit in progression-free or event-free survival in this notoriously recurrent disease; however, long-term outcomes could not consistently demonstrate to be improved with this intervention. In a meta-analysis of randomized trials overall survival (OS) showed a tendency to improvement when given to patients in relapse, but no single study reached a significant OS advantage. The risk of high-grade transformation does not seem to be reduced in prospective trials. On the other hand, MR clearly increases toxicity without an improvement in quality of life. Finally, MR is expensive, and it is not proven that the delayed relapse time can compensate for these costs. In conclusion, despite the proven increase in progression-free survival, MR can't be recommended as a standard for the treatment of FL. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Atomically thin gallium layers from solid-melt exfoliation

    PubMed Central

    Kochat, Vidya; Samanta, Atanu; Zhang, Yuan; Bhowmick, Sanjit; Manimunda, Praveena; Asif, Syed Asif S.; Stender, Anthony S.; Vajtai, Robert; Singh, Abhishek K.; Tiwary, Chandra S.; Ajayan, Pulickel M.

    2018-01-01

    Among the large number of promising two-dimensional (2D) atomic layer crystals, true metallic layers are rare. Using combined theoretical and experimental approaches, we report on the stability and successful exfoliation of atomically thin “gallenene” sheets on a silicon substrate, which has two distinct atomic arrangements along crystallographic twin directions of the parent α-gallium. With a weak interface between solid and molten phases of gallium, a solid-melt interface exfoliation technique is developed to extract these layers. Phonon dispersion calculations show that gallenene can be stabilized with bulk gallium lattice parameters. The electronic band structure of gallenene shows a combination of partially filled Dirac cone and the nonlinear dispersive band near the Fermi level, suggesting that gallenene should behave as a metallic layer. Furthermore, it is observed that the strong interaction of gallenene with other 2D semiconductors induces semiconducting to metallic phase transitions in the latter, paving the way for using gallenene as promising metallic contacts in 2D devices. PMID:29536039

  11. Effect of novel antibacterial gallium-carboxymethyl cellulose on Pseudomonas aeruginosa.

    PubMed

    Valappil, Sabeel P; Yiu, Humphrey H P; Bouffier, Laurent; Hope, Christopher K; Evans, Gary; Claridge, John B; Higham, Susan M; Rosseinsky, Matthew J

    2013-02-07

    Gallium has emerged as a new therapeutic agent due partly to the scarcity in development of new antibiotics. In this study, a novel antibacterial gallium exchanged carboxymethyl cellulose (Ga-CMC) has been developed and tested for the susceptibility on a common bacteria, Pseudomonas aeruginosa. The results show that an increase in average molecular weight (MW) from 90 k, 250 k to 700 k of Ga-CMC caused a decrease in antimicrobial activity against planktonic P. aeruginosa. Gallium loading of the Ga-CMC (250 k) samples was altered by varying the amount of functionality (0.7, 0.9 and 1.2 acid groups per mole of carbohydrate) which affected also its antimicrobial activity against planktonic P. aeruginosa. Further, the ability to prevent the growth of biofilms of P. aeruginosa was tested on MW = 250 k samples with 0.9 acid groups per mole of carbohydrate as this sample showed the most promising activity against planktonic P. aeruginosa. Gallium was found to reduce biofilm growth of P. aeruginosa with a maximum effect (0.85 log(10) CFU reduction compared to sodium-carboxymethyl cellulose, Na-CMC) after 24 h. Results of the solubility and ion exchange studies show that this compound is suitable for the controlled release of Ga(3+) upon their breakdown in the presence of bacteria. SEM EDX analysis confirmed that Ga(3+) ions are evenly exchanged on the cellulose surface and systematic controls were carried out to ensure that antibacterial activity is solely due to the presence of gallium as samples intrinsic acidity or nature of counterion did not affect the activity. The results presented here highlight that Ga-CMC may be useful in controlled drug delivery applications, to deliver gallium ions in order to prevent infections due to P. aeruginosa biofilms.

  12. Detection of deep venous thrombophlebitis by gallium 67 scintigraphy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, J.H.

    1981-07-01

    Deep venous thrombophlebitis may escape clinical detection. Three cases are reported in which whole-body gallium 67 scintigraphy was used to detect unsuspected deep venous thrombophlebitis related to indwelling catheters in three children who were being evaluated for fevers of unknown origin. Two of these children had septicemia from Candida organisms secondary to these venous lines. Gallium 67 scintigraphy may be useful in the detection of complications of indwelling venous catheters.

  13. Detection of deep venous thrombophlebitis by Gallium 67 scintigraphy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, J.H.

    1981-07-01

    Deep venous thrombophlebitis may escape clinical detection. Three cases are reported in which whole-body gallium 67 scintigraphy was used to detect unsuspected deep venous thrombophlebitis related to indwelling catheters in three children who were being evaluated for fevers of unknown origin. Two of these children had septicemia from Candida organisms secondary to these venous lines. Gallium 67 scintigraphy may be useful in the detection of complications of indwelling venous catheters.

  14. Dulanermin with rituximab in patients with relapsed indolent B-cell lymphoma: an open-label phase 1b/2 randomised study.

    PubMed

    Cheah, Chan Yoon; Belada, David; Fanale, Michelle A; Janikova, Andrea; Czucman, Myron S; Flinn, Ian W; Kapp, Amy V; Ashkenazi, Avi; Kelley, Sean; Bray, Gordon L; Holden, Scott; Seymour, John F

    2015-04-01

    Dulanermin-a non-polyhistidine-tagged soluble recombinant human apoptosis ligand 2 (Apo2L) or tumour-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-has pro-apoptotic activity in a range of cancers and synergistic preclinical activity with rituximab against lymphoma in vivo. We aimed to assess the safety, pharmacokinetics, and efficacy of dulanermin and rituximab in patients with relapsed indolent B-cell non-Hodgkin lymphoma. We did an open-label phase 1b/2 randomised study. Four study centres in the USA enrolled patients into phase 1b, and 27 study centres in the USA, Italy, Australia, France, Czech Republic, New Zealand, and Poland enrolled patients into phase 2. In phase 1b, patients (age ≥18 years) with indolent B-cell non-Hodgkin lymphoma with stable disease or better lasting at least 6 months after the most recent rituximab-containing regimen were included. In phase 2, patients (age ≥18 years) with follicular lymphoma grades 1-3a were included. In phase 1b, patients received 4 mg/kg or 8 mg/kg intravenous dulanermin on days 1-5 of up to four 21-day cycles and intravenous rituximab 375 mg/m(2) weekly for up to eight doses. In phase 2, patients were randomly assigned (1:1:1) centrally by an interactive voice response system to dulanermin (8 mg/kg for a maximum of four 21-day cycles), rituximab (375 mg/m(2) weekly for up to eight doses), or both in combination, stratified by baseline follicular lymphoma International Prognostic Index (0-3 vs 4-5) and geographic site (USA vs non-USA). The primary endpoints of the phase 1b study were the safety, tolerability, and pharmacokinetics of dulanermin with rituximab. The primary endpoint of phase 2 was the proportion of patients who achieved an objective response. All patients who received any dose of study drug were included in safety analyses. Efficacy analyses were per protocol. Treatment was open label; all patients and investigators were unmasked to treatment allocation. This study is registered with

  15. Pseudo-constitutivity of nitrate-responsive genes in nitrate reductase mutants

    PubMed Central

    Schinko, Thorsten; Gallmetzer, Andreas; Amillis, Sotiris; Strauss, Joseph

    2013-01-01

    In fungi, transcriptional activation of genes involved in NO3- assimilation requires the presence of an inducer (nitrate or nitrite) and low intracellular concentrations of the pathway products ammonium or glutamine. In Aspergillus nidulans, the two transcription factors NirA and AreA act synergistically to mediate nitrate/nitrite induction and nitrogen metabolite derepression, respectively. In all studied fungi and in plants, mutants lacking nitrate reductase (NR) activity express nitrate-metabolizing enzymes constitutively without the addition of inducer molecules. Based on their work in A. nidulans, Cove and Pateman proposed an “autoregulation control” model for the synthesis of nitrate metabolizing enzymes in which the functional nitrate reductase molecule would act as co-repressor in the absence and as co-inducer in the presence of nitrate. However, NR mutants could simply show “pseudo-constitutivity” due to induction by nitrate which accumulates over time in NR-deficient strains. Here we examined this possibility using strains which lack flavohemoglobins (fhbs), and are thus unable to generate nitrate internally, in combination with nitrate transporter mutations (nrtA, nrtB) and a GFP-labeled NirA protein. Using different combinations of genotypes we demonstrate that nitrate transporters are functional also in NR null mutants and show that the constitutive phenotype of NR mutants is not due to nitrate accumulation from intracellular sources but depends on the activity of nitrate transporters. However, these transporters are not required for nitrate signaling because addition of external nitrate (10 mM) leads to standard induction of nitrate assimilatory genes in the nitrate transporter double mutants. We finally show that NR does not regulate NirA localization and activity, and thus the autoregulation model, in which NR would act as a co-repressor of NirA in the absence of nitrate, is unlikely to be correct. Results from this study instead suggest

  16. Antitumor efficacy and tolerability of systemically administered gallium acetylacetonate-loaded gelucire-stabilized nanoparticles.

    PubMed

    Wehrung, Daniel; Bi, Lipeng; Geldenhuys, Werner J; Oyewumi, Moses O

    2013-06-01

    The widespread clinical success with most gallium compounds in cancer therapy is markedly hampered by lack of tumor specific accumulation, poor tumor permeability and undesirable toxicity to healthy tissues. The aim of this work was to investigate for the first time antitumor mechanism of a new gallium compound (gallium acetylacetonate; GaAcAc) while assessing effectiveness of gelucire-stabilized nanoparticles (NPs) for potential application in gallium-based lung cancer therapy. NPs loaded with GaAcAc (Ga-NPs) were prepared using mixtures of cetyl alcohol with Gelucire 44/14 (Ga-NP-1) or Gelucire 53/13 (Ga-NP-2) as matrix materials. Of special note from this work is the direct evidence of involvement of microtubule disruption in antitumor effects of GaAcAc on human lung adenocarcinoma (A549). In-vivo tolerability studies were based on plasma ALT, creatinine levels and histopathological examination of tissues. The superior in-vivo antitumor efficacy of Ga-NPs over GaAcAc was depicted in marked reduction of tumor weight and tumor volume as well as histological assessment of excised tumors. Compared to free GaAcAc, Ga-NPs showed a 3-fold increase in tumor-to-blood gallium concentrations with minimized overall exposure to healthy tissues. Overall, enhancement of antitumor effects of GaAcAc by gelucire-stabilized NPs coupled with reduced exposure of healthy tissues to gallium would likely ensure desired therapeutic outcomes and safety of gallium-based cancer treatment.

  17. 46 CFR 148.205 - Ammonium nitrate and ammonium nitrate fertilizers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Ammonium nitrate and ammonium nitrate fertilizers. 148... Materials § 148.205 Ammonium nitrate and ammonium nitrate fertilizers. (a) This section applies to the stowage and transportation in bulk of ammonium nitrate and the following fertilizers composed of uniform...

  18. 46 CFR 148.205 - Ammonium nitrate and ammonium nitrate fertilizers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Ammonium nitrate and ammonium nitrate fertilizers. 148... Materials § 148.205 Ammonium nitrate and ammonium nitrate fertilizers. (a) This section applies to the stowage and transportation in bulk of ammonium nitrate and the following fertilizers composed of uniform...

  19. 46 CFR 148.205 - Ammonium nitrate and ammonium nitrate fertilizers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Ammonium nitrate and ammonium nitrate fertilizers. 148... Materials § 148.205 Ammonium nitrate and ammonium nitrate fertilizers. (a) This section applies to the stowage and transportation in bulk of ammonium nitrate and the following fertilizers composed of uniform...

  20. 46 CFR 148.205 - Ammonium nitrate and ammonium nitrate fertilizers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Ammonium nitrate and ammonium nitrate fertilizers. 148... Materials § 148.205 Ammonium nitrate and ammonium nitrate fertilizers. (a) This section applies to the stowage and transportation in bulk of ammonium nitrate and the following fertilizers composed of uniform...

  1. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma

    PubMed Central

    Chamberlain, Marc C.; Johnston, Sandra K.

    2010-01-01

    We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18–93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m2/dose; 375 mg/m2/dose) for 4–6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m2/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4–10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6–10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months. PMID:20511181

  2. Cellular uptake and anticancer activity of carboxylated gallium corroles.

    PubMed

    Pribisko, Melanie; Palmer, Joshua; Grubbs, Robert H; Gray, Harry B; Termini, John; Lim, Punnajit

    2016-04-19

    We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50values (<20 µM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (Emax= 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 > 3 > 2 > 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging.

  3. Cellular uptake and anticancer activity of carboxylated gallium corroles

    PubMed Central

    Pribisko, Melanie; Palmer, Joshua; Grubbs, Robert H.; Gray, Harry B.; Termini, John; Lim, Punnajit

    2016-01-01

    We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50 values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50 values (<20 µM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (Emax = 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 >> 3 > 2 >> 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging. PMID:27044076

  4. High-surface Thermally Stable Mesoporous Gallium Phosphates Constituted by Nanoparticles as Primary Building Blocks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    V Parvulescu; V Parvulescu; D Ciuparu

    In constant, search for micro/mesoporous materials, gallium phosphates, have attracted continued interest due to the large pore size reported for some of these solids in comparison with analogous aluminum phosphates. However up to now, the porosity of gallium phosphates collapsed upon template removal or exposure to the ambient moisture. In the present work, we describe high-surface thermally stable mesoporous gallium phosphates synthesized from gallium propoxide and PCl{sub 3} and different templating agents such as amines (dipropylamine, piperidine and aminopiperidine) and quaternary ammonium salts (C{sub 16}H{sub 33}(CH{sub 3})3NBr and C{sub 16}PyCl). These highly reactive precursors have so far not been usedmore » as gallium and phosphate sources for the synthesis of gallophosphates. Conceptually, our present synthetic procedure is based on the fast formation of gallium phosphate nanoparticles via the reaction of gallium propoxide with PCl{sub 3} and subsequent construction of the porous material with nanoparticles as building blocks. The organization of the gallophosphate nanoparticles in stable porous structures is effected by the templates. Different experimental procedures varying the molar composition of the sol-gel, pH and the pretreatment of gallium precursor were assayed, most of them leading to satisfactory materials in terms of thermal stability and porosity. In this way, a series of gallium phosphates with surface are above 200 m{sup 2} g{sup -1}, and narrow pore size from 3 to 6 nm and remarkable thermal stability (up to 550 C) have been prepared. In some cases, the structure tends to show some periodicity and regularity as determined by XRD. The remarkable stability has allowed us to test the catalytic activity of gallophosphates for the aerobic oxidation of alkylaromatics with notable good results. Our report reopens the interest for gallophosphates in heterogeneous catalysis.« less

  5. Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

    PubMed

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

    2015-09-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2).

    PubMed

    Charles, Pierre; Terrier, Benjamin; Perrodeau, Élodie; Cohen, Pascal; Faguer, Stanislas; Huart, Antoine; Hamidou, Mohamed; Agard, Christian; Bonnotte, Bernard; Samson, Maxime; Karras, Alexandre; Jourde-Chiche, Noémie; Lifermann, François; Gobert, Pierre; Hanrotel-Saliou, Catherine; Godmer, Pascal; Martin-Silva, Nicolas; Pugnet, Grégory; Matignon, Marie; Aumaitre, Olivier; Viallard, Jean-François; Maurier, François; Meaux-Ruault, Nadine; Rivière, Sophie; Sibilia, Jean; Puéchal, Xavier; Ravaud, Philippe; Mouthon, Luc; Guillevin, Loïc

    2018-04-25

    To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group. Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations. AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions. NCT01731561; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless

  7. Bioactivation of organic nitrates and the mechanism of nitrate tolerance.

    PubMed

    Klemenska, Emila; Beresewicz, Andrzej

    2009-01-01

    Organic nitrates, such as nitroglycerin, are commonly used in the therapy of cardiovascular disease. Long-term therapy with these drugs, however, results in the rapid development of nitrate tolerance, limiting their hemodynamic and anti-ischemic efficacy. In addition, nitrate tolerance is associated with the expression of potentially deleterious modifications such as increased oxidative stress, endothelial dysfunction, and sympathetic activation. In this review we discuss current concepts regarding the mechanisms of organic nitrate bioactivation, nitrate tolerance, and nitrate-mediated oxidative stress and endothelial dysfunction. We also examine how hydralazine may prevent nitrate tolerance and related endothelial dysfunction.

  8. Liquid gallium rotary electric contract

    NASA Technical Reports Server (NTRS)

    Przybyszewski, J. S.

    1969-01-01

    Due to its low vapor pressure, gallium, when substituted for mercury in a liquid slip ring system, transmits substantial amounts of electrical current to rotating components in an ultrahigh vacuum. It features low electrical loss, little or no wear, and long maintenance-free life.

  9. Morphology, mechanical stability, and protective properties of ultrathin gallium oxide coatings.

    PubMed

    Lawrenz, Frank; Lange, Philipp; Severin, Nikolai; Rabe, Jürgen P; Helm, Christiane A; Block, Stephan

    2015-06-02

    Ultrathin gallium oxide layers with a thickness of 2.8 ± 0.2 nm were transferred from the surface of liquid gallium onto solid substrates, including conjugated polymer poly(3-hexylthiophene) (P3HT). The gallium oxide exhibits high mechanical stability, withstanding normal pressures of up to 1 GPa in contact mode scanning force microscopy imaging. Moreover, it lowers the rate of photodegradation of P3HT by 4 orders of magnitude, as compared to uncovered P3HT. This allows us to estimate the upper limits for oxygen and water vapor transmission rates of 0.08 cm(3) m(-2) day(-1) and 0.06 mg m(-2) day(-1), respectively. Hence, similar to other highly functional coatings such as graphene, ultrathin gallium oxide layers can be regarded as promising candidates for protective layers in flexible organic (opto-)electronics and photovoltaics because they offer permeation barrier functionalities in conjunction with high optical transparency.

  10. Ultrasonic cavitation of molten gallium: formation of micro- and nano-spheres.

    PubMed

    Kumar, Vijay Bhooshan; Gedanken, Aharon; Kimmel, Giora; Porat, Ze'ev

    2014-05-01

    Pure gallium has a low melting point (29.8°C) and can be melted in warm water or organic liquids, thus forming two immiscible liquid phases. Irradiation of this system with ultrasonic energy causes cavitation and dispersion of the molten gallium as microscopic spheres. The resultant spheres were found to have radii range of 0.2-5 μm and they do not coalesce upon cessation of irradiation, although the ambient temperature is well above the m.p. of gallium. It was found that the spheres formed in water are covered with crystallites of GaO(OH), whereas those formed in organic liquids (hexane and n-dodecane) are smooth, lacking such crystallites. However, Raman spectroscopy revealed that the spheres formed in organic liquids are coated with a carbon film. The latter may be the factor preventing their coalescence at temperatures above the m.p. of gallium. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Generator for ionic gallium-68 based on column chromatography

    DOEpatents

    Neirinckx, Rudi D.; Davis, Michael A.

    1981-01-01

    A physiologically acceptable solution of gallium-68 fluorides, having an activity of 0.1 to 50 millicuries per milliliter of solution is provided. The solution is obtained from a generator comprising germanium-68 hexafluoride bound to a column of an anion exchange resin which forms gallium-68 in situ by eluting the column with an acid solution to form a solution containing .sup.68 Ga-fluorides. The solution then is neutralized prior to administration.

  12. In vitro bio-functionality of gallium nitride sensors for radiation biophysics.

    PubMed

    Hofstetter, Markus; Howgate, John; Schmid, Martin; Schoell, Sebastian; Sachsenhauser, Matthias; Adigüzel, Denis; Stutzmann, Martin; Sharp, Ian D; Thalhammer, Stefan

    2012-07-27

    There is an increasing interest in the integration of hybrid bio-semiconductor systems for the non-invasive evaluation of physiological parameters. High quality gallium nitride and its alloys show promising characteristics to monitor cellular parameters. Nevertheless, such applications not only request appropriate sensing capabilities but also the biocompatibility and especially the biofunctionality of materials. Here we show extensive biocompatibility studies of gallium nitride and, for the first time, a biofunctionality assay using ionizing radiation. Analytical sensor devices are used in medical settings, as well as for cell- and tissue engineering. Within these fields, semiconductor devices have increasingly been applied for online biosensing on a cellular and tissue level. Integration of advanced materials such as gallium nitride into these systems has the potential to increase the range of applicability for a multitude of test devices and greatly enhance sensitivity and functionality. However, for such applications it is necessary to optimize cell-surface interactions and to verify the biocompatibility of the semiconductor. In this work, we present studies of mouse fibroblast cell activity grown on gallium nitride surfaces after applying external noxa. Cell-semiconductor hybrids were irradiated with X-rays at air kerma doses up to 250 mGy and the DNA repair dynamics, cell proliferation, and cell growth dynamics of adherent cells were compared to control samples. The impact of ionizing radiation on DNA, along with the associated cellular repair mechanisms, is well characterized and serves as a reference tool for evaluation of substrate effects. The results indicate that gallium nitride does not require specific surface treatments to ensure biocompatibility and suggest that cell signaling is not affected by micro-environmental alterations arising from gallium nitride-cell interactions. The observation that gallium nitride provides no bio-functional influence on

  13. Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener's granulomatosis

    PubMed Central

    Slart, R; Jager, P; Poot, L; Piers, D; Cohen, T; Stegeman, C

    2003-01-01

    Background: Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear. Objective: To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions. Methods: Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity. Results: WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections. Conclusion: Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower. PMID:12810430

  14. 40 CFR 421.180 - Applicability: Description of the primary and secondary germanium and gallium subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... primary and secondary germanium and gallium subcategory. 421.180 Section 421.180 Protection of Environment... POINT SOURCE CATEGORY Primary and Secondary Germanium and Gallium Subcategory § 421.180 Applicability: Description of the primary and secondary germanium and gallium subcategory. The provisions of this subpart are...

  15. 40 CFR 421.180 - Applicability: Description of the primary and secondary germanium and gallium subcategory.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... primary and secondary germanium and gallium subcategory. 421.180 Section 421.180 Protection of Environment... POINT SOURCE CATEGORY Primary and Secondary Germanium and Gallium Subcategory § 421.180 Applicability: Description of the primary and secondary germanium and gallium subcategory. The provisions of this subpart are...

  16. 40 CFR 421.180 - Applicability: Description of the primary and secondary germanium and gallium subcategory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... primary and secondary germanium and gallium subcategory. 421.180 Section 421.180 Protection of Environment... POINT SOURCE CATEGORY Primary and Secondary Germanium and Gallium Subcategory § 421.180 Applicability: Description of the primary and secondary germanium and gallium subcategory. The provisions of this subpart are...

  17. 40 CFR 421.180 - Applicability: Description of the primary and secondary germanium and gallium subcategory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... primary and secondary germanium and gallium subcategory. 421.180 Section 421.180 Protection of Environment... POINT SOURCE CATEGORY Primary and Secondary Germanium and Gallium Subcategory § 421.180 Applicability: Description of the primary and secondary germanium and gallium subcategory. The provisions of this subpart are...

  18. 40 CFR 421.180 - Applicability: Description of the primary and secondary germanium and gallium subcategory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... primary and secondary germanium and gallium subcategory. 421.180 Section 421.180 Protection of Environment... POINT SOURCE CATEGORY Primary and Secondary Germanium and Gallium Subcategory § 421.180 Applicability: Description of the primary and secondary germanium and gallium subcategory. The provisions of this subpart are...

  19. Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

    PubMed Central

    Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian; Glennie, Martin J.; Beers, Stephen A.; Cragg, Mark S.

    2015-01-01

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

  20. Low incidence of pneumocystis pneumonia utilizing PCR-based diagnosis in patients with B-cell lymphoma receiving rituximab-containing combination chemotherapy.

    PubMed

    Barreto, Jason N; Ice, Lauren L; Thompson, Carrie A; Tosh, Pritish K; Osmon, Douglas R; Dierkhising, Ross A; Plevak, Matthew F; Limper, Andrew H

    2016-11-01

    Recent literature has demonstrated concern over the risk of Pneumocystis jirovecii pneumonia (PJP) when administering rituximab with combination chemotherapy such as in R-CHOP; however, the exact risk and potential need for prophylaxis is unknown. We sought to determine the incidence of PJP infection following R-CHOP administration in patients with B-cell lymphoma. Consecutive patients diagnosed with B-cell lymphoma receiving R-CHOP were evaluated from chemotherapy initiation until 180 days after the last administration. The primary outcome was cumulative incidence of PJP infection. Secondary endpoints included the association of rituximab, prednisone and subsequent chemotherapy with PJP infection risk. A total of 689 patients (53% male, median age 66 years) were included. Seventy-three percent of patients completed at least 6 cycles of R-CHOP treatment. Median rituximab and prednisone cumulative doses were 3950 mg and 5325 mg, respectively. Median daily prednisone dose through end of treatment was 45 mg (range 7.6 mg to 119 mg). The cumulative incidence of PJP was 1.51% (95% CI 0.57-2.43, at maximum follow-up of 330 days), below 3.5%, the conventional threshold for prophylaxis. Univariate analysis did not detect a statistically significant association between PJP and rituximab, steroids, or receipt of additional chemotherapy in this patient population. Our results demonstrate a low occurrence of Pneumocystis pneumonia during R-CHOP treatment of B-cell lymphoma and argue against universal anti-Pneumocystis prophylaxis in this setting. Further investigations should focus on targeted anti-Pneumocystis prophylaxis for patients presenting with high-risk baseline characteristics or when receiving rituximab-inclusive intensive combination chemotherapy regimens as treatment for other aggressive lymphoma subtypes. Am. J. Hematol. 91:1113-1117, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Launching biosimilar rituximab: an industry opinion on biosimilar uptake in Europe.

    PubMed

    Trollope, Richard; Johnson, Sue; Ireland, Henry

    2017-06-01

    Richard Trollope and Sue Johnson talk with Henry Ireland, Senior Editor about the recent approval of biosimilar rituximab (Truxima ® ) & the current state of biosimilar uptake across Europe Richard Trollope, Head of Biosimilars, Mundipharma International Limited, qualified as a biochemist before joining Wyeth's commercial operations, prior to its acquisition by Pfizer. Richard later joined Yamanouchi Pharmaceuticals (now Astellas Pharma). His fascination with oncology led him to join Mundipharma in Europe and after joining the company's UK arm (Napp Pharmaceuticals Limited), Richard began his journey in biosimilars. He now heads up the biosimilar franchise at Mundipharma International as it launches biosimilar rituximab (Truxima ® ) - the first biosimilar monoclonal antibody for the treatment of cancer, which will be distributed by Napp Pharmaceuticals in the UK. Sue Johnson, PhD, Medical Insights at Mundipharma International Limited, is a scientist by background and completed her postdoc fellowship at Harvard Medical School. On returning to the UK, she began her career in the pharmaceutical industry, working in UK Medical Affairs before transitioning to a European role with Mundipharma 2 years ago, where she leads on Medical Insights for the biosimilars franchise.

  2. Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies.

    PubMed

    Cabral, Vanderlea Poeys; Andrade, Carlos Augusto Ferreira de; Passos, Sonia Regina Lambert; Martins, Maria de Fátima Moreira; Hökerberg, Yara Hahr Marques

    A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs. Copyright © 2016. Published by Elsevier Editora Ltda.

  3. Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

    PubMed

    Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

    2014-02-01

    Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

  4. Development of DOTA-Rituximab to be Labeled with 90Y for Radioimmunotherapy of B-cell Non-Hodgkin Lymphoma

    PubMed Central

    Johari doha, Fariba; Rahmani, Siyavash; Rikhtechi, Pedram; Rasaneh, Samira; Sheikholislam, Zahra; Shahhosseini, Soraya

    2017-01-01

    NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy. The cells which lack antigen or cells which cannot be reached due to poor vascularization and intratumoral pressure in a bulky tumor would be irradiated and killed by cross fire effect of beta emitter. 90Y, a pure high energy β-emitter with a half-life of 64 h, a maximum energy of 2.28 MeV, and maximum board of 11.3 mm in tissue is radionuclide of choice for radioimmunotherapy of outpatient administration. In this study, rituximab was conjugated to DOTA and radiolabeled with 90YCl3. The stability, affinity, and immunoreactivity of radiolabeled antibody was determined in vitro and the conditions were optimized. Biodistribution studies were done in normal mice. The optimum conditions of conjugation and radiolabeling was 1-2 h at 37 °C and 1 h at 45 °C, respectively. Results showed approximately 4 DOTA molecules conjugated per antibody molecule. The purified antibody was stable and intact over 6 months stored at -20 °C. The result of immunoreactivity (≈70%), affinity (≈3 nM) and biodistribution in normal mice are acceptable. PMID:28979315

  5. Cell behavior on gallium nitride surfaces: peptide affinity attachment versus covalent functionalization.

    PubMed

    Foster, Corey M; Collazo, Ramon; Sitar, Zlatko; Ivanisevic, Albena

    2013-07-02

    Gallium nitride is a wide band gap semiconductor that demonstrates a unique set of optical and electrical properties as well as aqueous stability and biocompatibility. This combination of properties makes gallium nitride a strong candidate for use in chemical and biological applications such as sensors and neural interfaces. Molecular modification can be used to enhance the functionality and properties of the gallium nitride surface. Here, gallium nitride surfaces were functionalized with a PC12 cell adhesion promoting peptide using covalent and affinity driven attachment methods. The covalent scheme proceeded by Grignard reaction and olefin metathesis while the affinity driven scheme utilized the recognition peptide isolated through phage display. This study shows that the method of attaching the adhesion peptide influences PC12 cell adhesion and differentiation as measured by cell density and morphological analysis. Covalent attachment promoted monolayer and dispersed cell adhesion while affinity driven attachment promoted multilayer cell agglomeration. Higher cell density was observed on surfaces modified using the recognition peptide. The results suggest that the covalent and affinity driven attachment methods are both suitable for promoting PC12 cell adhesion to the gallium nitride surface, though each method may be preferentially suited for distinct applications.

  6. Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.

    PubMed

    Aggarwal, Rohit; Oddis, Chester V; Goudeau, Danielle; Koontz, Diane; Qi, Zengbiao; Reed, Ann M; Ascherman, Dana P; Levesque, Marc C

    2016-06-01

    To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs). Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated autoantibodies levels and CSM were estimated using linear mixed models. Following rituximab, anti-Jo-1 levels decreased over time (P < 0.001) and strongly correlated with all CSMs (P < 0.008). Anti-TIF1-γ levels also decreased over time (P < 0.001) and were only associated with HAQ, MMT and physician and patient global disease activity. Anti-SRP levels did not change significantly over time, but were significantly associated with serum muscle enzymes. Anti-Mi-2 levels significantly decreased over time and were associated with muscle enzymes, MMT and the physician global score. Anti-Jo-1, anti-TIF1-γ and anti-Mi-2 levels in myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti-Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights

  7. Gallium scanning in cerebral and cranial infections. [/sup 67/Ga, /sup 99m/Tc tracer techniques

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Waxman, A.D.; Siemsen, J.K.

    1976-08-01

    Eighteen patients with cranial or intracranial infections were studied with technetium and gallium brain scans. Seven of 18 lesions were noted with gallium and not with pertechnetate, while the reverse pattern was not seen. Brain abscesses were visualized with gallium but not with pertechnetate in two of five cases. Osteomyelitis of the skull and mastoiditis showed intense gallium uptake in all cases, while meningitis or cerebritis gave inconsistent results.

  8. Synthesis and use of (polyfluoroaryl)fluoroanions of aluminum, gallium and indium

    DOEpatents

    Marks, Tobin J.; Chen, You-Xian

    2000-01-01

    Salts of (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium are described. The (polyfluoroaryl)fluoroanions have the formula [ER'R"R'"F].sup..crclbar. wherein E is aluminum, gallium, or indium, wherein F is fluorine, and wherein R', R", and R'" is each a fluorinated phenyl, fluorinated biphenyl, or fluorinated polycyclic group.

  9. Gallium phosphide nanowires as a substrate for cultured neurons.

    PubMed

    Hällström, Waldemar; Mårtensson, Thomas; Prinz, Christelle; Gustavsson, Per; Montelius, Lars; Samuelson, Lars; Kanje, Martin

    2007-10-01

    Dissociated sensory neurons were cultured on epitaxial gallium phosphide (GaP) nanowires grown vertically from a gallium phosphide surface. Substrates covered by 2.5 microm long, 50 nm wide nanowires supported cell adhesion and axonal outgrowth. Cell survival was better on nanowire substrates than on planar control substrates. The cells interacted closely with the nanostructures, and cells penetrated by hundreds of wires were observed as well as wire bending due to forces exerted by the cells.

  10. Complexometric determination of gallium with calcein blue as indicator

    USGS Publications Warehouse

    Elsheimer, H.N.

    1967-01-01

    A metalfluorechromic indicator, Calcein Blue, has been used for the back-titration of milligram amounts of EDTA in presence of gallium complexes. The indicator was used in conjunction with an ultraviolet titration assembly equipped with a cadmium sulphide detector cell and a microammeter for enhanced end-point detection. The result is a convenient and rapid method with an accuracy approaching 0.1 % and a relative standard deviation of about 0.4% for 10 mg of gallium. ?? 1967.

  11. Bit-systolic arithmetic arrays using dynamic differential gallium arsenide circuits

    NASA Technical Reports Server (NTRS)

    Beagles, Grant; Winters, Kel; Eldin, A. G.

    1992-01-01

    A new family of gallium arsenide circuits for fine grained bit-systolic arithmetic arrays is introduced. This scheme combines features of two recent techniques of dynamic gallium arsenide FET logic and differential dynamic single-clock CMOS logic. The resulting circuits are fast and compact, with tightly constrained series FET propagation paths, low fanout, no dc power dissipation, and depletion FET implementation without level shifting diodes.

  12. Feasibility and toxicity of concomitant radio/immunotherapy with MabThera (Rituximab®) for patients with non-Hodkin's Lymphoma: results of a prospective phase I/II study.

    PubMed

    Haidenberger, Alfred; Fromm-Haidenberger, Sabine; de Vries, Alexander; Popper, Bela-Andre; Steurer, Michael; Skvortsova, Ira; Kantner, Johanna; Gunsilius, Eberhard; Lukas, Peter

    2011-05-01

    Non-Hodgkin's lymphomas (NHL) have a high radio- and chemosensitivity. Although initially responsive, approximately 50% of low grade B-cell lymphomas relapse after 10-15 years. Besides chemo- and radiotherapy, rituximab, a mouse/human chimeric antibody targeting CD20 antigen on the surface of B-cell lymphoma cells, is another treatment approach. In vitro data showed potentiation of radiation-induced apoptosis by addition of rituximab. The purpose of this study was to evaluate the feasibility and toxicity of radiotherapy with concomitant application of rituximab in NHL patients. A total of 21 patients with B-cell lymphoma (stage I: n = 11; II: n = 5; III: n = 1; IV: n = 4) were included in this study, treated with radiotherapy of 30-40 Gy and weekly application of rituximab (375 mg/m²). Nine patients had R-CHOP chemotherapy previously, 1 patient leuceran chemotherapy, and 2 patients an initial treatment with 6 cycles of rituximab. Mean time of follow-up was 41.7 months. No grade 4 toxicity or treatment-related death was observed. In 1 patient, rituximab application had to be stopped after 3 cycles due to radiation-induced side effects. No late toxicities were reported. All patients were in complete remission after treatment. Progression or relapse was observed in 6 patients (28%); the mean time to progression was 27 months. The mean overall survival (OS) was 53 months. Combined radio/immunotherapy is feasible and safe. Treatment was well tolerated, no late toxicities were observed, and treatment outcome is promising. Randomized trials are necessary to clarify the benefit of this treatment approach and its applicability.

  13. Nitrate reduction

    DOEpatents

    Dziewinski, Jacek J.; Marczak, Stanislaw

    2000-01-01

    Nitrates are reduced to nitrogen gas by contacting the nitrates with a metal to reduce the nitrates to nitrites which are then contacted with an amide to produce nitrogen and carbon dioxide or acid anions which can be released to the atmosphere. Minor amounts of metal catalysts can be useful in the reduction of the nitrates to nitrites. Metal salts which are formed can be treated electrochemically to recover the metals.

  14. Theoretical exploration of structural, electro-optical and magnetic properties of gallium-doped silicon carbide nanotubes

    NASA Astrophysics Data System (ADS)

    Behzad, Somayeh; Chegel, Raad; Moradian, Rostam; Shahrokhi, Masoud

    2014-09-01

    The effects of gallium doping on the structural, electro-optical and magnetic properties of (8,0) silicon carbide nanotube (SiCNT) are investigated by using spin-polarized density functional theory. It is found from the calculation of the formation energies that gallium substitution for silicon atom is preferred. Our results show that gallium substitution at either single carbon or silicon atom site in SiCNT could induce spontaneous magnetization. The optical studies based on dielectric function indicate that new transition peaks and a blue shift are observed after gallium doping.

  15. Strategies for gallium removal after focused ion beam patterning of ferroelectric oxide nanostructures

    NASA Astrophysics Data System (ADS)

    Schilling, A.; Adams, T.; Bowman, R. M.; Gregg, J. M.

    2007-01-01

    As part of a study into the properties of ferroelectric single crystals at nanoscale dimensions, the effects that focused ion beam (FIB) processing can have, in terms of structural damage and ion implantation, on perovskite oxide materials has been examined, and a post-processing procedure developed to remove such effects. Single crystal material of the perovskite ferroelectric barium titanate (BaTiO3) has been patterned into thin film lamellae structures using a FIB microscope. Previous work had shown that FIB patterning induced gallium impregnation and associated creation of amorphous layers in a surface region of the single crystal material some 20 nm thick, but that both recrystallization and expulsion of gallium could be achieved through thermal annealing in air. Here we confirm this observation, but find that thermally induced gallium expulsion is associated with the formation of gallium-rich platelets on the surface of the annealed material. These platelets are thought to be gallium oxide. Etching using nitric and hydrochloric acids had no effect on the gallium-rich platelets. Effective platelet removal involved thermal annealing at 700 °C for 1 h in a vacuum followed by 1 h in oxygen, and then a post-annealing low-power plasma clean in an Ar/O atmosphere. Similar processing is likely to be necessary for the full recovery of post FIB-milled nanostructures in oxide ceramic systems in general.

  16. Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study.

    PubMed

    Emery, P; Gottenberg, J E; Rubbert-Roth, A; Sarzi-Puttini, P; Choquette, D; Taboada, V M Martínez; Barile-Fabris, L; Moots, R J; Ostor, A; Andrianakos, A; Gemmen, E; Mpofu, C; Chung, C; Gylvin, L Hinsch; Finckh, A

    2015-06-01

    To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)-erythrocyte sedimentation rate (ESR) over 6 months. 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3-ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3-ESR at 6 months was significantly greater in rituximab than TNFi patients: -1.5 (0.2) vs -1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (-1.7 vs -1.3; p=0.017) but not intolerance (-0.7 vs -0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3-ESR with rituximab than with TNFi (-1.6 (0.3) vs -1.2 (0.3); p=0.011), particularly those switching because of inefficacy (-1.9 (0.3) vs -1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy. Published by the BMJ Publishing Group Limited

  17. Rituximab is Ineffective for Treatment of Fatigue in Primary Biliary Cholangitis: A phase-2 Randomised Controlled Trial.

    PubMed

    Khanna, Amardeep; Jopson, Laura; Howel, Denise; Bryant, Andrew; Blamire, Andrew; Newton, Julia L; Jones, David E

    2018-05-23

    Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease. Half of patients experience debilitating fatigue which is currently untreatable. Previous studies have shown muscle bioenergetic abnormalities in PBC, including increased muscle acidosis with exercise linked to the anti-mitochondrial antibody (AMA) diagnostic of the disease, and reduced anaerobic threshold. In this study we addressed the hypothesis that fatigue in PBC is driven by muscle bioenergetic abnormality related to AMA, and that AMA reduction with B-cell depletion therapy will improve fatigue. In our single-centred Phase II randomised controlled trial (RCT) 57 participants aged ≥18 years with PBC and moderate or severe fatigue were randomized to receive 2 doses of either rituximab (1000mg) or saline (placebo). The primary outcome measure was fatigue severity assessed using the PBC-40 fatigue domain at 3 months. Secondary outcomes measures included patient-reported outcomes, immunological and bioenergetics disease parameters. Experimental outcomes included biochemical markers of disease severity. Improvement in fatigue score at 3 months was seen in both arms, with no significant difference (adjusted mean difference -0.9 95%CI -4.6 to 3.1). Little difference was observed in other patient reported outcomes or physical activity. Significant anaerobic threshold improvement was seen in the Rituximab group only but this was not associated with fatigue improvement. No treatment-emergent SAEs were seen. Rituximab was safe over the 12 month study period but showed no evidence of effectiveness for the treatment of fatigue in PBC. Anaerobic threshold improvement was seen; potentially linking AMA with muscle bioenergetics dysfunction, however, this was not related to improvement in fatigue. Rituximab had some evidence of a beneficial effect on alkaline phosphatase levels in this largely UDCA-responding, early disease stage cohort. This article is protected by copyright. All rights reserved.

  18. Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Siritanaratkul, Noppadol; Khuhapinant, Archrob; Nawarawong, Weerasak; Norasetthada, Lalita; Lekhakula, Arnuparp; Rujirojindakul, Pairaya; Sirijerachai, Chittima; Chansung, Kanjana; Suwanban, Tawatchai; Chuncharunee, Suporn; Niparuck, Pimjai; Wongkhantee, Somchai; Mongkonsritragoon, Wichean; Numbenjapon, Tontanai

    2013-01-01

    The impact of health insurance with inequitable rituximab coverage on the survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been reported. We conducted a nationwide multicenter analysis on the outcome of 553 adult patients consecutively diagnosed with DLBCL between July 2003 and June 2006, in whom treatment cost was reimbursed under the Civil Servant Medical Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352). The international prognostic index was comparable between the two payment groups. Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS patients, respectively (p <0.001). With a median follow-up of 24.6 months, the 6-year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs. 23.2%, p =0.005). "Not treated with rituximab-based therapy" was the strongest adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p <0.001). It is concluded that lack of access to rituximab is the principal factor accounting for the inferior PFS observed in Thai patients with DLBCL who are treated under the UCS.

  19. Thermodynamic properties of uranium in liquid gallium, indium and their alloys

    NASA Astrophysics Data System (ADS)

    Volkovich, V. A.; Maltsev, D. S.; Yamshchikov, L. F.; Osipenko, A. G.

    2015-09-01

    Activity, activity coefficients and solubility of uranium was determined in gallium, indium and gallium-indium alloys containing 21.8 (eutectic), 40 and 70 wt.% In. Activity was measured at 573-1073 K employing the electromotive force method, and solubility between room temperature (or the alloy melting point) and 1073 K employing direct physical measurements. Activity coefficients were obtained from the difference of experimentally determined temperature dependencies of uranium activity and solubility. Intermetallic compounds formed in the respective alloys were characterized using X-ray diffraction. Partial and excess thermodynamic functions of uranium in the studied alloys were calculated. Liquidus lines in U-Ga and U-In phase diagrams from the side rich in gallium or indium are proposed.

  20. Biofilm formation on titanium implants counteracted by grafting gallium and silver ions.

    PubMed

    Cochis, Andrea; Azzimonti, Barbara; Della Valle, Cinzia; Chiesa, Roberto; Arciola, Carla Renata; Rimondini, Lia

    2015-03-01

    Biofilm-associated infections remain the leading cause of implant failure. Thanks to its established biocompatibility and biomechanical properties, titanium has become one of the most widely used materials for bone implants. Engineered surface modifications of titanium able to thwart biofilm formation while endowing a safe anchorage to eukaryotic cells are being progressively developed. Here surfaces of disks of commercial grade 2 titanium for bone implant were grafted with gallium and silver ions by anodic spark deposition. Scanning electron microscopy of the surface morphology and energy dispersive X-ray spectroscopy were used for characterization. Gallium-grafted titanium was evaluated in comparison with silver-grafted titanium for both in vivo and in vitro antibiofilm properties and for in vitro compatibility with human primary gingival fibroblasts. Surface-modified materials showed: (i) homogeneous porous morphology, with pores of micrometric size; (ii) absence of cytotoxic effects; (iii) ability to support in vitro the adhesion and spreading of gingival fibroblasts; and (iv) antibiofilm properties. Although both silver and gallium exhibited in vitro strong antibacterial properties, in vivo gallium was significantly more effective than silver in reducing number and viability of biofilm bacteria colonies. Gallium-based treatments represent promising titanium antibiofilm coatings to develop new bone implantable devices for oral, maxillofacial, and orthopedic applications. © 2014 Wiley Periodicals, Inc.

  1. International standards for monoclonal antibodies to support pre- and post-marketing product consistency: Evaluation of a candidate international standard for the bioactivities of rituximab.

    PubMed

    Prior, Sandra; Hufton, Simon E; Fox, Bernard; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian

    2018-01-01

    The intrinsic complexity and heterogeneity of therapeutic monoclonal antibodies is built into the biosimilarity paradigm where critical quality attributes are controlled in exhaustive comparability studies with the reference medicinal product. The long-term success of biosimilars will depend on reassuring healthcare professionals and patients of consistent product quality, safety and efficacy. With this aim, the World Health Organization has endorsed the need for public bioactivity standards for therapeutic monoclonal antibodies in support of current controls. We have developed a candidate international potency standard for rituximab that was evaluated in a multi-center collaborative study using participants' own qualified Fc-effector function and cell-based binding bioassays. Dose-response curve model parameters were shown to reflect similar behavior amongst rituximab preparations, albeit with some differences in potency. In the absence of a common reference standard, potency estimates were in poor agreement amongst laboratories, but the use of the candidate preparation significantly reduced this variability. Our results suggest that the candidate rituximab standard can support bioassay performance and improve data harmonization, which when implemented will promote consistency of rituximab products over their life-cycles. This data provides the first scientific evidence that a classical standardization exercise allowing traceability of bioassay data to an international standard is also applicable to rituximab. However, we submit that this new type of international standard needs to be used appropriately and its role not to be mistaken with that of the reference medicinal product.

  2. International standards for monoclonal antibodies to support pre- and post-marketing product consistency: Evaluation of a candidate international standard for the bioactivities of rituximab

    PubMed Central

    Prior, Sandra; Hufton, Simon E.; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian

    2018-01-01

    ABSTRACT The intrinsic complexity and heterogeneity of therapeutic monoclonal antibodies is built into the biosimilarity paradigm where critical quality attributes are controlled in exhaustive comparability studies with the reference medicinal product. The long-term success of biosimilars will depend on reassuring healthcare professionals and patients of consistent product quality, safety and efficacy. With this aim, the World Health Organization has endorsed the need for public bioactivity standards for therapeutic monoclonal antibodies in support of current controls. We have developed a candidate international potency standard for rituximab that was evaluated in a multi-center collaborative study using participants' own qualified Fc-effector function and cell-based binding bioassays. Dose-response curve model parameters were shown to reflect similar behavior amongst rituximab preparations, albeit with some differences in potency. In the absence of a common reference standard, potency estimates were in poor agreement amongst laboratories, but the use of the candidate preparation significantly reduced this variability. Our results suggest that the candidate rituximab standard can support bioassay performance and improve data harmonization, which when implemented will promote consistency of rituximab products over their life-cycles. This data provides the first scientific evidence that a classical standardization exercise allowing traceability of bioassay data to an international standard is also applicable to rituximab. However, we submit that this new type of international standard needs to be used appropriately and its role not to be mistaken with that of the reference medicinal product. PMID:28985159

  3. First Results of the Testing of the Liquid Gallium Jet Limiter Concept for ISTTOK

    NASA Astrophysics Data System (ADS)

    Gomes, R. B.; Fernandes, H.; Silva, C.; Borba, D.; Carvalho, B.; Varandas, C.; Lielausis, O.; Klyukin, A.; Platacis, E.; Mikelsons, A.; Platnieks, I.

    2006-12-01

    The use of liquid metals as plasma facing components in tokamaks has recently experienced a renewed interest stimulated by their advantages to the development of a fusion reactor. Liquid metals have been proposed to solve problems related to the erosion and neutronic activation of solid walls submitted to high power loads allowing an efficient heat exhaustion from fusion devices. Presently the most promising materials are Lithium and Gallium. ISTTOK, a small size tokamak, will be used to test the behavior of a liquid Gallium jet in the vacuum chamber and its influence on the plasma. This paper presents a description of the conceived setup as well as experimental results. The liquid Gallium jet is generated by hydrostatic pressure and injected in a radial position close to a moveable stainless steel limiter. Both the jet and the limiter positions are variable allowing for a controlled exposure of the liquid Gallium to the edge plasma. The main components of the Gallium loop are a MHD pump, the liquid metal injector and a filtering system. The MHD pump is of the induction type, based on rotating permanent magnets. The injector is build from a ¼″ stainless steel pipe ended by a shaping nozzle. A setup has been developed to introduce oxide-free Gallium inside the loop's main supply tank. Raw liquid metal is placed inside a chamber heated and degassed under high vacuum while clean Gallium is extracted from the main body of the liquefied metal. Prior to installation on the tokamak, the experimental rig has been implemented using a Pyrex tube as test chamber to investigate the stability of the Gallium jet and its break-up length for several nozzle sizes. Results are presented in this paper. This rig was also useful to assess the behavior of the overall implemented apparatus.

  4. Rituximab as first choice for patients with refractory rheumatoid arthritis: cost-effectiveness analysis in Iran based on a systematic review and meta-analysis.

    PubMed

    Ahmadiani, Saeed; Nikfar, Shekoufeh; Karimi, Somayeh; Jamshidi, Ahmad Reza; Akbari-Sari, Ali; Kebriaeezadeh, Abbas

    2016-09-01

    The aim of this study was to evaluate the effectiveness and cost-effectiveness of using rituximab as first line for patients with refractory rheumatoid arthritis in comparison with continuing conventional DMARDs, from a perspective of health service governors. A systematic review was implemented through searching PubMed, Scopus and Cochrane Library. Quality assessment was performed by Jadad scale. After meta-analysis of ACR index results, QALY gain was calculated through mapping ACR index to HAQ and utility index. To measure the direct and indirect medical costs, a set of interviews with patients were applied. Thirty-two patients were selected from three referral rheumatology clinics in Tehran with definite diagnosis of refractory rheumatoid arthritis in the year before and treatment regimen of either rituximab or DMARDs within last year. Incremental cost-effectiveness ratio was calculated for base case and scenario of generic rituximab. Threefold of GDP per capita was considered as threshold of cost-effectiveness. Four studies were eligible to be considered in this systematic review. Total risk differences of 0.3 for achieving ACR20 criteria, 0.21 for ACR50 and 0.1 for ACR70 were calculated. Also mean of total medical costs of patients for 24 weeks were $3985 in rituximab group and $932 for DMARDs group. Thus, the incremental cost per QALY ratio will be $45,900-$70,223 in base case and $32,386-$49,550 for generic scenario. Rituximab for treatment of patients with refractory rheumatoid arthritis is not considered as cost-effective in Iran in none of the scenarios.

  5. Validation of 64Cu-DOTA-rituximab injection preparation under good manufacturing practices: a PET tracer for imaging of B-cell non-Hodgkin lymphoma.

    PubMed

    Natarajan, Arutselvan; Arksey, Natasha; Iagaru, Andrei; Chin, Frederick T; Gambhir, Sanjiv Sam

    2015-01-01

    Manufacturing of 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-rituximab injection under good manufacturing practices (GMP) was validated for imaging of patients with CD20+ B-cell non-Hodgkin lymphoma. Rituximab was purified by size exclusion high performance liquid chromatography (HPLC) and conjugated to DOTA-mono-(N-hydroxysuccinimidyl) ester. 64CuCl2, buffers, reagents, and other raw materials were obtained as high-grade quality. Following a semi-automated synthesis of 64Cu-DOTA-rituximab, a series of quality control tests was performed. The product was further tested in vivo using micro-positron emission tomography/computed tomography (PET/CT) to assess targeting ability towards human CD20 in transgenic mice. Three batches of 64Cu-DOTA-rituximab final product were prepared as per GMP specifications. The radiolabeling yield from these batches was 93.1 ± 5.8%; these provided final product with radiopharmaceutical yield, purity, and specific activity of 59.2 ± 5.1% (0.9 ± 0.1 GBq of 64Cu), > 95% (by HPLC and radio-thin layer chromatography), and 229.4 ± 43.3 GBq/µmol (or 1.5 ± 0.3 MBq/µg), respectively. The doses passed apyrogenicity and human serum stability specifications, were sterile up to 14 days, and retained > 60% immunoreactivity. In vivo micro-PET/CT mouse images at 24 hours postinjection showed that the tracer targeted the intended sites of human CD20 expression. Thus, we have validated the manufacturing of GMP grade 64Cu-DOTA-rituximab for injection in the clinical setting.

  6. Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

    PubMed

    Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

    2012-01-01

    Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

  7. Targeted Delivery of Glucan Particle Encapsulated Gallium Nanoparticles Inhibits HIV Growth in Human Macrophages

    PubMed Central

    Soto, Ernesto R.; O'Connell, Olivia; Dikengil, Fusun; Peters, Paul J.; Clapham, Paul R.

    2016-01-01

    Glucan particles (GPs) are hollow, porous 3–5 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of a wide range of payloads (DNA, siRNA, protein, small molecules, and nanoparticles) encapsulated inside the hollow GPs or bound to the surface of chemically derivatized GPs. Gallium nanoparticles have been proposed as an inhibitory agent against HIV infection. Here, macrophage targeting of gallium using GPs provides for more efficient delivery of gallium and inhibition of HIV infection in macrophages compared to free gallium nanoparticles. PMID:27965897

  8. CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review.

    PubMed

    Kakinoki, Yasutaka; Hashiguchi, Junichi; Ishio, Takashi; Chiba, Koji; Niino, Daisuke; Ohshima, Koichi

    2015-12-01

    There have been rare reported cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) that co-expressed CD20. A 44-year-old Japanese male was initially misdiagnosed as CD20-positive diffuse large B-cell lymphoma with a background of reactive CD3-positive T-cells in the stomach. After four cycles of R-CHOP [rituximab plus cyclophosphamide (CY), doxorubicin, vincristine, and prednisolone (PSL)], total gastrectomy with regional lymph node dissection was performed due to the poor response to R-CHOP. A final diagnosis of CD20-positive primary gastric PTCL-NOS was made based on the immunohistochemical, flow cytometric, and molecular genetic findings. In the present case, CD20 immunostaining for T-cell lymphoma cells in tumor tissue varied; in a large part, these were strong to weak-positive, and in some parts, absent. We additionally reviewed the literature focusing on CD20-positive PTCL-NOS treated with rituximab. The administration of rituximab has been performed as an initial treatment in 11 cases, including the case reported here. The response was good in cases with high expression of CD20, while it was poor in cases with variable intensity in CD20 staining, which is consistent with our experience in the present case. The efficacy of rituximab may be associated with intensity of CD20 expression in T cells and its homogeneity in the tumor tissue.

  9. Gallium scan in intracerebral sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Makhija, M.C.; Anayiotos, C.P.

    1981-07-01

    Sarcoidosis involving the nervous system probably occurs in about 4% of patients. The usefulness of brain scintigraphy in these cases has been suggested. In this case of cerebral sarcoid granuloma, gallium imaging demonstrated the lesion before treatment and showed disappearance of the lesion after corticosteroid treatment, which correlated with the patient's clinical improvement.

  10. Gallium-positive Lyme disease myocarditis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alpert, L.I.; Welch, P.; Fisher, N.

    1985-09-01

    In the course of a work-up for fever of unknown origin associated with intermittent arrhythmias, a gallium scan was performed which revealed diffuse myocardial uptake. The diagnosis of Lyme disease myocarditis subsequently was confirmed by serologic titers. One month following recovery from the acute illness, the abnormal myocardial uptake completely resolved.

  11. Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration.

    PubMed

    Fathallah, Anas M; Turner, Michael R; Mager, Donald E; Balu-Iyer, Sathy V

    2015-03-01

    The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration

    PubMed Central

    Fathallah, Anas M.; Turner, Michael R.; Balu-Iyer, Sathy V.

    2015-01-01

    Subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after sc administration remains a major challenge. In this work we investigated the effects of excipient dependent hyper-osmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as our animal model, we compared the effects of NaCl, mannitol and, O-Phospho-L-Serine (OPLS) on plasma concentration of rituximab over 5 days after sc administration. We observed an increase in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, as compared to isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph node in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatic, as estimated by the model, increased from 0.05 % in isotonic buffer to 13% in hyper-tonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. Our data suggests that hypertonic solutions may be a viable option to improve sc bioavailability. PMID:25377184

  13. Electron transport in zinc-blende wurtzite biphasic gallium nitride nanowires and GaNFETs

    DOE PAGES

    Jacobs, Benjamin W.; Ayres, Virginia M.; Stallcup, Richard E.; ...

    2007-10-19

    Two-point and four-point probe electrical measurements of a biphasic gallium nitride nanowire and current–voltage characteristics of a gallium nitride nanowire based field effect transistor are reported. The biphasic gallium nitride nanowires have a crystalline homostructure consisting of wurtzite and zinc-blende phases that grow simultaneously in the longitudinal direction. There is a sharp transition of one to a few atomic layers between each phase. Here, all measurements showed high current densities. Evidence of single-phase current transport in the biphasic nanowire structure is discussed.

  14. [Determination of trace gallium by graphite furnace atomic absorption spectrometry in urine].

    PubMed

    Zhou, L Z; Fu, S; Gao, S Q; He, G W

    2016-06-20

    To establish a method for determination trace gallium in urine by graphite furnace atomic absorption spectrometry (GFAAS). The ammonium dihydrogen phosphate was matrix modifier. The temperature effect about pyrolysis (Tpyr) and atomization temperature were optimized for determination of trace gallium. The method of technical standard about within-run, between-run and recoveries of standard were optimized. The method showed a linear relationship within the range of 0.20~80.00 μg/L (r=0.998). The within-run and between-run relative standard deviations (RSD) of repetitive measurement at 5.0, 10.0, 20.0 μg/L concentration levels were 2.1%~5.5% and 2.3%~3.0%. The detection limit was 0.06 μg/L. The recoveries of gallium were 98.2%~101.1%. This method is simple, low detection limit, accurate, reliable and reproducible. It has been applied for determination of trace gallium in urine samples those who need occupation health examination or poisoning diagnosis.

  15. Microscopic Nanomechanical Dissipation in Gallium Arsenide Resonators.

    PubMed

    Hamoumi, M; Allain, P E; Hease, W; Gil-Santos, E; Morgenroth, L; Gérard, B; Lemaître, A; Leo, G; Favero, I

    2018-06-01

    We report on a systematic study of nanomechanical dissipation in high-frequency (≈300  MHz) gallium arsenide optomechanical disk resonators, in conditions where clamping and fluidic losses are negligible. Phonon-phonon interactions are shown to contribute with a loss background fading away at cryogenic temperatures (3 K). Atomic layer deposition of alumina at the surface modifies the quality factor of resonators, pointing towards the importance of surface dissipation. The temperature evolution is accurately fitted by two-level systems models, showing that nanomechanical dissipation in gallium arsenide resonators directly connects to their microscopic properties. Two-level systems, notably at surfaces, appear to rule the damping and fluctuations of such high-quality crystalline nanomechanical devices, at all temperatures from 3 to 300 K.

  16. Microscopic Nanomechanical Dissipation in Gallium Arsenide Resonators

    NASA Astrophysics Data System (ADS)

    Hamoumi, M.; Allain, P. E.; Hease, W.; Gil-Santos, E.; Morgenroth, L.; Gérard, B.; Lemaître, A.; Leo, G.; Favero, I.

    2018-06-01

    We report on a systematic study of nanomechanical dissipation in high-frequency (≈300 MHz ) gallium arsenide optomechanical disk resonators, in conditions where clamping and fluidic losses are negligible. Phonon-phonon interactions are shown to contribute with a loss background fading away at cryogenic temperatures (3 K). Atomic layer deposition of alumina at the surface modifies the quality factor of resonators, pointing towards the importance of surface dissipation. The temperature evolution is accurately fitted by two-level systems models, showing that nanomechanical dissipation in gallium arsenide resonators directly connects to their microscopic properties. Two-level systems, notably at surfaces, appear to rule the damping and fluctuations of such high-quality crystalline nanomechanical devices, at all temperatures from 3 to 300 K.

  17. Process for forming pure silver ohmic contacts to N- and P-type gallium arsenide materials

    DOEpatents

    Hogan, S.J.

    1983-03-13

    Disclosed is an improved process for manufacturing gallium arsenide semiconductor devices having as its components a n-type gallium arsenide substrate layer and a p-type gallium arsenide diffused layer. The improved process comprises forming a pure silver ohmic contact to both the diffuse layer and the substrate layer wherein the n-type layer comprises a substantially low doping carrier concentration.

  18. Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

    PubMed

    Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

    2015-02-27

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Plasma nitrate and nitrite are increased by a high nitrate supplement, but not by high nitrate foods in older adults

    PubMed Central

    Miller, Gary D.; Marsh, Anthony P.; Dove, Robin W.; Beavers, Daniel; Presley, Tennille; Helms, Christine; Bechtold, Erika; King, S. Bruce; Kim-Shapiro, Daniel

    2012-01-01

    Little is known about the effect of dietary nitrate on the nitrate/nitrite/NO (nitric oxide) cycle in older adults. We examined the effect of a 3-day control diet vs. high nitrate diet, with and without a high nitrate supplement (beetroot juice), on plasma nitrate and nitrite kinetics, and blood pressure using a randomized four period cross-over controlled design. We hypothesized that the high nitrate diet would show higher levels of plasma nitrate/nitrite and blood pressure compared to the control diet, which would be potentiated by the supplement. Participants were eight normotensive older men and women (5 female, 3 male, 72.5±4.7 yrs) with no overt disease or medications that affect NO metabolism. Plasma nitrate and nitrite levels and blood pressure were measured prior to and hourly for 3 hours after each meal. The mean daily changes in plasma nitrate and nitrite were significantly different from baseline for both control diet+supplement (p<0.001 and =0.017 for nitrate and nitrite, respectively) and high nitrate diet+supplement (p=0.001 and 0.002), but not for control diet (p=0.713 and 0.741) or high nitrate diet (p=0.852 and 0.500). Blood pressure decreased from the morning baseline measure to the three 2 hr post-meal follow-up time-points for all treatments, but there was no main effect for treatment. In healthy older adults, a high nitrate supplement consumed at breakfast elevated plasma nitrate and nitrite levels throughout the day. This observation may have practical utility for the timing of intake of a nitrate supplement with physical activity for older adults with vascular dysfunction. PMID:22464802

  20. Gallium nitride junction field-effect transistor

    DOEpatents

    Zolper, John C.; Shul, Randy J.

    1999-01-01

    An all-ion implanted gallium-nitride (GaN) junction field-effect transistor (JFET) and method of making the same. Also disclosed are various ion implants, both n- and p-type, together with or without phosphorous co-implantation, in selected III-V semiconductor materials.

  1. Isoelectronic Traps in Gallium Phosphide

    NASA Astrophysics Data System (ADS)

    Christian, Theresa; Alberi, Kirstin; Beaton, Daniel; Fluegel, Brian; Mascarenhas, Angelo

    2015-03-01

    Isoelectronic substitutional dopants can result in strongly localized exciton traps within a host bandstructure such as gallium arsenide (GaAs) or gallium phosphide (GaP). These traps have received great attention for their role in the anomalous bandgap bowing of nitrogen or bismuth-doped GaAs, creating the dramatic bandgap tunability of these unusual dilute alloys. In the wider, indirect-bandgap host material GaP, these same isoelectronic dopants create bound states within the gap that can have very high radiative efficiency and a wealth of discrete spectral transitions illuminating the symmetry of the localized excitonic trap state. We will present a comparative study of nitrogen and bismuth isoelectronic traps in GaP. Research was supported by the U. S. Department of Energy, Basic Energy Sciences, Materials Sciences and Engineering Division under contract DE-AC36-08GO28308 and by the Department of Energy Office of Science Graduate Fellowship Program (DOE SCGF), made possible in part by the American Recovery and Reinvestment Act of 2009, administered by ORISE-ORAU under contract no. DE-AC05-06OR23100.

  2. Clinical Applications of Gallium-68

    PubMed Central

    Banerjee, Sangeeta Ray; Pomper, Martin G.

    2013-01-01

    Gallium-68 is a positron-emitting radioisotope that is produced from a 68Ge/68Ga generator. As such it is conveniently used, decoupling radiopharmacies from the need for a cyclotron on site. Gallium-68-labeled peptides have been recognized as a new class of radiopharmaceuticals showing fast target localization and blood clearance. 68Ga-DOTATOC, 8Ga-DOTATATE, 68Ga-DOTANOC, are the most prominent radiopharmaceuticals currently in use for imaging and differentiating lesions of various somatostatin receptor subtypes, overexpressed in many neuroendocrine tumors. There has been a tremendous increase in the number of clinical studies with 68Ga over the past few years around the world, including within the United States. An estimated ~10,000 scans are being performed yearly in Europe at about 100 centers utilizing 68Ga-labeled somatostatin analogs within clinical trials. Two academic sites within the US have also begun to undertake human studies. This review will focus on the clinical experience of selected, well-established and recently applied 68Ga-labeled imaging agents used in nuclear medicine. PMID:23522791

  3. The gallium melting-point standard: its role in our temperature measurement system.

    PubMed

    Mangum, B W

    1977-01-01

    The latest internationally-adopted temperature scale, the International Practical Temperature Scale of 1968 (amended edition of 1975), is discussed in some detail and a brief description is given of its evolution. The melting point of high-purity gallium (stated to be at least 99.99999% pure) as a secondary temperature reference point is evaluated. I believe that this melting-point temperature of gallium should be adopted by the various medical professional societies and voluntary standards groups as the reaction temperature for enzyme reference methods in clinical enzymology. Gallium melting-point cells are available at the National Bureau of Standards as Standard Reference Material No. 1968.

  4. Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

    PubMed Central

    Griffiths, Robert I.; Gleeson, Michelle L.; Mikhael, Joseph; Danese, Mark D.

    2012-01-01

    Rituximab improves survival in follicular lymphoma (FL), but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER) registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P)) or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302–$28,643) and longer adjusted cumulative survival (0.18 years; 95% CI 0.10–0.27) over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531–296,337) per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years. PMID:22969803

  5. The global anthropogenic gallium system: determinants of demand, supply and efficiency improvements.

    PubMed

    Løvik, Amund N; Restrepo, Eliette; Müller, Daniel B

    2015-05-05

    Gallium has been labeled as a critical metal due to rapidly growing consumption, importance for low-carbon technologies such as solid state lighting and photovoltaics, and being produced only as a byproduct of other metals (mainly aluminum). The global system of primary production, manufacturing, use and recycling has not yet been described or quantified in the literature. This prevents predictions of future demand, supply and possibilities for efficiency improvements on a system level. We present a description of the global anthropogenic gallium system and quantify the system using a combination of statistical data and technical parameters. We estimated that gallium was produced from 8 to 21% of alumina plants in 2011. The most important applications of gallium are NdFeB permanent magnets, integrated circuits and GaAs/GaP-based light-emitting diodes, demanding 22-37%, 16-27%, and 11-21% of primary metal production, respectively. GaN-based light-emitting diodes and photovoltaics are less important, both with 2-6%. We estimated that 120-170 tons, corresponding to 40-60% of primary production, ended up in production wastes that were either disposed of or stored. While demand for gallium is expected to rise in the future, our results indicated that it is possible to increase primary production substantially with conventional technology, as well as improve the system-wide material efficiency.

  6. Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

    PubMed

    Takahashi, Kota; Saito, Kazuhide; Takahara, Shiro; Fuchinoue, Shohei; Yagisawa, Takashi; Aikawa, Atsushi; Watarai, Yoshihiko; Yoshimura, Norio; Tanabe, Kazunari; Morozumi, Kunio; Shimazu, Motohide

    2017-08-01

    Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

  7. Gallium-67 scintigraphy, bronchoalveolar lavage, and pathologic changes in patients with pulmonary sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abe, S.; Munakata, M.; Nishimura, M.

    1984-05-01

    The intensity of gallium-67 scintiscans, lymphocyte counts in bronchoalveolar lavage fluid, and pathologic changes were studied in 26 patients with untreated pulmonary sarcoidosis. Noncaseating granulomas were recognized with significantly greater frequency in stage 2 (80 percent; 8/10 cases) than in stage 1 (43 percent; 6/14 cases). Alveolitis showed little relation to the roentgenographic stage. There was a strong correlation between the intensity of gallium uptake in pulmonary parenchyma and the detection rate of granuloma; however, the detection rate of alveolitis was not statistically different from the intensity of gallium uptake. A highly significant correlation was revealed between the lymphocyte countsmore » in bronchoalveolar lavage fluid and the intensity of alveolitis. These observations suggest that the gallium uptake reflects mainly the presence of granuloma, and the lymphocyte count in bronchoalveolar lavage fluid reflects the intensity of alveolitis in patients with pulmonary sarcoidosis.« less

  8. Measuring Nanoscale Heat Transfer for Gold-(Gallium Oxide)-Gallium Nitride Interfaces as a Function

    NASA Astrophysics Data System (ADS)

    Szwejkowski, Chester; Sun, Kai; Constantin, Costel; Giri, Ashutosh; Saltonstall, Christopher; Hopkins, Patrick; NanoSynCh Team; Exsite Team

    2014-03-01

    Gallium nitride (GaN) is considered the most important semiconductor after the discovery of Silicon. Understanding the properties of GaN is imperative in determining the utility and applicability of this class of materials to devices. We present results of time domain thermoreflectance (TDTR) measurements as a function of surface root mean square (RMS) roughness. We used commercially available 5mm x 5mm, single-side polished GaN (3-7 μm)/Sapphire (430 μm) substrates that have a Wurtzite crystal structure and are slightly n-type doped. The GaN substrates were annealed in the open atmosphere for 10 minutes (900-1000 °C). This high-temperature treatment produced RMS values from 1-60 nm and growth of gallium oxide (GaO) as measured with an atomic force microscopy and transmission electron microscopy respectively. A gold film (80nm) was deposited on the GaN surface using electron beam physical vapor deposition which was verified using ellipsometry and profilometry. The TDTR measurements suggest that the thermal conductivity decays exponentially with RMS roughness and that there is a minimum value for thermal boundary conductance at a roughness of 15nm.

  9. Evaluation of the male reproductive toxicity of gallium arsenide.

    PubMed

    Bomhard, Ernst M; Cohen, Samuel M; Gelbke, Heinz-Peter; Williams, Gary M

    2012-10-01

    Gallium arsenide is an important semiconductor material marketed in the shape of wafers and thus is not hazardous to the end user. Exposure to GaAs particles may, however, occur during manufacture and processing. Potential hazards require evaluation. In 14-week inhalation studies with small GaAs particles, testicular effects have been reported in rats and mice. These effects occurred only in animals whose lungs showed marked inflammation and also had hematologic changes indicating anemia and hemolysis. The time- and concentration-dependent progressive nature of the lung and blood effects together with bioavailability data on gallium and arsenic lead us to conclude that the testicular/sperm effects are secondary to hypoxemia resulting from lung damage rather than due to a direct chemical effect of gallium or arsenide. Conditions leading to such primary effects are not expected to occur in humans at production and processing sites. This has to be taken into consideration for any classification decision for reproductive toxicity; especially a category 1 according to the EU CLP system is not warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Native gallium adatoms discovered on atomically-smooth gallium nitride surfaces at low temperature.

    PubMed

    Alam, Khan; Foley, Andrew; Smith, Arthur R

    2015-03-11

    In advanced compound semiconductor devices, such as in quantum dot and quantum well systems, detailed atomic configurations at the growth surfaces are vital in determining the structural and electronic properties. Therefore, it is important to investigate the surface reconstructions in order to make further technological advancements. Usually, conventional semiconductor surfaces (e.g., arsenides, phosphides, and antimonides) are highly reactive due to the existence of a high density of group V (anion) surface dangling bonds. However, in the case of nitrides, group III rich growth conditions in molecular beam epitaxy are usually preferred leading to group III (Ga)-rich surfaces. Here, we use low-temperature scanning tunneling microscopy to reveal a uniform distribution of native gallium adatoms with a density of 0.3%-0.5% of a monolayer on the clean, as-grown surface of nitrogen polar GaN(0001̅) having the centered 6 × 12 reconstruction. Unseen at room temperature, these Ga adatoms are strongly bound to the surface but move with an extremely low surface diffusion barrier and a high density saturation coverage in thermodynamic equilibrium with Ga droplets. Furthermore, the Ga adatoms reveal an intrinsic surface chirality and an asymmetric site occupation. These observations can have important impacts in the understanding of gallium nitride surfaces.

  11. An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica.

    PubMed

    Collongues, Nicolas; de Seze, Jérôme

    2016-05-01

    Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future.

  12. Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study.

    PubMed

    Wang, Xuejuan; Yang, Zhi; Lin, Baohe; Zhang, Yan; Zhai, Shizhen; Zhao, Qichao; Xie, Qing; Liu, Fei; Han, Xuedi; Li, Jinfeng; Ouyang, Tao

    2016-06-21

    We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection. 99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection. The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively. 99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.

  13. Control of Defects in Aluminum Gallium Nitride ((Al)GaN) Films on Grown Aluminum Nitride (AlN) Substrates

    DTIC Science & Technology

    2013-02-01

    Nord, J.; Albe, K.; Erhart, P.; Nordlund, K. Modelling of Compound Semiconductors: Analytical Bond-order Potential for Gallium , Nitrogen and Gallium ...Control of Defects in Aluminum Gallium Nitride ((Al)GaN) Films on Grown Aluminum Nitride (AlN) Substrates by Iskander G. Batyrev, Chi-Chin Wu...Aluminum Gallium Nitride ((Al)GaN) Films on Grown Aluminum Nitride (AlN) Substrates Iskander G. Batyrev and N. Scott Weingarten Weapons and

  14. Extrapulmonary localization of gallium in sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rohatgi, P.K.; Singh, R.; Vieras, F.

    1987-01-01

    This paper describes the spectrum of extrapulmonary localization of gallium in patients with sarcoidosis. The usefulness of Ga-67 scintiscans in detecting clinically occult lesions, in directing clinicians to accessible sites for biopsy, and in following the course of extrapulmonary sites of involvement with therapy is emphasized.

  15. Gallium nitride junction field-effect transistor

    DOEpatents

    Zolper, J.C.; Shul, R.J.

    1999-02-02

    An ion implanted gallium-nitride (GaN) junction field-effect transistor (JFET) and method of making the same are disclosed. Also disclosed are various ion implants, both n- and p-type, together with or without phosphorus co-implantation, in selected III-V semiconductor materials. 19 figs.

  16. Phase 2 trial of bortezomib in combination with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with bortezomib, rituximab, methotrexate, and cytarabine for untreated mantle cell lymphoma.

    PubMed

    Romaguera, Jorge E; Wang, Michael; Feng, Lei; Fayad, Luis E; Hagemeister, Frederick; McLaughlin, Peter; Rodriguez, M Alma; Fanale, Michelle; Orlowski, Robert; Kwak, Larry W; Neelapu, Sattva; Oki, Yasuhiro; Pro, Barbara; Younes, Anas; Samaniego, Felipe; Fowler, Nathan; Hartig, Kimberly; Valentinetti, Marisa; Smith, Judy; Ford, Peggy; Naig, Adam; Medeiros, L Jeffrey; Kantarjian, Hagop M; Goy, Andre

    2018-05-03

    Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or synergistic effects in preclinical trials with known effective agents. This is a report of a prospective phase 2 trial of bortezomib added to rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (BzR-hyperCVAD)/rituximab, high-dose methotrexate, and high-dose cytarabine (BzR-MA) for 95 patients with newly diagnosed MCL. The overall and complete response rates were 100% and 82%, respectively. Hematologic toxicity was high but expected and did not lead to an increased incidence of neutropenic fever or dose reductions in comparison with a similar reported regimen without bortezomib. After a median follow-up of 44 months, the median overall survival had not been reached, and the time to treatment failure (TTF) was 55 months, which is not different from that of historical controls. BzR-hyperCVAD/BzR-MA at the dose and schedule studied produced high rates of response and a TTF similar to that of historical reports without bortezomib. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  17. Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with ⁹⁰Y and ¹¹¹In for domestic radioimmunotherapy and radioscintigraphy of non-Hodgkin's lymphoma.

    PubMed

    Gholipour, Nazila; Jalilian, Amir Reza; Khalaj, Ali; Johari-Daha, Fariba; Yavari, Kamal; Sabzevari, Omid; Khanchi, Ali Reza; Akhlaghi, Mehdi

    2014-07-29

    On the basis of results of our previous investigations on 90Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin's Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with 111In and 90Y was investigated. 111In and 90Y with high radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear reaction and a locally developed 90Sr/90Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with 111In and 90Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of 90Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL

  18. Short-term effects of a high nitrate diet on nitrate metabolism in healthy individuals.

    PubMed

    Bondonno, Catherine P; Liu, Alex H; Croft, Kevin D; Ward, Natalie C; Puddey, Ian B; Woodman, Richard J; Hodgson, Jonathan M

    2015-03-12

    Dietary nitrate, through the enterosalivary nitrate-nitrite-NO pathway, can improve blood pressure and arterial stiffness. How long systemic nitrate and nitrite remain elevated following cessation of high nitrate intake is unknown. In 19 healthy men and women, the time for salivary and plasma nitrate and nitrite to return to baseline after 7 days increased nitrate intake from green leafy vegetables was determined. Salivary and plasma nitrate and nitrite was measured at baseline [D0], end of high nitrate diet [D7], day 9 [+2D], day 14 [+7D] and day 21 [+14D]. Urinary nitrite and nitrate was assessed at D7 and +14D. Increased dietary nitrate for 7 days resulted in a more than fourfold increase in saliva and plasma nitrate and nitrite (p < 0.001) measured at [D7]. At [+2D] plasma nitrite and nitrate had returned to baseline while saliva nitrate and nitrite were more than 1.5 times higher than at baseline levels. By [+7D] all metabolites had returned to baseline levels. The pattern of response was similar between men and women. Urinary nitrate and nitrate was sevenfold higher at D7 compared to +14D. These results suggest that daily ingestion of nitrate may be required to maintain the physiological changes associated with high nitrate intake.

  19. Short-Term Effects of a High Nitrate Diet on Nitrate Metabolism in Healthy Individuals

    PubMed Central

    Bondonno, Catherine P.; Liu, Alex H.; Croft, Kevin D.; Ward, Natalie C.; Puddey, Ian B.; Woodman, Richard J.; Hodgson, Jonathan M.

    2015-01-01

    Dietary nitrate, through the enterosalivary nitrate-nitrite-NO pathway, can improve blood pressure and arterial stiffness. How long systemic nitrate and nitrite remain elevated following cessation of high nitrate intake is unknown. In 19 healthy men and women, the time for salivary and plasma nitrate and nitrite to return to baseline after 7 days increased nitrate intake from green leafy vegetables was determined. Salivary and plasma nitrate and nitrite was measured at baseline [D0], end of high nitrate diet [D7], day 9 [+2D], day 14 [+7D] and day 21 [+14D]. Urinary nitrite and nitrate was assessed at D7 and +14D. Increased dietary nitrate for 7 days resulted in a more than fourfold increase in saliva and plasma nitrate and nitrite (p < 0.001) measured at [D7]. At [+2D] plasma nitrite and nitrate had returned to baseline while saliva nitrate and nitrite were more than 1.5 times higher than at baseline levels. By [+7D] all metabolites had returned to baseline levels. The pattern of response was similar between men and women. Urinary nitrate and nitrate was sevenfold higher at D7 compared to +14D. These results suggest that daily ingestion of nitrate may be required to maintain the physiological changes associated with high nitrate intake. PMID:25774606

  20. Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance.

    PubMed

    Thadani, Udho

    2014-08-01

    Nitrate therapy has been an effective treatment for ischemic heart disease for over 100 years. The anti-ischemic and exercise-promoting benefits of sublingually administered nitrates are well established. Nitroglycerin is indicated for the relief of an established attack of angina and for prophylactic use, but its effects are short lived. In an effort to increase the duration of beneficial effects, long-acting orally administered and topical applications of nitrates have been developed; however, following their continued or frequent daily use, patients soon develop tolerance to these long-acting nitrate preparations. Once tolerance develops, patients begin losing the protective effects of the long-acting nitrate therapy. By providing a nitrate-free interval, or declining nitrate levels at night, one can overcome or reduce the development of tolerance, but cannot provide 24-h anti-anginal and anti-ischemic protection. In addition, patients may be vulnerable to occurrence of rebound angina and myocardial ischemia during periods of absent nitrate levels at night and early hours of the morning, and worsening of exercise capacity prior to the morning dose of the medication. This has been a concern with nitroglycerin patches but not with oral formulations of isosorbide-5 mononitrates, and has not been adequately studied with isosorbide dinitrate. This paper describes problems associated with nitrate tolerance, reviews mechanisms by which nitrate tolerance and loss of efficacy develop, and presents strategies to avoid nitrate tolerance and maintain efficacy when using long-acting nitrate formulations.

  1. Characterization of Gallium Indium Phosphide and Progress of Aluminum Gallium Indium Phosphide System Quantum-Well Laser Diode.

    PubMed

    Hamada, Hiroki

    2017-07-28

    Highly ordered gallium indium phosphide layers with the low bandgap have been successfully grown on the (100) GaAs substrates, the misorientation toward [01-1] direction, using the low-pressure metal organic chemical vapor deposition method. It is found that the optical properties of the layers are same as those of the disordered ones, essentially different from the ordered ones having two orientations towards [1-11] and [11-1] directions grown on (100) gallium arsenide substrates, which were previously reported. The bandgap at 300 K is 1.791 eV. The value is the smallest ever reported, to our knowledge. The high performance transverse stabilized AlGaInP laser diodes with strain compensated quantum well structure, which is developed in 1992, have been successfully obtained by controlling the misorientation angle and directions of GaAs substrates. The structure is applied to quantum dots laser diodes. This paper also describes the development history of the quantum well and the quantum dots laser diodes, and their future prospects.

  2. Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine.

    PubMed

    Mandrik, Olena; Corro Ramos, Isaac; Knies, Saskia; Al, Maiwenn; Severens, Johan L

    2015-01-01

    The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC) for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER) for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars) of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER. Furthermore, probabilistic sensitivity analyses have shown that for refractory/relapsed patients the probability of FCR being cost-effective is higher than for treatment-naïve patients and is close to one if the threshold is higher than US$15,000. State coverage of rituximab treatment may be considered a cost-effective treatment for the Ukrainian population under conditions of economic

  3. Influence of novel gallium complexes on the homeostasis of some biochemical and hematological parameters in rats.

    PubMed

    Gârban, Gabriela; Silaghi-Dumitrescu, Radu; Ioniţă, Hortensia; Gârban, Zeno; Hădărugă, Nicoleta-Gabriela; Ghibu, George-Daniel; Baltă, Cornel; Simiz, Florin-Dan; Mitar, Carmen

    2013-12-01

    The aim of this study was to detect possible homeostasis changes in some biochemical and hematological parameters after the administration of gallium (Ga) complexes C (24) and C (85) on an experimental animal model (Wistar strain rats). In order to observe chronobiological aspects, a morning (m) and an evening (e) animal series were constituted. Further on, each series were divided into three groups: control (C), experimental I (EI), and experimental II (EII). Both Ga complexes were solubilized in a carrier solution containing polyethylene glycol (PEG) 400, water, and ethanol. Animals of the C groups received the carrier solution by intraperitoneal injection, those from the EI groups received the solubilized C(24) gallium complex, and those of the EII groups received the solubilized C(85) gallium complex. At the end of the experiment, blood and tissue samples were taken and the following parameters were determined: serum concentration of the nonprotein nitrogenous compounds (uric acid, creatinine, and blood urea nitrogen), hematological parameters (erythrocytes, hemoglobin, leukocytes, and platelets), and the kidney tissue concentration of three essential trace elements (Fe, Cu, and Zn). With the exception of uric acid, the results revealed increased concentrations of the nonprotein nitrogenous compounds both in the morning and in the evening experimental groups. Hematological data showed increased levels of erythrocytes, hemoglobin, and leukocytes and decreased platelet levels in the experimental group given the C(24) gallium complex in the morning (EI-m) group; increased levels of leukocytes and decreased levels of the other parameters in the experimental group given the C(24) gallium complex in the evening (EI-e) group; and increased levels of all hematological parameters in the experimental groups receiving the C(85) gallium complex in the morning (EII-m) group and in the evening (EII-e) group. Decreased kidney tissue concentrations of metals were found in all

  4. The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB).

    PubMed

    Fernández-Nebro, A; Marenco, J L; López-Longo, F; Galindo, M; Hernández-Cruz, B E; Narváez, J; Rúa-Figueroa, I; Raya-Alvarez, E; Zea, A; Freire, M; Sánchez-Atrio, A I; García-Vicuña, R; Pego-Reigosa, J M; Manrique-Arija, S; Nieves-Martín, L; Carreño, L

    2014-09-01

    Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100 mg/dl (34%) and a high-density lipoprotein (HDL) level of <50 mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (p=0.001) and with TC (p=0.005) and TGs (p<0.001) at the end of the follow-up period. Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. Fabrication methods and applications of microstructured gallium based liquid metal alloys

    NASA Astrophysics Data System (ADS)

    Khondoker, M. A. H.; Sameoto, D.

    2016-09-01

    This review contains a comparative study of reported fabrication techniques of gallium based liquid metal alloys embedded in elastomers such as polydimethylsiloxane or other rubbers as well as the primary challenges associated with their use. The eutectic gallium-indium binary alloy (EGaIn) and gallium-indium-tin ternary alloy (galinstan) are the most common non-toxic liquid metals in use today. Due to their deformability, non-toxicity and superior electrical conductivity, these alloys have become very popular among researchers for flexible and reconfigurable electronics applications. All the available manufacturing techniques have been grouped into four major classes. Among them, casting by needle injection is the most widely used technique as it is capable of producing features as small as 150 nm width by high-pressure infiltration. One particular fabrication challenge with gallium based liquid metals is that an oxide skin is rapidly formed on the entire exposed surface. This oxide skin increases wettability on many surfaces, which is excellent for keeping patterned metal in position, but is a drawback in applications like reconfigurable circuits, where the position of liquid metal needs to be altered and controlled accurately. The major challenges involved in many applications of liquid metal alloys have also been discussed thoroughly in this article.

  6. New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance.

    PubMed

    Daiber, A; Wenzel, P; Oelze, M; Münzel, T

    2008-01-01

    Organic nitrates still represent a group of very effective anti-ischemic drugs used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. Long-term therapy with organic nitrates, however, results in a rapid development of nitrate tolerance blunting their hemodynamic and antiischemic efficacy. Recent studies revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role for the development of nitrate and crosstolerance. The present review focuses firstly on the role of ALDH-2 for organic nitrate bioactivation and secondly on the role of oxidative stress in the development of tolerance and cross-tolerance (endothelial dysfunction) in response to various organic nitrates. Finally, we would like to draw the reader's attention to the protective properties of the organic nitrate pentaerithrityl tetranitrate (PETN), which, in contrast to all other organic nitrates, is able to upregulate enzymes with a strong antioxidative capacity thereby preventing tolerance and the development of endothelial dysfunction.

  7. Nitrate transport is independent of NADH and NAD(P)H nitrate reductases in barley seedlings

    NASA Technical Reports Server (NTRS)

    Warner, R. L.; Huffaker, R. C.

    1989-01-01

    Barley (Hordeum vulgare L.) has NADH-specific and NAD(P)H-bispecific nitrate reductase isozymes. Four isogenic lines with different nitrate reductase isozyme combinations were used to determine the role of NADH and NAD(P)H nitrate reductases on nitrate transport and assimilation in barley seedlings. Both nitrate reductase isozymes were induced by nitrate and were required for maximum nitrate assimilation in barley seedlings. Genotypes lacking the NADH isozyme (Az12) or the NAD(P)H isozyme (Az70) assimilated 65 or 85%, respectively, as much nitrate as the wild type. Nitrate assimilation by genotype (Az12;Az70) which is deficient in both nitrate reductases, was only 13% of the wild type indicating that the NADH and NAD(P)H nitrate reductase isozymes are responsible for most of the nitrate reduction in barley seedlings. For all genotypes, nitrate assimilation rates in the dark were about 55% of the rates in light. Hypotheses that nitrate reductase has direct or indirect roles in nitrate uptake were not supported by this study. Induction of nitrate transporters and the kinetics of net nitrate uptake were the same for all four genotypes indicating that neither nitrate reductase isozyme has a direct role in nitrate uptake in barley seedlings.

  8. Do nitrates differ?

    PubMed Central

    Fung, H.-L.

    1992-01-01

    1 The organic nitrates all share a common biochemical and physiological mechanism of action. 2 The organic nitrates differ substantially in their pharmacologic potency and pharmacokinetics. In vitro potency differences appear larger than the corresponding in vivo activities. 3 The duration of action of organic nitrates, after a single immediate-release dose, is governed by the pharmacokinetics of the drug. However, the duration of action of available sustained-release preparations, whatever the nitrate or formulation, is limited to about 12 h, due to the development of pharmacologic tolerance. 4 Nitrates do not appear to differ in their production of undesirable effects. PMID:1633079

  9. The mobility of indium and gallium in groundwater systems: constraining the role of sorption in sand column experiments

    NASA Astrophysics Data System (ADS)

    Dror, I.; Ringering, K.; Yecheskel, Y.; Berkowitz, B.

    2017-12-01

    The mobility of indium and gallium in groundwater environments was studied via laboratory experiments using quartz sand as a porous medium. Indium and gallium are metals of very low abundance in the Earth's crust and, correspondingly, the biosphere is only adapted to very small concentrations of these elements. However, in modern semiconductor industries, both elements play a central role and are incorporated in devices of mass production such as smartphones and digital cameras. The resulting considerable increase in production, use and discharge of indium and gallium throughout the last two decades, with a continuous and fast increase in the near future, raises questions regarding the fate of both elements in the environment. However, the transport behavior of these two metals in soils and groundwater systems remains poorly understood to date. Because of the low solubility of both elements in aqueous solutions, trisodium citrate was used as a complexation agent to stabilize the solutions, enabling investigation of the transport of these metals at neutral pH. Column experiments showed different binding capacities for indium and gallium, where gallium is much more mobile compared to indium and both metals are substantially retarded in the column. Different affinities were also confirmed by examining sorption isotherms of indium and gallium in equilibrium batch systems. The effect of natural organic matter on the mobility of indium and gallium was also studied, by addition of humic acid. For both metals, the presence of humic acid affects the sorption dynamics: for indium, sorption is strongly inhibited leading to much higher mobility, whereas gallium showed a slightly higher sorption affinity and very similar mobility compared to the same setup without humic acid addition. However, in all cases, the binding capacity of gallium to quartz is much weaker than that of indium. These results are consistent with the assumption that indium and gallium form different types

  10. Phenolic aminocarboxylic acids as gallium-binding radiopharmaceuticals.

    PubMed

    Hunt, F C

    1984-06-01

    The phenolic aminocarboxylic acids ethylenediamine di [o-hydroxyphenylacetic acid] (EDDHA) and N,N'-bis [2-hydroxybenzyl] ethylenediamine N,N'-diacetic acid (HBED) form gallium complexes having high stability constants which enable them to resist exchange of gallium with plasma transferrin. 67Ga complexes were synthesized with these ligands, placing substituent groups in the phenolic ring to direct excretion via the renal or hepatobiliary route. The amount of 67Ga-Br-EDDHA excreted via the hepatobiliary route was comparable with that of some of the 99mTc agents. Excretion of 67Ga-Br-HBED was similar but with delayed transit from the liver. 67Ga COOH-EDDHA was excreted exclusively via the renal route. These findings provide a basis for developing new 67Ga or 68Ga radiopharmaceuticals, the latter for use in positron emission tomography, using these phenolic aminocarboxylates.

  11. Annotating MYC Status in Treatment-Resistant Metastatic Castration-Resistant Prostate Cancer With Gallium-68 Citrate PET

    DTIC Science & Technology

    2017-09-01

    ongoing and interim analysis is planned within the next 6 months. Planned analyses include: 1) correlation of gallium citrate uptake on PET with MYC...utility of Gallium citrate PET as a pharmacodynamic and predictive biomarker of MYC pathway inhibition in mCRPC. Correlative pre- and post-treatment...completed Milestone Achieved: Last patient completes study follow up scan 36 Not yet completed Assess correlation between SUVmax on gallium

  12. Tumoral calcinosis associated with sarcoidosis and positive bone and gallium imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wolpe, F.M.; Khedkar, N.Y.; Gordon, D.

    1987-07-01

    A 63-year-old female with biopsy proven tumoral calcinosis presented with progressive and recurrent swelling and tenderness of the right hip, thigh, elbow, and wrist. Both gallium and bone imaging demonstrated intense, congruent uptake in these areas. This is the third case of tumoral calcinosis with sarcoidosis documented in the literature. However, these are the first published bone and gallium scans in a patient with a history of sarcoidosis and tumoral calcinosis.

  13. Large disparity between gallium and antimony self-diffusion in gallium antimonide.

    PubMed

    Bracht, H; Nicols, S P; Walukiewicz, W; Silveira, J P; Briones, F; Haller, E E

    2000-11-02

    The most fundamental mass transport process in solids is self-diffusion. The motion of host-lattice ('self-') atoms in solids is mediated by point defects such as vacancies or interstitial atoms, whose formation and migration enthalpies determine the kinetics of this thermally activated process. Self-diffusion studies also contribute to the understanding of the diffusion of impurities, and a quantitative understanding of self- and foreign-atom diffusion in semiconductors is central to the development of advanced electronic devices. In the past few years, self-diffusion studies have been performed successfully with isotopically controlled semiconductor heterostructures of germanium, silicon, gallium arsenide and gallium phosphide. Self-diffusion studies with isotopically controlled GaAs and GaP have been restricted to Ga self-diffusion, as only Ga has two stable isotopes, 69Ga and 71Ga. Here we report self-diffusion studies with an isotopically controlled multilayer structure of crystalline GaSb. Two stable isotopes exist for both Ga and Sb, allowing the simultaneous study of diffusion on both sublattices. Our experiments show that near the melting temperature, Ga diffuses more rapidly than Sb by over three orders of magnitude. This surprisingly large difference in atomic mobility requires a physical explanation going beyond standard diffusion models. Combining our data for Ga and Sb diffusion with related results for foreign-atom diffusion in GaSb (refs 8, 9), we conclude that the unusually slow Sb diffusion in GaSb is a consequence of reactions between defects on the Ga and Sb sublattices, which suppress the defects that are required for Sb diffusion.

  14. The impact of gallium content on degradation, bioactivity, and antibacterial potency of zinc borate bioactive glass.

    PubMed

    Rahimnejad Yazdi, Alireza; Torkan, Lawrence; Stone, Wendy; Towler, Mark R

    2018-01-01

    Zinc borate glasses with increasing gallium content (0, 2.5, 5, 10, and 15 Wt % Ga) were synthesized and their degradation, bioactivity in simulated body fluid (SBF), and antibacterial properties were investigated. ICP measurements showed that increased gallium content in the glass resulted in increased gallium ion release and decreased release of other ions. Degradability declined with the addition of gallium, indicating the formation of more symmetric BO 3 units with three bridging oxygens and asymmetric BO 3 units with two bridging oxygens in the glass network as the gallium content in the series increased. The formation of amorphous CaP on the glass surface after 24 h of incubation in SBF was confirmed by SEM, XRD, and FTIR analyses. Finally, antibacterial evaluation of the glasses using the agar disc-diffusion method demonstrated that the addition of gallium increased the antibacterial potency of the glasses against P. aeruginosa (Gram-negative) while decreasing it against S. epidermidis (Gram-positive); considering the ion release trends, this indicates that the gallium ion is responsible for the glasses' antibacterial behavior against P. aeruginosa while the zinc ion controls the antibacterial activity against S. epidermidis. The statistical significance of the observed trends in the measurements were confirmed by applying the Kruskal-Wallis H Test. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 367-376, 2018. © 2017 Wiley Periodicals, Inc.

  15. Solar cell with a gallium nitride electrode

    DOEpatents

    Pankove, Jacques I.

    1979-01-01

    A solar cell which comprises a body of silicon having a P-N junction therein with a transparent conducting N-type gallium nitride layer as an ohmic contact on the N-type side of the semiconductor exposed to solar radiation.

  16. Gallium phosphide energy converters

    NASA Technical Reports Server (NTRS)

    Sims, P. E.; DiNetta, Louis C.; DuganCavanagh, K.; Goetz, M. A.

    1996-01-01

    Betavoltaic power supplies based on gallium phosphide can supply long term low-level power with high reliability. Results are presented for GaP devices powered by Ni-63 and tritiarated phosphors. Leakage currents as low as 1.2 x 10(exp -17) A/cm(exp 2) have been measured and the temperature dependence of the reverse saturation current is found to have ideal behavior. A small demonstration system has been assembled that generates and stores enough electricity to light up an LED.

  17. Gallium nitride nanotube lasers

    DOE PAGES

    Li, Changyi; Liu, Sheng; Hurtado, Antonio; ...

    2015-01-01

    Lasing is demonstrated from gallium nitride nanotubes fabricated using a two-step top-down technique. By optically pumping, we observed characteristics of lasing: a clear threshold, a narrow spectral, and guided emission from the nanotubes. In addition, annular lasing emission from the GaN nanotube is also observed, indicating that cross-sectional shape control can be employed to manipulate the properties of nanolasers. The nanotube lasers could be of interest for optical nanofluidic applications or application benefitting from a hollow beam shape.

  18. Arabidopsis Nitrate Transporter NRT1.9 Is Important in Phloem Nitrate Transport[W][OA

    PubMed Central

    Wang, Ya-Yun; Tsay, Yi-Fang

    2011-01-01

    This study of the Arabidopsis thaliana nitrate transporter NRT1.9 reveals an important function for a NRT1 family member in phloem nitrate transport. Functional analysis in Xenopus laevis oocytes showed that NRT1.9 is a low-affinity nitrate transporter. Green fluorescent protein and β-glucuronidase reporter analyses indicated that NRT1.9 is a plasma membrane transporter expressed in the companion cells of root phloem. In nrt1.9 mutants, nitrate content in root phloem exudates was decreased, and downward nitrate transport was reduced, suggesting that NRT1.9 may facilitate loading of nitrate into the root phloem and enhance downward nitrate transport in roots. Under high nitrate conditions, the nrt1.9 mutant showed enhanced root-to-shoot nitrate transport and plant growth. We conclude that phloem nitrate transport is facilitated by expression of NRT1.9 in root companion cells. In addition, enhanced root-to-shoot xylem transport of nitrate in nrt1.9 mutants points to a negative correlation between xylem and phloem nitrate transport. PMID:21571952

  19. Anticancer redox activity of gallium nanoparticles accompanied with low dose of gamma radiation in female mice.

    PubMed

    Kandil, Eman I; El-Sonbaty, Sawsan M; Moawed, Fatma Sm; Khedr, Ola Ms

    2018-03-01

    Guided treatments with nanoparticles and radiotherapy are a new approach in cancer therapy. This study evaluated the beneficial antitumor effects of γ-radiation together with gallium nanoparticles against solid Ehrlich carcinoma in female mice. Gallium nanoparticles were biologically synthesized using Lactobacillus helveticus cells. Transmission electron microscopy showed gallium nanoparticles with size range of 8-20 nm. In vitro study of gallium nanoparticles on MCF-7 revealed IC 50 of 8.0 μg. Gallium nanoparticles (0.1 mg/kg body weight) were injected intraperitoneally daily on the seventh day of Ehrlich carcinoma cells inoculation. Whole-body γ-radiation was carried out at a single dose of 0.25 Gy on eighth day after tumor inoculation. Biochemical analysis showed that solid Ehrlich carcinoma induced a significant increase in alanine aminotransferase activity and creatinine level in serum, calcium, and iron concentrations in liver tissue compared to normal control. Treatment of Ehrlich carcinoma-bearing mice with gallium nanoparticles and/or low dose of γ-radiation exposure significantly reduced tumor volume, decreased alanine aminotransferase and creatinine levels in serum, increased lipid peroxidation, and decreased glutathione content as well as calcium and iron concentrations in liver and tumor tissues with intense DNA fragmentation accompanied compared to untreated tumor cells. Moreover, mitochondria in the treated groups displayed a significant increase in Na+/K+-ATPase, complexes II and III with significant reduction in CYP450 gene expression, which may indicate a synergistic effect of gallium nanoparticles and/or low dose of γ-radiation combination against Ehrlich carcinoma injury, and this results were well appreciated with the histopathological findings in the tumor tissue. We conclude that combined treatment of gallium nanoparticles and low dose of gamma-radiation resulted in suppressive induction of cytotoxic effects on cancer cells.

  20. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

    PubMed Central

    Vose, Julie M.; Kelly, Jennifer L.; Young, Faith; Bernstein, Steven H.; Peterson, Derick; Rich, Lynn; Blumel, Susan; Proia, Nicole K.; Liesveld, Jane; Fisher, Richard I.; Armitage, James O.; Grant, Steven; Leonard, John P.

    2011-01-01

    Given the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m2 days 1 and 4; rituximab 375 mg/m2 day 1, and bortezomib 1.3 mg/m2 days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00547534. PMID:21239695

  1. The incidence of biopsy-proven transformation in follicular lymphoma in the rituximab era. A retrospective analysis from the Czech Lymphoma Study Group (CLSG) database.

    PubMed

    Janikova, Andrea; Bortlicek, Zbynek; Campr, Vit; Kopalova, Natasa; Benesova, Katerina; Hamouzova, Michaela; Belada, David; Prochazka, Vit; Pytlik, Robert; Vokurka, Samuel; Pirnos, Jan; Duras, Juraj; Mocikova, Heidi; Mayer, Jiri; Trneny, Marek

    2018-04-01

    The aim of this study is to assess the incidence, risk factors, and outcome of biopsy-proven transformation in follicular lymphoma (FL) patients in the rituximab era. Transformation was analyzed in 1233 patients with initially diagnosed FL grades 1-3A, identified between 2002 and 2012 in the prospectively maintained Czech Lymphoma Study Group database. Only patients with histologically proven transformation (HT) were included. HT occurred in 58 cases at a median of 3.0 years from the initial FL diagnosis; the HT rate was 4% at 5 years. Transformation occurred most frequently at the first relapse (84% patients). Median OS from the HT was 2.5 years (95% CI 0.4-4.6) and 6-year OS with HT was shorter compared to all FLs (60 vs. 83.9%; 95% CI). A bulky tumor (≥ 10 cm), increased lactate dehydrogenase, age ≥ 60 years, and International Prognostic Index (intermediate/high risk), but not Follicular Lymphoma International Prognostic Index, were associated with transformation (p < 0.05). In the first line, 70% of patients received rituximab (including 36% rituximab maintenance), 57% CHOP-like regimens, and 2.6% of patients were treated with fludarabine-based therapy, whereas 11% of patients were watched only. The patients treated with R-CHOP in the first line (n = 591) showed the transformation rate at 5 years of 4.23% (95% CI 2.52-5.93); subsequent rituximab maintenance (n = 276) vs. observation (n = 153) was associated with a lower transformation rate (p.033; HR 3.29; CI 1.10-9.82). The transformation rate seems to be lower than in previous series, which may be influenced by broad use of rituximab, but prognosis of HT developed during therapy continues to be poor.

  2. Measurement of Minority Charge Carrier Diffusion Length in Gallium Nitride Nanowires Using Electron Beam Induced Current (EBIC)

    DTIC Science & Technology

    2009-12-01

    MINORITY CHARGE CARRIER DIFFUSION LENGTH IN GALLIUM NITRIDE NANOWIRES USING ELECTRON BEAM INDUCED CURRENT (EBIC) by Chiou Perng Ong December... Gallium Nitride Nanowires Using Electron Beam Induced Current (EBIC) 6. AUTHOR(S) Ong, Chiou Perng 5. FUNDING NUMBERS DMR 0804527 7. PERFORMING...CARRIER DIFFUSION LENGTH IN GALLIUM NITRIDE NANOWIRES USING ELECTRON BEAM INDUCED CURRENT (EBIC) Chiou Perng Ong Major, Singapore Armed Forces B

  3. Efficient water reduction with gallium phosphide nanowires

    PubMed Central

    Standing, Anthony; Assali, Simone; Gao, Lu; Verheijen, Marcel A.; van Dam, Dick; Cui, Yingchao; Notten, Peter H. L.; Haverkort, Jos E. M.; Bakkers, Erik P. A. M.

    2015-01-01

    Photoelectrochemical hydrogen production from solar energy and water offers a clean and sustainable fuel option for the future. Planar III/V material systems have shown the highest efficiencies, but are expensive. By moving to the nanowire regime the demand on material quantity is reduced, and new materials can be uncovered, such as wurtzite gallium phosphide, featuring a direct bandgap. This is one of the few materials combining large solar light absorption and (close to) ideal band-edge positions for full water splitting. Here we report the photoelectrochemical reduction of water, on a p-type wurtzite gallium phosphide nanowire photocathode. By modifying geometry to reduce electrical resistance and enhance optical absorption, and modifying the surface with a multistep platinum deposition, high current densities and open circuit potentials were achieved. Our results demonstrate the capabilities of this material, even when used in such low quantities, as in nanowires. PMID:26183949

  4. Radiolabeling of rituximab with (188)Re and (99m)Tc using the tricarbonyl technology.

    PubMed

    Dias, Carla Roberta; Jeger, Simone; Osso, João Alberto; Müller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

    2011-01-01

    The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20(+) B-cell tumors. Rituximab radiolabeled with β(-) emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the (99m)Tc- and (188)Re-tricarbonyl core (IsoLink technology). The native format of the antibody (RTX(wt)) as well as a reduced form (RTX(red)) was labeled with (99m)Tc/(188)Re(CO)(3). The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. The radiolabeling efficiency and kinetics of RTX(red) were superior to that of RTX(wt) ((99m)Tc: 98% after 3 h for RTX(red) vs. 70% after 24 h for RTX(wt)). (99m)Tc(CO)(3)-RTX(red) was used without purification for in vitro and in vivo studies whereas (188)Re(CO)(3)-RTX(red) was purified to eliminate free (188)Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 °C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of (99m)Tc(CO)(3)-RTX(red) but not with pre-purified (188)Re(CO)(3)-RTX(red). Both conjugates revealed high binding affinity to the CD20 antigen (K(d) = 5-6 nM). Tumor uptake of (188)Re(CO)(3)-RTX(red) was 2.5 %ID/g and 0.8 %ID/g for (99m)Tc(CO)(3)-RTX(red) 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for (99m)Tc(CO)(3)-RTX(red) and for (188)Re(CO)(3)-RTX

  5. Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(-)-myrtenol nitrate.

    PubMed

    Bew, Sean P; Hiatt-Gipson, Glyn D; Mills, Graham P; Reeves, Claire E

    2016-01-01

    Here we report the chemoselective synthesis of several important, climate relevant isoprene nitrates using silver nitrate to mediate a 'halide for nitrate' substitution. Employing readily available starting materials, reagents and Horner-Wadsworth-Emmons chemistry the synthesis of easily separable, synthetically versatile 'key building blocks' (E)- and (Z)-3-methyl-4-chlorobut-2-en-1-ol as well as (E)- and (Z)-1-((2-methyl-4-bromobut-2-enyloxy)methyl)-4-methoxybenzene has been achieved using cheap, 'off the shelf' materials. Exploiting their reactivity we have studied their ability to undergo an 'allylic halide for allylic nitrate' substitution reaction which we demonstrate generates (E)- and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate, and (E)- and (Z)-2-methyl-4-hydroxybut-2-enyl nitrates ('isoprene nitrates') in 66-80% overall yields. Using NOESY experiments the elucidation of the carbon-carbon double bond configuration within the purified isoprene nitrates has been established. Further exemplifying our 'halide for nitrate' substitution chemistry we outline the straightforward transformation of (1R,2S)-(-)-myrtenol bromide into the previously unknown monoterpene nitrate (1R,2S)-(-)-myrtenol nitrate.

  6. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

    PubMed

    Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

    2017-02-01

    Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m 2 in month 1 and 500 mg/m 2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract

  7. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

    PubMed Central

    Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

    2017-01-01

    Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities

  8. Greater-than-bulk melting temperatures explained: Gallium melts Gangnam style

    NASA Astrophysics Data System (ADS)

    Gaston, Nicola; Steenbergen, Krista

    2014-03-01

    The experimental discovery of superheating in gallium clusters contradicted the clear and well-demonstrated paradigm that the melting temperature of a particle should decrease with its size. However the extremely sensitive dependence of melting temperature on size also goes to the heart of cluster science, and the interplay between the effects of electronic and geometric structure. We have performed extensive first-principles molecular dynamics calculations, incorporating parallel tempering for an efficient exploration of configurational phase space. This is necessary, due to the complicated energy landscape of gallium. In the nanoparticles, melting is preceded by a transitions between phases. A structural feature, referred to here as the Gangnam motif, is found to increase with the latent heat and appears throughout the observed phase changes of this curious metal. We will present our detailed analysis of the solid-state isomers, performed using extensive statistical sampling of the trajectory data for the assignment of cluster structures to known phases of gallium. Finally, we explain the greater-than-bulk melting through analysis of the factors that stabilise the liquid structures.

  9. Nitrate Transport Is Independent of NADH and NAD(P)H Nitrate Reductases in Barley Seedlings 1

    PubMed Central

    Warner, Robert L.; Huffaker, Ray C.

    1989-01-01

    Barley (Hordeum vulgare L.) has NADH-specific and NAD(P)H-bispecific nitrate reductase isozymes. Four isogenic lines with different nitrate reductase isozyme combinations were used to determine the role of NADH and NAD(P)H nitrate reductases on nitrate transport and assimilation in barley seedlings. Both nitrate reductase isozymes were induced by nitrate and were required for maximum nitrate assimilation in barley seedlings. Genotypes lacking the NADH isozyme (Az12) or the NAD(P)H isozyme (Az70) assimilated 65 or 85%, respectively, as much nitrate as the wild type. Nitrate assimilation by genotype (Az12;Az70) which is deficient in both nitrate reductases, was only 13% of the wild type indicating that the NADH and NAD(P)H nitrate reductase isozymes are responsible for most of the nitrate reduction in barley seedlings. For all genotypes, nitrate assimilation rates in the dark were about 55% of the rates in light. Hypotheses that nitrate reductase has direct or indirect roles in nitrate uptake were not supported by this study. Induction of nitrate transporters and the kinetics of net nitrate uptake were the same for all four genotypes indicating that neither nitrate reductase isozyme has a direct role in nitrate uptake in barley seedlings. PMID:11537465

  10. Epitaxial gallium arsenide wafers

    NASA Technical Reports Server (NTRS)

    Black, J. F.; Robinson, L. B.

    1971-01-01

    The preparation of GaAs epitaxial layers by a vapor transport process using AsCl3, Ga and H2 was pursued to provide epitaxial wafers suitable for the fabrication of transferred electron oscillators and amplifiers operating in the subcritical region. Both n-n(+) structures, and n(++)-n-n(+) sandwich structures were grown using n(+) (Si-doped) GaAs substrates. Process variables such as the input AsCl3 concentration, gallium temperature, and substrate temperature and temperature gradient and their effects on properties are presented and discussed.

  11. Contribution of atmospheric nitrate to stream-water nitrate in Japanese coniferous forests revealed by the oxygen isotope ratio of nitrate.

    PubMed

    Tobari, Y; Koba, K; Fukushima, K; Tokuchi, N; Ohte, N; Tateno, R; Toyoda, S; Yoshioka, T; Yoshida, N

    2010-05-15

    Evaluation of the openness of the nitrogen (N) cycle in forest ecosystems is important in efforts to improve forest management because the N supply often limits primary production. The use of the oxygen isotope ratio (delta(18)O) of nitrate is a promising approach to determine how effectively atmospheric nitrate can be retained in a forest ecosystem. We investigated the delta(18)O of nitrate in stream water in order to estimate the contribution of atmospheric NO(3) (-) in stream-water NO(3) (-) (f(atm)) from 26 watersheds with different stand ages (1-87 years) in Japan. The stream-water nitrate concentrations were high in young forests whereas, in contrast, old forests discharged low-nitrate stream water. These results implied a low f(atm) and a closed N cycle in older forests. However, the delta(18)O values of nitrate in stream water revealed that f(atm) values were higher in older forests than in younger forests. These results indicated that even in old forests, where the discharged N loss was small, atmospheric nitrate was not retained effectively. The steep slopes of the studied watersheds (>40 degrees ) which hinder the capturing of atmospheric nitrate by plants and microbes might be responsible for the inefficient utilization of atmospheric nitrate. Moreover, the unprocessed fraction of atmospheric nitrate in the stream-water nitrate in the forest (f(unprocessed)) was high in the young forest (78%), although f(unprocessed) was stable and low for other forests (5-13%). This high f(unprocessed) of the young forest indicated that the young forest retained neither atmospheric NO(3) (-) nor soil NO(3) (-) effectively, engendering high stream-water NO(3) (-) concentrations. Copyright (c) 2010 John Wiley & Sons, Ltd.

  12. Proton Irradiation-Induced Metal Voids in Gallium Nitride High Electron Mobility Transistors

    DTIC Science & Technology

    2015-09-01

    13. ABSTRACT (maximum 200 words) Gallium nitride/aluminum gallium nitride high electron mobility transistors with nickel/ gold (Ni/Au) and...platinum/ gold (Pt/Au) gating are irradiated with 2 MeV protons. Destructive physical analysis revealed material voids underneath the gate finger of the...nickel/ gold (Ni/Au) and platinum/ gold (Pt/Au) gating are irradiated with 2 MeV protons. Destructive physical analysis revealed material voids underneath

  13. Novel ethylenediamine-gallium phosphate containing 6-fold coordinated gallium atoms with unusual four equatorial Ga–N bonds

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Torre-Fernández, Laura; Espina, Aránzazu; Khainakov, Sergei A.

    2014-07-01

    A novel ethylenediamine-gallium phosphate, formulated as Ga(H{sub 2}NCH{sub 2}CH{sub 2}NH{sub 2}){sub 2}PO{sub 4}·2H{sub 2}O, was synthesized under hydrothermal conditions. The crystal structure, including hydrogen positions, was determined using single-crystal X-ray diffraction data (monoclinic, a=9.4886(3) Å, b=6.0374(2) Å, c=10.2874(3) Å, and β=104.226(3)°, space group Pc) and the bulk was characterized by chemical (Ga–P–C–H–N) and thermal analysis (TG–MS and DSC), including activation energy data of its thermo-oxidative degradation, powder X-ray diffraction (PXRD), solid-state nuclear magnetic resonance (SS-NMR) measurements, and transmission electron microscopy (TEM, SAED/NBD, and STEM BF-EDX). The crystal structure is built up of infinite zig-zag chains running along the c-axis, formedmore » by vertex-shared (PO{sub 4}) and (GaO{sub 2}N{sub 4}) polyhedra. The new compound is characterized by unusual four equatorial Ga–N bonds coming from two nonequivalent ethylenediamine molecules and exhibits strong blue emission at 430 nm (λ{sub ex}=350 nm) in the solid state at room temperature. - Graphical abstract: Single crystals of a new ethylenediamine-gallium phosphate, Ga(H{sub 2}NCH{sub 2}CH{sub 2}NH{sub 2}){sub 2}PO{sub 4}·2H{sub 2}O, were obtained and the structural features presented. This structure is one of the scarce examples of GaPO with Ga–N bonds reported. - Highlights: • A novel ethylenediamine-gallium phosphate was hydrothermally synthesized. • The new compound is characterized by unusual four equatorial Ga–N bonds. • Void-volume analysis shows cages and channels with sizes ideally suited to accommodate small molecules. • The new compound exhibits strong blue emission.« less

  14. Characterization of Gallium Indium Phosphide and Progress of Aluminum Gallium Indium Phosphide System Quantum-Well Laser Diode

    PubMed Central

    Hamada, Hiroki

    2017-01-01

    Highly ordered gallium indium phosphide layers with the low bandgap have been successfully grown on the (100) GaAs substrates, the misorientation toward [01−1] direction, using the low-pressure metal organic chemical vapor deposition method. It is found that the optical properties of the layers are same as those of the disordered ones, essentially different from the ordered ones having two orientations towards [1−11] and [11−1] directions grown on (100) gallium arsenide substrates, which were previously reported. The bandgap at 300 K is 1.791 eV. The value is the smallest ever reported, to our knowledge. The high performance transverse stabilized AlGaInP laser diodes with strain compensated quantum well structure, which is developed in 1992, have been successfully obtained by controlling the misorientation angle and directions of GaAs substrates. The structure is applied to quantum dots laser diodes. This paper also describes the development history of the quantum well and the quantum dots laser diodes, and their future prospects. PMID:28773227

  15. Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes.

    PubMed

    Herold, Kevan C; Pescovitz, Mark D; McGee, Paula; Krause-Steinrauf, Heidi; Spain, Lisa M; Bourcier, Kasia; Asare, Adam; Liu, Zhugong; Lachin, John M; Dosch, H Michael

    2011-08-15

    Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

  16. An unexpected truth: increasing nitrate loading can decrease nitrate export from watersheds

    NASA Astrophysics Data System (ADS)

    Askarizadeh Bardsiri, A.; Grant, S. B.; Rippy, M.

    2015-12-01

    The discharge of anthropogenic nitrate (e.g., from partially treated sewage, return flows from agricultural irrigation, and runoff from animal feeding operations) to streams can negatively impact both human and ecosystem health. Managing these many point and non-point sources to achieve some specific end-point—for example, reducing the annual mass of nitrate exported from a watershed—can be a challenge, particularly in rapidly growing urban areas. Adding to this complexity is the fact that streams are not inert: they too can add or remove nitrate through assimilation (e.g., by stream-associated plants and animals) and microbially-mediated biogeochemical reactions that occur in streambed sediments (e.g., respiration, ammonification, nitrification, denitrification). By coupling a previously published correlation for in-stream processing of nitrate [Mulholland et al., Nature, 2008, 452, 202-205] with a stream network model of the Jacksons Creek watershed (Victoria, Australia) I demonstrate that managing anthropogenic sources of stream nitrate without consideration of in-stream processing can result in a number of non-intuitive "surprises"; for example, wastewater effluent discharges that increase nitrate loading but decrease in-stream nitrate concentrations can reduce the mass of nitrate exported from a watershed.

  17. Nitration of naphthalene and remarks on the mechanism of electrophilic aromatic nitration.

    PubMed

    Olah, G A; Narang, S C; Olah, J A

    1981-06-01

    Naphthalene was nitrated with a variety of nitrating agents. Comparison of data with Perrin's electrochemical nitration [Perrin, C. L. (1977) J. Am. Chem. Soc. 99, 5516-5518] shows that nitration of naphthalene gives an alpha-nitronaphthalene to beta-nitronaphthalene ratio that varies between 9 and 29 and is thus not constant. Perrin's data, therefore, are considered to be inconclusive evidence for the proposed one-electron transfer mechanism for the nitration of naphthalene and other reactive aromatics. Moodie and Schoefield [Hoggett, J. G., Moodie, R. B., Penton, J. R. & Schoefield, K. (1971) Nitration and Aromatic Reactivity (Cambridge Univ. Press, London)], as well as Perrin, independently concluded that, in the general scheme of nitration of reactive aromatics, there is the necessity to introduce into the classical Ingold mechanism an additional step involving a distinct intermediate preceding the formation of the Wheland intermediate (sigma complexes). This view coincides with our two-step mechanistic picture [Kuhn, S. J. & Olah, G. A. (1961) J. Am. Chem. Soc. 83, 4564-4571] of the nitronium salt nitration of aromatic hydrocarbons (including benzene and toluene), in which low substrate selectivity but high positional selectivity was found, indicating the independence of substrate from positional selectivity.

  18. Nitration of naphthalene and remarks on the mechanism of electrophilic aromatic nitration*

    PubMed Central

    Olah, George A.; Narang, Subhash C.; Olah, Judith A.

    1981-01-01

    Naphthalene was nitrated with a variety of nitrating agents. Comparison of data with Perrin's electrochemical nitration [Perrin, C. L. (1977) J. Am. Chem. Soc. 99, 5516-5518] shows that nitration of naphthalene gives an α-nitronaphthalene to β-nitronaphthalene ratio that varies between 9 and 29 and is thus not constant. Perrin's data, therefore, are considered to be inconclusive evidence for the proposed one-electron transfer mechanism for the nitration of naphthalene and other reactive aromatics. Moodie and Schoefield [Hoggett, J. G., Moodie, R. B., Penton, J. R. & Schoefield, K. (1971) Nitration and Aromatic Reactivity (Cambridge Univ. Press, London)], as well as Perrin, independently concluded that, in the general scheme of nitration of reactive aromatics, there is the necessity to introduce into the classical Ingold mechanism an additional step involving a distinct intermediate preceding the formation of the Wheland intermediate (σ complexes). This view coincides with our two-step mechanistic picture [Kuhn, S. J. & Olah, G. A. (1961) J. Am. Chem. Soc. 83, 4564-4571] of the nitronium salt nitration of aromatic hydrocarbons (including benzene and toluene), in which low substrate selectivity but high positional selectivity was found, indicating the independence of substrate from positional selectivity. PMID:16593026

  19. Alkali metal nitrate purification

    DOEpatents

    Fiorucci, Louis C.; Morgan, Michael J.

    1986-02-04

    A process is disclosed for removing contaminants from impure alkali metal nitrates containing them. The process comprises heating the impure alkali metal nitrates in solution form or molten form at a temperature and for a time sufficient to effect precipitation of solid impurities and separating the solid impurities from the resulting purified alkali metal nitrates. The resulting purified alkali metal nitrates in solution form may be heated to evaporate water therefrom to produce purified molten alkali metal nitrates suitable for use as a heat transfer medium. If desired, the purified molten form may be granulated and cooled to form discrete solid particles of purified alkali metal nitrates.

  20. Ultra-low threshold gallium nitride photonic crystal nanobeam laser

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Niu, Nan, E-mail: nanniu@fas.harvard.edu; Woolf, Alexander; Wang, Danqing

    2015-06-08

    We report exceptionally low thresholds (9.1 μJ/cm{sup 2}) for room temperature lasing at ∼450 nm in optically pumped Gallium Nitride (GaN) nanobeam cavity structures. The nanobeam cavity geometry provides high theoretical Q (>100 000) with small modal volume, leading to a high spontaneous emission factor, β = 0.94. The active layer materials are Indium Gallium Nitride (InGaN) fragmented quantum wells (fQWs), a critical factor in achieving the low thresholds, which are an order-of-magnitude lower than obtainable with continuous QW active layers. We suggest that the extra confinement of photo-generated carriers for fQWs (compared to QWs) is responsible for the excellent performance.

  1. (Polyfluoroaryl) fluoroanions of aluminum, gallium, and indium of enhanced utility, uses thereof, and products based thereon

    DOEpatents

    Marks, Tobin J.; Chen, You-Xian

    2001-01-01

    The (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium are novel weakly coordinating anions which are highly fluorinated. (Polyfluoroaryl)fluoroanions of one such type contain at least one ring substituent other than fluorine. These (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium have greater solubility in organic solvents, or have a coordinative ability essentially equal to or less than that of the corresponding (polyfluoroaryl)fluoroanion of aluminum, gallium, or indium in which the substituent is replaced by fluorine. Another type of new (polyfluoroaryl)fluoroanion of aluminum, gallium, and indium have 1-3 perfluorinated fused ring groups and 2-0 perfluorophenyl groups. When used as a cocatalyst in the formation of novel catalytic complexes with d- or f-block metal compounds having at least one leaving group such as a methyl group, these anions, because of their weak coordination to the metal center, do not interfere in the ethylene polymerization process, while affecting the propylene process favorably, if highly isotactic polypropylene is desired. Thus, the (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium of this invention are useful in various polymerization processes such as are described.

  2. (Polyfluoroaryl) fluoroanions of aluminum, gallium, and indium of enhanced utility, uses thereof, and products based thereon

    DOEpatents

    Marks, Tobin J.; Chen, You-Xian

    2002-01-01

    The (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium are novel weakly coordinating anions which are highly fluorinated. (Polyfluoroaryl)fluoroanions of one such type contain at least one ring substituent other than fluorine. These (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium have greater solubility in organic solvents, or have a coordinative ability essentially equal to or less than that of the corresponding (polyfluoroaryl)fluoroanion of aluminum, gallium, or indium in which the substituent is replaced by fluorine. Another type of new (polyfluoroaryl)fluoroanion of aluminum, gallium, and indium have 1-3 perfluorinated fused ring groups and 2-0 perfluorophenyl groups. When used as a cocatalyst in the formation of novel catalytic complexes with d- or f-block metal compounds having at least one leaving group such as a methyl group, these anions, because of their weak coordination to the metal center, do not interfere in the ethylene polymerization process, while affecting the propylene process favorably, if highly isotactic polypropylene is desired. Thus, the (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium of this invention are useful in various polymerization processes such as are described.

  3. Nitrate Reduction Functional Genes and Nitrate Reduction Potentials Persist in Deeper Estuarine Sediments. Why?

    PubMed Central

    Papaspyrou, Sokratis; Smith, Cindy J.; Dong, Liang F.; Whitby, Corinne; Dumbrell, Alex J.; Nedwell, David B.

    2014-01-01

    Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are processes occurring simultaneously under oxygen-limited or anaerobic conditions, where both compete for nitrate and organic carbon. Despite their ecological importance, there has been little investigation of how denitrification and DNRA potentials and related functional genes vary vertically with sediment depth. Nitrate reduction potentials measured in sediment depth profiles along the Colne estuary were in the upper range of nitrate reduction rates reported from other sediments and showed the existence of strong decreasing trends both with increasing depth and along the estuary. Denitrification potential decreased along the estuary, decreasing more rapidly with depth towards the estuary mouth. In contrast, DNRA potential increased along the estuary. Significant decreases in copy numbers of 16S rRNA and nitrate reducing genes were observed along the estuary and from surface to deeper sediments. Both metabolic potentials and functional genes persisted at sediment depths where porewater nitrate was absent. Transport of nitrate by bioturbation, based on macrofauna distributions, could only account for the upper 10 cm depth of sediment. A several fold higher combined freeze-lysable KCl-extractable nitrate pool compared to porewater nitrate was detected. We hypothesised that his could be attributed to intracellular nitrate pools from nitrate accumulating microorganisms like Thioploca or Beggiatoa. However, pyrosequencing analysis did not detect any such organisms, leaving other bacteria, microbenthic algae, or foraminiferans which have also been shown to accumulate nitrate, as possible candidates. The importance and bioavailability of a KCl-extractable nitrate sediment pool remains to be tested. The significant variation in the vertical pattern and abundance of the various nitrate reducing genes phylotypes reasonably suggests differences in their activity throughout the sediment column. This

  4. [Treatment of idiopathic membranous nephropathy. Is the anti-CD20 antibody rituximab a reasonable option?].

    PubMed

    Busch, Martin; Gerth, Jens; Ott, Undine; Schip, Andre; Haufe, Christoph C; Gröne, Hermann-Josef; Wolf, Gunter

    2008-07-15

    Membranous nephropathy (MN) is characterized by proteinuria and other symptoms of the nephrotic syndrome. In many cases, the etiology is unknown. Whether and how to treat MN is still a controversial question. Despite the use of corticosteroids and alkylating agents, up to 40% of patients still progress to end-stage renal failure. A 40-year-old male patient with biopsy-proven idiopathic MN was initially treated with prednisolone and chlorambucil because of a proteinuria of 22 g/d. Treatment with cyclosporine was started because the nephrotic syndrome failed to improve. Proteinuria was reduced to a minimum of 4 g/d. Cyclosporine was stopped after 17 months leading to a fast relapse. Therapy with an ACE inhibitor and AT(1) receptor antagonist and retreatment with cyclosporine improved proteinuria. Cyclosporine was terminated after a total of 24 months. 5 months later, relapse occurred with a high proteinuria of 34 g/d. The monoclonal anti-CD20 antibody rituximab (375 mg/m(2)) was given four times every 4 weeks. 4 weeks and 4 months after the end of treatment, proteinuria decreased to 780 mg/d and <150 mg/d, but renal function remained impaired (creatinine clearance 65 ml/min, stage 2 according to K/DOQI). Now, remission of proteinuria (<150 mg/d) has been stable for almost 2 years. However, renal insufficiency progressed further (creatinine clearance 45 ml/min, stage 3 according to K/DOQI). Rituximab offers the possibility for a targeted treatment of idiopathic MN. Based on the existing evidence and experience from this case, rituximab can be recommended as a new treatment option for MN, possibly before starting any treatment with cytotoxic agents and high-dose prednisolone carrying the risk of severe side effects. However, long-term results of this treatment are still lacking.

  5. Computer simulation of radiation damage in gallium arsenide

    NASA Technical Reports Server (NTRS)

    Stith, John J.; Davenport, James C.; Copeland, Randolph L.

    1989-01-01

    A version of the binary-collision simulation code MARLOWE was used to study the spatial characteristics of radiation damage in proton and electron irradiated gallium arsenide. Comparisons made with the experimental results proved to be encouraging.

  6. Gallium Arsenide Domino Circuit

    NASA Technical Reports Server (NTRS)

    Yang, Long; Long, Stephen I.

    1990-01-01

    Advantages include reduced power and high speed. Experimental gallium arsenide field-effect-transistor (FET) domino circuit replicated in large numbers for use in dynamic-logic systems. Name of circuit denotes mode of operation, which logic signals propagate from each stage to next when successive stages operated at slightly staggered clock cycles, in manner reminiscent of dominoes falling in a row. Building block of domino circuit includes input, inverter, and level-shifting substages. Combinational logic executed in input substage. During low half of clock cycle, result of logic operation transmitted to following stage.

  7. Lacrimal gland uptake of (67)Ga-gallium citrate correlates with biopsy results in patients with suspected sarcoidosis.

    PubMed

    Tannen, Bradford L; Kolomeyer, Anton M; Turbin, Roger E; Frohman, Larry; Langer, Paul D; Oh, Cheongeun; Ghesani, Nasrin V; Zuckier, Lionel S; Chu, David S

    2014-02-01

    To investigate whether lacrimal gland uptake on (67)Ga-gallium citrate scintigraphy correlates with histopathologic evidence of sarcoidosis. A retrospective, pilot study of 31 patients with suspected sarcoidosis who underwent gallium scintigraphy and lacrimal gland biopsy. Lacrimal gland gallium uptake was assessed by subjective visual scoring (SVS) and lacrimal uptake ratio (LUR). Eleven (36%) patients had lacrimal gland biopsies containing noncaseating granulomas. A statistically significant correlation was found between lacrimal gland gallium uptake and biopsy positivity using SVS (p = 0.03) or LUR (p = 0.01). Using SVS, biopsy positivity rate increased from 0 to 50% in patients with mild to intense uptake. Using LUR, biopsy positivity rate increased linearly as the ratio increased from 13% (LUR < 4) to 100% (LUR > 8). Lacrimal biopsy positivity rate significantly correlated with gallium uptake on scintigraphy. Both SVS and LUR methods appear to correlate with histologic results and may potentially aid in patient selection for biopsy.

  8. Organic nitrates and nitrate tolerance--state of the art and future developments.

    PubMed

    Daiber, Andreas; Münzel, Thomas; Gori, Tommaso

    2010-01-01

    The hemodynamic and antiischemic effects of nitroglycerin (GTN) are lost upon chronic administration due to the rapid development of nitrate tolerance. The mechanism of this phenomenon has puzzled several generations of scientists, but recent findings have led to novel hypotheses. The formation of reactive oxygen and nitrogen species in the mitochondria and the subsequent inhibition of the nitrate-bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) appear to play a central role, at least for GTN, that is, bioactivated by ALDH-2. Importantly, these findings provide the opportunity to reconcile the two "traditional" hypotheses of nitrate tolerance, that is, the one postulating a decreased bioactivation and the concurrent one suggesting a role of oxidative stress. Furthermore, recent animal and human experimental studies suggest that the organic nitrates are not a homogeneous group but demonstrate a broad diversity with regard to induction of vascular dysfunction, oxidative stress, and other side effects. In the past, attempts to avoid nitrate-induced side effects have focused on administration schedules that would allow a "nitrate-free interval"; in the future, the role of co-therapies with antioxidant compounds and of activation of endogeneous protective pathways such as the heme oxygenase 1 (HO-1) will need to be explored. However, the development of new nitrates, for example, tolerance-free aminoalkyl nitrates or combination of nitrate groups with established cardiovascular drugs like ACE inhibitors or AT(1)-receptor blockers (hybrid molecules) may be of great clinical interest. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. One Year Follow-Up of Children and Adolescents With Chronic Immune Thrombocytopenic Purpura (ITP) Treated With Rituximab

    PubMed Central

    Mueller, Brigitta U.; Bennett, Carolyn M.; Feldman, Henry A.; Bussel, James B.; Abshire, Thomas C.; Moore, Theodore B.; Sawaf, Hadi; Loh, Mignon L.; Rogers, Zora R.; Glader, Bertil E.; McCarthy, Maggie C.; Mahoney, Donald H.; Olson, Thomas A.; Feig, Stephen A.; Lorenzana, Adonis N.; Mentzer, William C.; Buchanan, George R.; Neufeld, Ellis J.

    2017-01-01

    Background We previously showed in a prospective study that rituximab appears to be effective in some children and adolescents with severe chronic immune thrombocytopenia. Eleven of 36 patients achieved and maintained platelet counts over 50,000/mm3 within the first 12 weeks. These patients were followed for the next year. Methods Platelet counts were monitored monthly and all subsequent bleeding manifestations and need for further treatment was noted. Results Eight of the 11 initial responders maintained a platelet count over 150,000/mm3 without further treatment intervention. Three patients had a late relapse. One initial non-responder achieved a remission after 16 weeks, and two additional patients maintained platelet counts around 50,000/mm3 without the need for further intervention. Conclusions Rituximab resulted in sustained efficacy with platelet counts of 50,000/mm3 or higher in 11 of 36 patients (31%). PMID:18937333

  10. Thermochemical nitrate destruction

    DOEpatents

    Cox, John L.; Hallen, Richard T.; Lilga, Michael A.

    1992-01-01

    A method is disclosed for denitrification of nitrates and nitrates present in aqueous waste streams. The method comprises the steps of (1) identifying the concentration nitrates and nitrites present in a waste stream, (2) causing formate to be present in the waste stream, (3) heating the mixture to a predetermined reaction temperature from about 200.degree. C. to about 600.degree. C., and (4) holding the mixture and accumulating products at heated and pressurized conditions for a residence time, thereby resulting in nitrogen and carbon dioxide gas, and hydroxides, and reducing the level of nitrates and nitrites to below drinking water standards.

  11. [Successful treatment with rituximab in a patient with splenic marginal zone B-cell lymphoma accompanied by cold agglutinin disease].

    PubMed

    Yasuyama, Masako; Kawauchi, Kiyotaka; Otsuka, Kuniaki; Tamura, Hiroyuki; Fujibayashi, Mariko

    2014-01-01

    An 81-year-old man was admitted to our hospital due to dyspnea in July 2008. A physical examination revealed marked splenomegaly, and the results of laboratory tests were as follows: hemoglobin (Hb)=7.0 g/dL, Ret=6.4%, WBC=24,100/μL (Ly: 20,003/μL), indirect bilirubin=3.6 mg/dL, LDH=232 IU/L. The cold agglutinin titer was 1 : 8,192, and a direct antiglobulin test was positive. A PET scan showed abnormal accumulation in the spleen and bone marrow. A bone marrow aspirate examination and biopsy demonstrated diffuse involvement of abnormal lymphocytes that were found to be positive for CD20 and negative for CD5, CD10, and cyclin D1. The immunoglobulin genes were clonally rearranged. Based on these findings, splenic marginal zone B-cell lymphoma (SMZL) associated with cold agglutinin disease (CAD) was diagnosed. Because the patient refused splenectomy, he was treated with four cycles of rituximab therapy (375 mg/kg, once a week). The Hb level and lymphocyte count subsequently normalized and the splenomegaly resolved. One year later, he relapsed and was again treated with rituximab therapy with complete remission. CAD accompanied by SMZL is very rare. Rituximab may be chosen as an alternative and effective therapeutic option in patients with SMZL-particularly those with autoimmune hemolytic anemia.

  12. Liquid gallium and the eutectic gallium indium (EGaIn) alloy: Dielectric functions from 1.24 to 3.1 eV by electrochemical reduction of surface oxides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morales, Daniel; Yu, Zhiyuan; Dickey, Michael D., E-mail: mddickey@ncsu.edu, E-mail: aspnes@ncsu.edu

    Liquid metals based on gallium are promising materials for soft, stretchable, and shape reconfigurable electromagnetic devices. The behavior of these metals relates directly to the thicknesses of their surface oxide layers, which can be determined nondestructively by ellipsometry if their dielectric functions ε are known. This paper reports on the dielectric functions of liquid gallium and the eutectic gallium indium (EGaIn) alloy from 1.24 to 3.1 eV at room temperature, measured by spectroscopic ellipsometry. Overlayer-induced artifacts, a continuing problem in optical measurements of these highly reactive metals, are eliminated by applying an electrochemically reductive potential to the surface of the metalmore » immersed in an electrolyte. This technique enables measurements at ambient conditions while avoiding the complications associated with removing overlayers in a vacuum environment. The dielectric responses of both metals are closely represented by the Drude model. The EGaIn data suggest that in the absence of an oxide the surface is In-enriched, consistent with the previous vacuum-based studies. Possible reasons for discrepancies with previous measurements are discussed.« less

  13. Gallium scintigraphic pattern in lung CMV infections

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ganz, W.I.; Cohen, D.; Mallin, W.

    1994-05-01

    Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patientsmore » without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.« less

  14. Isolation and characterization of gallium resistant Pseudomonas aeruginosa mutants.

    PubMed

    García-Contreras, Rodolfo; Lira-Silva, Elizabeth; Jasso-Chávez, Ricardo; Hernández-González, Ismael L; Maeda, Toshinari; Hashimoto, Takahiro; Boogerd, Fred C; Sheng, Lili; Wood, Thomas K; Moreno-Sánchez, Rafael

    2013-12-01

    Pseudomonas aeruginosa PA14 cells resistant to the novel antimicrobial gallium nitrate (Ga) were developed using transposon mutagenesis and by selecting spontaneous mutants. The mutants showing the highest growth in the presence of Ga were selected for further characterization. These mutants showed 4- to 12-fold higher Ga minimal inhibitory growth concentrations and a greater than 8-fold increase in the minimum biofilm eliminating Ga concentration. Both types of mutants produced Ga resistant biofilms whereas the formation of wild-type biofilms was strongly inhibited by Ga. The gene interrupted in the transposon mutant was hitA, which encodes a periplasmic iron binding protein that delivers Fe³⁺ to the HitB iron permease; complementation of the mutant with the hitA gene restored the Ga sensitivity. This hitA mutant showed a 14-fold decrease in Ga internalization versus the wild-type strain, indicating that the HitAB system is also involved in the Ga uptake. Ga uptake in the spontaneous mutant was also lower, although no mutations were found in the hitAB genes. Instead, this mutant harbored 64 non-silent mutations in several genes including those of the phenazine pyocyanin biosynthesis. The spontaneous mutant produced 2-fold higher pyocyanin basal levels than the wild-type; the addition of this phenazine to wild-type cultures protected them from the Ga bacteriostatic effect. The present data indicate that mutations affecting Ga transport and probably pyocyanin biosynthesis enable cells to develop resistance to Ga. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. Optical properties of bismuth and gallium substituted thulium iron garnet films

    NASA Astrophysics Data System (ADS)

    Gerhardt, R.; Sure, S.; Dötsch, H.; Linkewitz, T.; Tolksdorf, W.

    1993-09-01

    Bismuth and gallium substituted films of thulium iron garnet, grown by liquid phase epitaxy on [111] oriented substrates of gadolinium gallium garnet, are investigated for optical isolator applications. At a wavelength of λ = 1.3 μm the optical damping, the refractive index, the optical anisotropy, and the Faraday rotation are measured as function of the substitution level. It turns out that the growth induced optical anisotropy is very small, similar to the magnetic anisotropy. The observed difference between forward and backward propagation constants of TM modes is in excellent agreement with calculations.

  16. Assessment of arsenic exposures and controls in gallium arsenide production.

    PubMed

    Sheehy, J W; Jones, J H

    1993-02-01

    The electronics industry is expanding the use of gallium arsenide in the production of optoelectronic devices and integrated circuits. Workers in the electronics industry using gallium arsenide are exposed to hazardous substances such as arsenic, arsine, and various acids. Arsenic requires stringent controls to minimize exposures (the current OSHA PEL for arsenic is 10 micrograms/m3 and the NIOSH REL is 2 micrograms/m3 ceiling). Inorganic arsenic is strongly implicated in respiratory tract and skin cancer. For these reasons, NIOSH researchers conducted a study of control systems for facilities using gallium arsenide. Seven walk-through surveys were performed to identify locations for detailed study which appeared to have effective controls; three facilities were chosen for in-depth evaluation. The controls were evaluated by industrial hygiene sampling. Including personal breathing zone and area air sampling for arsenic and arsine; wipe samples for arsenic also were collected. Work practices and the use of personal protective equipment were documented. This paper reports on the controls and the arsenic exposure results from the evaluation of the following gallium arsenide processes: Liquid Encapsulated Czochralski (LEC) and Horizontal Bridgeman (HB) crystal growing, LEC cleaning operations, ingot grinding/wafer sawing, and epitaxy. Results at one plant showed that in all processes except epitaxy, average arsenic exposures were at or above the OSHA action level of 5 micrograms/m3. While cleaning the LEC crystal pullers, the average potential arsenic exposure of the cleaning operators was 100 times the OSHA PEL. At the other two plants, personal exposures for arsenic were well controlled in LEC, LEC cleaning, grinding/sawing, and epitaxy operations.

  17. Haemophilus parainfluenzae bacteremia associated with a pacemaker wire localized by gallium scan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rosenbaum, G.S.; Calubiran, O.; Cunha, B.A.

    1990-05-01

    A young woman with a history of sick sinus syndrome and placement of a permanent pacemaker 6 months before admission had fever and Haemophilus parainfluenzae bacteremia. A gallium scan localized the infection to the site of the pacemaker wire. Echocardiograms were negative for any vegetations. The patient responded to cefotaxime and trimethoprim-sulfamethoxazole therapy. We believe that this is the first case of H. parainfluenzae bacteremia associated with a pacemaker wire and localized by gallium scan.

  18. Influence of various factors on the accuracy of gallium-67 imaging for occult infection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maderazo, E.G.; Hickingbotham, N.B.; Woronick, C.L.

    1988-05-01

    To examine whether the results and interpretation of gallium-67 citrate imaging may be adversely influenced by factors present in compromised patients, we reviewed our 1-year experience in 69 patients in intensive care units, renal transplants, and those on hemodialysis. Our results indicate that it is an inappropriate diagnostic procedure for acute pancreatitis since seven of nine had false-negative results. Using loglinear modeling and chi-square analysis we found that treatment with antiinflammatory steroids, severe liver disease, end-stage renal disease, and renal transplantation with immunosuppressive therapy did not interfere with gallium-67 uptake. Increased rate of true-negative results in patients with end-stage renalmore » disease was due to a greater and earlier use of the test in the febrile transplant patient and in hemodialysis patients with infections not amenable to diagnosis with gallium-67 scan (transient bacteremia and bacteriuria). We conclude that gallium-67 imaging is a useful diagnostic tool that, with the exception of acute pancreatitis, has very few false-negative results.« less

  19. Sodium Flux Growth of Bulk Gallium Nitride

    NASA Astrophysics Data System (ADS)

    Von Dollen, Paul Martin

    This dissertation focused on development of a novel apparatus and techniques for crystal growth of bulk gallium nitride (GaN) using the sodium flux method. Though several methods exist to produce bulk GaN, none have been commercialized on an industrial scale. The sodium flux method offers potentially lower cost production due to relatively mild process conditions while maintaining high crystal quality. But the current equipment and methods for sodium flux growth of bulk GaN are generally not amenable to large-scale crystal growth or in situ investigation of growth processes, which has hampered progress. A key task was to prevent sodium loss or migration from the sodium-gallium growth melt while permitting N2 gas to access the growing crystal, which was accomplished by implementing a reflux condensing stem along with a reusable sealed capsule. The reflux condensing stem also enabled direct monitoring and control of the melt temperature, which has not been previously reported for the sodium flux method. Molybdenum-based materials were identified from a corrosion study as candidates for direct containment of the corrosive sodium-gallium melt. Successful introduction of these materials allowed implementation of a crucible-free containment system, which improved process control and can potentially reduce crystal impurity levels. Using the new growth system, the (0001) Ga face (+c plane) growth rate was >50 mum/hr, which is the highest bulk GaN growth rate reported for the sodium flux method. Omega X-ray rocking curve (?-XRC) measurements indicated the presence of multiple grains, though full width at half maximum (FWHM) values for individual peaks were <100 arcseconds. Oxygen impurity concentrations as measured by secondary ion mass spectroscopy (SIMS) were >1020 atoms/cm3, possibly due to reactor cleaning and handling procedures. This dissertation also introduced an in situ technique to correlate changes in N2 pressure with dissolution of nitrogen and precipitation of

  20. A Comparison of Gallium and Indium Alkoxide Complexes as Catalysts for Ring-Opening Polymerization of Lactide.

    PubMed

    Kremer, Alexandre B; Andrews, Ryan J; Milner, Matthew J; Zhang, Xu R; Ebrahimi, Tannaz; Patrick, Brian O; Diaconescu, Paula L; Mehrkhodavandi, Parisa

    2017-02-06

    The impact of the metal size and Lewis acidity on the polymerization activity of group 13 metal complexes was studied, and it was shown that, within the same ligand family, indium complexes are far more reactive and selective than their gallium analogues. To this end, gallium and aluminum complexes supported by a tridentate diaminophenolate ligand, as well as gallium complexes supported by N,N'-ethylenebis(salicylimine)(salen) ligands, were synthesized and compared to their indium analogues. Using the tridentate ligand set, it was possible to isolate the gallium chloride complexes 3 and (±)-4 and the aluminum analogues 5 and (±)-6. The alkoxygallium complex (±)-2, supported by a salen ligand, was also prepared and characterized and, along with the three-component system GaCl 3 /BnOH/NEt 3 , was tested for the ring-opening polymerization of lactide and ε-caprolactone. The polymerization rates and selectivities of both systems were significantly lower than those for the indium analogues. The reaction of (±)-2 with 1 equiv of lactide forms the first insertion product, which is stable in solution and can be characterized at room temperature. In order to understand the differences of the reactivity within the group 13 metal complexes, a Lewis acidity study using triethylphosphine oxide (the Gutmann-Beckett method) was undertaken for a series of aluminum, gallium, and indium halide complexes; this study shows that indium halide complexes are less Lewis acidic than their aluminum and gallium analogues. Density functional theory calculations show that the Mulliken charges for the indium complexes are higher than those for the gallium analogues. These data suggest that the impact of ligands on the reactivity is more significant than that of the metal Lewis acidity.

  1. 49 CFR 176.410 - Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures. 176.410 Section 176.410 Transportation Other Regulations Relating to... nitrate and ammonium nitrate mixtures. (a) This section prescribes requirements to be observed with...

  2. 49 CFR 176.410 - Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures. 176.410 Section 176.410 Transportation Other Regulations Relating to... nitrate and ammonium nitrate mixtures. (a) This section prescribes requirements to be observed with...

  3. 49 CFR 176.410 - Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures. 176.410 Section 176.410 Transportation Other Regulations Relating to... nitrate and ammonium nitrate mixtures. (a) This section prescribes requirements to be observed with...

  4. 49 CFR 176.410 - Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Division 1.5 materials, ammonium nitrate and ammonium nitrate mixtures. 176.410 Section 176.410 Transportation Other Regulations Relating to... nitrate and ammonium nitrate mixtures. (a) This section prescribes requirements to be observed with...

  5. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

    PubMed

    Daiber, Andreas; Münzel, Thomas

    2015-10-10

    Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

  6. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

    PubMed Central

    2015-01-01

    Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

  7. First-principles melting of gallium clusters down to nine atoms: structural and electronic contributions to melting.

    PubMed

    Steenbergen, Krista G; Gaston, Nicola

    2013-10-07

    First-principles Born-Oppenheimer molecular dynamics simulations of small gallium clusters, including parallel tempering, probe the distinction between cluster and molecule in the size range of 7-12 atoms. In contrast to the larger sizes, dynamic measures of structural change at finite temperature demonstrate that Ga7 and Ga8 do not melt, suggesting a size limit to melting in gallium exists at 9 atoms. Analysis of electronic structure further supports this size limit, additionally demonstrating that a covalent nature cannot be identified for clusters larger than the gallium dimer. Ga9, Ga10 and Ga11 melt at greater-than-bulk temperatures, with no evident covalent character. As Ga12 represents the first small gallium cluster to melt at a lower-than-bulk temperature, we examine the structural properties of each cluster at finite temperature in order to probe both the origins of greater-than-bulk melting, as well as the significant differences in melting temperatures induced by a single atom addition. Size-sensitive melting temperatures can be explained by both energetic and entropic differences between the solid and liquid phases for each cluster. We show that the lower-than-bulk melting temperature of the 12-atom cluster can be attributed to persistent pair bonding, reminiscent of the pairing observed in α-gallium. This result supports the attribution of greater-than-bulk melting in gallium clusters to the anomalously low melting temperature of the bulk, due to its dimeric structure.

  8. (Polyfluoroaryl)fluoroanions of aluminum, gallium, and indium of enhanced utility, uses thereof, and products based thereon

    DOEpatents

    Marks, Tobin J.; Chen, You-Xian

    2001-01-01

    The (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium are novel weakly coordinating anions which are are highly fluorinated. (Polyfluoroaryl)fluoroanions of one such type contain at least one ring substituent other than fluorine. These (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium have greater solubility in organic solvents, or have a coordinative ability essentially equal to or less than that of the corresponding (polyfluoroaryl)fluoroanion of aluminum, gallium, or indium in which the substituent is replaced by fluorine. Another type of new (polyfluoroaryl)fluoroanion of aluminum, gallium, and indium have 1-3 perfluorinated fused ring groups and 2-0 perfluorophenyl groups. When used as a cocatalyst in the formation of novel catalytic complexes with d- or f-block metal compounds having at least one leaving group such as a methyl group, these anions, because of their weak coordination to the metal center, do not interefere in the ethylene polymerization process, while affecting the the propylene process favorably, if highly isotactic polypropylene is desired. Thus, the (polyfluoroaryl)fluoroanions of aluminum, gallium, and indium of this invention are useful in various polymerization processes such as are described.

  9. First principles study of gallium cleaning for hydrogen-contaminated α-Al2O3(0001) surfaces.

    PubMed

    Yang, Rui; Rendell, Alistair P

    2013-05-15

    The use of gallium for cleaning hydrogen-contaminated Al2O3 surfaces is explored by performing first principles density functional calculations of gallium adsorption on a hydrogen-contaminated Al-terminated α-Al2O3(0001) surface. Both physisorbed and chemisorbed H-contaminated α-Al2O3(0001) surfaces with one monolayer (ML) gallium coverage are investigated. The thermodynamics of gallium cleaning are considered for a variety of different asymptotic products, and are found to be favorable in all cases. Physisorbed H atoms have very weak interactions with the Al2O3 surface and can be removed easily by the Ga ML. Chemisorbed H atoms form stronger interactions with the surface Al atoms. Bonding energy analysis and departure simulations indicate, however, that chemisorbed H atoms can be effectively removed by the Ga ML. Copyright © 2013 Wiley Periodicals, Inc.

  10. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA

    PubMed Central

    Fitoussi, Olivier; Belhadj, Karim; Mounier, Nicolas; Parrens, Marie; Tilly, Hervé; Salles, Gilles; Feugier, Pierre; Ferme, Christophe; Ysebaert, Loic; Gabarre, Jean; Herbrecht, Raoul; Janvier, Maud; Van Den Neste, Eric; Morschhauser, Franck; Casasnovas, Olivier; Ghesquieres, Hervé; Anglaret, Bruno; Brechignac, Sabine; Haioun, Corinne; Gisselbrecht, Christian

    2011-01-01

    Background As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival. Design and Methods The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial. Results With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69–81) and 78% (CI: 72–83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494). Conclusions In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches. (Clinicaltrials.gov identifier: NCT00144807) PMID:21546499

  11. Formation, Evaporation, and Hydrolysis of Organic Nitrates from Nitrate Radical Oxidation of Monoterpenes

    NASA Astrophysics Data System (ADS)

    Ng, N. L.; Takeuchi, M.; Eris, G.; Berkemeier, T.; Boyd, C.; Nah, T.; Xu, L.

    2017-12-01

    Organic nitrates play an important role in the cycling of NOx and secondary organic aerosol (SOA) formation, yet their formation mechanisms and fates remain highly uncertain. The interactions of biogenic VOCs with NO3 radicals represent a direct way for positively linking anthropogenic and biogenic emissions. Results from ambient studies suggest that organic nitrates have a relatively short lifetime, though corresponding laboratory data are limited. SOA and organic nitrates produced at night may evaporate the following morning due to increasing temperatures or dilution of semi-volatile compounds. Once formed, organic nitrates can also undergo hydrolysis in the presence of particle water. In this work, we investigate the formation, evaporation, and hydrolysis of organic nitrates generated from the nitrate radical oxidation of a-pinene, b-pinene, and limonene. Experiments are conducted in the Georgia Environmental Chamber facility (GTEC) under dry and humid conditions and different temperatures. Experiments are also designed to probe different peroxy radical pathways (RO2+HO2 vs RO2+NO3). Speciated gas-phase and particle-phase organic nitrates are continuously monitored by a Filter Inlet for Gases and AEROsols High Resolution Time-of-Flight Chemical Ionization Mass Spectrometer (FIGAERO-HR-ToF-CIMS). Bulk aerosol composition is measured by a High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS). A large suite of highly oxygenated gas- and particle-phase organic nitrates are formed rapidly. We find a resistance to aerosol evaporation when it is heated. The extent of organic nitrate hydrolysis in the humid experiments is evaluated. The dynamics of the speciated organic nitrates over the course of the experiments will also be discussed. Results from this chamber study provide fundamental data for understanding the dynamics of organic nitrate aerosols over its atmospheric lifetime.

  12. Preclinical characterization of anticancer gallium(III) complexes: solubility, stability, lipophilicity and binding to serum proteins.

    PubMed

    Rudnev, Alexander V; Foteeva, Lidia S; Kowol, Christian; Berger, Roland; Jakupec, Michael A; Arion, Vladimir B; Timerbaev, Andrei R; Keppler, Bernhard K

    2006-11-01

    The discovery and development of gallium(III) complexes capable of inhibiting tumor growth is an emerging area of anticancer drug research. A range of novel gallium coordination compounds with established cytotoxic efficacy have been characterized in terms of desirable chemical and biochemical properties and compared with tris(8-quinolinolato)gallium(III) (KP46), a lead anticancer gallium-based candidate that successfully finished phase I clinical trials (under the name FFC11), showing activity against renal cell cancer. In view of probable oral administration, drug-like parameters, such as solubility in water, saline and 0.5% dimethyl sulfoxide, stability against hydrolysis, measured as the rate constant of hydrolytic degradation in water or physiological buffer using a capillary zone electrophoresis (CZE) assay, and the octanol-water partition coefficient (logP) providing a rational estimate of a drug's lipophilicity, have been evaluated and compared. The differences in bioavailability characteristics between different complexes were discussed within the formalism of structure-activity relationships. The reactivity toward major serum transport proteins, albumin and transferrin, was also assayed in order to elucidate the drug's distribution pathway after intestinal absorption. According to the values of apparent binding rate constants determined by CZE, both KP46 and bis(2-acetylpyridine-4,4-dimethyl-3-thiosemicarbazonato-N,N,S)gallium(III) tetrachlorogallate(III) (KP1089) bind to transferrin faster than to albumin. This implies that transferrin would rather mediate the accumulation of gallium antineoplastic agents in solid tumors. A tendency of being faster converted into the protein-bound form found for KP1089 (due possibly to non-covalent binding) seems complementary to its greater in vitro antiproliferative activity.

  13. Rituximab Restores IFN-γ-STAT1 Function and Ameliorates Disseminated Mycobacterium avium Infection in a Patient with Anti-Interferon-γ Autoantibody.

    PubMed

    Koizumi, Yusuke; Sakagami, Takuro; Nishiyama, Naoya; Hirai, Jun; Hayashi, Yuta; Asai, Nobuhiro; Yamagishi, Yuka; Kato, Hideo; Hagihara, Mao; Sakanashi, Daisuke; Suematsu, Hiroyuki; Ogawa, Kenji; Mikamo, Hiroshige

    2017-10-01

    A 67-year-old Japanese female with back pain and severe cachexia visited our hospital. The diagnosis was disseminated Mycobacterium avium complex infection (dMAC) with multiple bone involvement. Anti-mycobacterial chemotherapy was started, but fever persisted and dislocation of cervical vertebrae has made her bedridden. Because anti-interferon (IFN)-γ autoantibody was positive, four doses of rituximab 375 mg/m 2 , every 7 day, were administered. Soon after treatment, progression of osteolytic lesions and wasting has stopped. We proved that rituximab has recovered IFN-γ signaling as shown by IFN-γ-induced STAT1 phosphorylation. It can be a promising option for dMAC cases with anti-IFN-γ autoantibody.

  14. Evaluation of 89Zr-rituximab tracer by Cerenkov luminescence imaging and correlation with PET in a humanized transgenic mouse model to image NHL.

    PubMed

    Natarajan, Arutselvan; Habte, Frezghi; Liu, Hongguang; Sathirachinda, Ataya; Hu, Xiang; Cheng, Zhen; Nagamine, Claude M; Gambhir, Sanjiv Sam

    2013-08-01

    This research aimed to study the use of Cerenkov luminescence imaging (CLI) for non-Hodgkin's lymphoma (NHL) using 89Zr-rituximab positron emission tomography (PET) tracer with a humanized transgenic mouse model that expresses human CD20 and the correlation of CLI with PET. Zr-rituximab (2.6 MBq) was tail vein-injected into transgenic mice that express the human CD20 on their B cells (huCD20TM). One group (n=3) received 2 mg/kg pre-dose (blocking) of cold rituximab 2 h prior to tracer; a second group (n=3) had no pre-dose (non-blocking). CLI was performed using a cooled charge-coupled device optical imager. We also performed PET imaging and ex vivo studies in order to confirm the in vivo CLI results. At each time point (4, 24, 48, 72, and 96 h), two groups of mice were imaged in vivo and ex vivo with CLI and PET, and at 96 h, organs were measured by gamma counter. huCD20 transgenic mice injected with 89Zr-rituximab demonstrated a high-contrast CLI image compared to mice blocked with a cold dose. At various time points of 4-96 h post-radiotracer injection, the in vivo CLI signal intensity showed specific uptake in the spleen where B cells reside and, hence, the huCD20 biomarker is present at very high levels. The time-activity curve of dose decay-corrected CLI intensity and percent injected dose per gram of tissue of PET uptake in the spleen were increased over the time period (4-96 h). At 96 h, the 89Zr-rituximab uptake ratio (non-blocking vs blocking) counted (mean±standard deviation) for the spleen was 1.5±0.6 for CLI and 1.9±0.3 for PET. Furthermore, spleen uptake measurements (non-blocking and blocking of all time points) of CLI vs PET showed good correlation (R2=0.85 and slope=0.576), which also confirmed the corresponding correlations parameter value (R2=0.834 and slope=0.47) obtained for ex vivo measurements. CLI and PET of huCD20 transgenic mice injected with 89Zr-rituximab demonstrated that the tracer was able to target huCD20-expressing B cells. The in

  15. Mathematical Description Development of Reactions of Metallic Gallium Using Kinetic Block Diagram

    NASA Astrophysics Data System (ADS)

    Yakovleva, A. A.; Soboleva, V. G.; Filatova, E. G.

    2018-05-01

    A kinetic block diagram based on a logical sequence of actions in the mathematical processing of a kinetic data is used. A type of reactions of metallic gallium in hydrochloric acid solutions is determined. It has been established that the reactions of the formation of gallium oxide and its salts proceed independently and in the absence of the diffusion resistance. Kinetic models connecting the constants of the reaction rate with the activation energy and describing the evolution of the process are obtained.

  16. Cylodextrin Polymer Nitrate

    NASA Technical Reports Server (NTRS)

    Kosowski, Bernard; Ruebner, Anja; Statton, Gary; Robitelle, Danielle; Meyers, Curtis

    2000-01-01

    The development of the use of cyclodextrin nitrates as possible components of insensitive, high-energy energetics is outlined over a time period of 12 years. Four different types of cyclodextrin polymers were synthesized, nitrated, and evaluated regarding their potential use for the military and aerospace community. The synthesis of these novel cyclodextrin polymers and different nitration techniques are shown and the potential of these new materials is discussed.

  17. Is beetroot juice more effective than sodium nitrate? The effects of equimolar nitrate dosages of nitrate-rich beetroot juice and sodium nitrate on oxygen consumption during exercise.

    PubMed

    Flueck, Joelle Leonie; Bogdanova, Anna; Mettler, Samuel; Perret, Claudio

    2016-04-01

    Dietary nitrate has been reported to lower oxygen consumption in moderate- and severe-intensity exercise. To date, it is unproven that sodium nitrate (NaNO3(-); NIT) and nitrate-rich beetroot juice (BR) have the same effects on oxygen consumption, blood pressure, and plasma nitrate and nitrite concentrations or not. The aim of this study was to compare the effects of different dosages of NIT and BR on oxygen consumption in male athletes. Twelve healthy, well-trained men (median [minimum; maximum]; peak oxygen consumption: 59.4 mL·min(-1)·kg(-1) [40.5; 67.0]) performed 7 trials on different days, ingesting different nitrate dosages and placebo (PLC). Dosages were 3, 6, and 12 mmol nitrate as concentrated BR or NIT dissolved in plain water. Plasma nitrate and nitrite concentrations were measured before, 3 h after ingestion, and postexercise. Participants cycled for 5 min at moderate intensity and further 8 min at severe intensity. End-exercise oxygen consumption at moderate intensity was not significantly different between the 7 trials (p = 0.08). At severe-intensity exercise, end-exercise oxygen consumption was ~4% lower in the 6-mmol BR trial compared with the 6-mmol NIT (p = 0.003) trial as well as compared with PLC (p = 0.010). Plasma nitrite and nitrate concentrations were significantly increased after the ingestion of BR and NIT with the highest concentrations in the 12-mmol trials. Plasma nitrite concentration between NIT and BR did not significantly differ in the 6-mmol (p = 0.27) and in the 12-mmol (p = 0.75) trials. In conclusion, BR might reduce oxygen consumption to a greater extent compared with NIT.

  18. Application of Copper Indium Gallium Diselenide Photovoltaic Cells to Extend the Endurance and Capabilities of Unmanned Aerial Vehicles

    DTIC Science & Technology

    2009-09-01

    Group V element to make them n or p material. Another common group of semiconductors are called III–V compounds , such as gallium arsenide (GaAs), or...these compounds used for photovoltaics are Cadmium Telluride (CdTe), and Copper Indium Gallium DiSelenide, commonly referred to as CIGS [49]. Figure...INDIUM GALLIUM DISELENIDE PHOTOVOLTAIC CELLS TO EXTEND THE ENDURANCE AND CAPABILITIES OF UNMANNED AERIAL VEHICLES by William R. Hurd

  19. Evidence for the bias-driven migration of oxygen vacancies in amorphous non-stoichiometric gallium oxide

    NASA Astrophysics Data System (ADS)

    Guo, D. Y.; Qian, Y. P.; Su, Y. L.; Shi, H. Z.; Li, P. G.; Wu, J. T.; Wang, S. L.; Cui, C.; Tang, W. H.

    2017-06-01

    The conductivity of gallium oxide thin films is strongly dependent on the growth temperature when they deposited by pulsed laser deposition under vacuum environment, exhibiting an insulative-to-metallic transition with the decrease of the temperature. The high conductive gallium oxide films deposited at low temperature are amorphous, non-stoichiometric, and rich in oxygen vacancy. Large changes in electrical resistance are observed in these non-stoichiometric thin films. The wide variety of hysteretic shapes in the I-V curves depend on the voltage-sweep rate, evidencing that the time-dependent redistribution of oxygen vacancy driven by bias is the controlling parameter for the resistance of gallium oxide.

  20. 49 CFR 176.415 - Permit requirements for Division 1.5, ammonium nitrates, and certain ammonium nitrate fertilizers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... nitrates, and certain ammonium nitrate fertilizers. 176.415 Section 176.415 Transportation Other... requirements for Division 1.5, ammonium nitrates, and certain ammonium nitrate fertilizers. (a) Except as... Captain of the Port (COTP). (1) Ammonium nitrate UN1942, ammonium nitrate fertilizers containing more than...